Race 2020

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RACE 2020
Ramachandra Anesthesia Continuing Education
January 24th to 26th, 2020
Department of Anesthesiology and Pain Medicine

Sri Ramachandra Institute of Higher Education and Research
(Deemed to be University), Porur,Chennai
PREFACE
It is a New Year, with new beginnings, new opportunities, new dreams, new hopes, new people to meet, new memories
to create. It also brings with it the newest, latest edition of RACE, an acronym for “Ramachandra Anesthesia Continuing
Education”, which is by the way in its successful 21st year. It has been a wonderful journey so far.
Start where you are, Use what you have, Do what you can …Arthur Ashe
What started as a small program for about 200 delegates in the year 2000 has transformed today into an academic
gathering of more than 1000 people from all over the country and the world. We feel humbled by your response and feel
greatly responsible for ensuring we provide you with what you came for.
The oration this year is by a great anesthesiologist, a teacher par excellence, a clinician of great prowess and above all, a
great human being and a fine gentleman. It is none other than Prof. Pankaj Kundra, who is Dean(Academic) and Professor
of Anesthesiology at JIPMER. The topic he has chosen for the oration is very apt and relevant to this current era – “Being
a responsible anesthesiologist”.
What does being a responsible anesthesiologist mean? It means putting the patient’s safety above everything else, above
convenience and comfort (whether it is ours or the surgeons), above petty politics and above our ego. It is about ceasing to
complain and criticize and instead making the optimal use of what is available to give our best. It is about staying calm and
composed in the middle of chaos, but staying focused on the goal. It is about being prepared with necessary knowledge
and skills. It is about adopting tact and diplomacy to do what we must. I can’t wait to listen to Prof. Kundra and learn from
all that he has to share.
If I have seen further, it is by standing on the shoulders of giants …Isaac Newton
We have excellent faculty this year, the “Giants” of anesthesiology, teachers and clinicians who have as usual spared time
from their frenetic schedules to be here and enlighten us with their experience. The topics this year cover the entire spectrum
of anesthesia from basic sciences to recent advances. We have an assortment of lectures, How I do it sessions, focus
sessions, video sessions, SNAP sessions, case discussion and workshops. The workshops this year are on mechanical
ventilation, anesthesia machine and other equipments.
What’s new this year? We have a special session on Target controlled infusions by eminent international faculties, who
are masters in the field.To underscore this year, which is 2020, we have a special session called 20/20, where twenty facts
about a particular topic would be discussed in 20 minutes. We are also planning to provide you with “Watchout facts” as
Questions and Answers through “Telegram” with prize for the first delegate answering them correctly. With all this, the three
days at “RACE” augur an enjoyable acquisition of anesthesia knowledge.
Good company in a journey makes the way seem shorter ...Izaak Walton
The entire department of Anesthesiology at Sri Ramachandra Institute of Higher Education and Research has been behind
the preparations and planning, making tough days easier to bear. Dr. Ramkumar is the organizing secretary this year and
is at the helm of affairs. He has had advice and support from all the seniors, Prof. Mahesh Vakamudi, Prof. Akilandeswari,
Prof. Ranjith Karthekeyan, Prof. Tamaraiselvi, Prof. Jayaraman, Prof. Venkatesh and Dr. Arulmurugan. All the others have
contributed in one way or the other. Every single person is responsible in some small or big way for all that you see.
Preface
Don’t watch the clock. Do what it does. Keep going. …Sam Levenson
Every year, the sessions in RACE are in fact a “RACE” against time and we have to keep going at a frenzied pace. Our aim
has always been to give you a surplus, a superabundance of academics, much more than what you had come for and we
hope we accomplish that, this year as well. Don’t count the hours. Make the hours count. Learn all you can from the doyens
around and carry it back home to practice and perfect it.
We hope you have a terrific three days with us and go back with great memories. We hope you come back year after year,
because it is all of you who make RACE what it is.
Wishing you all a wonderful New Year….
Dr. Aruna Parameswari

On behalf of the Anesthesia Family
Sri Ramachandra Medical College and Research Institute
SRIHER
CONTENTS
BASIC SCIENCE LECTURES
1. Physics of flow – Fick, Venturi, Laminar, and Turbulent flow Dr. Gurudatt C L 3
2. Preload, Afterload and Contractility Dr. Harishbabu Ravulapalli 17
3. Pharmacokinetics of Inhalational Anesthetics Dr. Aruna Parameswari 25
4. Pharmacokinetics of Intravenous anesthetics Dr. Pankaj Kundra 47
5. Physiology of gas exchange during anesthesia Dr. Naheed Azar 55
6. Heart Lung Coordination Dr. Jigi Divatia 63
CLINICAL LECTURES
7. Management of obstetric hemorrhage Dr. Sunanda Gupta 75
8. Anesthetic management of elderly patient for truamatic hip surgery Dr. Balavenkata Subramanian J 89
9. Anesthesia for scoliosis correction Dr. Anju Grewal 97
10. Pancreatic malignancy with obstructive jaundice for Whipple’s procedure Dr. Akilandeswari M 109
11. Anesthesia for neonatal emergencies Dr. Anila Malde 115
12. Damage control resuscitation in trauma Dr. Sudarsan Kasthuri 137
FOCUS SESSIONS
13. Perioperative pharmacological risk reduction strategies in patients with MI Dr. Ranjith B Karthekeyan 145
14. History of development of anesthesia practice Dr. David B. Waisel 151
15. Dexmedetomidine in NORA Dr. Keira Mason 153
16. Sepsis - Current update Dr. Chinyere Egbuta 155
17. Traumatic brain injury - Dogma & controversies Dr. Padmaja Durga 159
18. Starlings equation - Understanding the physiology Dr. HM Krishna 177
19. Interpreting chest X rays Dr. Anupama Chandrasekaran 183
20. Depth of anesthesia - Concepts and monitoring Dr. Seema Deshpande 193
Contents
21. Monitoring intraoperative coagulopathy Dr. Bhavani Shankar Kodali 205
22. Anesthetic management of brain dead donor for organ retrieval Dr. Jayanti Shankar 213
23. Preeclampsia- Current concepts Dr. Sunil Pandya 229
HOW I DO IT?
24. Unanticipated difficult airway in Catagory II LSCS Dr. Bhavani Shankar Kodali 243
25. Anesthesia for Paediatric VATS Dr. Neerja Bhardwaj 251
26. Anesthetic management of patients with COPD for laparoscopic surgery Dr. Rajeshwari S 257
27. Rescue strategies in ARDS including ECMO Dr. Michael Mazzeffi 263
28. Anesthesia for robotic surgeries - Principles and practice Dr. Jayashree Sood 281
VIDEO SESSIONS
29. Neuraxial Ultrasound Dr. Sivashanmugam T 285
30. Double lumen tubes / Bronchial blockers Dr. Rakesh kumar 291
31. Quadratus lumborum block and its variations Dr. Ekta Rai 303
32. Neuromuscular monitoring Dr. Venkatesh S 307
BREAKFAST SESSIONS
33. Vaporizers Dr. Pankaj Kundra 315
34. ABG Interpretation Dr. Jigi Divatia 335
SNAP SESSIONS
35. Aspiration under anesthesia Dr.Balabhaskar S 343
36. Anaphylaxis - Recognition and management Dr. Bhimeswar MV 351
37. HIPEC Dr. Jyotsna Agarwal 355
38. Perioperative hyponatremia - Causes and treatment Dr. Nibedita Pani 361
39. Ventilation strategies during rigid bronchoscopy Dr. Neerja Bhardwaj 371
Contents
40. Malignant hyperthermia Dr. Vishnu Mahesh Babu 377
41. Extrajunctional receptors and their implications Dr. Selvakumar R 389
42. Principles of temperature monitoring Dr. Ramkumar D 393
43. Coeliac plexus block Dr. Arul Murugan R 409
20/20
44. Intraoperative fluid therapy - Clinical pearls Dr. Lakshmi Kumar 417
45. PEEP physiology and its applications Dr. Arunkumar AS 423
TCI SESSIONS
46. TCI: The state of the art Dr. Rossella Garra 433
47. TCI: Different scenarios in clinical settings Dr. Maria Sammartino 437
FACULTY
Dr.Anju Grewal Dr.Arul Murugan R

Professor Associate Professor,
Department Of Anesthesiology Department of Anesthesiology
Dayanand Medical College and Hospital and Pain Medicine,
Ludhiana, Punjab Sri Ramachandra Institute of Higher Education and Research
Chennai
Dr. Anila Malde

Professor and Head Dr. Bhavani Shankar Kodali
Department of Anesthesiology, Professor
Lokmanya Tilak Municipal Medical College Department of Anesthesiology
and General Hospital, Mumbai University of Maryland Medical Center,
University of Maryland
Dr.Arunkumar AS Baltimore
Professor and Head

Department of Critical Care Medicine Dr.J.Balavenkatasubramanian
Saveetha Medical College Senior Consultant,
Chennai Department of Anesthesiology,
Ganga Medical Centre & Hospital
Dr. Anupama Chandrasekaran Coimbatore
Professor
Department of Radiology Dr.Bala Bhaskar S
Sri Ramachandra Institute of Higher Education and Research Professor
Chennai Department of Anesthesiology and Critical Care
Vijayanagar Institute of Medical Sciences, Bellary,
Dr.Aruna Parameswari Karnataka
Professor & Head,

Department of Anesthesiology Dr. Bhimeswar MV
and Pain Medicine, Controller of Examinations,
Sri Ramachandra Institute of Higher Education and Research DR.NTR University of Health Sciences,
Chennai Vijayawada.
Dr.Akilandeswari M Dr.Chinyere Egbuta

Professor, Associate in Anesthesiology & Critical Care Medicine
Department of Anesthesiology Boston Children’s Hospital
and Pain Medicine, Instructor in Anaesthesia,
Sri Ramachandra Institute of Higher Education and Research Harvard Medical School,Boston.
Chennai
Faculty
Dr.David D Waisel Dr.Jayanti Shankar
Associate Professor Lead Consultant
Harvard Medical School Department of Transplant Anaesthesia
Department of Anesthesiology Sakra World Hospital
Senior Associate in Anesthesia Bangalore.
Boston Children’s Hospital,
Boston.
Dr.Jyotsna Agarwal
Associate Professor
Dr. Ekta Rai
Department of Anesthesiology
Professor
Hamdard Institute of Medical Sciences and Research
New Delhi
Christian Medical College
Vellore
Dr.Keira Mason
Boston Children’s Hospital,
Dr. Gurudatt C L
Associate Professor of Anaesthesia,
Professor and Head
Department of Anesthesiology Harvard Medical School
JSS Medical College Boston.
Mysore.
Dr. Lakshmi Kumar
Dr.Harish Babu Ravulapalli Professor
Associate Professor Department Of Anesthesiology,
Department of Cardiac Anesthesiology, Amrita Institute of Medical Sciences & Research Centre
Narayana super speciality hospital, Kochi
Nellore.
Dr.Maria Sammartino
Dr.H M Krishna Professor, Anesthesia,
Professor and Unit Head
Catholic University of the Sacred Heart,
Department Of Anesthesiology,
Rome, Italy.
Kasturba Medical College,
Manipal.
Dr.Michael Mazzeffi
Associate Professor
Dr. Jigi Divatia
Professor & Head
University of Maryland School of Medicine
Department of Anesthesiology, Critical Care & Pain
Baltimore.
Tata Memorial Hospital
Mumbai.
Dr.Murugan T
Dr. Jayashree Sood Professor and Head
Chairperson Department of Anesthesiology
Department of Anesthesiology, Pain & Perioperative Medicine, Govt. Kilpauk Medical College
Sir Ganga Ram Hospital Chennai
New Delhi.
Faculty
Dr.Neena Seth Dr.Rossella Garra
Pediatric Consultant Anesthetist, Department of Anesthesia and Intensive Care
Evelina London Children’s Hospital, Catholic University of Sacred Heart,
London. Rome, Italy
Dr.Naheed Azhar Dr. Rajeshwari Subramaniam

Professor Professor & Head
Department of Anesthesiology Department of Anesthesiology and Intensive Care
Stanley Medical College & Hospital All India Institute of Medical Sciences
Chennai. New Delhi
Dr. Neerja Bhardwaj Dr. Ravi Shankar M

Professor Professor & Dean
Department of Anesthesiology Department of Anesthesiology
PGIMER, Mahatma Gandhi Medical College and Research Institute
Chandigarh. Puducherry.
Dr.Nibedita Pani Dr.Rakesh Kumar

Professor Director & Professor
SCB Medical College, Maulana Azad Medical College & Lok Nayak Hopsital
Cuttack, Odisha New Delhi
Dr. Padmaja Durga Dr.Ranjith Karthekeyan B

Professor Professor & Head,
Department of Anesthesiology, Department of Cardiac Anesthesiology
Nizam’s Institute of Medical Sciences Sri Ramachandra Institute of Higher Education and Research
Hyderabad Chennai
Dr. Pankaj Kundra Dr.Ramkumar D

Dean Academic Associate Professor,
Professor of Anesthesiology and Critical Care, Department of Anesthesiology
JIPMER and Pain Medicine,
Puducherry Sri Ramachandra Institute of Higher Education and Research
Chennai
Dr.PSN Raju
Senior Consultant Dr.Seema Deshpande
Department of Anesthesiology Assistant Professor,
Apollo Hospital Department of Anesthesiology
Chennai University of Maryland School of Medicine
Baltimore.
Faculty
Dr. Sunil T Pandya WORKSHOP
Director,
Department of Anaesthesia, Pain medicine, Surgical & Dr. Thamarai Selvi K
Obstetric Intensive care Professor,
Century Super specialty Hospital Department of Anesthesiology
Hyderabad. and Pain Medicine,
Dr. Sunanda Gupta Chennai.
Professor and Head
Department of Anesthesiology Dr. Renuka MK
Geetanjali Medical College Associate Professor,
Udaipur Department of Anesthesiology
and Pain Medicine,
Dr. Sudarsan Kasthuri Sri Ramachandra Institute of Higher Education and Research
Professor and Head Chennai.
GEM Hospital & Research Centre Dr.Kamalakkannan G S
Coimbatore Associate Professor,
Department of Cardiac Anesthesiology
Dr. Selvakumar R Sri Ramachandra Institute of Higher Education and Research
Professor, Chennai
Madurai Medical College Dr.Rajesh Kumar Kodali
Madurai Associate Professor,
Dr. Sivashanmugam T and Pain Medicine,
Professor Sri Ramachandra Institute of Higher Education and Research
Department of Anesthesiology Chennai
Mahatma Gandhi Medical College & Research Institute
Puducherry Dr. Senthil Kumar S
Assistant Professor,
Dr.Venkatesh S Department of Anesthesiology
Professor, and Pain Medicine,
Department of Anesthesiology Sri Ramachandra Institute of Higher Education and Research
and Pain Medicine, Chennai.
Chennai Dr.Soma Ganesh Raja N
Dr.Vishnu Mahesh Babu Department of Anesthesiology
Associate Professor and Pain Medicine,
Department of Anesthesiology Sri Ramachandra Institute of Higher Education and Research
Rangaraya Medical College Chennai.
Kakinada.
Faculty
Dr.Sathish K Dr.Mansi Sejpal
Assistant Professor, Senior Resident,
and Pain Medicine, and Pain Medicine,
Sri Ramachandra Institute of Higher Education and Research Sri Ramachandra Institute of Higher Education and Research
Chennai. Chennai.
Dr.Gautham G Dr.Srinidhi
Chennai. Chennai.
Dr.Sree kumar E J Dr.Aishwarya Ramesh

Chennai. Chennai.
Dr.Kausalya
and Pain Medicine,
Chennai.
Dr.Isaac Sam Clement

and Pain Medicine,
Chennai.
Dr.Jois Shravan Datta

Senior Resident,
and Pain Medicine,
Chennai.
SRI RAMACHANDRA INSTITUTE OF
HIGHER EDUCATION & RESEARCH (DU)
DEPARTMENT OF ANESTHESIOLOGY & PAIN MEDICINE
Professor & Head

Dr.Aruna Parameswari
Professors
Dr.Mahesh Vakamudi
Dr.Akilandeswari M
Dr.Thamarai Selvi K
Dr.Ranjith Karthekeyan B
Dr.Venkatesh S
Dr.Jayaraman V
Associate Professors
Dr.Renuka MK Dr.Kamalakkannan G S
Dr.Arul Murugan R Dr.Rajesh Kumar Kodali V
Dr.Ramkumar D
Assistant Professors
Dr.Soma Ganesh Raja N Dr.Senthil Kumar S
Dr.Gautham G Dr.Sreekumar E
Dr.Isaac Sam Clement Dr.Sathish K
Dr.Dwarakesh T Dr.Kousalya V
Senior Residents
Dr.Mithila G Dr.Anisha Pauline
Dr.Jois Shravan Dutta Dr.Mansi Sejpal
Dr.Jayasree Dr.Aishwarya
Dr.Srinidhi V Dr.Addpa S S Subrahmanian
Dr.Rajat Roy Dr.Shilpa
Dr.Ashwathy Dr.Abhishek
Dr.Suresh Kumar Dr.Rajpaul Shruti Harish
Dr.Veneetha Devadas Dr.Thangjangul Khongsai
Dr.Uma Subramanian
Post Graduates
Final Year MD
Dr. Arulmozhi Priyadharshini Dr.Arunnya Ganesan
Dr.Aswalin Susan Sunil Dr.Gowri Aishwarya S
Dr.Janga Siddhartha Reddy Dr.Mounica R
Dr.Navya Sri Lalitha K Dr.Prabavathi S
Dr.Raja Sundari Dr.Ramapriya S
Dr.Sarat Chander Dr.Shruti Raja
Dr.Sowbarnika K K
Second Year MD
Dr.Arthi K Dr.Deepshikha
Dr.Gowtham A Dr.Iswariya M
Dr.Jennifer Sindhu Salgunan Dr.Pavithra Palaniappan
Dr.Ritika Swaminathan Dr.Sathya Priya S
Dr.Sivasankari G Dr.Tara Ranjan
Dr.Varun Karuppiah T Dr. Venkata Poornima
First Year MD
Dr. Aravindan M Dr. Dilakshika Letchumanan Reddiyar
Dr. Gayathri Santhanam Dr. Hariharan Ps
Dr. Pramika R Dr. Saranya Pb
Dr. Srikanth T Dr. Sujatha S
Dr. Thirumalai Priya Nk Dr. Vidarshna V
Dr. Vikraman R Dr. Kiran Muthu Rajah
BASIC SCIENCE LECTURES
1 PHYSICS OF FLOW – FICK, VENTURI, LAMINAR AND TURBULENT FLOW
Professor and Head, Gurudatt C L

J S S Medical College,
Mysore.
Key points
Ø Fluids are substances that are capable of flowing and changing their shape at a steady rate when acted upon by
a force.
Ø Flow is the volume of gas or liquid passing a cross sectional area per unit time.
Ø Flow can be either laminar or turbulent depending on various conditions.
Ø Laminar flow occurs when a fluid flows at low flow rates through smooth tubes.
Ø Obstacles and bifurcations can cause eddies, vortices or full-blown turbulence.
Ø Laminar flow is proportional to driving pressure, and turbulent flow is proportional to the square root of the driving
pressure.
Ø A fast-moving fluid exerts less pressure than a static fluid according to the Bernoulli principle.
Ø The Bernoulli principle produces the Venturi effect and the Coanda effect, both of which are used in anaesthetic
apparatus and ventilators.
Ø Hegan- Poissuilles’ law is applied for laminar flow.
Substances may exist in solid, liquid or gaseous form. These terms of their hydraulic and thermodynamic properties are
forms or phases differ from each other according to the very similar. The similar physical behaviours of gases and
random movement of their constituent atoms or molecules. liquids in motion have led to the development of the science
In solids, molecules oscillate about a fixed point, whereas in of fluid mechanics.
liquids, the molecules possess higher velocities and therefore
higher kinetic energy. They move more freely and thus do Flow - is defined as the volume of gas or liquid passing a
not bear a constant relationship in space to other molecules. cross sectional area per unit time.
The molecules of gases possess even higher kinetic energy F= Q / t
and move freely to an even greater extent.
Where F is the mean flow, Q is the quantity and t is the time.
Fluids are defined as, substances that are capable of flowing
and changing their shape at a steady rate when acted upon Conservation of flow
by a force. Fluids possess no rigidity, and change their shape
to fill the container into which they are poured. Consider a wide river containing a narrow section. The
water can be seen to move much faster in the narrow
Both gases and liquids are termed fluids. Liquids are section, than in the wider part. Flow remains constant, but
incompressible, and at constant temperature occupy a the velocity of the various sections changes according to
fixed volume, conforming to the shape of a container; gases cross-sectional area, in order to conserve a constant flow
have no fixed volume but expand to occupy the total space rate. Now consider a cylindrical tube whose cross-sectional
of a container. Nevertheless, the techniques for analysing area changes, as shown in Figure1.
the behaviour of liquids and gases (or fluids in general) in
RACE 2020 Ramachandra Anesthesia Continuing Education

Physics of flow – Fick, Venturi, Laminar and 4 Gurudatt C L
Turbulent flow
For a tube of varying diameter, at two different points (1 and 2):
Q = A1 ×v1 = A2 ×v2
Where; A is the cross-sectional area, v is the velocity of the fluid at each point
Figure 1 - The conservation of flow: the velocity is seen to increase as a fluid flows through a constriction.
Flow is conserved at all points.
Flow can be divided into two different types, laminar and turbulent.
Laminar flow -
Flow is usually considered to be laminar, when a fluid flows through a tube and the rate of flow is low. In laminar flow ,the
molecules of the fluid can be imagined to be moving in numerous ‘layers’ or laminae . Although all the molecules are moving
in straight lines they are not all uniform in their velocity (figure 2). Molecules in the centre of the tube are moving faster than
the molecules in the periphery and the tip of the flow is forming a cone.
Figure 2 – Laminar flow
As fluid flows through tubes, there is resistance between the fluid and vessel wall that opposes the flow which produces
decrease in the movement of particles near the inner wall. The molecules of the gas in the centre of the system encounter
lesser frictional resistance, and move at a greater velocity than those at the sides of the system.

Turbulent flow
Hegan- Poissuilles’ law: is applied for laminar flow. Clinical applications of Hegan- Poissuilles’ law
It states that the flow through the tube is directly
proportional to the pressure gradient and 4th power of 1. The size of the endotracheal tube ( ETT) selected for
radius and inversely proportional to the length of the a particular patient should not increase resistance
tube and viscosity of the gas (figure 3). for breathing. So for an adult male patient, 8.5 or 9
mm internal diameter ETT & for female patient ,7 or
Q = Π r 4(P1 – P2) 7.5 mm internal diameter ETT should be selected.
8ƞL As we know that for laminar flow, according to
Hegan- Poissuilles law, the resistance increases by
Where Q= flow of liquid 4th power whenever radius of the tube is decreased.
r= radius of the tubing Any increase in the resistance will increase the work
P1 – P2 = pressure gradient across the tubing of breathing of a spontaneously breathing patient
Ƞ ( eta)= viscosity and produces an early fatigue of the respiratory
muscles of the patient. Normal resistance offered
L= length of the tubing.
by the adult airway is < 2 cms of H2O/ litre/sec.
With the right sized ETT, the resistance increases
to 5 cms of H2O/ liter/sec. Whenever secretions get
collected inside the tube &decreases the lumen, the
resistance can further increase to 10 cms of H2O/
liter/sec. Hence, the introduction of pressure support
ventilation, as a mode for spontaneously breathing
patients in newer anaesthesia work stations and also
in intensive care ventilators to decrease the work of
breathing.
2. When we administer intravenous fluids to a patient,

the flow rate through the venous catheter is, according
to Hagen–Poiseuille equation, directly proportional to
the pressure difference between the solution bag and
the vein, which, in turn,is proportional to the height
Figure 3 – linear relationship between flow and of the bag with respect to the patient. We squeeze
pressure in laminar flow a bag of IV fluid or increase the height of the stand,
to increase the pressure difference between the bag
Since flow is inversely proportional to resistance (R) the and the vein, so that the fluid is given more quickly.
equation can also be rearranged as
3. If rapid fluid resuscitation is required, a shorter
R = 8ƞL / r 4(P1 – P2) intravenous catheter is preferable to a longer one
of the same gauge. In fact, according to Hagen–
Viscosity is the property of a fluid that causes it to resist flow;
Poiseuille equation, the volume flow rate produced
it refers to the stickiness of a fluid. When comparing the flow
by the same pressure difference will be higher
of water through a tube with a more viscous substance such
through a lower length catheter. Hence, although a
as honey, water flows faster. The velocities of the adjacent
triple-lumen central venous catheter usually includes
layers of the fluid differ, and a ‘slip’ occurs between parallel
a 16-gauge lumen, a 16-gauge peripheral venous
layers as a result of the shear forces acting between them.
catheter will allow a faster fluid administration ,since
Flow is dependent on the intermolecular forces. At higher
it is much shorter than an 8-inch. (about 20 cm)
temperatures, the molecules have more kinetic energy and,
central venous catheter.
therefore, it is easier to break the intermolecular bonds and
thus viscosity decreases. For any given force applied, the 4. One of the reasons why tracheotomy reduces the
flow will then increase as viscosity decreases. work of breathing (WOB) in mechanically ventilated
patients is that, tracheotomy cannulas are usually

Turbulent flow
shorter than endotracheal tubes. WOB is proportional 5. Blood flows much slower through the intravenous
to the pressure difference ΔP which is needed cannula compared to a crystalloid fluid. Hence a
to develop the tidal volume (the so-called driving larger IV cannula should be used while administering
pressure). According to Hagen– Poiseuille equation, blood.
the patient will need to develop a lower ΔP to receive
the same gas flow if the length of the tube is lower 6. In anaemia and also in pregnancy, the viscosity of
and, thus, he/she will do less work. Furthermore, a blood decreases, and flow of blood to the tissues
larger internal diameter tracheotomy or endotracheal will increase, as flow is inversely proportional to
tube (ETT) may facilitate (and accelerate) the viscosity. Though the oxygen content of blood
weaning from mechanical ventilation. In fact, for a decreases, oxygen supply (DO2) is still maintained.
given pressure difference, the patient will receive
7. Using mucolytic agents like N- acetyl cysteine in
a much greater gas flow through a slightly larger
patients with chronic bronchitis and bronchiectasis
tracheotomy cannula or ETT (since flow depends
to decrease the viscosity of the secretions,helps
on the fourth power of radius) and, accordingly, the
the patient easily bring them out of the bronchi and
same flow will be obtained with a much lower driving
bronchioles.
pressure, again reducing WOB.
Turbulent Flow
Figure 4 – Turbulent flow
Not all fluid flow is laminar. Under certain physical turbulent compared to when flow is laminar. This is best
conditions, it becomes turbulent (figure 4). When this demonstrated by the fact that in turbulent flow, the flow rate
happens, instead of the fluid moving in seemingly ordered is proportional to the square root of the pressure gradient,
layers, the molecules become more disorganised and begin whereas in laminar flow, flow rate is directly proportional
to swirl with the formation of eddy currents. Flow is less
to the pressure gradient (figure 3 and 5). This means that
ordered and the eddy currents interfere with each other,
to double the flow, the pressure across the tube must be
increasing drag or resistance to flow. As a result, a greater
energy input is required for a given flow rate, when flow is quadrupled.

Turbulent flow
Figure 5 - Non linear relationship between flow and pressure in turbulent flow
When does turbulent flow occur? Measurements in tubes have shown that:
Turbulent flow occurs when fluids flow at high velocity in • When the Reynolds number is less than 2000 there is
large diameter tubes and, when the fluids are relatively laminar flow,
dense (figure 6). Also, decreasing the viscosity of a fluid
leads to turbulent flow. The factors that determine when • When the Reynolds number is 2000-4000 there is
turbulent flow commences can be combined to form an transitional flow i.e. a mixture of laminar and turbulent
equation which calculates the Reynolds number: flow,
Reynolds number = v ρ d /η • When the Reynolds number is greater than 4000 flow
will be turbulent. Note that Reynolds number does
where, v = velocity ρ = density d = diameter η = viscosity not have any units associated with it - it is called a
dimensionless number.
Figure 6– Onset of turbulent flow

Turbulent flow
Graham’s law for turbulent flow: States that flow rate atmospheric pressure is very low, the density of the
is directly proportional to the square root of the pressure gas decreases, but viscosity will not change. As
gradient on either sides of the tube and inversely proportional higher flows depend on density, and as per Graham’s
to the square root of the density of the fluid. law for turbulent flow, flow is inversely proportional to
square root of density i.e. FLOW ά 1/√ density, flow
Clinical applications - will be higher than the actual flows that are set in the
flow meters. The opposite will occur under hyperbaric
1. Flow meters of anaesthesia machine are tapered
conditions.
glass tubes. The internal diameter is narrower in the
lower part and wider in the upper part. In the lower 2. We should not use connectors with sharp curves. At
part, flow of the gas is laminar and in the upper part, the sharp bends, the flow converts into a turbulent
the flow is orificial or turbulent, as the diameter of the flow. This will increase the resistance to the flow.
tube is more than the vertical length of the float or Every piece of anaesthetic equipment, because
the bobbin. So for lower flows it is laminar flow and of diameters & shape of connectors, number &
for higher flows it is turbulent. The flow meters are arrangement will affect flow to the patient. Wide
always calibrated at 760 mm of Hg. If the anaesthesia bore & curved rather than sharp angles should be
machine is used in a high altitude area, where the preferred (figures 7A and B).
Figure 7- A & B - A well-designed connector should produce laminar flow. By contrast, turbulent flow can occur in poorly
designed connectors, yielding a higher resistance for a given flow.

Turbulent flow
3. Using mixture of oxygen and helium, improves flow increase in the Reynolds number, so turbulence
in a patient with tracheal narrowing, or in patients develops which is audible through the stethoscope.
with chronic obstructive lung disease instead of air.
Whenever there is narrowing of the airways, the flow 5. In the lungs, turbulent flow dominates in the large
airways, which has the effect of purging the trachea
of gases will be turbulent and hence the pressure
and larger bronchi with fresh air, each time a breath
gradient required to maintain the flow increases.
is taken. In the small airways, the air moves more
This will increase the work of breathing of the patient.
slowly ,so the Reynolds number is small and laminar
Flow and resistance will depend on the density of the
flow dominates. This ensures airflow to the alveoli
gas as per Graham’s law when the flow is turbulent.
occurs with minimal energy expenditure.
Mixture of oxygen and helium will have a decreased
density compared to O2 or air. And hence, using Bernoulli’s principle:
HELIOX will decrease the resistance and increase
the flow. Heliox is a mixture of 21% oxygen and Daniel Bernoulli published his work in 1738, in his
79% helium. It must be noted that although flow with book titled Hydrodynamica. When a gas flowing
heliox increases in upper airway obstruction, it only through a tube encounters a constriction, at that
contains 21% oxygen. Hence it may not be of benefit point the pressure drops and the velocity increases
i.e. kinetic energy increases and the potential energy
in the hypoxic patient.
decreases. This is called as Bernoulli’s principle
4. In medicine, turbulence generates sound waves (Figure 8).
such as ejection murmurs and carotid bruits, as well
The energy of a flowing fluid exists in two forms:
as the Korotkoff sounds observed when using a cuff
kinetic energy (as a result of its velocity) and potential
to measure blood pressure. Pumping up the cuff to a
energy (as a result of its pressure). As the velocity
pressure greater than the diastolic pressure, causes
increases at a constriction, the kinetic energy
partial occlusion of the brachial artery because the increases. The total energy must remain constant, so
radius of the artery is reduced. The blood velocity the potential energy must fall. The potential energy of
increases since flow is maintained unless the cuff a gas is proportional to the pressure it exerts and so
pressure approaches the systolic pressure. Both the pressure exerted on the wall of the tube therefore
reduced radius and increased velocity, cause an decreases with increasing velocity.
Figure 8 - According to Bernoulli’s principle, a fluid moving at high velocity through a tube exerts less pressure on the walls
of the tube than a static or slowly-moving fluid.

Turbulent flow
Venturi is a tube with a cross section that gradually decreases and then increases. Entrainment of air from the surrounding
due to fall in pressure at the point of constriction is called as Venturi’s effect (Figure 9).
Figure 9 - Venturi effect
Clinical applications – the outer tube due to the rapid flow of 30-70 litres
of O2 after activation of the O2 flush, a sudden fall
1. In Ohmeda anaesthesia machines, there are in the pressure occurs, sucking the O2 from the bag
second stage pressure regulators, which reduce & collapsing it. If there is any leak in the inner tube,
the output pressures of O2 to 14 Psi and N2O to then the reservoir bag will not collapse.
26 Psi, in order to maintain more accurate flow
through the flow meters. Where as in Drager 3. Venturi oxygen masks are designed to mix a
anaesthesia machines, there are no second stage predictable amount of oxygen (running through
regulators but a different mechanism reduces the oxygen tubing) with air (entrained through
the pressure of gases before the flow meters. In the orifice). The Venturi mask delivers a set
Drager anaesthesia machines, as the gases from concentration of oxygen to a patient, from a 100%
the pressure regulators at a pressure of 45 to 60 oxygen supply without complicated gas mixing
psig move towards the flow meter assembly they apparatus. The mask contains a Venturi valve, a
have to flow through the “Flow restrictors” which simple device moulded from plastic (Figure 10)
are nothing but sudden narrowing of the tubes. which makes use of the Venturi effect, a special
According to Bernoulli’s principle, before reaching case of the Bernoulli principle. Oxygen (from a
the flow meter assembly, the pressure is further cylinder or other source) is supplied to the valve
reduced, but flow is increased. through plastic tubing and passes through the
centre of the valve. The oxygen passes through a
2. Venturi effect is used in checking the integrity of the small constriction, so its velocity increases (through
inner tube of the Bain’s Circuit. The integrity of the flow conservation) and air is entrained through holes
inner tube is very essential, as any leak in that can in the sides of the valve adjacent to the constriction,
result in large apparatus dead space. One of the and so mixes with the oxygen. The air is entrained
tests used for the same is PETHIK’S TEST. In this because, the high velocity of oxygen causes a
test, after keeping 3 litres of flow of O2, closing the reduction in pressure inside the valve due to the
expiratory valve and the outer tube with the thumb, Bernoulli principle. Because the entrainment of air
one should make sure that the reservoir bag is and the resulting oxygen concentration is constant,
full. Then O2 flush is activated and simultaneously these masks are referred to as fixed-performance
the thumb occluding the outer tube is released. If devices. A Venturi valve is also referred to as a
the inner tube does not have any leak, then the high airflow with oxygen enrichment (HAFOE)
reservoir bag will collapse. This is due to Venturi valve.
effect, because at the opening of the inner tube into

Turbulent flow
The entrainment ratio is simply the ratio of entrained flow to driving flow:
Entrainment Ratio = Entrained Flow/ Driving Flow
Figure 10 - A Venturi mask showing a high airflow oxygen entrainment (HAFOE) valve.
In practice the entrainment ratio is not constant at all flow

Delivered Rate of flow of Colour of venture
rates, and a partially obstructed air inlet can result in delivery
of higher oxygen concentration, i.e. a reduced entrainment
O2 % O2 to the mask – valve attached to
ratio. The percentage of oxygen delivered depends on the L/min the mask
rate of entrainment, which is determined by the size of the 24% 2 Blue
holes in the facemask valve and to a lesser extent by the 28% 4 White
rate of flow of oxygen. Different colours of valve (figure 11)
31% 6 Orange
are engineered to deliver a fixed percentage of oxygen, e.g.
a red HAFOE valve delivers 40% O2 concentration. 35% 8 Yellow
40% 10 Red
Note that the quoted figure is accurate for a fixed oxygen
60% 15 Green
flow rate only.
Table 1- High Air Flow Oxygen Entrainment (HAFOE)
Table 1 gives a list of available HAFOE valves and their
valves.
colours.
4. Sander’s venturi injector device for rigid bronchoscopy
–its use during rigid bronchoscopy was first described
by Sanders in 1967.
• Oxygen from a high pressure source is injected

intermittently through a narrow needle placed
at the proximal end of the bronchoscope.
• The venturi effect which this creates entrains

atmospheric air so that, the lungs can be
inflated with O2 enriched air as long as the
distal end of the bronchoscope is beyond the
Figure 11- Different colours of Venturi valves larynx

Turbulent flow
Figure12 -Rigid endoscope with modified Sanders jet ventilation technique. The oxygen supply at 50 psi is connected to
a reducing valve that allows the pressure to be adjusted from 0 to 50 psi. The side port of the endoscope is used as the
Venturi injector site, and the open end can be used for continuous viewing by the endoscopist.
Coanda effect: 2. Mucus plug at the branching of tracheo-bronchial

tree may cause maldistribution of respiratory gases.
Coanda effect is the tendency of the fluid jet to be attached
It may also explain some cases of Myocardial
to a nearby surface. This phenomenon is also called as wall
Infraction, where there may be some narrowing,
attachment. When a narrow tube encounters a Y junction
before the branching of the coronaries. All the blood
of the wide bore, because the flow tends to cling to one
could be flowing into one limb of the coronary artery
side, the flow will not evenly divide between the two outlets,
but flows through only one limb of the Y, due to Coanda despite the fact that there is still an apparently patent
effect (figure 13). lumen in the other branch. Unequal flow may result
because of atherosclerotic plaques in the vascular
tree.
The Coanda effect is put to good use in a switching-flow

ventilator valve (figure 14).
This is a carefully designed valve whose shape causes

gas to flow from an oxygen supply or ventilator to a patient
during inspiration.
• The gas hugs the wall of the valve and bypasses an

open vent on the opposite side of the wall.
Figure 13 – Coanda effect
Clinical applications – • During expiration, air from the patient is redirected

to the vent, because the flow pressure from the gas
1. There can be unequal gas flow to the alveoli where supply forces the gas to the opposite side of the
there has been a slight narrowing of the bronchiole tube.
before it divides. As there is narrowing before the
branching, the pressure drops, the velocity of the air • This type of valve has no moving parts, so is reliable
increases (Bernoulli principle), but the flow tends to and can be produced very cheaply. This technique
cling to one side & doesn’t divide evenly between the is sometimes referred to as fluid logic.
branches (Coanda effect).

Turbulent flow
glass tube, tapered so that it is wider at the top than

the bottom, contains a bobbin which is supported
by the upward flow of gas through the tube.
• When flow commences, the bobbin rises until the
downward pull of gravity is balanced by the upward
force of gas. This upward force decreases further
as the bobbin rises, because the gas escapes
around the bobbin more easily as the tube gets
wider.
• The position of the bobbin is thus dependent on the
Figure 14 – Valve effect based on the Coanda effect rate of gas flow.
• Common designs feature a flat-topped bobbin, so
Fick principle
the flow rate is read off from the top of the bobbin
Fick principle states that “the total uptake of (or release onto a scale.
of) a substance by the peripheral tissues is equal to the
• Flutes in the bobbin cause it to rotate which reduces
product of the blood flow to the peripheral tissues and
the risk of the bobbin sticking to the sides of the
the arterial-venous concentration difference (gradient)
tube.
of the substance.”
• Variable orifice flowmeters are calibrated for a
Clinical applications -
particular gas, since the gas density and viscosity
In the determination of cardiac output, the substance most both affect the bobbin’s position.
commonly measured is the oxygen content of blood thus
• Most variable orifice flowmeters can read over a
giving the arteriovenous oxygen difference, and the flow
wide range of flow rates, and this is achieved either
calculated is the flow across the pulmonary system.
by using a variable taper, or by using high-flow and
This gives a simple way to calculate the cardiac output: low-flow devices in series.
CO = [O2 consumption (ml/min)] / A - Mixed Venous
O2 difference (ml O2/ 100ml blood) x 10
Assuming there is no intracardiac shunt, the pulmonary
blood flow equals the systemic blood flow. Measurement
of the arterial and venous oxygen content of blood involves
the sampling of blood from the pulmonary artery (low
oxygen content) and from the pulmonary vein (high oxygen
content). In practice, sampling of peripheral arterial blood is
a surrogate for pulmonary venous blood.
Volume and flow measurement
Gas flow measurement
Continuous and reliable indication of the flow of oxygen and
other gases is invaluable to anaesthetists.
The variable orifice flow meter (Figure 15), also known
by the trade name of Rotameter, provides a failsafe
measurement of gas flow. Figure 15- Variable orifice flowmeter
• This type of flowmeter is a simple design with the Measurement of respiratory flow
important benefit of not requiring a power supply.
Modern spirometers are able to measure respiratory
• A control knob allows precise adjustment of gas
flow rate and volume simultaneously. The most popular
flow through a needle-valve. Above this, a vertical

Turbulent flow
approach is to measure flow rate at the mouth and record from the patient pushes against a diaphragm which moves
it on an electronic data acquisition system. Commonly in the direction of air flow. The movement of the diaphragm
used respiratory volume flowmeters fall into two categories: is opposed by a spring, but causes a narrow slot to open
rotating-vane and differential pressure flowmeters (eg.
through which the expired air escapes, reducing pressure
pneumotachometer, Wright peak flow meter).
on the diaphragm. A sliding marker indicating the peak
Wright peak flow meter flow rate is pushed by the diaphragm, which continues to
move along the tube until the spring force overcomes the
The Wright peak flow meter (Figure 16, 17) is a simple low-
cost device ,which records the maximal expired flow. Air air pressure.
Figure 16 -Wright peak flow meter – working mechanism
Figure 17- Wright peak flow meter

Turbulent flow
Summary the Coanda effect, both of which are used in anaesthetic

apparatus and ventilators.
• Flow can be either laminar or turbulent depending on
various conditions. References
• Laminar flow occurs when a fluid flows at low flow rates 1. Basic Physics and Measurement in Anaesthesia,
through smooth tubes. Davis, P.D., and Kenny G.N.C, 5th Edition,
Butterworth Heinemann, 2005.
• Obstacles and bifurcations can cause eddies, vortices
or full-blown turbulence. 2. Basic science for Anaesthetists, Sylvia Dolenska,
Cambridge University Press, Cambridge; 2006
• The transition to turbulent flow also depends on
velocity, tube radius, density and viscosity according to 3. Physics in Anesthesia, Ben Middleton,Justin
the Reynolds number. Phillips,Rik Thomas, Simon Stacey; Scion Publishing
Ltd, Oxfordshire, 2012,
• If the Reynolds number is less than 2000, flow is
predominantly laminar, but if it is greater than 4000, 4. Jones, E.R. and Childers, R.L, “Gas Laws and Kinetic
turbulence dominates. Theory” in Contemporary College Physics Addison-
Wesley, Reading, Massachusetts, 1993, p 281.
• Laminar flow is proportional to driving pressure, and
5. Park, John L. “The Kinetic Molecular Theory of Ideal
turbulent flow is proportional to the square root of the
Gases, http://dbhs.wvusd.k12.ca.us/GasLaw/Basics-
driving pressure.
of-KMT.html
• A fast-moving fluid exerts less pressure than a static
6. Physics for Anesthesiologists From Daily Life to
fluid according to the Bernoulli principle.
the Operating Room, Antonio Pisano, Springer
• The Bernoulli principle produces the Venturi effect and International Publishing AG, 2017

Turbulent flow
MCQ
1.Normal resistance offered by adult airway is <2cm of 3.When the Reynolds number is less than 2000, the flow is
H2O/lit/sec
A.Laminar
A.True B.Turbulent
B.False
4.The flowmeters are always calibrated at 760 mmHg
2. According to Hagen Poiseuille equation, flow rate
A.True
through venous catheter is directly proportional to
B.False
A.Pressure
B.Length 5.Pethik’s test is used in checking the integrity of JR circuit
C.Viscosity
A.True
D.Density
B.False
5.False 4.True 3.A 2.A 1.True
ANSWERS:

2 PRELOAD, AFTERLOAD AND CONTRACTILITY
Associate Professor, Harish Babu Ravulapalli

Department of Cardiac Anesthesiology,
Narayana super speciality hospital, Nellore
Key points
Ø Sarcomere length cannot be determined in the intact heart, so indirect indices of preload, such as ventricular EDV
or pressure, must be used
Ø Increases in preload lead to an increase in magnitude and rate of active tension developed in the cardiac muscle
Ø The Frank-Starling mechanism states that increasing venous return and ventricular preload leads to an increase
in SV
Ø A major component of the afterload for the left ventricle is the aortic pressure. The greater the aortic pressure, the
greater the afterload on the left ventricle
Ø Assuming the ventricle is a sphere, ventricular wall stress is proportional to the product of the intra ventricular
pressure and ventricular radius, divided by the wall thickness
Ø At a given preload, an increase in afterload decreases SV
Ø Anrep effect is an increase in inotropy following increase in afterload
Ø The three determinants of ventricular function(preload, afterload and contractility) are interdependent
Cardiac output, expressed in liters/minute, is the amount number of beats per minute (heart rate, HR), equals the
of blood the heart pumps in 1 minute. Cardiac output is cardiac output (CO).
logically equal to the product of the stroke volume and the
number of beats per minute (heart rate). Easy enough, CO= SV x HR
one may think, but the term cardiac in cardiac output Equation 1
is potentially misleading – with clinician’s sometimes Therefore, changes in either SV or heart rate alter cardiac
assuming that to interpret cardiac output they must focus output.
on the heart. The heart is just one part of the much larger
cardiovascular system, however, and the amount of blood To understand the influence of stroke volume on cardiac
it pumps is dependent on both cardiac and extra cardiac output it is necessary to understand the basic physiological
factors. Although most clinicians should/will be able to concepts of preload, afterload and contractility and their
recite the four determinants of cardiac output – heart rate, interdependence on each other.
contractility, preload, and afterload – understanding of the
Preload 2
applicability and practical relevance of each of these four
components is all too often less well ingrained 1. It is the initial stretching of the cardiac myocytes prior
to contraction; therefore, it is related to the sarcomere
The primary function of the heart is to impart energy to blood
length at the end of diastole. Sarcomere length cannot be
to generate and sustain an arterial blood pressure sufficient
determined in the intact heart, so indirect indices of preload,
to adequately perfuse organs. The heart achieves this by
such as ventricular EDV or pressure, must be used. These
contracting its muscular walls around a closed chamber to
measures of preload are not ideal because they may not
generate sufficient pressure to propel blood from the left
always reflect sarcomere length because of changes in the
ventricle, through the aortic valve, and into the aorta. Each
structure and mechanical properties of the heart. Despite
time the left ventricle contracts, a volume of blood is ejected
these limitations, acute changes in end-diastolic pressure
into the aorta. This stroke volume (SV), multiplied by the

Preload, Afterload and Contractility 18 Harish Babu Ravulapalli
and volume are useful indices for examining the effects of relationship between pressure and volume is nonlinear
acute preload changes on SV. in the ventricle (as in most biological tissues); therefore,
compliance decreases with increasing pressure or volume.
Effects of Preload on Stroke Volume When pressure and volume are plotted as in Figure 1, we
Effects of Ventricular Compliance on Preload find that the slope of the filling curve increases at higher
volumes; that is, the ventricle becomes less compliant
As the ventricle fills with blood, the pressure generated at or “stiffer” at higher volumes. Ventricular compliance
a given volume is determined by the compliance of the is determined by the physical properties of the tissues
ventricle, in which compliance is defined as the ratio of a making up the ventricular wall and the state of ventricular
change in volume divided by a change in pressure. The relaxation.
Fig 1: Left ventricular compliance (or filling) curves. The slope of the tangent of the passive pressure volume curve at
a given volume represents the reciprocal of the ventricular compliance. The slope of the normal compliance curve is
increased by a decrease in ventricular compliance (e.g., ventricular hypertrophy), whereas the slope of the compliance
curve is reduced by an increase in ventricular compliance (e.g., ventricular dilation). Decreased compliance increases the
end-diastolic pressure (EDP) at a given end-diastolic volume (EDV), whereas increased compliance decreases EDP at a
given EDV. LV, left ventricle.
The length of a sarcomere prior to contraction, which initial length of a muscle (i.e., preload) affect the ability
represents its preload, depends on the ventricular EDV. of the muscle to develop force (tension). Increases
This, in turn, depends on the ventricular end-diastolic in preload lead to an increase in active tension. Not
pressure and compliance. An elevated end-diastolic only is the magnitude of active tension increased, but
pressure may be associated with sarcomere lengths that also the rate of active tension development (i.e., the
are increased, decreased, or unchanged, depending on the maximal slope with respect to time of the tension curve
ventricular volume and compliance at that volume. during contraction). The duration of contraction and
the time-to-peak tension, however, are not changed.
Effects of Preload on Tension Development (Length- The length–tension relationship, although usually used
Tension Relationship) to describe the contraction of isolated muscles, can be
This change in preload will alter the ability of the myocyte applied to the whole heart. By substituting ventricular
to generate force when it contracts. The length– volume for length and ventricular pressure for tension,
tension relationship examines how changes in the the length–tension relationship becomes a pressure–

volume relationship for the ventricle. This can be the ventricle. Figure 2 shows that as ventricular EDV
done because a quantitative relationship exists increases, an increase in isovolumetric ventricular
between tension and pressure and between length pressure development occurs during ventricular
and volume that is determined by the geometry of contraction.
Fig 2: Effects of increasing ventricular volume (preload) on ventricular pressure development. Increasing ventricular volume
from a to c and then stimulating the ventricle to contract isovolumetrically increases the developed pressure and the peak-
systolic pressure
Effects of Venous Return on Stroke Volume (Frank- the myocytes causes an increase in force generation, which
Starling Mechanism) enables the heart to eject the additional venous return and
thereby increase SV. This is called the Frank-Starling
Altered preload is an important mechanism by which the mechanism. The Frank-Starling mechanism states that
ventricle changes its force of contraction and therefore its increasing venous return and ventricular preload leads
SV. When venous return to the heart is increased, ventricular to an increase in SV. Figure 3 shows the Frank-Starling
filling increases, and therefore its preload. This stretching of relationship for the left ventricle.
Fig 3: Frank-Starling mechanism. Increasing venous return to the left ventricle increases left ventricular end-diastolic
pressure (LVEDP) by increasing ventricular volume; this increased preload increases stroke volume (SV) from point A
(normal operating point) to B. Decreasing venous return decreases preload and stroke volume (point C)

Factors Determining Ventricular Preload
Ventricular filling, and therefore preload of the right ventricle,

is altered by several factors.
Equation 2
1. Venous pressure: An increase in venous blood pressure
outside of the right atrium increases right ventricular Wall stress can be thought of as the average tension that
preload. individual muscle fibers within the ventricular wall must generate
2. Ventricular Compliance: The compliance of the ventricle to shorten against the developed intraventricular pressure. At
a given intraventricular pressure, wall stress is increased by
determines the EDV for any given intraventricular filling
an increase in radius (ventricular dilation). Therefore, afterload
pressure. Therefore greater the compliance, the greater
is increased whenever intraventricular pressures are elevated
the ventricular filling at a given filling pressure.
during systole and by ventricular dilation. On the other hand,
3. Heart Rate: Heart rate and ventricular filling are inversely a thickened, hypertrophied ventricle will have reduced wall
related. stress and afterload on individual fibers.
4. Atrial Contraction: It is important for maintaining preload
Effects of Afterload on the Velocity of Fiber Shortening
at high heart rates when there is less time for diastolic
(Force-Velocity Relationship)
filling of the ventricle.
5. Inotropy: When there is systolic dysfunction, the preload Afterload influences the contraction of cardiac muscle
increases because of inability of the ventricle to eject fibers. Increased afterload decreases the velocity of fiber
normal volumes of the blood. shortening, whereas decreased afterload increases the
velocity of shortening. This inverse relationship between
Afterload afterload and velocity of fiber shortening is basis for the
force–velocity relationship. The greater the afterload,
Afterload is the “load” against which the heart must contract the slower the velocity of shortening. It is important to
to eject blood. A major component of the afterload for the left note that a cardiac muscle fiber does not operate on a
ventricle is the aortic pressure, or the pressure the ventricle single force–velocity curve, changes in preload also
must overcome to eject blood. The greater the aortic effect the velocity of fiber shortening. Increasing the
pressure, the greater the afterload on the left ventricle. For preload enables the muscle to contract faster against a
the right ventricle, the pulmonary artery pressure represents given afterload. Changes in preload however do not alter
the major afterload component. the maximum velocity of contraction (Vmax). Therefore,
an increase in preload on a cardiac myocyte can help to
Effects of Afterload on Stroke Volume offset the reduction in velocity that occurs when afterload
is increased.
Ventricular afterload, however, involves factors other than
the pressure that the ventricle must develop to eject blood. Effects of Afterload on Frank-Starling curves
One way to estimate the afterload on the individual cardiac
An increase in afterload rotates the Frank-Starling curve
fibers within the ventricle is to examine ventricular wall
down and to the right. Therefore, at a given preload (left
stress (σ), which is proportional to the product of the intra
ventricular end-diastolic pressure [LVEDP] in Fig 4.), an
ventricular pressure (P) and ventricular radius (r), divided
increase in afterload decreases SV. Conversely, decreasing
by the wall thickness (h) (Equation 2). This relationship for afterload shifts the curves up and to the left, thereby
wall stress assumes that the ventricle is a sphere. increasing the SV at a given preload.

Fig 4: Effects of afterload on Frank-Starling curves. An increase in afterload shifts the Frank-Starling curve downward,
whereas a decrease in afterload shifts the Frank-Starling curve upward. Therefore, at a given preload (vertical dashed line)
increased afterload decreases stroke volume, and decreased afterload increases stroke volume
Contractility (inotropy) Effects of Inotropy on Force-Velocity Relationship

Effects of Inotropy on Stroke Volume Changes in inotropy also alter the force–velocity
Ventricular SV is altered not only by changes in preload relationship. If the inotropic state of the myocyte is
and afterload, but also by changes in ventricular inotropy. increased, the force–velocity curve exhibits an upward
Changes in inotropy are caused by cellular mechanisms parallel shift, resulting in an increase in both Vmax (y-
that regulate the interaction between actin and myosin intercept) and maximal isometric force (x-intercept)
independent of changes in sarcomere length. (Fig.5). The increase in velocity at any given afterload (a
to b to c) results from the increased inotropy enhancing
Effects of Inotropy on Length-Tension Relationship
force generation by the actin and myosin filaments
An increase in inotropy augments the force of myocyte and increasing the rate of cross-bridge turnover. The
contraction independent of changes in either preload or increase in Vmax represents an increased intrinsic
afterload. Because the increase in active tension occurs capability of the muscle fi ber to generate force
at a given preload length, the inotropic response exhibits
independent of load. In contrast, changes in preload
length-independent activation.
do not alter Vmax.
Fig 5: Effects of increasing inotropy (parallel shift from curve a to c) on the force–velocity relationship. Increased inotropy
increases the velocity of shortening at any given afterload (vertical dashed line), and increases Vmax (y-intercept).
Furthermore, increased inotropy increases maximal isometric force (x-intercept)

Effects of Inotropy on Frank-Starling Curves any given preload and afterload and therefore causes the
Frank-Starling curve to shift up or down (Fig 6). If, at a given
The change in velocity of muscle shortening associated preload, inotropy is enhanced, SV will increase. Conversely,
with a change in inotropy results in an increase in SV at a decrease in inotropy at a given preload will decrease SV.
Fig 6: Effects of inotropy on Frank-Starling curves. An increase in inotropy shifts the Frank-Starling curve upward, whereas
a decrease in inotropy shifts the Frank-Starling curve downward. Therefore, at a given preload (vertical dashed line),
increased inotropy increases stroke volume, and decreased inotropy decreases stroke volume
Factors Influencing Inotropic state to β1-adrenoceptors on myocytes, serve a prominent role

in ventricular and atrial inotropic regulation. Elevated levels
Several factors influence ventricular inotropy (Fig 7); the of circulating catecholamines have positive inotropic effects
most important of these is the activity of sympathetic nerves. similar to sympathetic activation.
Sympathetic nerves, by releasing norepinephrine that binds
Fig 7: Factors that increase inotropy

In humans and some other mammalian hearts, an abrupt an increase in SV, but the increase is less than what would
increase in afterload can cause a modest increase in have occurred had the afterload not increased.
ino-tropy (Anrep effect) by a mechanism that is not fully
understood. In addition, an increase in heart rate can cause An increase in afterload, as previously discussed, leads to a
a positive inotropic effect (also termed the Bowditch effect, decrease in SV and an increase in ESV. However, because
treppe, or frequency-dependent activation). This latter the ESV is increased, changes in afterload produce
phenomenon probably is due to an inability of the Na+/ secondary changes in preload.The increased ESV inside the
K+-ATPase to keep up with the sodium influx at the higher ventricle is added to the venous return, thereby increasing
frequency of action potentials at elevated heart rates, EDV. This increase in preload secondary to an increase in
leading to an accumulation of intracellular calcium via the afterload activates the Frank-Starling mechanism, which
sodium–calcium exchanger. partially compensates for the reduction in SV caused by the
initial increase in afterload.
Interdependence of Preload, Afterload and Contractility
The direct, independent effects of an increase inotropy
It is important to understand that these determinants of are an increase in SV and a decrease in ESV. However,
ventricular function are also interdependent. For example, a the increased SV increases cardiac output and arterial
change in preload leads to secondary changes in afterload pressure, which increases afterload on the ventricle.
that can alter the initial response to the change in preload. Increased afterload tends to increase ESV, which partially
Furthermore, a change in afterload leads to changes in offsets the effects of increased inotropy on ESV. With a
preload, and a change in inotropy can alter both preload decrease in ESV from control, less blood remains in the
and afterload. ventricle that can be added to the venous return, so the
EDV will be smaller, although this will be partially offset by
Let us first consider how ventricular responses to a the tendency of the increased afterload to increase EDV.
change in preload can be modified by secondary changes After a new steady state is reached following the increase
in afterload. The independent effect of an increase in in inotropy, the net effect of these changes is an increase
preload (EDV) is an increase in SV without a change in in SV, which is accompanied by a reduction in ESV and a
ESV. However, because SV is increased, cardiac output is smaller reduction in EDV.
increased, and this will likely lead to an increase in arterial
pressure, which increases afterload. Furthermore,the References
increase in EDV increases ventricular wall stress, which
represents an increase in afterload. Therefore, a change in 1] Jean-Louis Vincent : Understanding cardiac output.
preload is normally accompanied by a secondary change in Critical care 2008,12:174.
afterload. If afterload increases when there is an increase
2] Richard E. Klabunde : cardiovascular physiology
in preload, then this will lead to a small increase in ESV that
concepts, 2nd edition . Wolters kluwer ,Lippincott Williams &
will partially attenuate the increase in SV brought about by
Willkins : 2012, 69-87.
the increased preload. The increased preload still results in

MCQ
1. Frank starling law states: which is true? c) Increase in catecholamine circulation

d) Increase in parasympathetic circulation
a) Length of ventricular contraction is dependent on
the afterload 4. Which of the following statement is true?
b) Length of the ventricular contraction is dependent
on the length of the resting fibres a) After load is directly proportional to velocity of short-
c) Length of the ventricular contraction is independent ening of fibre
of the length of resting fibres b) After load is indirectly proportional to velocity of
d) None of the above shortening of fibre
c) Independent of each other
2. Factors detemining the ventricular preload: d) None of the above
a) Heart rate 5. Choose the right statement of the following:

b) Venous pressure
c) Ventricular compliance a) Venous blood pressure outside of right atrium, de-
d) Ionotropy creases the right ventricular preload
e) All of the above b) Heart rate and ventricular filling are inversely related
c) Greater the ventricular compliance, lesser the ven-
3. Which of the following factors does not cause increase tricular filling
in ventricular ionotropy? d) When there is systolic dysfunction, the preload
decreases and the ventricle ejects normal volume of
a) Increase in sympathetic circulation blood
b) Increse in afterload
5.b 4.b 3.d 2.e 1.b
ANSWERS:

3 PHARMACOKINETICS OF INHALATIONAL ANESTHETICS
Professor & HOD Aruna Parameswari

SRIHER
Chennai
Key points
Ø Inhalational anesthetics are all nonionized and have low molecular weights, which allows them to rapidly diffuse
across lipid barriers without the need for facilitated diffusion or active transport
Ø Partial pressure of a gas in solution refers to the pressure of gas in the gas phase in equilibrium with the liquid
Ø The concentration of anesthetic in blood depends on the partial pressure at equilibrium and the blood solubility
Ø Relative solubilities in different locations can be described according to the partition ratio or partition coefficient
Ø The time taken for the breathing circuit concentration to equilibrate with delivered concentration is calculated by
the time constant
Ø More soluble agents are removed more by the pulmonary blood flow and hence, this slows the rate of rise of
alveolar concentration of these agents, decreasing the height of the FA/FI curve
Ø Induction can be hastened by increasing the minute ventilation or by decreasing the FRC
Ø A change in ventilation produces a greater relative change in FA/FI with a more soluble anesthetic
Ø Administration of an anesthetic concentration that produces significant respiratory depression progressively

decreases the delivery of anesthetic to the alveoli, in a spontaneously breathing patient. Anesthetics thereby can
exert a negative feedback effect on their own alveolar concentration
Ø A change in cardiac output scarcely affects the concentration of a poorly soluble agent; the alveolar concentration
of a highly soluble agent will be much more influenced
Ø Right to left shunt slows inhalational induction, more so for the less soluble anesthetics
Ø Recovery from anesthesia depends on two elements, MACawake and clearance from effector site
Ø Recovery of pharyngeal function requires that the patient reach effect site concentrations well below MACawake
Ø Isocapnic hyperventilation is a technique of using 6% CO2 and 94% oxygen and increasing the minute ventilation
to the patient at the end of surgery to hasten recovery from inhalational anesthetics
Outline Introduction
• Introduction The inhaled anesthetics are different from all other drugs
• Physical principles and definitions used by anesthesiologists, because they are in the gaseous
phase, administered by inhalation and are taken up and
• Steps in transfer of anesthetic from alveolus to
eliminated through alveolar blood – gas exchange. As
brain and back
gases, the inhalational anesthetics are all nonionized and
• Induction - Factors affecting have low molecular weights, which allows them to rapidly
• Distribution – Factors affecting diffuse across lipid barriers like the capillary membranes,
• Recovery – Elimination and Factors affecting without the need for facilitated diffusion or active transport.
This leads to unique pharmacokinetics and an understanding
• Conclusion

Pharmacokinetics of Inhalational Anesthetics 26 Aruna Parameswari
of these pharmacokinetic principles is fundamental to the Gases in solution
appropriate and safe use of these agents.
For any gas in equilibrium with a liquid, a certain volume
Physical Principles and Definitions of gas dissolves in a given volume of liquid, depending on
the nature of the gas and that of the liquid (solvent). The
Certain physical principles and definitions are important
solubility of a gas is the amount of gas that can be dissolved
in understanding the pharmacokinetics of inhalational
homogenously into a solvent at equilibrium.
anesthetics. The clinical effect of inhalational anesthetics
is dependent on reaching therapeutic tissue levels in the Partial pressure of a gas in solution refers to the pressure
CNS (effect-site). The anesthetic level in a compartment of gas in the gas phase in equilibrium with the liquid. In this
or location is measured in terms of partial pressure or situation of gas in solution, partial pressure is also referred
concentration. to as tension.
Partial pressure and Concentration
Concentration of a gas in solution
Gases in gaseous phase
According to Henry’s law, the amount of gas dissolved in
For any mixture of gases in a closed container, each gas solution is directly proportional to the partial pressure of
exerts a pressure proportional to its fractional mass. This is the gas in contact with the liquid. That is, the concentration
its partial pressure. The sum of the partial pressures of each of gas dissolved in solution is directly proportional to the
gas in a mixture of gases equals the total pressure of the partial pressure.
entire mixture (Dalton’s law).
Cg = k Pg, where Cg is the concentration of the gas in
For example, solution, k is the solubility of the gas in solution and Pg is
the partial pressure of the gas.
1.5% isoflurane in air (21% O2 and 79% N2) at 1 atm
So, the concentration of any one gas in a mixture of gases
in solution depends on two factors:
• Its partial pressure in the gas phase in equilibrium

with the solution and
• Its solubility within that solution
The implications of these properties are that anesthetic

gases administered via the lungs diffuse into blood until the
partial pressures in alveoli and blood are equal. Likewise,
transfer of anesthetic from blood to target tissues also
proceeds toward equalizing partial pressures. It is important
to talk of partial pressures, because gases equilibrate based
on partial pressures, not concentrations. The concentration
Fig 1: Container with 1.5% isoflurane in air. It contains of anesthetic in blood depends on the partial pressure at
~
79% Nitrogen, ~21% Oxygen and 1.5% isoflurane at a total equilibrium and the blood solubility.
pressure of 760 mm Hg. So, the partial pressure exerted
Equilibrium is achieved when the tensions in compartments
by Nitrogen is 79/100 x 760 = 591.4 mmHg, the partial
are equal. The compartments of relevance for inhalational
pressure exerted by Oxygen is 21/100 x 760 = 157.2 mmHg
agents are breathing circuit (inspired gas), lungs (alveolar
and the partial pressure exerted by isoflurane is 1.5/100 x
gas), arterial blood and the body tissues which are classified
760 = 11.4 mm Hg(approximately)
as vessel rich group (brain, heart, kidneys), muscle, fat and
157.2 mm Hg of O2 (21/100 x 760 mm Hg) mixed venous blood.
591.4 mm Hg of N2 (79/100 x 760 mm Hg) That is at equilibrium, alveolar partial pressure arterial
11.4 mm Hg of isoflurane (1.5/100 x 760 mm Hg) partial pressure brain partial pressure.
Concentration is related to partial pressure by multiplying the Although equilibrium is achieved when the anesthetic
fractional concentration by the total pressure, as explained partial pressures (aka tensions) in compartments are equal,
in the previous example. anesthetic concentrations in connected compartments

differ at this equilibrium according to agent solubility in each it is between tissue and blood, and in tissue-gas partition
location. This is where the concept of partition coefficient coefficient, it is between tissue and gas.
comes into play. Relative solubilities can be described
according to the partition ratio or partition coefficient. Blood-gas partition coefficient
Partition coefficient For blood and alveolar gas in equilibrium (anesthetic at

same partial pressures in both compartments), the ratio of
Represented by the Greek letter, lambda, a partition concentration in blood to concentration in similar volume of
coefficient is the ratio of two solute concentrations at
alveolar gas is the blood/gas solubility ratio or blood gas
equilibrium (that is, at equal partial pressure) in two separate
partition coefficient. The blood-gas partition coefficient thus
but adjacent solvents or compartments, such that the solute
describes how the gas will partition itself between the two
moves freely between the compartments. The partition
coefficient specifies what the two compartments are. For phases after equilibrium has been reached. It gives the
example, in blood-gas partition coefficient, the relationship is concentration in the blood for a particular concentration in
between blood and gas, in tissue-blood partition coefficient, the alveolus, as explained in Fig 2.
λ λ λ
Fig 2: Blood gas partitioning of inhaled anesthetics. At equilibrium, the partial pressures in the gas and blood are equal, but the
concentrations of the inhaled anesthetics are different based on their blood/gas partition coefficients. PP – Partial pressure, halo-
halothane, iso- isoflurane, des – desflurane, is blood-gas partition coefficient
Another way to describe the partition coefficient would be to increase the volume of the second compartment so that it
would hold the same concentration of anesthetic as the first compartment. This is shown in Fig 3.
Left panel Right panel
Fig 3

In Fig 3, the left panel depicts the partitioning of isoflurane Tissue-blood partition coefficient
between gas, blood and brain. At equilibrium, a volume For blood and tissue in equilibrium, the ratio of concentration
of blood contains 1.4-fold the quantity of isoflurane as the in tissue to concentration in blood is the tissue/blood
same volume of alveolar gas, whereas a volume of brain partition coefficient. It varies among the inhalational agents
tissue contains 2.2-fold the quantity of isoflurane as the and also among the tissues due to the different biochemical
composition of the different tissues.
same volume of blood. The right panel depicts partition
coefficients as effective (equivalent) volumes of another Steps in Transfer of Inhalational Anesthetic
biophase. For example, one volume of blood contains the Uptake and distribution of inhaled anesthetic can be readily
same amount of isoflurane as 1.4 volumes of alveolar gas, understood as a series of transfer steps from upstream
compartments with high partial pressure to downstream
whereas 1 volume of brain contains the same amount of
compartments with low partial pressure. This happens in
isoflurane as 2.2 volumes of blood or 3.1 volumes of gas.
several steps as depicted in Fig 4.
Fig 4: Steps in the transfer of inhalational anesthetic: Flow diagram for uptake and distribution of inhaled anesthetics. Fresh
gas flow (FGF) moves anesthetic from the vaporizer to the circuit; ventilation drives exchange of anesthetic between the
circuit and alveoli; pulmonary blood flow transfers anesthetic from alveoli into the circulation, which then distributes drug
to different compartments depending on blood flow to various tissues. Relative blood flow is approximately proportional
to the width of the arrows into and out of tissue compartments, as well as for shunts. The diagram depicts an early phase
of anesthetic uptake when organs of the VRG, including the brain, are approaching equilibrium with alveolar and arterial
anesthetic partial pressure, while anesthetic partial pressures in muscle and fat remain relatively low.
Pcirc, Partial pressure in the circuit; Pdel, delivered anesthetic partial pressure.

The several steps in the transfer of inhalational anesthetic With a FGF of 1 L/min and sevoflurane vaporizer set at 2%,
can be summarized as follows: 1000 x 2/100 = 20 ml of sevoflurane vapor is delivered per
minute to the breathing circuit.
1. From anesthesia machine to breathing circuit
2. From breathing circuit to alveoli Factors affecting inspired concentration (FI)
3. From alveoli to pulmonary capillary blood The fractional concentration of anesthetic leaving the circuit
4. From arterial blood to tissues, including primary is designated as FI. The factors that affect the speed at which
target tissue, the brain the gas mixture delivered from the anesthesia machine
5. From tissues back to venous blood and replaces gases in the breathing circuit (wash-in) are FGF
and breathing circuit volume and they thus influence the
6. From mixed venous blood back to alveoli
FI. The time taken for the breathing circuit concentration to
Several factors govern the movement of anesthetics at equilibrate with delivered concentration is calculated by the
each of these steps. Let us look at each of these steps one time constant that is given as:
at a time. Time constant = Volume/Flow = Breathing circuit volume/
1. FROM ANESTHESIA MACHINE (DELIVERED FGF.
CONCENTRATION) TO BREATHING CIRCUIT
In 1 time constant, 63% equilibration occurs between FD and FI
(INSPIRED CONCENTRATION)
In 2 time constants, 86% equilibration occurs between FD and FI
When the fresh gas flow and vaporizer are turned on, fresh
gas with a fixed fractional concentration of anesthetic leaves In 3 time constants, 95% equilibration occurs between FD and FI
the fresh gas outlet and mixes with the gas in the breathing
circuit. It is immediately diluted to a lower fractional In 5 time constants, 99% equilibration occurs between FD and FI
concentration by gas in the breathing circuit, then slowly
If we consider a typical situation in which FGF at the
rises as this compartment (circuit) equilibrates with the
beginning of an anesthetic is 6 L/min and the breathing
fresh gas flow. Wash-in of the breathing circuit represents
circuit volume of 6L, time taken for 63% equilibration (one
an example of bulk transfer exchange.
time constant) will be Volume/FGF = 6L/6L = 1 min and
The delivered concentration depends on the fresh gas flow so in 3 minutes, 95% equilibration occurs and FI reaches
and the vaporizer output. For example, when 6 L/min of 95% of FD, that is wash-in of inhalational anesthetic into the
FGF are delivered with a vaporizer setting of sevoflurane of breathing circuit is almost done. If the FGF is 12L for the
2%, amount of sevoflurane vapor delivered to the breathing same breathing circuit volume, time constant is 6/12 = 0.5
circuit is calculated as: min, so wash-in of inhalational anesthetic into the breathing
circuit is quicker. If the FGF is 3 L/min, time constant is 6/3
2% = 2 ml of sevoflurane vapor for every 100 ml of FGF = 2, so wash in takes longer. This is how FGF determines
speed of equilibration between delivered and inspired
So, for 6000 ml of FGF, 6000 x 2/100 = 120 ml of sevoflurane
anesthetic concentration, as shown in Fig 5.
vapor is delivered per minute to the breathing circuit
1.0 in
L/m
12 in
/m
6L
0.8
in
/m
3L
0.6
FI/FD
0.4
0.2
0.0
0 1 2 3 4 5 6
Minutes
Fig 5: Time taken for breathing circuit to equilibrate with the delivered concentration depends on the fresh gas flow (FGF). Higher the
FGF, quicker the equilibration. Time for the same level of equilibration is 0.5 minutes with 12 L/min FGF, 1 minute with 6 L/min FGF and
2 minutes with 3 L/min FGF

The magnitude and direction of net anesthetic gas flow 2. FROM BREATHING CIRCUIT TO THE ALVEOLI
depends on the difference in partial pressure/concentration
between delivered and inspired mixture. At induction, where Transfer of anesthetic gases from the breathing circuit
FI (or Pcirc) is less than FD (Pdel), it moves from anesthetic to the pulmonary airspace is another bulk exchange
machine to circuit. At recovery, Pcirc is more than Pdel process similar to that from the vaporizer to the breathing
and movement of anesthetic molecules is reversed, and circuit. The difference is that gas flow is via ventilation
anesthetic is removed from circuit gas. and is hence cyclical and bidirectional.
In addition to FGF, the inspired concentration in the breathing Alveolar concentration of the anesthetic
circuit will depend on the volume of the breathing circuit and
absorption of anesthetics by the circuit. Breathing circuit The alveolar concentration of an anesthetic is determined
components, such as CO2 adsorbents and the plastic or by a balance between that introduced into the lungs by
rubber of the circuit tubing and connectors, influence the ventilation and that removed through uptake by blood.
rate of equilibration between vaporizer and circuit, because
The alveolar tension is of particular interest to the anesthetist
such materials can absorb volatile anesthetics, increasing
because it is equivalent (after a small time lag) to the brain
the effective circuit volume.
tension and it can be measured in exhaled end tidal gases.
The clinical relevance of the wash-in process is the speed
at which induction of anesthesia occurs. An example of the The increase in alveolar concentration or equilibration of
importance of FGF is “priming” the anesthetic circuit for a alveoli with circuit is described in terms of FA/FI curves
single-breath induction technique. Another example is the (FA – fraction of anesthetic in alveoli and FI – Fraction of
effect of FGF, as in low flow anesthesia on the speed of anesthetic in inspired gas).
altering inspired concentration and anesthetic depth, whenever
The classic FA/FI curves for the inhaled anesthetics is
vaporizer settings are altered. The use of high FGF initially is
also to hasten the speed of equilibration of circuit. shown in Figure 6.
Fig 6: The Classic FA/FI curve of an inhalational anesthetic

The shape of the FA/FI curve shows an initial upslope, a The first knee in the curve is because of the effect of cardiac
knee, and an alveolar plateau which is upsloping with a output, which results in uptake or removal of the anesthetic
second knee. The rapid upslope is because of the FRC from the alveoli, tapering the rapid rate of rise of alveolar
wash in. There is no anesthetic in the lungs in the first minute concentration. If the effect of ventilation is unopposed, the
of administration of inhalational anesthetic. This results in alveolar concentration of the agent increases rapidly (within
a large gradient between inspired gas and alveolar gas, 2 min) to equal the concentration in the inspired gas. The
leading to a rapid rise in the concentration of anesthetic in administration of oxygen achieves such a rapid change with
the alveoli. oxygen, as seen in the Figure 7.
Fig 7: Rapid equilibration of inspired oxygen concentration within seconds of administration of 100% oxygen.
However, uptake opposes the effect of ventilation, leading to the classic FA/FI curves. How much is removed by uptake
depends on the solubility of the agent.
Pulmonary blood
flow
Fig 8: The alveolar concentration is the balance of what is delivered to the lungs and what is removed by pulmonary blood
flow. For a less soluble agent like desflurane, less anesthetic is removed by the blood (small red arrow) compared to
sevoflurane (large red arrow) which is more compared to isoflurane (very large red arrow)

More soluble agents are removed more by the pulmonary blood flow and hence, this slows the rate of rise of alveolar
concentration of these agents, decreasing the height of the FA/FI curve, as shown in Figure 9.
Fig 9: FA/FI curves of the commonly used inhalational agents.

Agents which are more soluble have a shorter height of the curve.
The second knee in the curve leads to an upsloping alveolar time constant, and hence a more rapid increase in FA/FI
plateau. This is because of the anesthetic concentration (FA – fraction of anesthetic in alveoli and FI – Fraction of
in the mixed venous blood. Mixed venous blood returning anesthetic in inspired gas).
to the lungs has increasing concentrations of anesthetic
with time (as tissue equilibration with VRG is complete in The effect of ventilation is a powerful one. If unopposed
a few minutes). This decreases the alveolar-venous partial on induction, ventilation rapidly increases the alveolar
pressure difference of the anesthetic, slowing the uptake concentration (that is FA/FI quickly approaches 1). This
with time. This leads to increasing FA levels, leading to is seen with preoxygenation to achieve nitrogen washout:
upsloping alveolar plateau on the FA/FI curve. If not for this normally a 95% washout of nitrogen occurs in 2 minutes
factor, the alveolar plateau would be a straight line (That is, or less with a high FGF. However, the rapid washout of
if uptake is constant, as in the case of oxygen). nitrogen or wash-in of oxygen is not mimicked by inhaled
anesthetics. The solubility of anesthetics is far higher than
The factors that determine the rate of exchange (excluding
that of nitrogen or oxygen, and the high solubility causes
effect of uptake) are minute ventilation and total pulmonary
the transfer of substantial quantities of anesthetic to the
airspace. The time constant for equilibration between circuit
blood passing through the lung. This uptake opposes the
and alveoli is again given by Volume/Flow, which in this
effect of ventilation to increase the alveolar anesthetic
case would be FRC/Minute ventilation.
concentration.
So, induction can be hastened by increasing the minute
Effect of ventilation on rate of rise of alveolar concentration
ventilation or by decreasing the FRC. To speed induction
is shown in the Figure 10.
by mask, the patient can exhale deeply before applying
the mask (to decrease the initial FRC) and the patient can
A change in ventilation produces a greater relative change
breathe deeply and rapidly (to increase) after the mask
in FA/FI with a more soluble anesthetic. This is because,
is applied. One of the reasons that pediatric inductions
with a poorly soluble agent such as nitrous oxide, the rate
by spontaneous breathing of inhaled anesthetics are so
of rise of FA/FI is rapid even with hypoventilation. Since
much quicker than adult inductions is that the low FRC
FA normally cannot exceed FI, there is little room for an
relative to alveolar ventilation of children makes for a low
augmentation of ventilation to increase FA/FI.

Sevoflurane Halothane
1.0 1.0
0.8 5 L/min 0.8 5 L/min

10 L/min 10 L/min
0.6 2.5 L/min 0.6 2.5 L/min
FA/FI
FA/FI
0.4
0.4
0.2
0.2
0.0
0.0
0 10 20 30 40
0 10 20 30 40
Minutes
Minutes
Fig 10: Effect of ventilation in increasing the FA/FI. Increase in alveolar ventilation increases the rate of rise. A change in
ventilation produces a greater relative change in FA/FI with a more soluble anesthetic
Administration of an anesthetic concentration that produces Uptake = Q x x (Palv – Pmixed venous blood)
significant respiratory depression progressively decreases
the delivery of anesthetic to the alveoli, in a spontaneously This is the Fick equation applied to blood uptake of inhaled
breathing patient. Anesthetics thereby can exert a negative anesthetics.
feedback effect on their own alveolar concentration, an
The fact that this uptake is a product rather than a sum
effect that increases the safety of spontaneous ventilation
means that if any component of uptake approaches zero,
by limiting the maximum concentration that is attained in
uptake must approach zero, and the effect of ventilation
the alveoli.
to rapidly drive the alveolar concentrations upward will
The alveolar anesthetic partial pressure governs the partial be unopposed. So, if solubility is small (as with nitrogen),
pressure of anesthetic in all body tissues: all must approach cardiac output approaches zero (profound myocardial
and ultimately equal the alveolar partial pressure. depression or death), or if the alveolar to venous partial
pressure difference becomes inconsequential (as might
3. FROM ALVEOLI TO PULMONARY CAPILLARY occur after a very long anesthetic), uptake would be minimal
BLOOD – UPTAKE and FA/FI would equal 1. Let us now look at each of these
three components which affect uptake.
Anesthetic flows from alveolar gas to pulmonary blood
across the alveolo-capillary interface separating these Effect of solubility
compartments. This is called uptake and is the most
important factor in the rate of rise of FA/FI, which in turn Solubility of the anesthetic in blood is measured in terms
reflects the speed at which alveolar anesthetic (FA) of blood gas partition coefficient. A partition coefficient
equilibrates with that being delivered to the lungs (FI). The describes the relative affinity of an anesthetic for two
greater the uptake, the slower the rate of rise of FA/FI and phases and hence how that anesthetic partitions itself
slower the induction with inhalational anesthetics. between the two phases, when equilibrium has been
achieved. The blood/gas partition coefficient reflects the
This movement from the alveoli to the pulmonary capillary solubility of the volatile agent in blood and is defined
blood is driven by the partial pressure gradient between as the ratio of its concentration in blood to alveolar gas
alveolar gas and mixed venous blood entering the when their partial pressures are in equilibrium. Isoflurane
pulmonary arteries and also depends on the blood flow and has a blood-gas partition coefficient of 1.4, meaning that
the solubility of the anesthetic in blood. at equilibrium, when there is no difference in the partial
pressures between blood and alveolus, the concentration
So, anesthetic uptake into the blood depends on the of isoflurane in blood is 1.4 times the concentration in the
pulmonary blood flow (cardiac output), the solubility of the gas (alveolar) phase. Each ml of blood can hold 1.4 times
anesthetic agent in the blood (blood gas partition coefficient) as much isoflurane as one ml of alveolar gas. The blood-
and the partial pressure difference of anesthetic between gas partition coefficients of inhalational anesthetics are
alveolar gas and mixed venous blood. So given in Table 1.

Anesthetic Blood-gas partition coefficient (

Xenon 0.2
Nitrous oxide 0.47
Desflurane 0.45
Sevoflurane 0.65
Isoflurane 1.4
Enflurane 1.9
Halothane 2.5
Cyclopropane 0.415
Chloroform 10.3
Methoxyflurane 12
Ether 15.2
Table 1. Blood gas partition coefficients of inhalational anesthetics
Effect of blood gas solubility on rate of rise of alveolar partial sevoflurane and desflurane have lesser uptake and reach
pressure is given in Figure 11. equilibrium faster.
Blood-gas partition coefficients depend on the concentrations

of serum constituents such as albumin, globulin, triglycerides
and cholesterol. These serum molecules effectively act as
molecular sinks to bind anesthetic agents.
Lower blood gas coefficients are seen with
• Hemodilution
• Obesity
• Hypoalbuminemia and starvation
Higher blood gas coefficients are seen with
• Adults versus children
Fig 11: Effect of blood gas partition coefficient (solubility) on • Hypothermia

the rate of rise of partial pressure. As solubility increases, • Postprandially
the rate of rise of FA slows, as uptake into blood is greater.
Effect of cardiac output and presence of shunt
A higher blood-gas partition coefficient (higher solubility)
In the absence of shunt, pulmonary blood flow equals cardiac
leads to greater uptake by the pulmonary circulation, but
output. Higher cardiac output results in a greater uptake of
a slower increase in alveolar partial pressure of the agent
anesthetic from the lungs and more rapid delivery to the
(FA/FI ratio) and therefore more prolonged induction and
issues including the CNS. Enhanced delivery accelerates
recovery from anesthesia. The more soluble an anesthetic
the equilibration of tissue anesthetic partial pressures
is in blood, the more each volume of blood can take up
with that of arterial blood. However, this does not hasten
anesthetic from alveolar gases and hence slower the rise
induction, as the alveolar concentration is lowered by the
in alveolar partial pressure towards the inspired partial
high uptake of anesthetic. Anesthetic partial pressure in
pressure. FA/FI increases more slowly. The more soluble the
the arterial blood is lower than it would be if cardiac output
inhaled anesthetic, the larger the capacity of the blood and
were normal. In contrast, low cardiac output state results in
tissues for that anesthetic, and the longer it takes to saturate
slow uptake of anesthetic agents and higher alveolar partial
at any given delivery rate. So, less soluble anesthetics, like
pressure of anesthetic (higher FA/FI ratio), and therefore

faster induction of anesthesia as well as unexpectedly high no anesthetic, resulting in a large alveolar venous partial
alveolar anesthetic concentrations leading to other side pressure gradient and high uptake. With tissue equilibration,
effects. venous blood contains more anesthetic and contributes to
decrease in uptake with time.
A change in cardiac output scarcely affects the concentration
of a poorly soluble agent; the alveolar concentration of a Factors affecting alveolar concentration thus can be
highly soluble agent will be much more influenced. summarized as
• Inspired concentration (FI) (depends on delivered
concentration, FGF, circuit volume)
• Alveolar ventilation (VA)
• FRC
• Factors that influence uptake (, Q, PA – PV)
There are two more effects which affect the alveolar
concentration. These are:
Concentration effect
The higher the concentration of an inhaled anesthetic, the
faster its alveolar concentration approaches the inhaled
concentration. This is termed the concentration effect and
is only of clinical relevance with gases administered at high
concentrations such as nitrous oxide and xenon. When an
inhaled anesthetic, such as nitrous oxide is administered in
Fig 12: Effect of cardiac output on rate of rise of alveolar high concentrations, the gas is rapidly taken up into blood,
concentration of the inhalational anesthetic at a very high rate initially (1 L/min). Since Nitrous oxide is
Effect of shunt, deadspace and V/Q mismatch about 30 times more soluble than nitrogen, the volume of
N2O entering the pulmonary capillaries is greater than the
The presence of shunt results in blood not reaching the
N2 leaving the blood and entering the alveolus. This leads to
lungs (right to left shunt) or reaching the lungs but not picking
a reduction in lung volume, thereby increasing the fractional
up inhaled anesthetic (intrapulmonary shunt). This shunted
concentration of the remaining gases. This reduction in lung
blood has no inhaled anesthetic, and mixes with blood from
volume augments ventilation as more inspired gas is now
the lungs containing inhaled anesthetic. The shunt thus
drawn into the alveolus to compensate for the diminished
effectively dilutes the concentration of inhaled anesthetic
alveolar volume. So, there are two reasons for the increase
in the arterial blood, that is Pa decreases. However, shunt
in alveolar concentration, a concentrating effect in a smaller
decreases uptake of anesthetic in alveoli and increases the
lung volume and an augmentation of ventilation, bringing
rate of rise of PA (or FA) towards PI (FI). Since it is Pa which
further anesthetic into the alveoli.
equilibrates with site of action (Brain), decrease in Pa will
slow the equilibration with brain and hence slow induction, Second gas effect
although PA is higher due to shunt. So right to left shunt The second gas effect refers to the effect of nitrous oxide
slows inhalational induction, more so for the less soluble administration in increasing the alveolar concentration of
anesthetics. a concurrently administered volatile inhalational agent.
Effect of mixed venous blood anesthetic concentration If a second gas (like halothane, isoflurane, sevoflurane
(alveolar to venous anesthetic gradient) or desflurane) is administered at the same time as a low-
potency gas that is taken up in large volumes like nitrous
The alveolar to venous anesthetic partial pressure
oxide, the concentration of the second gas rises faster in the
difference results from tissue uptake of anesthetic. Were
alveoli, than it would in the absence of nitrous oxide. This
there no tissue uptake, the venous blood returning to the
is termed the second gas effect and is due to the uptake of
lungs would contain as much anesthetic as it had when it
large volumes of nitrous oxide in the alveoli that leads to
left the lungs as arterial blood, that is the alveolar (equals
both concentrating the residual second gas in a smaller lung
arterial) to venous partial pressure difference would be
volume and an augmentation of alveolar ventilation. This
zero. In the beginning of anesthesia, the venous blood has
process can speed induction of inhalational anesthesia.

Fig 13: Concentration effect – Uptake of half of nitrous oxide should halve the alveolar concentration from 80% to 40%, but
due to the decrease in alveolar volume, the N2O concentration is 66.7%. After the next breath, the N2O concentration is
72%. This is called the concentration effect
Second gas effect – Uptake of half of nitrous oxide factors that govern uptake at the lungs: tissue solubility,
concentrates the simultaneously administered second gas tissue blood flow, and arterial to tissue anesthetic partial
leading to an increase in concentration from 1% to 1.7%. pressure difference. Various tissues have different tissue
The effect of the inspired gas inhaled in the next breath leads specific partition coefficients that depends largely on their
to a final concentration of 1.4% of the second gas. Thus, the biochemical composition.
alveolar concentration of the second gas increases from 1
to 1.4% because of nitrous oxide. This is called the second Tissue solubility is of importance in two ways. First, it
gas effect. determines the quantity of anesthetic removed from the
blood that is traversing the tissue. Higher the tissue/blood
Over pressure effect
partition coefficient, greater the amount of anesthetic
At induction, we compensate for the high uptake of anesthetic removed from blood and entering the tissue and longer the
by delivering a far higher concentration of inhalational tissue is able to extract anesthetic from blood. This in turn,
agent than we hope to achieve in the alveoli. For example, delays the rise in alveolar anesthetic tension, since the low
using 8% sevoflurane at induction to achieve an alveolar venous blood anesthetic tension permits removal of greater
concentration of 2%. This is called the overpressure effect quantities of agent from the alveoli. Secondly, the higher
and is used to speed up the process of inhalational induction. the tissue/blood partition coefficient, the longer it will take
to saturate the tissue. For both these reasons, induction is
Pediatric inductions are faster due to
prolonged, when tissue solubility is high.
• Larger ratio of alveolar ventilation to functional
residual capacity Time constant for equilibration with tissue is given by the
formula,
• Greater delivery of cardiac output to vessel rich
tissues V/Q, where time constant for equilibration, V is the volume
• Lower albumin and cholesterol levels leading to a of tissue, Q is the tissue blood flow and is the tissue blood
reduction in blood-gas solubility coefficients. partition coefficient.
4. FROM ARTERIAL BLOOD TO TISSUES, The algebraic sum of uptake by individual tissues determines
INCLUDING PRIMARY TARGET TISSUE, THE the alveolar to venous partial pressure difference and hence
BRAIN (TISSUE UPTAKE) uptake at the lungs. In terms of perfusion and solubility
characteristics, four tissue groups are identified as shown
The factors that determine the fraction of anesthetic
in Table 2
removed from blood traversing a given tissue parallel those

Group
Vessel-Rich Muscle Fat Vessel-Poor
Percentage of 10 50 20 20
body mass
Perfusion as 75 19 6 0
percentage of
cardiac output
Tissues included Heart, brain, Skeletal muscle Fat Skin, cortical
spinal cord, liver, bone, connective
kidney tissue
Table 2: Classification of the tissue groups
Vessel rich group (VRG) includes the heart, brain, spinal CNS, where anesthetic effects are mediated. Time constant
cord, liver and kidney. Together, these organs compose for equilibration with blood is Effective volume/blood flow.
approximately 10% of the adult human body mass but Effective volume is calculated as tissue volume x tissue/
receive 75% of the cardiac output under resting conditions. blood. Table gives the CNS – arterial blood equilibration
As a result, time constants for anesthetic equilibration time for some of the commonly used inhaled anesthetic
between blood and these organs are typically only a few agents.
minutes. Of particular interest is the equilibration time for the
Agent/Tissue CNS
Tissue vol- tissue/blood Effective Blood flow Time constant
ume (L) volume (L)

(L/min) (min)
Isoflurane 1.43 1.5 2.1 0.62 3.5
Sevoflurane 1.43 1.7 2.4 0.62 4.0
Desflurane 1.43 1.3 1.9 0.62 3.0
Nitrous oxide 1.43 1.1 1.6 0.62 2.6
Table 3: Tissue volume, tissue/blood partition coefficients, blood flow and time constant for equilibration of blood with the
CNS
After the highly perfused VRG tissues, skeletal muscle resulting in an increased effective volume for anesthetic
is the next compartment to equilibrate with inhaled uptake into this compartment. Muscle receives 20% of
anesthetics. Muscle comprises approximately 50% of body cardiac output. Taken together, these factors generally
mass in a healthy adult, making muscle the largest single result in slow equilibration between anesthetic in blood and
compartment based on weight. Moreover, most inhaled muscle, with typical time constants of hours.
anesthetics partition into muscle more than into brain,

Agent/Tissue Muscle
Tissue vol- tissue/blood Effective Blood flow Time constant
ume (L) volume (L)
(L/min) (min)
Isoflurane 30 2.9 87 0.75 116
Sevoflurane 30 3.1 93 0.75 120
Desflurane 30 2.0 60 0.75 80
Nitrous oxide 30 1.2 36 0.75 48
Table 4: Tissue volume, tissue/blood partition coefficients, blood flow and time constant for equilibration of blood with the
CNS
The third tissue group is fat, which in a normal adult to several hours, the blood, VRG organs, and muscle are
composes 20% of body mass and receives 6% of cardiac the compartments into which inhaled anesthetics mostly
output. The more soluble volatile anesthetics partition avidly distribute.
into fat; therefore, fat represents the largest effective volume
for uptake of these drugs. The extremely large effective A fourth group, including skin, cortical bone and connective
volume coupled with relatively low blood flow results in very tissue is referred to as vessel poor tissues. They comprise
slow equilibration of anesthetics between blood and fat, 20% of adult body mass and receive less than 5% of the
with time constants approaching days. Equilibration with fat cardiac output.
is so slow that this compartment usually plays a relatively
Equilibration times from shortest to longest are vessel-rich
minor role in the pharmacokinetics of inhaled anesthetics.
group, muscle group and fat.
During a typical general anesthetic lasting from 30 minutes
Fig 14: The rate of anesthetic partial pressure rises in different compartments

Intertissue diffusion of the ventilation to transport the anesthetic between the
mouth and the lungs and of the circulation to transport it
Current opinion is that there is a fifth compartment of between the lungs and the tissues.
distribution of inhalational anesthetics, which is represented
by adipose tissue adjacent to lean tissue that receives The VRG viscera have a small total volume, and therefore
anesthetic via intertissue diffusion. This transfer of a small storage capacity, and so are represented by a
anesthetic is not insignificant and may account for upto one- small container; but they have a rich blood supply which
third of uptake during long administration. is therefore represented by a large pipe. There is a large
volume of muscle (and therefore a large container) but this
Mapleson’s water analogue: Distribution of inhalational
has a poor blood supply at rest (a narrow pipe). There is a
anesthetics
moderate volume of fat, but it has a large storage capacity
The mathematical equations which govern the uptake and because inhaled anesthetics are more soluble in fat than in
distribution of inhaled anesthetics in the body are, with water (hence a large container) but it has a very poor blood
some reservations the same as those which govern the supply (a very narrow pipe).
movement of water in a system of cylindrical containers
interconnected by pipes. Consequently, such a system can The depth of water in each container represents the partial
be designed to be an analogue of the uptake of inhaled pressure or tension of anesthetic in the corresponding
anesthetics. Then the movement of water in the analogue organs or tissues. The overflowing container at the mouth
mimics the movement of anesthetic in the patient. represents a constant inspired tension provided by a non-
rebreathing anesthetic breathing system.
The water represents the anesthetic itself, volume of
water corresponding to the quantity of anesthetic vapor. With a more soluble anesthetic like halothane, all the
The containers correspond to various groups of organs tissue containers are much larger than with a less soluble
and tissues and represent the storage capacities of those agent like nitrous oxide, because of the greater solubility of
groups for the anesthetic. The pipes represent the ability halothane, especially in fat.
Fig 15: Mapleson’s water analogue for distribution of inhalational anesthetics

Fig 16: Mapleson’s water analogue to explain the distribution of nitrous oxide, a relatively insoluble anesthetic in comparison
to halothane, a relatively soluble anesthetic.
An anesthetic which is more soluble in blood will be

carried more effectively by a given blood supply: therefore
‘transporting ability’ represented by the size of the pipe,
is proportional to blood flow multiplied by the blood/gas
partition coefficient. Therefore, the pipes representing the
blood flow are all larger for the high solubility halothane than
for the low solubility N2O. Though the blood flow pipes are
larger with halothane, the ventilation pipe is the same size
in both cases. Therefore, equilibrium takes longer with high
solubility anesthetics.
Recovery from anesthesia and elimination of

inhalational anesthetics
Recovery from anesthesia depends on two elements. First

is the concentration of anesthetic in the effect compartment
or MACawake. Similar values are found for MACawake
for desflurane, isoflurane and sevoflurane and thus this
Fig 17: MACawake of the inhalational anesthetics as a
factor does not distinguish among the anesthetics in time
percentage of MAC.
to recovery.

The second element that determines recovery is the than insoluble anesthetics. Return to consciousness, which
clearance or removal of anesthetic from the effect site. usually occurs after PCNS drops below MAC-awake, is faster
Several factors influence clearance. following desflurane or sevoflurane anesthesia than after
isoflurane anesthesia.
For recovery, there has to be a reduction in alveolar
anesthetic concentration and elimination of the inhaled One important difference between anesthetic uptake and
anesthetic agent from the effect site. During recovery, the clearance is that although overpressure can be used to
alveolar concentration results from a balance between hasten uptake and induction of anesthesia, the vaporizer
the anesthetic released into the alveoli from blood and setting cannot be set to less than zero. Thus, the most
that removed from the alveoli by ventilation. The greater readily modifiable factors to affect the rate of anesthetic
the solubility of the anesthetic, the greater the reservoir clearance are fresh gas flow and minute ventilation.
available to maintain the alveolar levels in the face of Second important difference is: Washout is affected by the
ventilation. Tissue solubility affects recovery as it does differential elimination from the four tissue compartments.
induction. Higher solubility results in a larger reservoir which Whereas all tissues begin induction with zero anesthetic,
takes longer to deplete. each begins recovery with quite different anesthetic
concentrations. The VRG tissues begin recovery with the
Most anesthetic is thus eliminated from the blood same anesthetic partial pressure as that in alveoli, since
via exhalation from the lungs; other routes include PCNS = Pblood = Palveoli. The partial pressures in muscle and
transcutaneous and visceral losses (both minor) and a fat depend on the inspired concentration during anesthesia,
more significant agent-specific metabolic component. The the duration of administration and the anesthetic tissue
metabolism of different inhalational agents in decreasing solubilities. Body composition has an increasing effect as
order of biodegradation is: Methoxyflurane > Halothane > the length of anesthetic exposure increases, especially for
Sevoflurane > Enflurane > Isoflurane > Desflurane. (75%, highly soluble anesthetics. Patients with increased muscle
20%, 5%, 2%, 0.2%, 0.02% respectively) or fat have larger volumes of anesthetic drug distribution
over time, resulting in slower clearance rates. Anesthetics
Clearance of inhaled anesthetics from target tissues (brain
also redistribute between various tissue groups. Thus, when
and spinal cord) is primarily via the same pathways used for
anesthetic administration ceases, the alveolar anesthetic
anesthetic induction and involve the following 2 steps
concentration decreases in a multiexponential manner.
5. FROM TISSUES BACK TO VENOUS BLOOD That is, the concentration decreases very rapidly at first,
AND then slower, then still slower until at last it decreases at
a rate dictated by the slowest component, the elimination
6. FROM MIXED VENOUS BLOOD BACK TO of anesthetic vapor from fat. Thus, initially, the washout
ALVEOLI from the rapidly equilibrating VRG dictates blood and
alveolar concentration during recovery. Subsequently,
These two steps will be considered together. Washout of elimination from muscles and fat also determines the
inhaled anesthetics follows a multiexponential decay time alveolar concentration during recovery from anesthesia. A
course. If Palv (partial pressure of anesthetic in the alveoli) longer anesthesia will cause more anesthetic to accumulate
is less then PMV, (partial pressure of anesthetic in mixed in muscle and fat, and , as the duration of anesthesia
venous blood), then the net flow of anesthetic will be out increases, the final part of the elimination curve moves
of the blood and into alveoli, where it is subsequently higher and higher, increasing the time for recovery from
exhaled. To achieve the fastest clearance possible, Pcirc (FI) anesthesia. But, for an insoluble anesthetic, the increase is
must therefore be as low as possible, and this is achieved trivial and for an extremely soluble anesthetic, the increase
using high flows of non-anesthetic carrier gases (oxygen is considerable.
and air) after discontinuing delivery of anesthetic. The
same factors that affect transalveolar anesthetic exchange Context sensitive decrement times
during induction also affect clearance via this route.
Increasing ventilation will accelerate clearance whereas Washout rate of anesthetics during recovery can be expressed
increased cardiac output slows clearance, because more as context sensitive decrement times. Context sensitive
gas exchange volumes are required to remove anesthetic decrement times can help us understand why one anesthetic
from the larger blood flow. Highly soluble anesthetics, may differ greatly from another in time to recovery from
which increase the effective blood flow, clear more slowly anesthesia (Fig 18).

For inhaled anesthetics, context-sensitive decrement times Similarly, a greater anesthetic solubility in tissue
connect two values: promotes a greater accumulation of anesthetic in tissues,
an accumulation that will linger during recovery from
a) anesthetic duration – the “context” and
anesthesia. More soluble drugs also equilibrate slower and
b) the time needed to decrease the alveolar or effect site this can affect recovery in a complex manner. The body
concentration by some fractional “decrement” of the stores more molecules of a highly soluble drug in tissue
starting concentration. For example, an 80% decrement than a poorly soluble drug at the same partial pressure of
time would be the time needed to reach 20% of the the drug in the brain.
starting concentration.
If we choose a smaller decrement (say 50%), anesthetics will
The times for a given decrement in the alveoli closely
differ minimally in the time to reach that decrement; the time
approximate those for the VRG (and hence the brain, the
to reach a 50% decrement is small for isoflurane, sevoflurane
effect site).
and desflurane regardless of anesthesia duration. At a 90%
An anesthetic of short duration produces a shorter time to a decrement, moderately soluble anesthetics like isoflurane
specific decrement (say, 95%) because a longer anesthetic will show a considerable increase in decrement times with
duration increases anesthetic accumulation in tissue depots. increasing duration of anesthesia, and this increase occurs
This accumulation limits the decrease in drug concentration after relatively brief anesthetics.
at the conclusion of anesthesia.
Fig 18: Context sensitive decrement times for different anesthetics

Which percentage decrement time is important for recovery? entering the alveolus is greater than the volume of N2
This is difficult to answer, as 90% decrement time means entering the pulmonary capillary blood, thereby adding as
90% of the MAC chosen for the anesthetic; if it was 2 MAC, much as 1L/min of nitrous oxide to alveolar air. This gas
90% decrement would mean 0.2 MAC; if we had chosen effectively dilutes alveolar air and available oxygen, so that
1MAC, 90% decrement would mean 0.1 MAC. What is the hypoxia may result. This is called diffusion hypoxia. This
MAC that is needed for recovery? This depends on what can be prevented by giving 100% oxygen (no nitrogen
our endpoint is. If it is just that 50% of patients have to be present) at the end of a nitrous oxide anesthetic.
awake and respond properly to command, it is MACawake.
But recovery of pharyngeal function requires that the patient Role of isocapnic hyperventilation during recovery
reach effect site concentrations well below MACawake. An
The use of hyperventilation to hasten the elimination of
approach to complete recovery probably demands that the
inhaled anesthetics from the alveoli, at the time of recovery,
patient be at 0.05 MAC or less. Desflurane would allow
has one major disadvantage. It causes hypocapnia, which
the earliest return to this level, compared to isoflurane or
can cause post-hyperventilation apnea and decrease
sevoflurane, and is thus a more “forgiving” anesthetic.
the cerebral blood flow, thus affecting the movement of
Another point to remember is that in clinical anesthesia, we anesthetics from the brain (effect site) to the blood and
taper the delivery towards the end of anesthesia, ending thence to the alveoli. Hyperventilation could facilitate
with a smaller concentration that allows a faster recovery recovery from volatile anesthetics if the disadvantages of
from anesthesia. hypocapnia could be prevented. Isocapnic hyperventilation
is a technique of using 6% CO2 and 94% oxygen and
Other factors which contribute to delay in recovery increasing the minute ventilation to the patient at the end
of surgery to hasten recovery from inhalational anesthetics
Another factor adding complexity to the recovery is the and is a technique that has been sparsely used, but there
release of anesthetic from fat adjacent to highly perfused have been some publications in recent years, highlighting
tissues. Bulk fat probably affects recovery less than another the usefulness of this technique.
form of fat, the fat adjacent to highly perfused or less
than highly perfused lean tissues. Such fat (omental and Conclusion
mesenteric fat juxtaposed to intestine and liver, perirenal
fat, pericardial fat, and fat intercalated throughout the The aim of anesthesia is to achieve a certain level of
muscle or underlying dermis) receives anesthetic by inhalational agent in the brain, at a sufficient speed, so that
intertissue diffusion and has a much shorter half-time than the patient is unaware of and is immobile to the surgical
bulk fat. For desflurane, the half-time may be 180 minutes, stimulus, and that the patient is maintained at an appropriate
and for sevoflurane, 300 minutes. Fat receiving anesthetic depth throughout the procedure. It also involves ensuring the
by intertissue diffusion may account for as much as 30% brain levels drop adequately at the end of the anesthetic, so
of anesthetic taken up, usually more than that removed by the patient is awake with protective reflexes. Understanding
bulk fat. Fat contributing to intertissue diffusion may delay the pharmacokinetics of inhalational anesthetics is
early recovery from anesthesia. fundamental to the safe use of these anesthetic drugs to
provide appropriate clinical care.
Circuit components including tubing, connectors, manual
ventilation bag and CO2 absorbent material, absorb inhaled Recommended Reading
anesthetics, effectively creating another compartment that
1. Forman SA, Ishizawa Y (2015) Inhaled anesthetic
fills while anesthetic is flowing and needs to be emptied
pharmacokinetics: Uptake, distribution, metabolism
during washout. Low-level release of anesthetic gases from
and toxicity. In: Miller RD (ed) Miller’s Anesthesia,
these components can continue for a considerable time.
8th edn. Elsevier Saunders, Philadelphia, pp 638-
Diffusion hypoxia (Fink effect or Third gas effect) 69.
This was first described by Fink in 1955. Nitrous oxide is 2. Ebert TJ, Lindenbaum L (2013) Inhaled anesthetics
roughly 30 times more soluble in blood as nitrogen (blood/ In: Barash PG, Cullen BF, Stoelting RK, Cahalan
gas partition coefficient of N2O is 0.47 and that of N2 is MK, Stock MC, Ortega R (ed) Clinical Anesthesia,
0.015). At the end of nitrous oxide anesthesia, when the 7th edn. Wolters Kluwer Health, Philadelphia, USA,
patient is allowed to breathe room air, the volume of N2O pp 447-77.

3. Mapleson WW (1989). Pharmacokinetics of 8. Korman B, Mapleson WW. Concentration and
inhalational anesthetics. In: Nunn. JF, Utting JE, second gas effects: can the accepted explanation
Brown BR (eds) General Anaesthesia, 5th edn. be improved? Br J Anaesth 1997;78:618-25.
Butterworth & Co., London, pp 44-59.
9. Eger EI, Shafer SL. Tutorial: Context-sensitive
4. Hudson AE, Hemmings HC (2019) Pharmacokinetics decrement times for inhaled anesthetics. Anesth
of inhaled anesthetics. In: Hemmings HC, Egan TD Analg 2005;101:688-96.
(eds) Pharmacology and physiology for anesthesia:
Foundations and clinical application, 2nd edn. 10. Eger EI, Shafer S. Editorial. The complexity
Elsevier Saunders, Philadelphia, pp 44-69. of recovery from anesthesia. J Clin Anesth
2005;17:411-2.
5. Eger EI, Larson P. Anaesthetic solubility in blood
and tissues: values and significance. Br J Anaesth 11. De Baerdemaeker A, De Wolf AM, Poelaert
1964;36:140-9. J, Kennedy RR, Hendrickx J. Effectiveness of
isocapnic hyperventilation: It is not the technique,
6. Eger EI, Saidman LJ. Illustrations of inhaled it is the way you use it. Acta Anaesthesiol Scand
anesthetic uptake, including intertissue diffusion to 2019;1-2. https://doi.org/10.1111/aas.13357
and from fat. Anesth Analg 2005;100:1020-33.
12. Eger EI. After you, please: The second annual John
7. Stoelting RK, Eger EI. An additional explanation W. Severinghaus lecture on translational science.
for the second gas effect: A concentrating effect. Anesthesiology 2010;112:786-93.
Anesthesiology 1969;30:273-7.

MCQ
1. The blood/gas partition coefficient of isoflurane is 1.4. 3. What is true regarding Uptake of inhalational anesthetic
Which of the following statement is then true? from the alveoli ?
a. Each 100 ml of blood has 1.4 times as much iso- a. Uptake = Cardiac output + Blood gas partition coef-
flurane as that present in 100 ml of alveolar gas at ficient + Alveolar to venous partial pressure differ-
equilibrium between the two phases ence of the anesthetic
b. Each 100 ml of alveolar gas has 1.4 times as much b. Uptake of an insoluble anesthetic by the blood is
isoflurane as that present in 100 ml of blood at equi- more than that of a soluble anesthetic
librium between the two phases c. Uptake = Cardiac output x Blood gas partition coeffi-
c. The partial pressure of isoflurane in blood is 1.4 cient x Alveolar to venous partial pressure difference
times the partial pressure in alveolar gas of the anesthetic
d. The partial pressure of isoflurane in alveolar gas is d. Uptake is initially low and then keeps increasing with
1.4 times the partial pressure in blood. time
2. Regarding the FA/FI versus time curve for inhalational 4. Pediatric inhalational inductions are faster because?
anesthetics, which of the following is true?
a. Large alveolar ventilation to FRC ratio
a. The height of the curve is lesser for an anesthetic b. Greater delivery of cardiac output to the vessel rich
that is relatively insoluble in blood tissues
b. The height of the curve is more for an anesthetic that c. Lower albumin and cholesterol levels leading to a
is relatively soluble in blood reduction in blood-gas solubility coefficients.
c. The first knee in the curve is because of the effect of d. All of the above
cardiac output leading to uptake
d. The curve has an upslope of the alveolar plateau 5. Diffusion hypoxia occurs on administration of air after
due to the effect of inhalational anesthetic levels discontinuing N2O because
decreasing in mixed venous blood with time
a. Nitrous oxide is more soluble in blood than oxygen
b. Nitrous oxide is more soluble in blood than nitrogen
c. Nitrogen is more soluble in blood than nitrous oxide
d. None of the above
5. b 4. d 3. c 2. c 1. a
ANSWERS:

4 PHARMACOKINETICS OF INTRAVENOUS ANESTHETICS
Dean Academic Pankaj Kundra

Professor
JIPMER, Pondicherry
Key points
Ø Pharmacokinetics is a branch of pharmacology that describes the processes of absorption, distribution, metabolism
and excretion of a drug by the body as a mathematical function of time and concentration
Ø Pharmacokinetics models the concentration- time profile using key parameters, such as volume of distribution,
area under the curve, clearance, half-life, and bioavailability.
Ø These models are useful for planning and interpreting in vivo studies of efficacy and toxicity and planning clinical
human trials.
Ø The distribution volume of the drug is directly proportional to the free fraction of that drug
Ø Variability in apparent volume of distribution between drugs reflects the proportion of the administered dose that
remains in the plasma
Ø Target drug concentrations can only be maintained if doses are given at a rate that balances the clearance rate
Ø The steady state concentration depends solely upon the balance between the infusion rate (IR) and the clearance
rate (Cl)
Ø The most serious pharmacokinetic interactions are when one drug changes the rate of elimination of another
Ø Context sensitive half time is the time, plasma concentrations take to reduce by 50% after discontinuing an
infusion
Ø Transporter proteins play a role in disposition of various drugs
Ø Pharmacokinetic behaviour can be predicted and simulated, therefore providing early insight as in what to make
or to avoid, using different programs
Basic pharmacokinetics drug that can leave the circulation. For any given drug, the
distribution volume of that drug is directly proportional to the
Pharmacokinetics is the mathematics of the time course free fraction of that drug.
of Absorption, Distribution, Metabolism, and Excretion
(ADME) of drugs in the body. The biological, physiological, Vd C = Vp C + Vt Ct (Equation 1)
and physicochemical factors which influence the transfer
processes of drugs in the body also influence the rate and Vd = Apparent vol. of distribution as measured by plasma
extent of ADME of those drugs in the body. drug conc.
Importance of protein binding C = Total plasma drug concentration.
The capillaries and venules of most tissues are relatively Vp = Plasma volume
impermeable to molecules whose molecular weight is Vt = Extracellular tissue volume where the drug is distributed
greater than 30,000 g/mole. The plasma proteins to which
drugs bind have molecular weights which are greater Ct = Total tissue drug conc.
than 30,000 g/mole. So, a drug molecule which is protein
Divide both sides by C in equation 1
bound cannot readily leave the circulation. Thus, tissue
drug concentration is reached by the free fraction of the Ct
Vd = Vp + Vt
C

Pharmacokinetics of Intravenous Anesthetics 48 Pankaj Kundra
Now the free fraction of the drug in the plasma is given by dose, hence small volume of distribution. In contrast,
Cu drugs that are lipid soluble and bind extensively to
Fu = tissues are present in plasma in low concentrations
C
Fu = Fraction unbound drug in the plasma and, therefore, have large volumes of distribution.
Cu = Concentration of unbound drug in the plasma Target concentration
Like-wise the tissue free fraction is given by: An estimate of the drug’s volume of distribution and the
Cut concentration range that is associated with the desired
Fut = clinical response can be used to calculate the loading dose
Ct
that would achieve the target concentration in a particular
Example: Drug 90% protein bound
patient.
Plasma free concentration (Fu) = 10 ÷ 100 = 0.1
Loading dose = Therapeutic concentration ´ Vd
Apparent vol. of distribution (Vd) = 2.5 + 12.5 ´ (0.1÷1) =
For example, therapeutic concentration of propofol required
3.75 L
for induction of anaesthesia is 0.5 mg/L and taking the
Total plasma concentration after 100 mg bolus dose = C = typical estimate of volume of distribution for propofol as
100 ÷ 3.75 = 26.7 mg/L 4 L/kg, the loading dose will be 2 mg/kg. However, it can
also be used to calculate the bolus dose required to rapidly
Volume of distribution increase the concentration during a continuous infusion:
 When the patient requires administration of an Bolus dose = (Desired concentration - actual
intravenous agent, a loading dose is given, so that concentration) ´ Vd
therapeutic concentrations are reached rapidly. In
many respects ,calculating the loading dose of the Maintenance dose and clearance
drug is similar to calculating the amount of drug
In some respects, patients are like leaky bottles, because
required to achieve a desired concentration in a
drugs start to be eliminated from the body as soon as they
bottle of liquid i.e. dose = volume ´ concentration.
are absorbed. Target drug concentrations can, therefore,
Conversely, the volume of the bottle can be
only be maintained if doses are given at a rate that balances
estimated if the amount of the drug and the
the clearance rate. Maintenance dose regimes are designed
measured concentration is known i.e.
to achieve this balance.
volume = dose ÷ concentration
 In clinical practice, volume of distribution of the

drug (Vd) can be estimated from a known dose and
measured concentrations. Because concentrations
are typically analyzed in blood, serum or plasma,
the estimate represents the apparent volume
throughout which the amount of drug would need
to distribute in order to produce the measured
concentration. For example, if two drugs, A and B,
are both given as 100 mg intravenous bolus doses
and the measured plasma concentrations are 10
mg/L and 1 mg/L, the corresponding volumes of
distribution would be 10 L and 100 L respectively
(volume = dose ÷ concentration).
 Variability in apparent volume of distribution between Figure 1: Concentration time profile for a drug given by
drugs reflects the proportion of the administered constant rate infusion
dose that remains in the plasma. Drugs that are
Figure 1 shows the serum concentration profile of a drug
water soluble or highly bound to plasma proteins
that is being administered by constant rate infusion, with no
have a high plasma concentration relative to the

loading dose. Although the concentration initially increases
with time, the increase gets progressively smaller until the Time Amount remaining Amount Fraction
overall profile is flat. This is known as “steady state” and the (hrs) in body eliminated eliminated
steady state conc. (Css) depends solely upon the balance 0 1000 - -
between the infusion rate (IR) and the clearance rate (Cl).
1 850 150 0.15
Css = IR ÷ Cl
2 723 127 0.15
This relationship means if the measured steady state 3 614 109 0.15
concentration is too low or too high, a new dose can be
determined by direct proportion. For example, to double
4 522 92 0.15
the Css, the infusion rate should be doubled, whereas to 5 444 78 0.15
half the concentration, the infusion rate should be halved.
Alternatively, the IR required to achieve target steady state To illustrate first order kinetics, consider what would
conc. can be calculated as follows: happen if a drug was given as an intravenous bolus
injection, measurement of plasma concentrations of
Dose rate or infusion rate (IR) = Target Css (Cdesired) ´ the drug will show a steady decrease in concentration
clearance (Cl) as the drug is eliminated, as shown in Figure 2. If the
slope of this curve is measured at a number of times
Clearance
we are actually measuring the rate of change of
Clearance represents the volume of blood, serum or plasma concentration at each time point, ΔCp/Δ, represented
completely cleared of drug per unit of time and therefore by the straight line tangents in Figure 2.
has units of volume/time. It is usually expressed as L/hr or
Now if we plot this rate of change versus the plasma
ml/min. Although clearance is often related to the size of
concentration, for each data point, we will get a straight
the patient it is also influenced by number of other clinical
line when first order kinetics is obeyed. This is shown
characteristics.
in Figure 3. The slope of the straight-line correlates to
Water soluble drugs are generally cleared by excretion into elimination rate constant (Kel).
urine, whereas lipid soluble drugs have to be metabolized
to water soluble metabolites by liver before they can be
excreted. This means maintenance dose requirements
can be affected by a range of factors, including age, renal
disease, hepatic disease and drug interactions.
• Zero order kinetics: The elimination rate is a constant
• First order kinetics: The rate of elimination is directly

proportional to the serum drug concentration. With
first order elimination, at a certain point in therapy, the
amount of drug administered during dosing interval
exactly replaces the amount of drug excreted. When Figure 2
this equilibrium occurs (rate in = rate out), steady-state
is reached
Elimination rate constant: Since the rate of elimination

is directly proportional to the serum drug concentration,
there is a linear relationship between rate of elimination
and serum drug conc. Although the amount of drug
eliminated in a first-order process changes with
concentration, the fraction of a drug eliminated
remains constant. The elimination rate constant (Kel)
represents the fraction of drug eliminated per unit of
time. Example of first order process:
Figure 3
Rate of change of Cp versus time = ΔCp (change in conc)/ 1 – Compartment model: All drugs initially distribute into
Δt (change in time) = kel ´ Cp a central compartment (Vc) before distributing into the
peripheral compartment (Vt). However, one compartment
Half life (t ½)
model describes the body as a single compartment. This
Another important parameter that relates to the rate of drug model is only appropriate for drugs which “rapidly” and
elimination is half-life (t ½). The half-life is the time necessary readily distribute between the plasma and other body
for the concentration of drug in the plasma to decrease by tissues. Thus, one-compartment model has only one
half. Both t ½ and Kel, attempt to express the same idea, volume term, Vd, expressed in litres.
how quickly a drug is removed, and therefore, how often
The second criteria for one-compartment linear model are
a dose has to be administered. An important relationship
that, the drug is eliminated from the body in a first-order
between t ½ and Kel can be shown by mathematical
fashion. That is, the rate of elimination is proportional to
manipulation:
the amount of drug in the body. In this model, the Kel is
T ½ = 0.693 / Kel a constant, it does not change when different doses or
multiple doses are given.
Relationship between Kel, Vd, and Cl
Kel (and t ½) are dependent upon clearance and the 2 – Compartment model: Drugs which exhibit a slow
volume of distribution. However, it is invalid to make any equilibration with peripheral tissues are best described
assumptions about the Vd or CL of a drug based solely with a two compartment model. Serum level plot for 2
upon knowledge of its half-life. Kel = Cl / Vd compartment model yields a biphasic line when using a log
scale on the y-axis i.e;
Pharmacokinetic modeling
• Distribution phase: During the initial, rapidly
Pharmacokinetic models are relatively simple mathematical declining distribution phase, drug is moving from
schemes that represent complex physiologic spaces or the central compartment to the tissue compartment
processes. Accurate pharmacokinetic modeling is important (Figure 4).
for precise determination of elimination rate. The most
commonly used pharmacokinetic models are: • Elimination phase: Elimination of drug is the
predominant process during the second phase of
• 1 – compartment model the biphasic plot. Because elimination is a first-
• 2 – compartment model order process, the log plot of this phase is a straight
• Multiple compartment model line (Figure 4).
Figure 4

3 – Compartment model:
Figure 5: The three compartments (CA1 = central compartment, CA2 = highly perfused compartment, and CA3 = poorly
perfused compartement) are presented as open vessels. The connecting tubes correspond with the intercompartmental
clearances (G2, G3). The tube below the central compartment represents the clearance of the drug (G1)
The typical three-compartment model (Figure 5), assumes Limitations of compartment models
injection of the drug into a first or central compartment. The
drug then distributes to two other compartments. Distribution • They assume immediate mixing of drug in the
to the second compartment represents a rapid distribution compartments. The model cannot be used therefore
phase as if to highly perfused tissues. Distribution to the to describe lung uptake or in circumstances
third compartment represents a slow distribution phase where recirculation of a drug causes a second
as if to tissues less well perfused. The rate constants (t) concentration front and, in practice, a dose of
describe the rate of movement by the drug between the drug given intravenously does not equilibrate
central compartment and each of the other compartments instantaneously.
and also the rate of elimination, usually from the central • The model is ‘static’ and does not incorporate other
compartment. processes such as altered protein binding, blood
Most hypnotic and opioid anaesthetic drugs display a loss or haemodilution, which are aspects of the
bi- or tri-exponential decline in blood concentration after dynamic state of the individual patient.
administration. This declining concentration profile occurs Correlation of observed drug disposition with traditional
mainly because most anaesthetic drugs are significantly half-lives
distributed out of the plasma to other areas of the body.
As the drug concentration decreases, separate declining The half-life describing drug disposition, changes depending
exponential processes occur caused not only by drug on when it is measured. For instance, after a bolus dose, the
elimination but also by drug distribution. In a three- reduction in concentration will be as a result of redistribution
compartment model this distribution is split into two and elimination acting concurrently.
phases. Constants that describe the rate of these separate
While the observed initial decline in blood concentration will
exponential processes, called rate constants, can be
be close to the distribution half-life (t½ α), it will be closer
derived mathematically and applied to the two or three
to the elimination half-life (t½ β) after a prolonged infusion.
compartment models. The models will then predict more
In short, the observed fall in blood concentration or indeed
accurately than the one compartment model the actual
duration of clinical effect is poorly predicted by either of
changing concentrations observed for these types of drug.
these half-lives. Hence, these are not particularly useful

terms for the practicing anesthetist. The situation with drug  It is calculated by simulating drug infusions of varying
infusions is more complicated. duration using pharmacokinetic model-driven
computer programs thus allowing comparisons of
It has become clear that the observed half-life at any CSHT to be made between different drugs using the
particular time depends on the duration that the infusion has simulations. A short CSHT might appear desirable
been running, this is the context sensitive half-time (CSHT). if a drug is to be used for TIVA, as it would infer a
Context sensitive half time quick recovery following anesthesia.
 Simply looking at the elimination half-life of drugs  In practice however, the CSHT is actually a poor
described by multi-compartment pharmacokinetic predictor of recovery. The reason for this is that the
models is not sufficient in itself to give an indication time a patient takes to recover from a drug does
of how long the drug concentration will take to not necessarily correlate simply with a decrease
decrease after infusion. in plasma concentration of 50%. The plasma
concentration at this point may not be one where,
 Following a single dose of drug, the reduction recovery would be expected or alternatively plasma
in plasma concentration depends on the drug concentrations associated with recovery may be
distribution profile as well as and possibly more reached before decreasing to the 50% value.
than, the elimination half-life of the drug. The same This clinically relevant half-life, increases with the
is true of drugs given by infusion. In addition, after duration of the infusion until all compartments or
stopping the infusion, the relative importance which body tissues are in equilibrium. This reflects the
the elimination and distribution processes play in peripheral compartments becoming filled with
drug offset, depends on the duration of infusion that drug. The context sensitive half time eventually
has taken place. plateaus at steady state. At this point it is the same
as the elimination half-life, and is no longer context
 New measures that take distribution and not just
sensitive.
elimination into account have been developed to
quantify the time, drug concentrations take to fall  The context sensitive half-time graphs provide
after an infusion. better comparisons to the clinically observed drug
disposition than the traditional pharmacokinetic
 The context sensitive half time (CSHT) is one such
parameters.
measure described by Hughes and colleagues. It
is defined as the time, plasma concentrations take  The content-sensitive half-life increases for some
to reduce by 50% after discontinuing an infusion; in drugs over time but is relatively constant for a drug
other words, in the ‘context’ of a specified duration such as remifentanil.
of infusion.
Figure 7: Context sensitive half-

time. The time required for drug
concentrations of diazepam,
thiopentone, midazolam, ketamine,
propofol, etomidate and remifentanil
to decrease by half their value as a
function of the duration of the infusion

Effect site equilibration as physical properties of the drug and receptor
binding properties may influence the delay between
 There is a lag time or delay between achieving a achieving plasma concentrations and observing a
specific plasma concentration and observing a response.
particular clinical response such as awakening.
The reason for this is that the site of drug action  The effect compartment and rate constant
is not in the plasma for hypnotic agents but in the (Keo) can be included in the three compartment
brain. Drug must move from the plasma to the site pharmacokinetic model to allow simulation of effect
of action in the brain, or effect site, before a clinical site concentration changes (Figure 8a and 8b).
response is detected. The effect site decrement time can then be used
to predict recovery. This is the time taken for the
 There is a mathematical or temporal relationship effect site concentration to decrease by a specified
between the concentration in the plasma and the percentage, usually one where clinical awakening
clinical response observed. This time taken to would be expected. Like CSHT, this predictor of
equilibrate can be described by a rate constant recovery also has limitations, however because
(Keo). pharmacodynamic factors to be discussed later
 The time to equilibrate with the effect site is influence how well the decrement time correlates
different for different drugs and factors such with actual time to clinical awakening.
Figure 8a: standard representation of the 3-compartment model with rate constants k12, k21, k13, k31, k10 and k0. Figure
8b :the three compartments are presented as open vessels. The connecting tubes correspond with the intercompartmental
clearances (x, y). The tube below the central compartment represents the clearance of the drug (z). The small tube inside
the first compartment corresponds with the effect concentration.

MCQ
1. Volume of distribution is defined as: c) Warfarin

d) Propofol
a) Dose/ concentration
b) Maintanence dose * concentration 4. Which of the following drugs shows context insensitivi-
c) Dose / learance ty?
d) Loading dose * concentration
a) Propofol
2. Zero order kinetics is defined as- choose the true state- b) Remifentanyl
ment: c) Fentanyl
d) Thiopentone sodium
a) Rate of elimination is directly proportional to the
serum drug concentration 5. Which of the following is not true about propofol phar-
b) A constant amount of drug is eliminated per unit macokinetics?
time
c) Rate of elimination is indirectly proportional to serum a) Initial distribution half life of propofol is about 2-8
drug concentration minutes
d) None of the above b) Clearance of propofolexceedes hepatic blood flow
c) Its not a CYP3A4 inhibitor
3. Which of the following drug follows first order kinetics? d) None of the above
a) Aspirin
b) Phenytoin
5.c 4.b 3.d 2.b 1.a
ANSWERS:

5 PHYSIOLOGY OF GAS EXCHANGE DURING ANESTHESIA
Professor Naheed Azhar

Stanley Medical College
Chennai
Key points
Ø The first and consistently occurring event caused by anaesthesia is a fall in functional residual capacity
Ø There does not seem to be any difference between the modern volatile anesthetics sevoflurane, and desflurane in
their inhibition of HPV for equivalent MAC doses
Ø Anatomical dead space is reduced or unchanged during anesthesia. The total or physiological dead space is
increased in the anesthetized subject, suggesting that alveolar dead space is increased
Ø Critical ˙VaI/˙Q is the V/Q ratio at which alveoli will eventually collapse and close
Ø In clinical practice, avoiding the preoxygenation procedure and ventilation with 30% instead of 100% O2 prevents
formation of atelectasis during the induction and subsequent anesthesia
Ø PEEP however does not reopen all previously collapsed lung tissue, even if applied during a prolonged period of
time
Ø Atelectasis formation does not increase with age. Airway closure increases with increasing age and this might be
considered a worsening of lung function when one gets older
Ø The major cause of gas exchange impairment during anesthesia at ages below 50 years is shunt, whereas at
higher ages mismatch
Ø FRC is dramatically reduced by the combined effect of the supine position and anesthesia, so it might be
advantageous to choose a more upright position in the anesthetized subject to preserve FRC
Mechanical ventilation during general anesthesia is in functional residual capacity (FRC). This is due to a loss of
unphysiological. The changes in lung and cardiovascular muscle tone which changes the balance between outward
physiology because of the use of positive pressure forces, respiratory muscles, and inward forces, ichelastic
ventilation, the drugs used for general anaesthesia and tissue in the lung. This leads to reduced compliance of
the patient’s position during surgery generate a state lung and an increase in the respiratory resistance. The fall
somewhere between physiological and pathophysiological in FRC also promotes airway closure and gas adsorption
conditions. This occurs immediately after induction of behind occluded airways, leading to atelectasis formation.
anaesthesia even in spontaneously breathing patients The distribution of ventilation is affected and the matching
and is further aggravated after commencing mechanical of ventilation and blood flow is impaired. This impedes
ventilation. These changes do not have any clinical oxygenation of blood and removal of carbon dioxide.
impact for the majority of patients. However, underlying
co-morbidities may amplify these changes in lung and Respiratory muscle tone and lung volume
cardiovascular physiology. The functional residual capacity (FRC) is defined as the
Normal Gas Exchange amount of gas left in the lungs after normal expiration.
This is about 2.5 L in the average-sized adult or 35 mL/kg.
Pulmonary gas exchange during anesthesia, the The FRC acts as a buffer by preventing rapid changes in
mechanisms resulting in its impairment is mainly related alveolar gas tensions from inspired air. The FRC is reduced
to changes in the absolute and relative distribution of gas by 0.7 to 0.8 L by changing body position from upright to
within the lung and in respiratory mechanics. The first and supine, and it decreases by 0.4 to 0.5 L with induction of
consistently occurring event caused by anaesthesia is a fall general anesthesia except with ketamine which maintains

Physiology of gas exchange during anesthesia 56 Naheed Azhar
muscle tone. The FRC is reduced from approximately 3.5 to lung regions. So in ARDS patients who are mechanically
2 L, which is close or equal to residual volume. Anesthesia ventilated, there is a tendency to develop atelectasis in the
itself causes a fall in FRC despite the maintenance of posterior dependant lung regions. This difference between
spontaneous breathing. FRC decrease occurs whether the spontaneous breathing and mechanical ventilation on
anesthetics are inhaled or given intravenously, due to loss atelectasis seem not to apply to anesthesia with regular
of respiratory muscle tone, shifting the balance between the tidal volumes.
elastic recoil force of the lung and the outward forces of
the chest wall leading to a lower chest and lung volume. Ventilation and Perfusion of the Lung
Muscle paralysis and mechanical ventilation do not further The elimination of carbon dioxide and the oxygenation
decrease the FRC. The reduction in FRC leads to an altered of blood are impaired in most patients during anesthesia
distribution of ventilation and impaired oxygenation of blood. with mechanical ventilation. The impeded CO2 elimination
can mainly be attributed to increased physiological dead
space. Impaired gas exchange occurs due to regions of no
perfusion or no ventilation (dead space and shunt) and to
the ventilation-perfusion mismatch. The contributing factors
to the gas exchange disturbance include age, obesity,
smoking habits, and coexisting disease.
Distribution of ventilation
A redistribution of inspired gas away from dependent to

nondependent lung regions occurs in anesthetized and
mechanically ventilated supine person with ventilation
distributed mainly to nondependent lung regions, a linear
decrease in regional ventilation down the lower half of the
FRC increases with age and is decreased in obesity. lung. At the bottom of the lung, there was no ventilation
The major cause of the fall in FRC during anesthesia is a at all and it corresponds to the distribution of atelectasis.
cranial displacement of the diaphragm with only a minor PEEP increases dependent lung ventilation in anesthetized
contribution by decreased transverse area of the thorax. subjects in the lateral position and improves ventilation
distribution. Recruitment manoeuvers further expand the
In the supine position, the posterior, dependent part of upper lung regions and make them less compliant, forcing
the diaphragm is displaced more cranially than anterior, ventilation toward more dependent lung regions.
nondependent regions, because of higher intraabdominal
pressure in dependent region due to the higher hydrostatic Distribution of lung blood flow
pressure in dorsal regions of the abdomen. During
An increase of perfusion down the lung, from ventral to
spontaneous breathing which is a active process, dorsal
dorsal regions, can be found under influence of gravitational
part of the diaphragm is moved caudally more than upper
distribution of lung perfusion. PEEP causes a further
regions. This is because in the dorsal part of the diaphragm,
redistribution of blood flow toward dependent lung regions
the muscle fibers are more elongated and can therefore
and increases shunt, while nondependent lung regions
develop more force like the starlings law. Also the dorsal,
may be poorly perfused, causing a dead space like effect.
crural part of the diaphragm contains more muscle fibers
PEEP also decreases the venous return to the right heart,
than the anterior part so that more force can be developed.
reduces cardiac output and also affects pulmonary vascular
In a paralyzed patient being ventilated, the diaphragm is resistance.
passive and flaccid, and the anterior, nondependent part
Hypoxic pulmonary vasoconstriction
will move more than the posterior, dependent regions during
inspiration. This is because the hydrostatic pressure in the HPV reduces perfusion to hypoxic (atelectatic) lung regions.
anterior abdomen will be less, so it will be easier to move During one-lung anesthesia, HPV helps to maintain systemic
the upper diaphragm region. In spontaneous breathing oxygenation. Several inhalational anesthetics have been
awake subject, normal ventilation distribution occurs to found to inhibit HPV. No such effect has been seen with
the posterior, dependent lung regions. During mechanical intravenous anesthetics. Isoflurane and halothane depress
ventilation, ventilation is distributed mainly to anterior the HPV response by roughly 50% at 2 MAC. There does

not seem to be any difference between the modern volatile It consists of one compartment with “normal” ventilation
anesthetics sevoflurane, and desflurane in their inhibition and perfusion, one compartment with airway closure that
of HPV for equivalent MAC doses. HPV is also modified impedes ventilation (low ˙Va/Q˙ ) and a third compartment
by many other factors such as alkalosis, hypothermia, with collapsed lung (atelectasis) and no ventilation at all
and vasodilators (nitroprusside, calcium antagonists, etc.) (shunt). The most consistent findings during anesthesia are
and is enhanced by almitrine. The HPV response may an increased ˙Va/˙Q mismatch and an increase in shunt.
also be mimicked by simultaneous changes in myocardial
contractility, cardiac output, vascular tone, blood volume Compliance and resistance
distribution, blood pH, CO2 tension, and lung mechanics. The static compliance of the total respiratory system (Crs,st,
There is an attenuation of the hypoxic pulmonary lungs and chest wall) is reduced by an average from 95 to
vasoconstrictor response with increasing FIO2 leading to 60 ml/cmH2O during anesthesia. Resistance of the total
development of atelectasis and shunt in lung units with low respiratory system and of the lungs is increased during
˙Va/˙Q ratios anesthesia, both during spontaneous breathing and during
Ventilation-perfusion relationship mechanical ventilation.
Elimination of carbon dioxide is primarily dependent on Atelectasis

ventilation, taking into account the relative share of dead Bendixen and coworkers proposed “a concept of atelectasis”
space. Airway or “anatomical” dead space is reduced or as a cause of impaired oxygenation during anesthesia due
unchanged during anesthesia. The total or “physiological” to a decrease in compliance of the respiratory system.
dead space is increased in the anesthetized subject, Atelectasis appears in around 90% of all patients who are
suggesting that “alveolar” dead space is increased. anesthetized. It occurs during both spontaneous breathing
Impaired CO2 elimination can be easily dealt with by and after muscle paralysis and whether intravenous or
increasing ventilation and is never a problem during routine inhalational anesthetics are used. 15% to 20% of the lung is
anesthesia with mechanical ventilation. 75% of impaired regularly collapsed at the base of the lung during uneventful
oxygenation can be explained by atelectasis and airway anesthesia, before any surgery has been done. Abdominal
closure taken together, according to the equation. A simple surgery does not greatly increase the atelectasis. The lung
three-compartment lung model can thus be constructed collapse can remain for several days in the postoperative
to explain oxygenation impairment during anesthesia. period and can become a foci of infection and produce

pulmonary complication. The amount of atelectasis can be found. Electrical pacing of the diaphragm and
decreases toward the apex that is mostly spared. After phrenic nerve stimulation during anaesthesia may reduce
thoracic surgery and cardiopulmonary bypass, more than the amount of atelectasis.
50% of the lung can be collapse still several hours after
surgery. Use of PEEP during mechanical ventilation
Oxygen and atelectasis The application of 10 cmH2O PEEP increases the inspiratory
airway pressure and prevents atelectasis. PEEP however
Critical ˙VaI/˙Q is the V/Q ratio at which alveoli will does not reopen all previously collapsed lung tissue, even
eventually collapse and close. Dantzker et al. studied the if applied during a prolonged period of time. PEEP higher
influence of inspired alveolar ventilation/perfusion ratio than 10 cmH2O may be associated with derangement in
(˙VaI/Q˙) and inspired oxygen concentration on alveolar hemodynamics due to an increased intrathoracic pressure
stability. At a ˙Vai/˙Q ratio of 0.001, it may take half an hour which will impede venous return and decrease cardiac
or more during air breathing but no more than 6 min with output and may contribute to a decrease in oxygenation of
an FIO2 of 1.0. The alveolar collapse occurs faster in the arterial blood.
dependent lung regions on induction of anesthesia where
initial alveolar size is smaller than elsewhere in the lung and Recuritment maneuver
where blood flow is higher. Anesthesia with nitrous oxide in A sustained inflation of the lungs to an airway pressure
O2 or Air in oxygen induces atelectasis to the same extent of 30 cmH2O decreases atelectasis to approximately
and with the same speed. In clinical practice, avoiding the half the initial size. To reopen all collapsed lung tissue in
preoxygenation procedure and ventilation with 30% instead anesthetized adults with healthy lungs, an airway pressure
of 100% O2 prevents formation of atelectasis during the (recruitment pressure) of 40 cmH2O maintained for no
induction and subsequent anesthesia. Preoxygenation is more than 7 to 10 sec is required. Such a large inflation
provided to prevent hypoxemia in the event of a difficult corresponds to a maximum spontaneous inspiration in
intubation of the airway. The formation of atelectasis can the awake, supine patient. During recruitment, the alveoli
shorten the “apnea tolerance time,” and hypoxemia may expand nonuniformly and there may be local overdistension.
develop. Dantzker et al concluded that atelectasis is a Excessive inspiratory pressures during a recruitment
minor contribution to potential hypoxemia during prolonged menoeuver may cause transient hemodynamic instability
apnea during the induction. After a couple of minutes of with severe side effects, especially in hypovolemic subjects.
apnea, SpO2 will fall down to a saturation of 90% after 7 It can also produce overdistension of lung regions leading
min if preoxygenation has been performed with 100% O2 to release of inflammatory mediators and promotion of
and 3.5 min after preoxygenation with 60% O2. Decreases ventilator induced lung injury. As an alternative, a stepwise
in saturation are due to the net effect of decreasing oxygen increase in PEEP can be used. Airway pressure as high as
store in the lung and shunt formation. To decrease the 55 cmH2O is used for lung recruitment in morbidly obese,
incidence and severity of atelectasis during anaesthesia, anesthetized patients who have higher chest wall elastance.
it is recommended to ventilate with a moderate fraction Recruitment of an atelectasis is more difficult in the healthy
of inspired oxygen (FIO2, e.g., 0.3-0.4) and be increased lung during anesthesia than in the severely afflicted ARDS
only if arterial oxygenation is compromised. High inspired lung. In ARDS, recruitment may occur at pressures starting
concentration of O2 in the postoperative period carries the from around 20 cmH2O, depending on the severity of the
risk of developing pulmonary infection in atelectatic regions, disease. The atelectasis in the healthy lung will reopen only
known to promote inflammation, or other adverse effects of at airway pressure of 30 cmH2O. A normal lung may be fully
a high-oxygen strategy. recruited at an airway pressure of 40 cmH2O, whereas a
Procedures to prevent or treat atelectasis during considerable amount of collapse may still exist in the ARDS
anesthesia lung.
Maintenance of muscle tone Airway closure
The maintenance of respiratory muscle tone and also FRC Intermittent closure of airways may contribute to reduced
and the regional distribution of ventilation may prevent ventilation in dependent lung regions. If regional perfusion
formation of atelectasis. Ketamine does not impair muscle is maintained or not reduced to the same extent as regional
tone and does not cause atelectasis. If a neuromuscular ventilation, such lung regions may then become “low ˙Va/
blocking agent is used in addition to Ketamine, atelectasis Q” units. Airway closure increases with age. Airway closure

becomes more prominent in the anesthetized subject due or continuous positive airway pressure (CPAP) or by
to the decrease in FRC. Airway closure contributes to appropriate head up positioning. The use of high inspiratory
impaired oxygenation during anesthesia. Airways begin to oxygen concentration (FIO2 = 1.0), to keep an acceptable
close at an average expiratory airway pressure of 7 cmH2O. level of oxygenation during the ongoing anesthesia and
Recruitment followed by PEEP of <7 cm H2O keeps the surgery and addition of 10 cmH2O of PEEP improves
lung open and prevents cyclic airway closure. respiratory mechanics and oxygenation. The improvement
in oxygenation is thus more marked when the application of
Factors that Influence Respiratory Function During PEEP was preceded by a recruitment maneuver. In obese
Anesthesia subjects, a much higher airway pressure of 55 cmH2O is
Patient-related factors needed to reach the transpulmonary pressure necessary to
reexpand previously collapsed lung units.
Atelectasis formation does not increase with age. Airway
closure increases with increasing age and this might be Smokers and patients with lung disease show more
considered a worsening of lung function when one gets severe gas exchange impairment in both awake state and
older. The relationship between airway closure and age is anaesthesia because they have much more airway closure.
biphasic, and airway closure is more common in children Factors related to anesthetic techniques and type or
than in the teenager. A linear correlation occurs with surgery
decreasing CV-VC or CC-FRC with increasing age starting
at around 6 years and lasting upto around 20 years. Thus, FRC is reduced to the same extent during anesthesia,
the optimum age for patent airways and accessible alveolar whether a muscle relaxant is used or not and atelectasis
gas volume is around 20 years. This biphasic relation can occurs to almost the same extent in the anesthetized,
be explained by the growth of the lung with narrow airways spontaneously breathing subject as during muscle paralysis.
being less supported in the very During spontaneous breathing the lower, dependent portion
of the diaphragm moved the most whereas with muscle
young subject and after the age of 20, loss of elastic paralysis the upper, nondependent part showed the largest
tissue in the lung makes the airways more vulnerable to displacement. A “normal” spontaneous breath may not be
collapse. The addition of PEEP is often of help in improving enough to exert the force needed for recruitment.
oxygenation in pediatric Anesthesia. There is an increasing
˙Va/˙Q mismatch with age with an enhanced perfusion FRC is dramatically reduced by the combined effect
of low ˙Va/˙Q regions both in awake subjects and when of the supine position and anesthesia, so it might be
anesthetized causing the arterial oxygenation to decrease advantageous to choose a more upright position in the
with increasing age. The major cause of anesthetized subject to preserve FRC. Pulmonary blood
flow is impeded by the semirecumbent position due to a
gas exchange impairment during anesthesia at ages below possible decrease in cardiac output and enhanced vertical
50 years is shunt, whereas at higher ages mismatch. inhomogeneity of blood flow distribution. In the lateral
In Obesity a restrictive pattern of lung volumes is present. position, differences in lung mechanics, resting lung volumes
There is a marked change in FRC and ERV with increasing and atelectasis formation between the dependent and the
BMI. Between a BMI of 20 to 30 kg/m2, FRC and ERV nondependent lung have been demonstrated , resulting in
decrease about 3% and 5% with each unit increase in BMI. a ventilation-perfusion match with a impairment of arterial
The change in FRC is even more marked in the supine oxygenation. ˙Va/˙Q mismatch was also demonstrated in
position and in the anesthetised, mechanically ventilated anesthetized, paralyzed patients in the lateral position but
subject. If FRC decreases below the volume of closing an improvement in the prone position suggesting that the
capacity, this will result in lung units that are poorly or not vertical inhomogeneity of the perfusion distribution is less
at all ventilated. The combined effect of compression of obvious in the prone position. The ventilation distribution
dependent lung regions and gas adsorption in lung units was also more uniform in anesthetized subjects who were
with low ˙Va/Q˙ or airway closure during anesthesia results in the prone position. A study showed that in prone position
in a considerable amount of atelectasis. This interferes with in normal, anesthetized patients, the mechanical properties,
normal gas exchange, resulting in impaired oxygenation gas exchange and respiratory mechanics remain essentially
and causes shorter time to desaturation during induction of unchanged, whereas oxygenation was improved.
anesthesia. The shortening of time may be prevented by Ventilatory effects of regional anesthesia depend on the type
application of PEEP and extension of motor blockade caused by the regional

anesthetic. Extensive epidural or spinal anesthesia, in volatile concentrations of more than 1MAC, which are
extending to thoracic segments, reduce inspiratory capacity not usually reached in balanced anesthesia. To improve
by 20% and expiratory reserve volume approaches zero. the impaired gas exchange caused by pulmonary shunt
The closing capacity and FRC and ventilation-perfusion during OLV, a variety of measures have been tested. They
ratios during epidural anesthesia are unchanged. Regional include various modes of mechanical ventilation, such as
anesthesia affects pulmonary gas exchange only minimally. the use of PEEP in the ventilated lung and of CPAP in
Effects of anesthetics on the respiratory drive the nonventilated lung, procedures to reexpand collapsed
lung regions, and the use of drugs that affect pulmonary
Inhalational anesthetics, intravenous barbiturates and circulation.
opioids reduce the sensitivity to CO2 and lead to a
dose dependent, decrease in ventilation with deepening Laparoscopic Surgery
anesthesia. Anesthetics also reduce the response to
The most prominent changes concerning the respiratory
hypoxia due to its effect on the carotid body chemoreceptors.
Anesthesia can also produce an impeded function of the system are a cephalad displacement of the diaphragm,
intercostal muscles. decreased FRC and VC, formation of atelectasis (4),
reduced respiratory compliance, and increased peak
One-lung ventilation airway pressure. Dead space ventilation was found to be
unchanged. Shunt is reduced and arterial oxygenation
During OLV, persisting perfusion through the nonventilated
lung results in intrapulmonary shunt (i.e., venous is mostly improved during CO2 pneumoperitoneum due
admixture from nonventilated but perfused lung regions) to enhancement in HPV due to CO2. The maintained or
and can decrease arterial oxygen tension. With normal improved arterial oxygenation during pneumoperitoneum
autoregulation, blood flow to the nonventilated lung is implies that the size of atelectasis cannot be reliably
reduced by HPV. All volatile anesthetics can attenuate HPV predicted from PaO2 or shunt calculation. However, the
but with little difference between anesthetics. Clinically arterial to end-tidal CO2 difference (Pa-ETCO2) correlates
significant effects on HPV attenuation are only seen well with it.

MCQ
1. All are false regarding inhibition of HPV for equivalent 4.Critical VaI/Q is the V/Q ratio at which
MAC doses except
A.Collapsed alveoli open after recruitment
A.Desflurane > Sevoflurane B.Alveoli will eventually collapse and close
B.Desflurane < Sevoflurane C.Alveoli of dependant region begin to close
C.Desflurane = Sevoflurane D.Alveoli of nondependant region begin to close
2. Isoflurane and halothane depress HPV response by 5.Airway closure increases with increasing age
roughly 50% at
A.True
A.0.7 MAC B.False
B.1 MAC
3.1.5 MAC
4.2 MAC
3. During anaesthesia which of the following is true? (FRC-

functional residual capacity, C-Lung compliance, R-Re-
sistance)
A.FRC decreases, C decreases, R increases

B.FRC decreases, C decreases, R decreases
C.FRC decreases, C increases, R decreases
D.FRC decreases, C decreases, R increases
5.A 4.B 3.A 2.B 1.C
ANSWERS:

6 HEART LUNG COORDINATION
Professor Jigi Divatia

Mumbai
Key points
Ø The major determinants of heart-lung interactions are changes in Intrathoracic Pressure (ITP), changes in Lung
volume, ventricular interdependence and changes in intraabdominal pressure due to descent of diaphragm
Ø Pulmonary vascular resistance is least at FRC and increases above and below the FRC
Ø Changes in RV output or RVEDV influence the output from the LV
Ø Pulsus paradoxus is accentuated in patients with very vigorous breathing efforts and negative swings of intra
thoracic pressure like acute exacerbation of asthma
Ø PPV and SVV might help to identify a subset of patients with airway disease and significant PEEP who may
respond to Heliox
Ø PPV and SVV are unreliable during lung protective low tidal volume ventilation
The complex physiology of heart lung interactions plays in LV. A parallel effect occurs because the RV and LV
the pathophysiology during disease states like respiratory share a common septum, and are enclosed in the
failure or cardiac failure, especially when positive pressure pericardium which limits expansion of both ventricles.
ventilatory support is applied. To support the failing
system, these interactions become more complex. A • In addition, during inspiration, the diaphragm
proper understanding of heart lung interactions can help in descends and produces changes in intra-abdominal
predicting treatment effects, anticipating complications, and pressure.
to direct appropriate therapies in critically ill patients in ICU.
Effects of changes in intrathoracic pressure
The major determinants of heart-lung interactions are:
Effect on preload (Fig 1)
• Changes in Intrathoracic Pressure (ITP), leading to
During spontaneous ventilation, right atrial pressure
changes in the preload of the right ventricle (RV) and
(Pra) decreases, enhancing venous return. As the
afterload of the left ventricle (LV)
intra thoracic pressure becomes more negative,
• Changes in Lung volume, affecting the pulmonary the intra thoracic part of the great vessels collapse,
vascular resistance (PVR), causing compression limiting the fall in venous return. During intermittent
of the heart and changes in autonomic tone and positive pressure ventilation (IPPV), the increased Pra
humoral effects results in reduced venous return and a fall in cardiac
output. The extent of this hemodynamic change is
• Ventricular interdependence: A series effect occurs influenced by the volume status of the patient as well
because the output of the RV is the preload of the as the compliance of the lungs and chest wall.

Heart Lung Coordination 64 Jigi Divatia
Fig 1: Effect of intrathoracic pressure on preload
Effect on Left ventricular (LV) afterload and to LV ejection. Similarly, the transmural pressure
intrathoracic transmural pressure across the intrathoracic aorta is increased, also
increasing LV afterload. During IPPV, the effect of
The LV afterload depends on the LV end-diastolic positive intrapleural pressure is to decrease the LV
volume (LVEDV) and the transmural pressure afterload, thus improving ejection of the LV. This
of the LV, which is the difference between the is clinically beneficial in heart failure. Conversely,
intraventricular pressure and pleural pressure. If the during weaning from mechanical ventilation, the
pleural pressure is negative, as during spontaneous increase in preload coupled with increased afterload
breathing, the LV transmural pressure and hence on resumption of spontaneous unassisted ventilation
its afterload is increased, increasing the impedance may result in pulmonary edema and failure to wean.

Fig 2A: Changes in inspiration during positive pressure ventilation
Fig 2B: Hemodynamic changes in exhalation during positive pressure ventilation

Effect on hemodynamic measurements Right ventricular (RV) afterload is determined
mainly by the PVR. PVR is often elevated in
Increased intrapleural pressure also increases several pulmonary and vascular conditions. Further
the measured central venous pressure (CVP) and increases in PVR during mechanical ventilation
pulmonary artery occlusion pressure (PAOP). with high PEEP or tidal volume can precipitate
However, the filling pressure of the cardiac chambers acute cor pulmonale.
is actually the transmural pressure, which cannot be
determined unless the pleural pressure is measured. Ventricular interdependence
It is difficult to quantify the proportion of pleural
pressure that is transmitted to the CVP and PAOP. Changes in RV output or RVEDV influence the output
The index of transmission has been described, and from the LV.
is affected by the pulmonary compliance. Parallel effect
Cardiovascular effects of increase in lung volume Diastolic filling of one ventricle affects the diastolic
Changes in PVR compliance of the other.
At high lung volumes, PVR is increased as Spontaneous breathing is associated with increased
overdistended alveoli compress the alveolar venous return and RVEDV. The increased RVEDV
capillaries. At low lung volumes, when lung volume may cause shift of the septum into the LV reducing
decreases below the functional residual capacity LV diastolic compliance, LVEDV and LV output. If
(FRC), the tortuosity of extra-alveolar vessels pericardial disease or effusion prevents dilatation of
increases causing kinking and collapse of these the RV, the pressure is transmitted to the left atrium
vessels. As the lung is inflated from residual volume with reduction in pulmonary venous return as well as
towards FRC, there is a decrease in extra-alveolar reduced cardiac output.
vessel resistance, but possible increase in alveloar This clinically results in an exaggerated drop in
capillary PVR due to overdistension. The net PVR systolic pressure during inspiration in a spontaneously
is least at FRC and increases above and below the breathing patient, called pulsus paradoxus.
FRC.
Fig 3: Ventricular interdependance

Series effect either LV stroke volume or its surrogate arterial pulse
pressure variation (SVV and PPV, respectively)
During IPPV, phasic increases in lung volume during ventilation identifies patients as being volume
and intrathoracic pressure increase the right atrial responsive. This interaction can be used clinically to
pressure, resulting in decreased venous return to monitor preload responsiveness using parameters
the RV and decreased intrathoracic blood volume. such as the systolic pressure variation (SPV), pulse
After about three heart beats, the decreased flow pressure variation (PPV) and stroke volume variation
reaches the LV, and if it is preload-responsive, then (SVV) in mechanically ventilated patients.
its output also transiently decreases. Thus, seeing
Fig 4: Systolic pressure variation
Clinical application of heart lung interactions increased intra thoracic blood volume. This increases
the venous hydrostatic pressure causing increased
• Understanding Pulsus paradoxus(4) transudation at the capillary end with lymphatic
Pulses paradoxus is a physiological phenomenon outflow. Later, as the lymphatic drainage is outpaced,
occurring due to ventricular interdependence. During interstitial edema develops resulting in negative
inspiration, as ITP becomes negative, there is an pressure pulmonary edema.
accentuated venous return and volume overload
• Predicting fluid responsiveness (8)
of the right ventricle, a shift of the interventricular
septum towards the left, increased left ventricular During respiration, there is a cyclic change in the intra
afterload and a fall in left ventricle stroke volume and thoracic pressure causing cyclic changes in right ventricular
fall in systolic pressure. This systolic reduction in and left ventricular function (Fig 4). These cyclical changes
blood pressure is called pulsus paradoxus. This fall in preload acts as an auto fluid challenge to the left ventricle
is further accentuated in patients with very vigorous
and demonstrates the current cardiac function and fluid
breathing efforts and negative swings of intra thoracic
responsiveness. These are identified at the bedside as
pressure like acute exacerbation of asthma.
changes in systolic pressure, stroke volume and pulse
• Negative pressure pulmonary edema(6) pressure and are increasingly used to determine fluid
responsiveness. (Fig 5)
In cases where there is a markedly negative intra
thoracic pressure, the intra thoracic pressure Currently, both PPV and SVV can be calculated by
decreases, resulting in increased venous return. commercially available minimally invasive monitors using
The left ventricular outflow is impeded resulting in inbuilt mathematical algorithms.

Fig 5: Calculation of PPV and SVV
Clinical use and caveats of PPV and SVV
Clinical use of PPV and SVV Caveats of PPV or SVV

• Surrogates for cardiac function and pre- • Patients should be intubated, ventilated
load responsiveness - a SVV >10% and with at least 8 ml/kg tidal volume and
a PPV> 13-15% predicts fluid respon- having no spontaneous breathing efforts
siveness or arrhythmia.
• During de- resuscitation, an increase in • The lung compliance should be more

PPV suggests further fluid removal might than 30 ml/cm of H2O
be deleterious.
• Normal heart lung interactions (absence
• PPV and SVV might help to identify a of open chest, intra-abdominal hyperten-
subset of patients with airway disease sion)
and significant PEEP who may respond
to Heliox
Tidal volume challenge test
Both PPV and SVV are unreliable during lung kg tidal volume for a minute), an absolute change
protective low tidal volume ventilation, as the in PPV by 3.5, or SVV by 2.5, accurately identified
changes in pleural pressure and lung volume may preload responders.
not be sufficient to produce “swings” in stroke volume
Other tests that depend on heart lung interactions to predict
and pulse pressure. This limits the applicability of
fluid responsiveness
PPV in the ICU significantly. A modification of PPV
– the Tidal volume challenge test(ΔPPV) overcomes • Venecaval variation
this limitation of low tidal volume in using PPV(10). Venecaval variation depend on the phasic variation
During the tidal volume challenge (ventilating at 6ml/ of intrathoracic pressure induced by mechanical
kg tidal volume and a transient increase to 8 ml/ ventilation, measured by echocardiography at

the bedside. A SVC diameter variation of 36% as thoracic swings increasing intrathoracic blood volume
measured by trans oesophageal echocardiography and intrathoracic hypervolemia. Positive pressure
and an IVC diameter variation of 12% as measured acts on each step thereby improving symptoms, (12)
on transthoracic echocardiography accurately predict
Similarly, when patients who are planned for weaning,
fluid status. The effects of low tidal volume, and poor
lung compliance on Venecaval variation is not clear as we take out the positive pressure, the left ventricular
but seems to be limiting factor as like PPV and SVV. afterload increases, and the work of left ventricle increases.
(11) This imposes a stress on the cardiac system, and the
respiratory muscles, which now work independently, and
• End expiratory occlusion test
further increases the oxygen demand. The negative intra
In mechanical ventilation, during inspiration, there thoracic pressure occurring during inspiration, increases
is a reduction in venous return. If this impediment
the venous return and increases LV afterload, and the
was abolished, by prolongation of expiration for
risk of pulmonary edema increases. Such patients, if
adequate time (>15 secs), the cardiac preload will
increase. An increase in cardiac output or aortic VTI identified early, may benefit from reduction in preload and
more than 5% can be assumed as a positive preload improvement in afterload or extubation to NIV which also
responsiveness of both ventricles. This is easy to works in the same manner.
perform and has been validated in patients with Conclusion
reduced lung compliance, and arrhythmias.(11)
The heart-lung interactions in mechanical ventilation
• Management of Cardiogenic pulmonary edema and are different with respect to spontaneous breathing.
Pulmonary edema of weaning The clinically significant effects of heart lung
Cardiogenic pulmonary edema is complicated by 3 interaction seem to be secondary to the changes in
factors. 1) failure of the left ventricle due to a relative intra thoracic pressure. It is important to understand
hypervolemia or impaired cardiac function due to the basic concepts of heart lung interactions as they
increased afterload, 2) low cardiac state resulting in can be used for better patient monitoring and patient
hypoxemia, 3) respiratory distress causing wide intra management as per the situation.
Fig 6: Effects of CPAP on pulmonary edema

Summary 6. Bhattacharya M, Kallet RH, Ware LB, Matthay
MA. Negative-Pressure Pulmonary Edema. Chest.
IPPV results in several effects on hemodynamics, 2016;150(4):927–33.
some of which are beneficial while others are
detrimental. Adverse effects may predominate in the 7. Kenny JS. Predicting the Haemodynamic Response
presence of pre-existing acute or chronic pulmonary to Prone Positioning : A Novel and Simultaneous
disease, hypovolemia and RV dysfunction, while Analysis of the Guyton and Rahn Diagrams. Crit Care
benefit may be seen in cardiac failure. These Horizons. 2017;1–7.
interactions may have implications for other organs.
It is important to understand these cardiopulmonary 8. Michard F, Teboul JL. Using heart-lung interactions
interactions to understand the hemodynamic status to assess fluid responsiveness during mechanical
of the patient and to optimise ventilatory management ventilation. Crit Care. 2000;4(5):282–9.
in critically ill patients.
9. Kubitz JC, Reuter DA. Using heart-lung interactions
References for functional hemodynamic monitoring: Important
factors beyond preload. Intensive Care Med Annu
1. Pinsky MR. Heart – lung interactions. Curr Opin Crit Updat 2007. 2007;d:511–9.
Care. 2007;Current Op:528–31.
10. Myatra SN, Prabu NR, Divatia JV, Monnet X,
2. Henderson WR, Griesdale DEG, Walley KR, Sheel Kulkarni AP, Teboul J-L. The Changes in Pulse
AW. Clinical review: Guyton - the role of mean Pressure Variation or Stroke Volume Variation After
circulatory filling pressure and right atrial pressure in a Tidal Volume Challenge Reliably Predict Fluid
controlling cardiac output. Crit Care. 2010;14(6). Responsiveness During Low Tidal Volume Ventilation.
Crit Care Med. 2017 Mar;45(3):415–21.
3. Magder S. Hemodynamic monitoring in the
mechanically ventilated patient. Curr Opin Crit Care. 11. Monnet X, Teboul J-L. Assessment of fluid
2011;17(1):36–42. responsiveness. Curr Opin Crit Care. 2018;1.
4. Hamzaoui O, Monnet X, Teboul JL. Pulsus paradoxus. 12. Monnet X, Teboul JL, Richard C. Cardiopulmonary
Eur Respir J. 2013;42(6):1696–705. interactions in patients with heart failure. Curr Opin
Crit Care . 2007;13(1):6–11.
5. Mansoor AM, Karlapudi SP. Kussmaul’s Sign. N Engl J
Med [Internet]. 2015;372(2):e3. Available from: http://
www.nejm.org/doi/10.1056/NEJMicm1310957

MCQ
1. The major determinants of heart-lung interactions is/are 4. Which of the following variable helps to predict fluid
responsiveness
a.ventricular interdependence
b changes in .intrathoracic pressure a. a SVV >10% and a PPV> 13-15%
c.changes in .intraabdominal pressure b.a SVV <10% and a PPV> 13-15%
d.all of the above c.a SVV >10% and a PPV<13-15%
d.a SVV <10% and a PPV< 13-15%
2. Following are the effects of change in increased
intrathoracic pressure except 5. IPPV may benefit patients with
a.increased LV preload a.chronic pulmonary disease

b.decreased RV preload b.hypovolemia
c.increasedtransmural pressure c.cardiac failure
d.none of the above d.RV dysfunction
3. An increase in cardiac output or aortic VTI more

than 5% can be assumed as a positive preload
responsiveness in one of the following
a.tidal volume challenge test

b.venecaval variation
c.end expiratory occlusion test
d.stroke volume variation
5.C 4.A 3.C 2.D 1.D
ANSWERS:

CLINICAL LECTURES
7 MANAGEMENT OF OBSTETRIC HEMORRHAGE
Savita Choudhary Sunanda Gupta

Professor, Professor and Head,
Geetanjali Medical College and Hospital, Geetanjali Medical College and Hospital,
Udaipur Udaipur
Key points
Ø Obstetric haemorrhage is defined as excessive bleeding antepartum, intrapartum or postpartum from uterus and
genital tract during pregnancy and peripartum period
Ø Restoration of oxygen carrying capacity and blood volume with correction of washout phenomenon are the
cornerstones of resuscitation during Obstetric Hemorrhage
Ø Initial resuscitation should be performed with large volumes of crystalloid solution through peripheral intravenous
sites
Ø PPH of up to 1500 mL in a healthy pregnant woman can usually be managed by crystalloid infusion alone if the
cause of bleeding is arrested
Ø No colloid solution has been demonstrated to be superior to NS, and, because of the expense and the risk of
adverse effects with colloids, crystalloids are recommended for volume replacement.
Ø Exsanguinating hemorrhage results in acidosis, hypothermia, and coagulopathy, commonly referred to in the
trauma literature as “the lethal triad”
Ø A mixture of red blood cells (RBCs):plasma:platelets in a 1:1:1 ratio contains a hemoglobin concentration of
around 9 g/dL due to the anticoagulants and RBC additive solutions
Ø With the 1:1:1 component approach, the patient will soon reach a critical fibrinogen level due to low levels in
freeze dried and fresh frozen plasma, and extra fibrinogen concentrate must be considered
Ø Clinical endpoints of successful resuscitation includes a maintained mean arterial pressure greater than 65mm of
Hg, sustained mental status, urine output and acid-base status
Ø Minimally invasive interventional radiological techniques offers a promising and very effective alternative for
controlling hemorrhage
Ø Immediately postpartum, women who have been laboring are considered to have delayed gastric emptying (full
stomach physiology) and may, therefore, be at increased risk for aspiration of gastric content
Introduction the financial burden. The rising trend of caesarean section

and other surgical interventions, increases the incidence
Obstetric hemorrhage(OH) is one of the most common of abnormal placentae spectrum which is an important risk
obstetric emergencies and also one of the most common factor for postpartum hemorrhage.
causes of preventable maternal mortality which constitutes
24.7% of worldwide maternal deaths, 16.3% in developed Definition
countries and as high as 27.1% in developing countries. It
can also contribute to complications such as transfusion Obstetric haemorrhage is defined as excessive bleeding
reactions, multi organ failure, obstetric hysterectomy with antepartum, intrapartum or postpartum from uterus and
subsequent loss of reproductive functions and psychological genital tract during pregnancy and peripartum period.
trauma. It is amongst the most common indication of intensive Postpartum hemorrhage is commonly defined as blood loss of
care unit admission in the obstetric population increasing >500 ml after vaginal delivery and >1000 ml after caesarean

Management of Obstetric Hemorrhage 76 Sunanda Gupta
Savita Choudhary
delivery or clinically can be defined as 10% fall of hematocrit Obstetric hemorrhage can be broadly divided in two
or need of blood transfusion; or blood loss associated with categories(Table 1)
signs and symptoms of hypovolemia. ACOG has recently
defined PPH as cumulative blood loss > 1000ml or blood • Antepartum: Hemorrhage after 24 weeks of gestation
loss accompanied by signs and symptoms of hypovolemia and before delivery
within 24 hrs of birth. • Postpartum haemorrhage: Primary PPH is hemorrhage
Massive obstetric hemorrhage is variably defined as blood occuring within 24 hrs of birth, while secondary PPH is
loss >1500ml from uterus or genital tract, decrease in Hb excessive bleeding occurring more than 24 hrs after birth,
concentration >4g/dL or transfusion ≥4 units of blood. up to 12 weeks postpartum.
Antepartum Postpartum
 Placenta previa  Uterine atony
 Abruptio placentae  Placentae accrete spectrum
 Uterine rupture  Use of tocolytics
 Vasa previa  Uterine inversion
 Coagulation disorders  Prolonged third stage of labour
 Trauma  Retained products
 Coagulation disorders
 Puerperal sepsis
 Amniotic fluid embolism
 Genital tract trauma

Local causes: cervicitis, carcinoma, polyp etc.
Table 1: Causes of Obstetric Haemorrhage
Risk factors & Pathophysiology as placentation anomalies, should be transferred to centres

that specialize in the management of such pregnancy
OH results from any one or combination of factors affecting complications with the help of a multidisciplinary team.
uterine tone, retained product of conception (tissue), genital Even though there are multiple validated risk assessment
tract trauma and coagulation abnormalities (thrombin). tools available to help providers identify women at high
Risk Factors risk, these tools can only be used as a guidance, as
they identify only a fraction of women who will develop
Risk assessments should be undertaken during prenatal postpartum hemorrhage.
visits, antepartum care, admission to labor and delivery,
during the labor and postpartum course, as risk factors can Although much attention has focused on identification of risk
change or evolve during the course of labor. Women with factors (Table 2), many women who have PPH will not have
pregnancy complications that are at risk for hemorrhage such any pre-existing risk factors.

Savita Choudhary
Sociodemographic Obstetric Surgical
 Asian ethnicity  Prolonged Stage 3 labor  Emergency cesarean

 Hispanic ethnicity  Preeclampsia section
 Age ≥ 30 years  Retained placenta  Elective cesarean delivery
 Known placenta previa  Forceps delivery
 Previous PPH  Vacuum delivery
 Suspected/proven placental  Episiotomy
abruption  Perineal suture
 Multiple gestation  Systemic or medical
 HELLP syndrome  Antepartum hemorrhage
 Fetal macrosomia  Von Willebrand disease
 Polyhydramnios  Anemia (hemoglobin <9 g/dL)
 Oxytocin exposure  Pyrexia in labor
 Induction of labor  Obesity (BMI > 35)
 Prolonged labor  Cardiac disease
Table 2: Risk Factors associated with PPH
Recently, there has been an increase in the proportion of women whose pregnancy is complicated by anemia, obesity,
advanced maternal age, and invasive placentation who experience PPH. Uterine atony–failure of the uterus to contract after
delivery resulting in excessive bleeding from the dilated uterine spiral arteries–is the leading cause of PPH. The incidence of
uterine atony is rising at a dramatic rate and now represents the driving force behind the rise in postpartum blood transfusion.
While more than half of women who experience obstetric haemorrhage have no identifiable risk factors, for those women
who do, risk stratification can help providers better prepare for those patients predicted to be at higher risk for obstetric
hemorrhage, particularly PPH (Table 3). Active management of third stage of labor comprising uterotonic administration after
delivery, early cord clamping and controlled gentle traction of placenta is helpful in reduction of PPH.
Low Risk Medium Risk High Risk
 No previous uterine  Prior cesarean birth(s) or uterine  Placenta previa, low lying
incision surgery placenta
 Singleton pregnancy  Multiple gestation  Suspected placenta
 ≤ 4 previous vaginal  >4 previous births accreta/percreta
births  Chorioamnionitis  Hematocrit <30% & other
 No known bleeding  History of previous PPH risk factors
disorder  Large uterine fibroids  Platelet count <70,000
 No history of PPH  BMI>40  Active bleeding (more than
 Hematocrit <30% show) on admission
 Prolonged II stage  Known Coagulopathy
 Magnesium SO4  2 or more medium risk factors
Table 3: Admission Hemorrhage Risk Factor Evaluation
Pathophysiology
At term, the uterus and placenta receive 500-800ml of blood per min through their low resistance network of blood vessels. The
spiral arteries ‘fan out’ to create a low resistance vascular bed in the intervillous space, which facilitates placental blood flow. This
flow has been shown to decrease with muscular activity. The physiology of postpartum hemostasis depends primarily on mechanical
events mediated by hormones, which induces strong uterine muscular contractions. Third stage contractions are powerful and
prolonged, stopping the placental blood flow and thus facilitating separation of placenta and membranes.

Savita Choudhary
Two classes of hormones have been implicated in third- stage teaching tools have not been proven yet nor does it correlate
uterine contractility, namely Oxytocin and Prostaglandins. with years of training and experience.
Oxytocin acts on myometrial oxytocin receptors to increase
Quantitative blood loss (QBL)
uterine contractions. Prostaglandins are potent stimulators
of myometrial contractility, acting via cyclic AMP – mediated The California Maternal Quality Care Collaborative (CMQCC)
calcium release, mainly the PGE2 and PGF2α. developed an obstetric hemorrhage toolkit which emphasizes
the need for cumulative quantitative assessment of blood
The secondary mechanism involves, the hemostatic loss. Under-buttock drapes during vaginal deliveries and
mechanisms, during and after placental separation, involving gram scales to weigh blood soaked materials have been
the contraction of muscle sheath around the spiral arteries. proposed to quantitate blood loss more precisely. Research
This leads to retraction of the uterus, causing mechanical has shown that EBL was shown to underestimate postpartum
occlusion of arterioles facilitating platelet plug formation, blood loss by 33% when compared to QBL. It is speculated
and activation of both the clotting cascade and fibrinolysis. that QBL has multiple advantages in comparison to EBL. It
is believed that it leads to earlier interventions and improves
Diagnosis & management: Concerns and Goals the culture of drawing attention to blood loss and mobilizing
Physiological changes of pregnancy usually mask the additional resources earlier.
early signs of blood loss so high index of suspicion, early Triton, a novel mobile monitoring system measures
recognition, addressing the preventable causes and prompt hemoglobin loss absorbed by surgical sponges using a
response with multidisciplinary team is warranted. platform. Images of blood soaked sponges are captured
and transferred to a remote server. Feature Extraction
Diagnosis Technology is used to provide an accurate and precise
Estimated blood loss(EBL) measurement of blood loss. It is speculated that it provides
precise measurement of hemoglobin on surgical sponges
Also known as “eyeball” estimation, is perhaps the most compared to manual rinsing measurements and is more
common method used to estimate blood loss at the time of accurate than gravimetric evaluation.
delivery. Standard estimation of blood loss with the visual
Vital signs and symptoms of haemorrhage
aids, pads, diapers and swabs have been proven inaccurate
both for vaginal delivery and CS. It is often erroneous and Tachycardia may be the only sign until 30-40% of blood
underestimated due to contamination with amniotic fluid, volume is lost. (Table 4) Usage of modified maternal early
or concealed haemorrhage in abdominal cavity or hidden warning system charts to monitor and guide the management
beneath the surgical drapes. Simulation, teaching sessions of women at risk may be helpful. A low score is 1-4, a medium
and clinical reconstructions have been widely used in the score is 5-6, and a high score is ≥ 7. Any single score of 3
clinical setting in an effort to improve clinical blood loss indicates an extreme variation from the normal and should
estimation skills. However, the long-term benefits of such be urgently addressed.
Stage I Compensated II Mild III Moderate IV Severe

Blood loss (ml, 750-1000ml 1000-1500ml 1500-2000ml ≥ 2000ml
% of total volume) < 15% 15-30% 30-40% ≥40%
Heart rate <100 >100 >120 >140
(beats/min)
Blood pressure normal Orthostatic hypotension SBP< 90 mm Hg SBP< 80 mm Hg
Respiration Normal Mild increase Moderate tachypnoea Marked
tachypnoea
Respi failure
Mental status Normal/ slightly anxious Mildly anxious/ agitated Confused/ agitated Obtunded
Urine output (ml/hr) >30 20-30 <20 anuria
Capillary refill Normal, <2 s Clammy skin, Cool, pale skin Cold, mottled
(seconds) >2 s >3 s skin, >3 s
Table 4: Stages of Hypovolaemic Shock in Obstetrics

Savita Choudhary
Since change of vital signs does not always correlate with • Placement of urinary catheter for urine output monitoring
amount of blood loss, other clinical signs that could have a
• Maintain normothermia (warmers for fluid and blood,
predictive value in PPH have been studied.
forced warm air blanket)
Shock index • Call for multidisciplinary team
It is calculated as the heart rate divided by the systolic BP In case of severe ongoing haemorrhage, insertion of Intra-
and can be an accurate predictor of cardiovascular changes arterial line should be considered for invasive BP monitoring
secondary to blood loss even in patients who otherwise and frequent blood sampling for frequent assessment of Hb
would be considered normotensive. The normal Obstetric concentration, coagulation profile and ABG analysis; and
shock index range should be 0.7-0.9 which is higher than central venous line for rapid fluid and blood replacement,
non-pregnant women. An elevated OSI >0.9 has been and also for administration of vasoactive drugs.
shown to be associated with massive transfusion and is a
strong predictor of ICU admissions and adverse outcomes Management of APH
in women with PPH.
Minor APH (Bleeding<500ml)
Management
Management depends on gestational age and fetal viability;
Initial management conservative management with hospitalization, continuous
CTG monitoring, corticosteroid administration for fetal lung
Management strategy of OH should be focused on ensuring
maturity, repeated USG examination for both maternal and
adequate uterine tone, maintenance of hemodynamic
fetal well being can be advised after proper counselling.
stability, aggressive monitoring with early replacement of
coagulation factors and relieving the causative factors. Early Major APH
recognition of warning signs of hemorrhage, continuous vital
monitoring, frequent reassessment of bleeding are of utmost Management aims at hemodynamic stability of mother and
importance. Some of the common steps to follow include: expedited delivery of baby, aggressive resuscitation along
with assessment of fetal wellbeing by ultrasound and CTG,
• Ask for help monitoring blood loss, and assessing the need for blood and
• Ensuring uterine contraction by administration of transfusing judiciously. The mode of delivery depends on
uterotonics and bimanual compression placental site, stage of labour and fetal and maternal well
being. APH also carries significant risk of PPH, so oxytocin
• Diagnosing etiology of hemorrhage
infusion should be immediately started after delivery and
• Check for retained products of placenta other line of management should be kept ready.
• Examination of lower genital tract for trauma and repair Pharmacotherapy
• Continuous vital parameter monitoring
Uterotonic agents (Table 5)
• Insertion of 2 large bore intravenous cannula
Active management of third stage of labour with use of
• Aggressive volume resuscitation
uterotonics immediately after delivery significantly decreases
• Oxygen supplementation the risk of postpartum haemorrhage. Caution regarding use
of uterotonics is warranted in cardiac patients who are more
• Blood sample for assessment of hematocrit, coagulation
sensitive to their side-effects and management should be
status
individualised. If adequate and sustained uterine tone is not
• Blood typing and Cross matching achieved by first line drug, then second line drugs should be
• Activation of massive transfusion protocol considered early to prevent major blood loss.

Savita Choudhary
Drug Commonly Prescribed Dose
 Oxytocin  1-4 IU iv bolus over>30 sec
 Infusion 5-15 IU/hr
 Carbetocin  100 µg over≥ 30 sec-1min iv/im
 Methyl ergometrine  200 µg im or slow iv/2-4h
 Carboprost  250 µg im or intramyometrial, maxm 2mg
 Misoprost  400-600 µg sublingual, oral
 800-1000 µg per rectum
 Sulprostone  500 µg iv@100 µg/hr maxm 1500 µg
Table 5: Dose of Uterotonic Drugs
1st line drugs and 5-HT receptors. It has a plasma half life of 30-120
min. IV administration has the potential for causing
• Oxytocin: It acts by binding to G protein coupled hypertension and CVA.
receptors. These receptors are widely distributed
throughout the body including uterus, cardiovascular Side effects: Hypertension, nausea, vomiting, diarrhoea,
system and central nervous system. Oxytocin has headache, abdominal pain, myocardial ischemia,
contractile effect on myometrium by receptor stimulation dyspnoea; and rarely cerebrovascular accidents,
and production of prostaglandin PGF2α in endometrium. seizures
Oxytocin requirement for intrapartum caesarean section
is greater than low risk elective caesarean section due Contraindications: Hypertension and pre-eclampsia
to rapid homologous desensitisation. • Carboprost: It is a synthetic Prostaglandin-F2α (PGF2α)
Side effects: hypotension, tachycardia, myocardial analogue. It is used commonly for refractory uterine
injury, water retention, hyponatremia, feeling of warmth, atony, its administration may succeed in controlling
flushing, palpitation, dry mouth, metallic taste, nausea, haemorrhage when all other pharmacological treatments
headache, shivering, pruritus. These are dose related fail.
adverse effects with increased propensity in cardiac Side effects: Bronchospasm, abnormal ventilation-
and PIH patients. perfusion ratio, hypoxemia in susceptible patients,
• Carbetocin: It is a longer acting synthetic analogue of nausea, vomiting, diarrhea, epistaxis, hypertension,
oxytocin, 1-deamino-1-monocarbo-(2-O-Methyltyrosine)- flushing, hyperpyrexia and myalgia.
oxytocin, with similar mechanism of action and adverse • Misoprost: It is a Prostaglandin-E1 analogue (PGE-
effect profile. It has a half life of 40 minutes (4-10 times 1); used for cervical ripening and induction of labour.
longer than Oxytocin). Owing to longer duration of It is also helpful in prevention of PPH. Thermostable
action the need for infusion is eliminated. A single dose in tropical conditions and does not require intravenous
of carbetocin has been proposed to act as a 16 hours access for administration. Absorbed 9 – 15 min after
intravenous oxytocin infusion with increase in uterine tone sublingual, oral, vaginal or rectal use, its half life is 20
and reduction of the risk of PPH in elective caesarean – 40 mins.
section. The drug continues to remain effective in hot
and humid conditions and does not need a cold chain. Side effects: Hyperpyrexia, chills, nausea, vomiting,
However, the availability and cost of carbetocin are the diarrhea, chest pain, flatulence.
major deterrents for its routine use.
• Tranexamic acid is an antifibrinolytic that competitively
2nd line drugs inhibits the activation of plasminogen to plasmin.
Tranexamic acid is a synthetic analogue of the amino
• Methyl ergometrine: an ergot alkaloid, increases the acid lysine. It serves as an antifibrinolytic by reversibly
uterine muscle tone by sustained uterine contractions binding four to five lysine receptor sites on plasminogen
via non-specific activation of adrenergic, dopaminergic or plasmin. This prevents plasmin from binding to and

Savita Choudhary
degrading fibrin and preserves the framework of fibrin’s uncontrolled, aggressive fluid resuscitation may increase the
matrix structure. Its use should be considered in cases risk of bleeding. Volume replacement leads to the dilution of
of major and ongoing blood loss; also as prophylactic all coagulation factors, which affects thrombin generation and
measure in high risk patients for major hemorrhage. It also leads to a fall in fibrinogen levels and platelet counts,
has a short half life (2h) and is cleared renally; hence is affecting clot strength. Indeed, fluid resuscitation also leads
contraindicated in renal dysfunction. It may antagonize to poor oxygen delivery, metabolic acidosis, electrolyte
GABA receptors and in high doses, new onset seizures imbalance and induction of hypothermia. Thus, all IV fluids
may set in. The most significant potential adverse effect is should be warmed, as hypothermia impairs coagulation. In
the development of thrombosis. However in the recently addition, increasing the arterial pressure may impede clot
published WOMAN trial it is found to decrease maternal formation. The use of colloids, especially the hydroxyethyl
mortality secondary to bleeding among postpartum starches, may further interfere with fibrin clot strength. Initial
women if given within 3 hrs of onset of haemorrhage. resuscitation should be performed with large volumes of
Thus WHO, ACOG and QMCC have issued updates in crystalloid solution, either normal saline (NS) or Lactated
their OH protocol to include TA as a second line agent Ringer’s solution (LRS), through peripheral intravenous sites.
and to be used in conjunction with obstetrical, surgical
and hematologic management. Dextrose-containing solutions, such as 5% dextrose in
water or diluted NS in 5% dextrose in water, have no role in
Dose: 1 gm at the rate 100 mg/min (over 10 min) with a the management of PPH. The loss of 1 L of blood requires
repeat dose of 1 gm after 30 min if required. replacement with 4-5 L of crystalloid because most of the
infused fluid is not retained in the intravascular space but
Side effects: Hypotension (on rapid injection), nausea, instead shifts to the interstitial space. This shift, along
vomiting, diarrhoea, anaphylaxis. with oxytocin use, may result in peripheral edema in the
• Activated Factor VIIa binds to exposed tissue factor postpartum period following PPH, which is normally excreted
at the site of endothelial damage. This tissue factor- by healthy kidneys. Use large bore cannula for initial infusion
FVIIa complex activates factor X that initiates the rates, with the goal of infusing the required replacement
conversion of prothrombin to thrombin on the surface of volume over minutes rather than hours. PPH of up to 1500
tissue factor-bearing cells. This process results in the mL in a healthy pregnant woman can usually be managed by
activation of platelets. Factor VIIa also activates factor crystalloid infusion alone if the cause of bleeding is arrested.
IX which complexes with factor VIIIa on the surface of Blood loss in excess of this usually requires the addition of
activated platelets catalysing further formation of factor a PRBC transfusion.
Xa and subsequent large-scale platelet surface thrombin Because a large portion of crystalloid fluid volume is lost
generation. The result is the conversion of fibrinogen to the interstitial space, the use of colloids in resuscitation
to fibrin and stabilisation of the platelet plug to form a has been examined. These solutions are largely retained
haemostatic clot. Concerns exist regarding the risk of within the intravascular space and include albumin, dextran,
rFVIIa use in PPH, especially considering that the risk hydroxyethyl starch, and modified fluid gelatin.
of thromboembolism is highest in the first postpartum
week. Increasingly, expert opinion recommends its use Large volumes of colloid solutions (>1000-1500 mL/day) can
as a last resort in OH; when all other therapy has failed. have an adverse effect on hemostasis. No colloid solution
Correction of thrombocytopenia, hypofibrinogenemia and has been demonstrated to be superior to NS, and, because
acidosis prior to giving rVIIa is important. of the expense and the risk of adverse effects with colloids,
crystalloids are recommended for volume replacement.
Crystalloids vs colloids
Transfusion strategies and its risks
The aim of haemodynamic resuscitation in hemorrhagic
shock is to maintain systemic haemodynamics so as to Restoration of oxygen carrying capacity and blood volume
limit microcirculatory hypoperfusion and tissue hypoxia with correction of washout phenomenon are the cornerstones
and thus protect organ function. Hypo-perfusion should be of resuscitation during OH.
aggressively treated with crystalloid in 3:1 ratio with blood
loss and colloid 1:1 should be transfused till blood products The management of PPH has traditionally been limited to
arrive. In the acute phase of hemorrhage, the priority is to stop pharmacological agents that target uterine atony as a cause
the bleeding as soon as possible. As long as this bleeding is of bleeding. Although uterotonics remain first-line drugs,

Savita Choudhary
antifibrinolytics like tranexamic acid, and agents that act on red blood cells (RBCs):plasma:platelets in a 1:1:1 ratio
the coagulation cascade, such as fibrinogen concentrate, contains a hemoglobin concentration of around 9 g/dL
recombinant activated factor VII, and prothrombin complex due to the anticoagulants and RBC additive solutions.
concentrates are likely to play increasingly relevant roles Whole Blood(WB),approximately 450 ml blood and 163 ml
Fig 1: Blood and Blood products
in PPH management. When postpartum hemorrhage is preservation solution,
encountered, care should be taken to accurately diagnose
the source of bleeding as treatment strategies vary. Close
inspection of the placenta to ensure that it is intact and Whole Blood donation
completely extracted, as well as appropriate visualization of
500ml
the cervix and birth canal to rule out laceration is important.
Once the source of the bleeding has been identified,
appropriate steps to swiftly address the etiology should
ensue.
Platelet rich plasma
Packed Red Blood Cells
Blood and Blood products (Fig 1) 300 ml
200ml +100ml ADSOL
Transfusion of blood products is a critical component of Shelf life: 42 days 1-6°C
resuscitation in response to postpartum hemorrhage. In
certain circumstances, when maternal blood loss is drastic,
or the rate of bleeding is rapid, several units of blood products Plasma 250 ml
will not suffice to ensure avoidance of maternal morbidity or Shelf life: 1 yr at -18°C
even mortality.
Platelets 50 ml
Massive transfusion is defined as greater than 10 units Shelf life: 5 days at room
of packed red blood cells (pRBCs) in a 24-h period, and temp
has resulted in a reduction in mortality from haemorrhage.
Exsanguinating hemorrhage results in acidosis, hypothermia, Cryoprecipitate 15 ml
and coagulopathy, commonly referred to in the trauma Shelf life: 1 yr at -18°C
literature as “the lethal triad” and aggressive correction of
coagulopathy improves outcomes and increases survivorship.
Therefore, reduction in mortality is achieved with decreased
fresh frozen plasma to packed red blood cell ratios, with most Fig 1: Blood and Blood products
MTP protocols prescribing a 1:1 or1:1.5 ratio.
has a mean hematocrit of 40%-45%, which gives a mean
There are currently two practices in massive hemorrhage: hemoglobin level of 13-14 g/dL (using healthy young
fixed product ratio or individualized pro-coagulant intervention individuals as donors). According to Fick’s equation, the
and factor substitution. The coagulopathy associated with WB approach gives a DO2 30% higher than the component
massive blood loss is because of loss of coagulation factors, approach in a volume replacement transfusion.
activation of coagulation, and dilutional coagulopathy
secondary to fluid resuscitation. FFP is an inefficient measure This may be crucial for mitigating oxygen debt during
to restore coagulation factors, because the concentration of ongoing bleeding and delayed evacuation. Furthermore,
coagulation factors in FFP is low. Relative amounts of the the practical resuscitative efforts in the context of workload
various blood products selected for transfusion affect the should be easier with the WB approach compared to 1:1:1
overall survival of patients with massive haemorrhage therapy, simply because it is easier to transfuse one bag
instead of three. Fibrinogen levels should also be taken
However, the optimal RBC:plasma transfusion ratio remains into consideration. With the 1:1:1 component approach, the
a topic of debate. The majority included 6 units of RBCs per patient will soon reach a critical fibrinogen level due to low
pack and targeted a 1:1 RBC:plasma ratio. The rationale levels in freeze dried and fresh frozen plasma, and extra
for this approach is to maintain thrombin generation and fibrinogen concentrate must be considered. WB fibrinogen
fibrinogen by the replacement of coagulation factors as levels from healthy young donors levels mean about 3 g/L,
early as possible, as it takes too long in practice to obtain mitigating fibrinogen depletion in the patient during ongoing
laboratory results and issue components. A mixture of

Savita Choudhary
bleeding. RBC function in increasing DO2 may be altered or Obstetric hemorrhage guidelines have varied in their
diminished in stored RBC-containing blood products. recommendations.
Whole blood in massive transfusion The International Society for Thrombosis and Hemostasis
(ISTH) and RCOG suggest maintaining fibrinogen of at least
The use of fresh whole blood has been shown to reduce 200 mg/dL during ongoing obstetric bleeding
potassium overload, electrolyte abnormalities, and
hyperbilirubinemia, and to improve O2 carrying capacity and In the US, the most recent ACOG PPH guidelines do not
mortality in hypotensive traumatic injury patients. Although specifically cite recommendations for fibrinogen targets in
whole blood has been shown to be superior in large volume PPH, and the CMQCC recommend fibrinogen repletion with
hemorrhagic resuscitations of certain patient populations, ongoing hemorrhage and fibrinogen levels <125 mg/dL. The
it does have some disadvantages. While warm fresh blood heterogeneity of guideline recommendations reflects the
used within 8 h maintains factor integrity, stored whole current uncertainty of what is the optimal fibrinogen level
blood can have lability in Factor V and VIII within 12-18 hrs to maintain in patients experiencing obstetric hemorrhage.
of storage at 4°C. Aside from factor break down, other risk Cryoprecipitate is needed in massive transfusion protocols
of fresh warm blood includes increased risk of infections, to augment survival as fresh frozen plasma alone is
bacterial growth in stored specimens, and microchimerism, often a suboptimal source of fibrinogen and large volume
which is harboring genetically different cells in one’s own required to reach adequate levels place patient at risk
system. Whole blood can be used as a viable supplement of transfusion related lung injury (TRALI), pulmonary
and/or replacement in hospital settings, especially in edema, and blood transfusion reaction. During massive
hypovolemic hemorrhagic shock. hemorrhage and transfusion, fibrinogen concentrate could
serve as an expeditious adjunct to protocols and help
Additional transfusion related complications include
limit delay in fibrinogen containing blood products and
Transfusion Related Acute Lung Injury (TRALI) and
decrease complications of volume overload. In contrast to
Transfusion Associated Circulatory Overload (TACO). TRALI
FFP and traditional cryoprecipitate, fibrinogen concentrates
is a potential transfusion related complication that is caused
also decreases the risk of a viral transmission as well as
by antibodies in the plasma against antigens on recipient
delay in administration. A similar adjunct to hemorrhage is
leukocytes. Leukocyte antigens are more common in
prothrombin complex concentrates (PCC). PCCs contain
females due to exposure to previous pregnancies; therefore,
vitamin K dependent clotting factors (Factors II, VII, IX, and X)
TRALI is a particularly relevant complication of transfusion
as well as Protein C and Protein S. However, PCCs could be
to postpartum hemorrhage. TRALI is more commonly
of benefit in women with severe liver disease (i.e., cirrhosis,
encountered with transfusion of plasma, however it can occur
HELLP syndrome, etc.) or with acquired, factor-deficient
with transfusion of any blood product. bleeding disorders, though there is yet no strong evidence
TRALI clinically presents with inflammatory changes such supporting its use in OH. In hospital settings that do not have
as hypotension, fever, leukocytosis, alongside a classic high volume blood banks, TXA, fibrinogen concentrate, and
presentation of bilateral infiltrates and severe hypoxemia. PCCs could serve as lifesaving medications in the prevention
TACO is a transfusion related reaction in which pulmonary of DIC and haemorrhage when 1:1 massive transfusion
cannot be achieved.
edema develops secondary to volume overload. This typically
occurs in patients who receive a large volume of transfusion Cell-salvaged blood
products and/or cardiovascular or renal impairment, and
should be suspected in any patient who develops signs of It can be processed from the surgical field and is another
respiratory distress, elevated brain natriuretic peptide, and strategy that may limit the need for autologous blood
hypertension with six hours of initiation of a blood transfusion. donation. Newer machines in combination with leukocyte
depletion filters have demonstrated effective clearance of
Fibrinogen Repletion fetal squamous cells, phospholipid lamellar bodies, plasma
heparin, cytokines, and other coagulopathic mediators.
While fibrinogen has been identified as a biomarker for
Separate suction for amniotic fluid should be used. Cell-
progression to severe postpartum hemorrhage, it is less
salvaged blood does contain up to 2% fetal erythrocytes;
clear what is an appropriate fibrinogen level to maintain for
Rhesus-negative women will require dose-adjusted RhoGAM
PPH treatment.
administration. Emergency cell salvage services may be

Savita Choudhary
most appropriate in situations where cell saver devices are blood loss (Thrombin). These techniques fall broadly into
routinely used as they require dedicated technicians to set three categories
up the equipment.
• Restoring uterine contractility (removing Tissue,repairing
Monitoring Coagulopathy And Treatment Response Trauma)
Clinical endpoints of successful resuscitation includes a • Decreasing blood loss (Thrombin) while allowing time
maintained mean arterial pressure greater than 65mm of Hg, for uterotonic effect in restoring tone and
sustained mental status, urine output and acid-base status.
Although there are many parameters to measure, lactate and • Providing “Tone” through internal or external tamponade
its clearance is the most adopted surrogate marker of tissue
To approach the 4 T’s, there are three groups of surgical
perfusion. Because the half-life of lactate is approximately
techniques. The first group restores uterine physiology and
20min, a persistent lactic acidosis (>2mmol/L) is indicative of
normal anatomy. This involves the repair of lacerations,
persistent tissue hypoperfusion. Therefore, the use of serial
lactate estimation has been useful in predicting mortality removal of retained products, as well as restoring normal
in both in septic shock and traumatic injury. Therefore, uterine anatomy after inversion. By restoring normal anatomy,
lactate levels should be initially collected at recognition of these techniques aim to restore the process of uterine
hemorrhage and can be followed during resuscitation as an involution.
adjunct to ensure tissue perfusion while ensuring hemostatic
The second group decreases uterine blood flow and
control.
decreases blood loss through surgical vascular ligation and
In recent years, an interest in the implications of relative uterine artery embolization, giving time for involution to take
hypofibrinogenaemia, point-of-care monitoring of coagulation effect.
abnormalities, and the potential to give goal-directed therapy
The third group replicates vascular compression of uterine
to correct coagulopathies, have created the possibility of
involution by tamponade through B-lynch or uterine balloon.
significantly challenging and changing guidance.
Failing these uterine and fertility salvaging procedures,
Additional adjuncts to resuscitation are the use of viscoelastic hysterectomy becomes the final method to treat post-partum
tests namely, thromboelastography (TEG) and rotational hemorrhage.
thromboelastometry (ROTEM). TEG provides a qualitative
assessment of hemostasis in a patient’s whole blood by Intrauterine balloon tamponade
testing both platelet function and coagulation by assaying
If medical management has not effectively stopped the
several parameters of clot formation within whole blood. The
bleeding and other sources like lacerations are excluded,
test is rapid in comparison to conventional tests, which takes
mechanical tamponade in a hemodynamically stable patient
30-60min and can be done at the bedside.
with atonic uterus can be attempted. It is hypothesized that
ROTEM assay can be used as surrogate marker for Clauss an inflated balloon in the uterus causes inward compression
fibrinogen which is a useful biomarker for worsening of the vasculature which decreases blood flow and helps in
hemorrhage. Goal directed therapy based on these, results activating the coagulation cascade. Balloon catheter such
in lower blood product replacement. as Rusch/ Bakri or Dual balloon system or even Foleys
catheter are inserted in uterine cavity for tamponade. It can
Another adjunct to resuscitation is electrolyte repletion.
be used quickly, with minimum analgesia in uterine atony or
During large resuscitations, patients can experience
lower segment bleeding. Preservation of fertility and easy
hyperkalemia from RBC overload, hypocalcemia from citrate
recognition of failure are few advantages associated with it.
in blood products, and hypomagnesemia.
Uterine compression sutures
Surgical Treatment Options
The approach to PPH can be thought of as the “4 Ts” including B-Lynch suture/ modified Lynch compression sutures are
Tone (atony), Trauma (lacerations), Tissue (retained), and useful in controlling blood loss from placental site by opposing
Thrombin (coagulation). Surgical hemorrhage management anterior and posterior wall in refractory uterine atony and
prior to hysterectomy is concerned with improving Tone, may preserve fertility. Infection, uterine necrosis and suture
removing Tissue and repairing Trauma, while preventing erosion are side effects associated with it.

Savita Choudhary
Arterial ligation internal iliac artery or uterine artery, in hemodynamic stable
patients.
Interrupting blood supply from its four main sources: the
uterine artery-above and below the ureter, the vaginal Choice of anaesthesia
branch of the uterine and the ovarian artery, bilateral ligation
Epidural anaesthesia is safe and effective as it avoids possible
of internal iliac, ovarian, uterine arteries may be utilized in
complications of general anaesthesia, facilitates placement
few cases to control blood loss. Uterine devascularisation
of arterial sheath / occlusion catheter and allows conversion
procedures are challenging and need surgical expertise.
to surgical anaesthesia. Epidural catheter placement before
Manual compression of abdominal aorta arterial sheath or balloon occlusion catheter insertion is
preferred, as positioning for epidural can displace balloon/
Is done against vertebral body. It can also be utilised in
sheath and also to avert complications with use of heparin
massive bleeding to decrease blood flow to pelvis and
during procedure. Alternatively, interventional procedure
allowing hemodynamic, hemostatic resuscitation and surgical
can be performed under local anaesthesia followed by
control.
general anaesthesia for caesarean section to have better
Triple P Procedure hemodynamic control in high risk cases. Interventional
procedure performed by experienced Intervention Radiologist
This is a conservative surgical alternative to hysterectomy reduces radiation exposure, amount and duration of
for morbidly adherent placenta. This procedure includes anaesthesia.
perioperative placental localization and delivery via
transverse uterine incision just above the upper margin of Anaesthetic Considerations
placenta along with pelvic devascularization and placental
The critical role of the surgeon-anesthesiologist relationship
non-separation with myometrial excision then followed by
has been shown to improve quality of care and patient
reconstruction of uterine wall.
safety. Significant risk factors which increase the risk of
Hysterectomy PPH should be considered for an antenatal consultation.
The anesthesiologist should be involved in all aspects of
Peripartum total or subtotal hysterectomy as a life saving care for the obstetric patient with PPH, from development of
measure should be considered early if alternative measures protocols, to the provision of bed-side or operating room care,
fail to achieve hemostasis especially in cases of adherent along with the creation of algorithms to enhance recovery
placenta and uterine atony. Peripartum hysterectomy is after delivery. The pre anaesthetic consultation allows ample
technically difficult owing to enlarged uterus, increased time for the anesthesiologist to have a thorough discussion
vascularity and tissue oedema; so it is imperative to involve and counsel the patient about her specific risks and options
experienced surgical team for limiting morbidity. for anaesthetic management, including the possible need
for invasive monitors, central vascular access, general
Interventional Therapy and Anaesthesia Strategies
anesthesia, or admission to an intensive care unit (ICU) and
Minimally invasive interventional radiological techniques such expectations for postpartum pain management; standardized
as selective arterial embolization and intra arterial balloon PPH protocols should be followed in each institute.
occlusion offers a promising and very effective alternative for
Three Obstetric anaesthesiologists should be allocated to
controlling hemorrhage with preservation of fertility, averting
each planned CS with hysterectomy for known morbidly
hysterectomy and decreased need for transfusion thus
adherent placenta, with pre assigned roles:
avoiding serious morbidity associated with these.
• Two, overseeing the anaesthetic technique, monitoring
These procedures are planned in patients who have been
and resuscitation
previously diagnosed as PAS or placenta previa by antenatal
USG and MRI. These procedures can be performed under • The third one is responsible for the transfusion process:
local anaesthesia, with monitoring by anaesthesiologist. monitoring blood loss, cell salvage, transfusion of blood
products and whole blood. Technicians should be
Prophylactic artery balloon occlusion to reduce postpartum
available for help. Continuous communication among
blood flow to uterus with decrease in severity of PPH, is
team members is of utmost importance.
commonly done in internal iliac artery, anterior division of
Savita Choudhary
General anaesthesia after placement of a spinal anaesthetic as compared to
GA. If there is significant urgency, patient has bled and
It is recommended in urgent caesarean delivery in is hypovolemic, coagulopathy is present, it is best to
haemodynamically unstable patients, placenta previa with avoid a neuraxial block. General anaesthesia in such
active bleeding, uterine rupture, ruptured vasa previa, known cases is not without risk. Immediately postpartum,
case of placenta percreta and coagulopathies. Severely women who have been laboring are considered to have
hypotensive patients, may require airway protection, massive delayed gastric emptying (full stomach physiology) and
transfusion may affect ventilation-oxygenation; in these may, therefore, be at increased risk for aspiration of
patients also general anaesthesia is preferred. Unanticipated gastric content. In addition, immediately after delivery,
difficulty in airway management of obstetric population is well likely due to expulsive Valsalva maneuvers, a woman’s
known, so brief examination of airway should be done and airway is likely to be edematous and may place a
difficult airway cart should be ready in units catering obstetric woman more at risk for difficult or failed intubation.
population. Availability of vasopressors and ionotropic drugs General anaesthesia itself, has been shown to be a risk
must be ensured. factor for postpartum hemorrhage during scheduled
Neuraxial anaesthesia or intrapartum cesarean delivery. If the patient has
bled and is hypovolemic, neuraxial block can result in
Epidural /spinal or combined epidural spinal anaesthesia severe hypotension or even hemodynamic collapse.
can be planned if patient is haemodynamically stable In a coagulopathic patient, placement of a neuraxial
(without active bleeding or intravascular volume deficit) but block can result in epidural hematoma, with spinal
in such cases, conversion to GA may be required. Patient cord compression and permanent lower extremity
with epidural in-situ can be operated after top-ups. Spinal paralysis. Thus each patient should be assessed for
anaesthesia causes lesser degree of hypotension in pre- risk benefit analysis and decision for neuraxial or GA
eclamptic patients, they also have advantage of better uterine taken accordingly.
contractility and neonatal outcome compared to general
anaesthesia. 4) Anaesthesia for management of PPH during CD:
Adequate IV access, both arterial and central venous
Some scenarios highlighting different anaesthetic access and longer acting local anaesthetics as in
management Combined spinal epidural, which can be later converted
to GA, if there is significant intraoperative hemorrhage.
1) Unexpected PPH during vaginal delivery with working
epidural catheter in situ: If a surgical repair of a laceration 5) Anaesthesia for a known case of morbidly adherent
is necessary, the patient can be managed with an epidural placenta: The case can be started under neuraxial
bolus of a quick acting local anaesthetic like lignocaine or anaesthesia (CSE) delaying or avoiding GA until
chloroprocaine, if patient is haemodynamically stable. it becomes necessary for surgical reasons like
complicated abdominal hysterectomy, or maternal
2) No epidural catheter and minor bleeding: Small doses
instability due to excessive hemorrhage.
of IV opioids, local anaesthetics at repair site or a
paracervical block may suffice. Sedation with minimal 6) Medical conditions which require transferring the
doses of opioids usually fentanyl and benzodiazepines patient to the ICU include:
usually midazolam, and may be supplemented with
minimal doses of ketamine. Moderate sedation requires • Prolonged mechanical ventilation
maintenance of meaningful contact with the patient; • Multiorgan system failure
the patient should retain the ability to respond to verbal • Persistent coagulopathy
stimuli. • Hemodynamic instability
3) For patients with no epidural catheter and significant Reporting and System Learning
blood loss: the main concerns of placing a neuraxial Regardless of the threshold for determining what cases
block in a patient experiencing PPH are: time to require detailed review, an initial debriefing should always
induction of the anaesthetic, degree of hypovolemia, occur after a hemorrhage event and should function as a
and coagulation status. Studies have shown that it quick “recap” of the event. This would include a huddle with
takes 5-10 minutes longer to achieve surgical readiness all available team members, a quick written report that can

Savita Choudhary
be reviewed later as part of a systematic review process. This multidisciplinary team are important in preventing the adverse
is important to foster continuous improvement and identify incidents and their sequelae.
opportunities for improvement in management of OH program
in the hospital. Women at risk for severe blood loss should be identified in
antenatal visits duly supported by radiological examination
Bundles and checklists have been shown to be effective tools and referral to higher centre with better diagnostic modalities,
for improving patient safety in a variety of clinical settings. The blood bank, intensive care set-up should be considered to
obstetric hemorrhage bundle consists of four action domains, improve outcome. Reporting and systems learning provides
often referred to as the Four Rs. These include: the backbone for a sustainable comprehensive response
to maternal hemorrhage. “Report back education” for all
Readiness of every unit providers, debriefing and audits, should be an integral part
Blood bank (massive transfusion protocol); cart and of recognising the pivotal role of the anaesthesia team.
medication kit; hemorrhage team with education and drills Suggested reading
for all stakeholders
1. Scavone BM. Antepartum and Postpartum Haemorrhage.
Recognition and prevention of hemorrhage for every In: Wong CA, Editors. Chestnut’s obstetric anaesthesia:
patient Principles and practice. 5th ed. Philadelphia: Elsevier
Risk assessment; universal active management of the third Saunders;2016.
stage of labor 2. Hessen M, Carvalho B, Carvalho JCA, Duvekot JJ, Dyer
RA, Lucas DN. International consensus statement on
Response to every hemorrhage
the use of uterotonic agents during caesarean section.
Staged checklist; support for patients, families, and staff for Anesthesia 2019;74:1305-19.
all significant hemorrhages 3. Sebghati M, Chandraharan E. An update on the risk
Reporting/systems learning for every unit factors for and management of obstetric haemorrhage.
Women’s health 2017; 13(2):34-40.
Culture of huddles and debriefing; multidisciplinary review of
4. Obstetric Haemorrhage Clinical Guidelines V2.2 NHS
serious hemorrhages; monitoring of outcomes and processes
Trust. Royal Cornwall Hospitals. June 2018, pg 1-37.
metrics
5. Ring L, Landau R. Postpartum hemorrhage: Anesthesia
Obstetric hemorrhage safety bundle from the National management. Seminars in perinatology 2019; 43:35-43.
Partnership for Maternal Safety, Council on Patient Safety
in Women’s Health states that every hospital that cares 6. Walfish M, Neuman A, Wlody D. Maternal Haemorrhage.
for obstetric patients should have a functioning massive BJA 2009;103:47-56.
transfusion protocol (MTP), a functioning protocol for 7. Gilmandiyar D, Thornburg LL. Surgical management of
emergency release of uncrossmatched, O-negative red blood PPH. Seminars in Perinatology ; 2019,43:27-34.
cells, an ability to rapidly obtain typed packed red blood cells
8. Pacheco LD, Saade GR, Hankins GDV. Medical
(PRBCs) and fresh frozen plasma (FFP), and a mechanism
management of PPH: an update. Seminars in Perinatology
in place to obtain platelets and additional products in a
2019; 43:22-26.
timely fashion. As an essential element of readiness, every
unit should establish an MTP that allows the blood bank to 9. Higgins N, Patel SK, Toledo P. PPH revisited: new
continuously release these products to the Labor Unit at challenges and solutions. 2019, 32(3): 278-284.
a predefined ratio until the MTP is deactivated. At the end 10. Andrikopoulou M, D’Alton ME. PPH: early identification
of every simulation, as well as at the end of every real-life challenges. Seminars in Perinatology 2019,43:11-17.
emergency, a debrief should take place to identify what went
well, what went poorly, and what could be done to improve 11. Kogutt BK, Vaught AJ. PPH: Blood product management
in the future. and massive transfusion. Seminars in Perinatology 2019,
43:44-50.
Summary & recommendations
12. O’Brien KL, Shainker SA, Lockhart EL Transfusion
Early recognition of risk factors, estimating the extent of blood Management of Obstetric Hemorrhage. Transfusion
loss accurately, initiating treatment timely and readiness of Medicine Reviews. 2018, 32:249-255.

Savita Choudhary
MCQ
1. Which of the following is not a component of lethal triad 5.Oxytocin to be stored at (degree Celsius)?
due to massive hemorrhage?
A.20
A. Acidosis B.2-8
B.Hypothermia C.0-4
C.Coagulopathy D.10-14
D.Hypercarbia
6.Halflife of lactate(indicator of tissue hypoperfusion)?
2. What is the normal obstetric shock index?
A.10 min
A.0.7-0.9 B.20 min
B.0.8-1.0 C.30 min
C.0.6-0.8 D.40 min
D.0.5-0.7
7.Which of the following is not a component of prothrombin
3. What is the maximum dose of carboprost that can be complex concentrates?
administered?
A.Protein C
A.3 mg B.Prothrombin
B.2 mg C.Protein S
C.2.5 mg D.Vitamin K dependant clotting factors
D.1.5 mg
4.Clinical endpoint of successful resuscitation?
A.MAP>60 mmHg
B.MAP>65 mmHg
C.MAP>70 mmHg
D.MAP>55 mmHg
7.B 6.B 5.B 4.B 3.B 2.A 1.D
ANSWERS:

8 ANAESTHETIC MANAGEMENT OF ELDERLY
PATIENT FOR TRAUMATIC HIP SURGERY
Senior Consultant Anaesthesiologist, Balavenkatasubramanian J

Ganga Medical Centre & Hospital
Coimbatore
Key points
Ø The incidence of hip fracture increases with age after the sixth decade
Ø More than half of patients who present with hip fracture are classified into ASA physical status III and a significant
number are physical status IV
Ø Aggressive education and frequent reassurance must be employed continuously, so as to preserve the patient’s
motivation
Ø The femoral neck fracture is most often associated with osteoporosis and may occur with relatively minor stress
applied in just the right vector through very thin bone
Ø Any consideration of hip fracture surgery mandates secondary trauma survey including a search for signs of
intracranial injury, injury to neck, thorax, abdomen, pelvis or pelvic organs
Ø If the patient’s comorbidities or poor reserve does not allow immediate surgical intervention, we need to institute
excellent quality of analgesia
Ø Preoperative Ultrasound guided femoral block or PENG Block could be routinely performed to all these patients
which helps to position the patients comfortably for placing a neuraxial block
Ø Blood loss, pulmonary embolism and DVT are significantly less in hip fracture patients having regional anesthesia
than in those having general anesthesia
Introduction Etiology
Hip fracture becomes, one of the most common surgical The geriatric hip fracture occurs in a patient population subject
procedures for patients after the 6th decade of life. The to the bone weakening of osteoporosis. The incidence of such
frequency of this occurrence will increase as the percentage fracture increases with age after the sixth decade. Because
of advanced-age population increases, reflecting the it is much more common in females (who live longer on the
progressive aging of the population going into the twenty- average), women with hip fractures outnumber their male
first century. The financial and social impact of a hip counterparts by a margin of three to one. They also experience
fracture is tremendous, permanently altering the lives of a higher percentage of the most common fracture associated
a high percentage of those affected. One of the biggest with osteoporosis: the subcapital or femoral neck fracture.
challenges that face the anaesthesiologists while offering The femoral neck is the site of most severe involvement of
osteoporosis within the hip joint. Fracture can occur just below
perioperative care for these patients, are the concurrent
the head of the femur, through the femoral neck (subcapital),
coexisiting diseases and the decreased organ reserves.
and it can be caused by the patient’s sudden movement rather
However, with advanvcements in our understanding
than by the fall which follows.
of the pathophysiology of ageing, pharmacotherapy,
safer anaesthetic techniques, advanced monitoring, Point of Concern
better surgical solutions, multimodal pain therapy, early
mobilization protocols, proactive physiotherapy, counseling Coexisting Diseases
and rehabilitation, the perioperative morbidity and mortality The hip fracture patient population presents with significant
has considerably decreased. coexisting disease, even considering their advanced age.

Anaesthetic Management of Elderly 90 Balavenkatasubramanian J
patient for Traumatic Hip Surgery
More than half are classified as ASA physical status III and a combined with the effects of bedrest, pain, and the strange
significant number are physical status IV. The most common hospital environment. Family members can be significant in
reason for advanced physical status is heart disease with, maintaining the orientation status of the acute hip fracture
the majority having clinically evident coronary artery disease. patient. It is wise to include them in the anesthesia preop
Common in such patients, are prior neurological problems erative visit. Having them understand clearly, the plans to
(e.g., stroke, Parkinson’s Disease and dementia) and the repair the hip, control pain, and proceed toward earliest
prevalence of multidrug therapy for coexisting disease. Side possible ambulation will assist in maintaining orientation
effects of polypharmacy, drug interactions, and electrolyte and mental status. It also provides a goal which increases
disturbances must be considered. The incidence of hip motivation to survive.
fracture in these patients may be increased by the presence
of depression, dementia, confusion, and treatment with major Anatomy
tranquilizers, all of which may interact with potential anes There are three classes of geriatric hip fracture related
thetic agents. Numerous agents, (e.g., steroid therapy for to the site on the proximal femur where they occur. Their
rheumatoid arthritis) may accelerate bone weakening and occurrence is related to the degree of osteoporosis at the
increase the risk of hip fracture. site, and the amount of trauma which has occurred. The
Hypoxemia is a constant factor in hip fracture patients; it subtrochanteric fracture is the most violent, is associated
may be related to coexisting disease, the pathophysiology of with the most blood loss, and is not related necessarily
the fracture, or the effect of bedrest. Pre-existing pulmonary to osteoporosis. It causes the highest incidence of
compromise magnifies the pulmonary pathophysiology traumatic injuries to other organs, often occurring with
from the hip fracture (e.g., fat embolism or atelectasis). In motor vehicle-related trauma: auto-passenger or auto-
advanced geriatric patients, lung function has decreased pedestrian accidents. The intertrochanteric fracture lies
with age, and closing volume is very close to tidal vol in the intermediate range of severity, and occurs with
ume. Some atelectasis occurs in the normal state and significant trauma and moderate blood loss into the
rapidly worsens with bedrest and pain from the hip fracture. tissues. It can occur in osteoporotic hips with a violent
Atelectasis is inevitable and increases the potential for mechanism of injury. The femoral neck fracture is most
pneumonia from defective secretion clearance. often associated with osteoporosis and may occur with
relatively minor stress applied in just the right vector
Geriatric mortality is high during the initial admission for hip through very thin bone. Although presurgical blood loss is
fracture, (normally 10 percent during the admission and not trivial, it is the least of hip fractures. While the femoral
20 percent within the first year). The most likely causes of neck fracture can be caused by a fall, many occur from
death are pulmonary embolism (DVT related), pneumonia, violent movement and, in. turn, create the fall. Because
cardiac failure, and acute myocardial infarction. All are of the smaller surface area of fracture and decreased
incidence-related to age, prefracture physical status, and cancellous bone, the blood loss is less.
(inversely) ambulatory status. Conservative treatment of
hip fracture (bedrest without surgery) accounts for a much The anatomical differences in hip fractures also dictate their
higher mortality rate, owing to numerous complications treatment patterns. Subtrochanteric and intertrochanteric
(pneumonia, DVT, pulmonary embolism, or urinary tract fractures occur in more viable bone, hence yield excellent
sepsis). prognosis for healing if there is anatomic internal fixation.
There are wide fracture lines involved, rich with cancellous
Psychological Factors bone. The blood supply to the bone is usually not impaired.
This condition dictates techniques which draw these
The emotional significance of hip fracture to the geriatric fragments together and stabilize the reduction. In the
patient must also be considered. Many cultures, associate femoral neck fracture, on the other hand, the fracture line
a fracture hip with the end of life, basing that belief, on the occurs through the tissues which contain the blood supply
high one-year mortality rate and the frequently decreased to the femoral head. While the distal side remains well
level of activity with survival. Aggressive education and vascularized, the proximal side (including the entire femoral
frequent reassurance must be employed continuously to head and the proximal neck) is almost always deprived
prevent this cultural norm from decreasing the patient’s of blood supply, likely producing short-term avascular
motivation and contributing to higher mortality. Agitation and necrosis. The practical significance here is that, hardware
disorientation can be caused by a high degree of anxiety, inserted to reduce the fracture will not necessarily cause

healing, because one side of the fracture line will become prosthetic femoral head could be severe enough to require
avascular. With progressive weight-bearing, the fixation more difficult procedures for acetabular arthroplasty. That
devices tend to cut through the avascular bone. Any need possibility is eliminated when total hip replacement is
for further surgery is caused by progressively increasing chosen as the definitive treatment of acute hip fracture.
pain with attempted ambulation, either from the avascular This potential advantage must be considered in light of the
necrosis or nonunion or impingement of the fixation devices disadvantages of longer surgical time, greater blood loss
on the bony joint surface of the acetabulum. The surgical and hemodynamic change, and more painful, involved
strategy with these fractures focuses on procedures for rehabilitation. More involved rehabilitation can defeat
replacing the fractured femoral head and proximal neck with the primary purpose of the procedure, (to achieve rapid
a prosthetic device and as with all hip fractures, encourage ambulation) if the patient is not physically viable enough to
early ambulation. rehabilitate the total hip arthroplasty.
Surgical Considerations: Femoral Neck Fractures The opposite extreme is the demented or extremely sick
patient who sustains a femoral neck fracture. Here, total hip
Because the probability of avascular necrosis of the femoral replacement is out of the question. Because of morbidity,
head is so high in this type of fracture, hemiarthroplasty is the patient is unlikely to be physically active enough to
most commonly selected. The procedure may employ a derive the benefit. Even the hemiarthroplasty may be
simple ball and stem or the bipolar hemiarthroplasty involving an aggressive choice, due to the length of the surgical
a mobile head-neck (plastic on metal) interface within the procedure and the hemodynamic changes associated
prosthesis. The advantage of the bipolar prosthesis is the with increased blood loss. In some cases, simple pinning
resultant mobile, prosthetic femoral head within the existing of the fracture in the encountered position is chosen. This
acetabulum, a feature that will afford less trauma to the technique, is selected for a patient expected to ambulate
acetabulum with similar ambulation and less damage to the partially or minimally, but unable to because of pain, to
acetabulum. tolerate the stress of conservative (nonsurgical) fracture
The patient is placed in the lateral or semi-lateral position. management. The nonambulating patient faces increased
Incision and approach are similar to those for total hip morbidity from conservative hip fracture treatment, because
replacement, as is the preparation of the femoral canal for nursing care is so much more difficult and painful with
the endoprosthesis. The progressive reaming of the canal is the unstable fracture. Even simple internal fixation with
associated with steady blood loss, and the placement of the limited probability of fracture union will decrease the pain
prosthesis can involve the use of methylmethacrylate if the from the site until fibrous union occurs. The pins can be
native bone is very osteoporotic. The cementing can cause placed percutaneously or by small incision with fluoroscopic
the same hemodynamic fluctuations that occur during other assistance, either from the trochanter into the femoral head
cemented joint replacements. These fluctuations are related or via the medullary canal from a site as distal as the knee.
to the vasodilatory and mast-cell degranulating properties of Either involves minimal surgery and blood loss. The fracture
the monomeric form of methylmethacrylate; because these thus becomes immobilized. Most importantly, fracture pain
patients tend to be relatively sick with limited reserves, is relieved, and normal physiological functions of daily living
care must be taken to prepare the patient for cement use. can return to the prefracture state.
Hypovolemia is poorly tolerated. Embolization of fat or air Anesthetic Issues for Hip Fracture Patients
can result from pushing the stem of the prosthesis into the
femoral canal (with or without the presence of cement), a The majority of preoperative anesthetic issues with
condition that can further compromise the hemodynamic geriatric hip fracture patients involve the amount of patient
status of the patient if either ventilation or cardiac output preparation for surgery in relation to the deleterious effects
are impaired by emboli. of painful bedrest during such preparation. The minimum
preparation for this type of patient should start with the
The advantage of hemiarthroplasty lies in early rehabilitation survey for other injuries from the trauma that precipitated
of the patient and the resumption of a high degree of activity. the fracture. Any consideration of hip fracture surgery
However, the hemiarthroplasty can induce degenerative mandates this secondary trauma survey. The search must
changes in the native acetabulum, which will become look for signs of intracranial injury; neck injury; injury to
painful and, eventually, necessitate total hip replacement. the thorax (especially pneumothorax from rib fracture, or
At that point, the destruction of the acetabulum by the more severe injuries such as myocardial and pulmonary

contusion from fractures caused by greater trauma); intra- count is required; anemia or electrolyte disturbances should
abdominal injuries (e.g., spleen rupture); and injuries to be addressed prior to anesthesia induction. Even if blood
the pelvis or pelvic organs. Consideration must be given loss will not be replaced with transfusion, the blood volume
to the possibility that, the fall which caused the fracture must be replaced with crystalloid or colloid to avoid precipi
could have been precipitated by an acute cardiac or tous drops in the blood pressure from anesthesia induction.
neurovascular incident.
On arrival, if the patient’s comorbidities or poor reserve
Preoperative Preparation does not allow immediate surgical intervention, we need
to institute excellent quality of analgesia. The current
Once the initial trauma assessment is complete, the advancements in regional anaesthetic techniques, enables
interaction of coexisting diseases must be evaluated for us to place perineural catheters eg continuous femoral nerve
potential impact on anesthesia and surgery. At this point, it block for hip fracture. This site specific analgesia provides
becomes relatively urgent to optimize the patient’s condition excellent quality of analgesia with least side effects. It not
for surgery. Although delay of 12 to 24 hours may be prudent only helps to alleviate the pain and the discomfort but also
for subspecialty consultation and intervention, it should be gives a tremendous amount of positiveness and a sense of
kept to the minimum necessary to achieve the best possible wellbeing for the patient.
condition, always keeping in mind the deleterious effects of
bedrest. The rate of mortality increases for surgery within The choice of anesthesia is determined by surgical factors,
24 hours, and there is general agreement that it increases patient factors, and estimates of risk associated with
further, as significantly more than 24 hours elapse. anesthetic technique. For hip fracture repair, regional or
general anesthesia can be selected. The current evidence
Almost every geriatric hip fracture patient will present with favours a regional anaesthetic technique, as there are certain
hypoxemia at some point within the first 24 hours. The proven advantages of regional techniques over general
hypoxemia can be related to the influence of pain and anaesthesia. The benefits include decreased intraoperative
bedrest on the decreased pulmonary reserves associated blood loss, early mobilization, decreased incidence of deep
with aging. The high incidence of fat embolism with hip vein thrombosis, less postoperative nausea and vomiting
fracture repair and cemented endoprosthesis, contributes and a generalised state of well being.
further to pulmonary dysfunction. It can worsen this
process if associated with right-sided heart dysfunction, The regional anesthesia techniques commonly used
a combination reported to lead to mortality from right- are spinal or epidural anesthesia or a combined spinal
sided heart failure. When methylmethacrylate is used with epidural anaesthesia. Psoas compartment with sciatic
hemiarthroplasty or total hip replacement, the probability of blocks can be used especially in patients with fixed cardiac
fat or marrow embolism may increase the potential of right- output in whom a neuraxial block is not preferred due to
sided heart involvement. possible haemodynamic changes, specifically, profound
hypotension. The alternative option in fixed cardiac output
The most common, serious coexisting disease encountered states include segmental epidural, here the titrated doses
will be cardiac disease. Evaluation of the functional of local anaesthetic administration, and just blocking
cardiovascular reserves may be difficult due to the bedridden the segments involved, offers the benefits of regional
state, the confusion encountered, and the fracture. Simple anaesthesia in critically ill patient and at the same time
steps (e.g., auscultation, ECG, and chest x-ray) can detect provides stable haemodynamics.
acute decompensation. Echocardio graphy is feasible
at the bedside and can give useful information about left The choice between epidural and spinal anesthesia is
ventri
cular and valvular function. Conventional stress partially determined by the surgeon’s speed. In a teaching
testing is not possible, although alternative pharmacologic center, the learning of orthopedic residents may require
choices (dipyridilole-thallium scanning or dobutamine the use of continuous techniques with an epidural or
ehocardiography) can be applied to detect the threshold subarachnoid catheter rather than the one-shot spinal
for myocardial ischemia. If acute stroke is the precipitating anesthetic. This option especially applies in those centers
cause of the fracture, evaluation of the patient’s neu where the epidural catheter can be left in place and used for
rological condition may dictate the anesthetic choice, postoperative pain relief.
because hemorrhagic stroke is a relative contraindication
to regional anesthesia. Evaluation of electrolytes and blood Technical factors also help to determine the choice
between epidural and spinal block for hip fracture. Epidural

techniques require more time for placement and onset. With anesthesia. The majority of deep venous clots probably form
acute fracture positioned in a painful manner for placement intraoperatively, caused by combined vessel trauma from
of the block; the patient maybe able to tolerate the quick stretch with venous pooling. Spinal or epidural anesthesia
spinal block. The dose of local anesthetic is much higher might slightly influence vessel trauma by intense relaxation.
for epidural anesthesia, decreasing the safety margin The more likely etiology of decreased thrombus formation is
compared to spinal anesthesia. Conversely, the abrupt the increased flow to the tissues during a regional anesthetic,
onset of the spinal anesthetic may be poorly tolerated in when the blood pressure is maintained within reasonable
the hypovolemic or anemic patient with limited cardiac limits. Postoperative DVT prophylaxis and detection efforts
reserves, thus the epidural may be preferable because local are still necessary.
anesthetic dose can be administered in increments. While
the continuous spinal technique offers the same advantages There may be a difference in mental status and alertness
of titrated dosing and low rates of spinal headache, the risk related to anesthetic technique. Hip fracture is known to
of meningitis dampens any enthusiasm for keeping these be associated with preoperative confusion and hypoxemia.
catheters for postoperative pain control. Platelet factors may contribute to hypoxemia and subclinical
fat embolism. It is generally agreed that the oxygenation
The combined spinal epidural anaesthesia offers the of the patient in the immediate postoperative period will be
advantage of both. A lower dose of local anaesthetic significantly higher after regional anesthesia than during
is administered intrathecally, so that there are no recovery from general anesthesia. As many as one-third
haemodynamic changes, the only important factor is to will remain confused for 24 hours, significantly less for
precisely check the level of surgical anaesthesia after a spinal anesthesia when compared to general anesthesia.
low dose and if any segments are spared. We could give This differentiation is probably caused by residual effects
epidural supplements so as to achieve the desired level of of potent inhalation agents and anticholinergics. Prior
surgical anaesthesia. psychiatric illness increases this risk and the incidence is
especially high in patients with preexisting mild dementia
Outcome or depression. Regardless of the etiology, confused
In the anesthetic literature, numerous comparisons have patients have a significantly increased length of stay in
been made between regional and general anesthesia for the hospital. Studies are not as conclusive about the
hip fracture surgery. They progressed to a point where the variations in continuing confusion caused by regional and
lay press reported better outcomes after hip fracture when general anesthesia, hence it is possible that there is no
the surgery was performed with spinal anesthesia. As significant difference. Spinal anesthesia may decrease the
always, the truth is not as clear. Several issues have clear perioperative incidence of pneumonia compared to general
outcomes. Other outcomes and overall outcome studies are anesthesia.
controversial. The decrease in DVT and confusion in the short-term
There is a clear advantage to regional anesthesia for hip postoperative period may also be related to the fact that,
fracture surgery, with a decrease in intraoperative blood loss regional anesthesia decreases the interval between solid
and postoperative deep venous thrombosis (DVT). Blood hip repair and first ambulation attempts. A considerable
loss and the amount of transfusion will be consistently less heat loss in the perioperative period of hip fracture repair
with regional anesthesia. The cause of this favorable effect results from the large amount of body surface area exposed
is probably a combination of lower average blood pressure for the surgery. There is no apparent difference between
when blood loss is occurring and the dilation of capacitance spinal and general anesthesia as regards the amount of
vessels deep to the hip wound, resulting in dependent hypothermia produced.
drainage of blood away from the operative site. Decreased Overall outcome after hip fracture surgery reflects an 8 to
blood loss may decrease the potential for intraoperative 10 percent mortality within eight months of the surgery. The
hemodynamic changes. influence of anesthetic technique on outcome variables,
Pulmonary embolism and DVT are significantly less in hip has shown a preference for regional anesthesia rather
fracture patients having regional anesthesia than in those than general anesthesia, relating to the DVT rate, blood
having general anesthesia. Since pulmonary embolism is loss, decreased stress response (ADH, epinephrine,
one of the primary causes of mortality after hip fracture, norepinephrine), and the incidence of profound dementia.
this alone should be an indication for the use of regional However, large series comparing similar patients at similar

time intervals from fracture documented no difference care must be taken with transfer of the anesthetized patient
between groups for mortality. Nonsurgical treatment is to a fracture table or into the lateral position. A further
associated with at least double the mortality. challenge is presented in determining the emergence of
confused or demented geriatric patients from anesthesia.
Techniques for Regional Anesthesia for Hip Fracture
Repair Postoperative Care
There is a challenge in the conduct of spinal or epidural Immediate postoperative care should be directed to
anesthesia in the patient with acute hip fracture. The supporting oxygenation, controlling pain, and facilitating
patient is in bed in the supine position, so that the slightest the patient’s return to the baseline mental status by
movement can cause severe pain. In intertrochanteric emphasizing orientation. Appropriate pain control
fractures, the fracture fragments present a risk to the sciatic should be established prior to release from the recovery
nerve if they are manipulated in an uncontrolled manner. room, to set a safe template for further analgesia on the
Positioning the patient in the lateral position, may require regular nursing floor. Poor pain control may contribute to
intravenous administration of narcotic analgesics and the increased confusion in advanced geriatric hip fracture
presence of a member of the surgical team. Pain will make patients. Postoperative pain therapy is best, a multimodal
it difficult to achieve the spinal flexion normally sought to approach. A continuous infusion of 0.125% or 0.0625%
facilitate dural puncture. It can be partially accomplished Bupivacaine with 2-3microgram Fentanyl/ ml at a rate of
by flexing the upper body and the unaffected hip. In most 6 to 8 ml/hour either through the epidural or through the
cases, the fractured hip is turned to the superior side and continuous perineural catheter offers an excellent quality of
held by the orthopedic surgery team in the least painful analgesia. In the multimodal therapy, the local anaesthetic
manner. Preoperative Ultrasound guided femoral block infusions can be supplemented with analgesics including a
or PENG Block could be routinely performed to all these combination of paracetamol, tramadol, NSAID(when there
patients which helps to position the patients comfortably for is no contraindication) and opioids. The VAS scores have
placing a neuraxial block. to be ideally below 3.
The spinal anesthetic equipment should be prepared prior The trigger haemoglobin level at which a transfusion has
to positioning. Once the patient is in place, the block should to be adminiatered would be 10gms% in the presence of
be achieved as rapidly as possible. If epidural anesthesia is cardiorespiratory compromise and 8gms% in the others.
chosen, injection of local anesthetic should occur as fast and Hyponatraemia is a common electrolyte abnormality that
as safely possible. With spinal anesthesia, near-total relief is noticed in these patients. Hence we need to closely
of the acute fracture pain occurs within moments of the local monitor serum sodium levels in the postoperative period.
anesthetic injection, allowing (with slight hesitation) a pain- Adequate hydration and oral intake have to be monitored
free turn back to supine and into the hip surgery position. It as dehydration is very common in these patients who
is also frequently noted that patients immediately relax and suddenly decrease their oral intake due to mood swings.
often spontaneously sleep for the first time since the fracture. Most of these patients suffer from constipation and hence
The combination of this reaction and their advanced age stool softners could be made a part of their postoperative
makes it mandatory to avoid ventilator embarrassment by very drug regimen.
conservative use of further intravenous sedative drugs.
Conclusion
General anesthesia can be a technical challenge, if
minimizing pain necessitates induction on the orthopedic Geriatric patients with hip fracture offer a great challenge to
bed and transfer under general anesthesia to the operating the anaesthesiologists. A careful preoperative examination,
table. Access to the airway can also be challenging. To preoperative optimization and prehabilitation, safe
avoid injury from unstable fracture fragments in osteoporotic intraoperative anaesthetic techniques, good postoperative
extremities or structures in the ipsilateral lower extremity, pain relief, good postoperative followup with rehabilitation
would aid in decreasing the morbidity in these patients.

MCQ
1. Predominantly seen constant factors of concern in 4. Advantages of neuraxial blockade over general
elderly hip fracture patients are : anesthesia in elderly orthopaedic surgery are:
a) Osteoporosis a) Decrease in blood loss

b) Immobilization b) Decrease in stress response
c) Hypoxemia c) Decrease in DVT incidence
d) All the above d) All the above
2. Most common, serious co-existing disease encountered 5. Best post-operative analgesic and pain management
in elderly patients is therapy for hip surgeries are:
a) Cardiovascular disease a) Sciatic nerve block

b) Dementia b) Epidural infusions through epidural catheter
c) Ostoporosis c) Iv analgesics
d) Renal failure d) Multimodal approach
3. Which of these is not a triad of fat embolism syndrome
a) Petechial rash
b) Hypoxemia
c) Tachycardia
d) Neurologic abnormalities
5.d 4.d 3.c 2.a 1.d
ANSWERS:

9 ANAESTHESIA FOR SCOLIOSIS CORRECTION
Professor Anju Grewal

Dayanand Medical College and Hospital
Ludhiana
Key points
Ø Scoliosis is an abnormal lateral curvature of spinal column occurring in 2-3% of population
Ø Severity of scoliosis is usually measured using the Cobb’s angle.When the Cobb’s angle exceeds 65 degrees,
respiratory function is likely compromised
Ø Uncorrected progression leads to respiratory failure, pulmonary hypertension and right heart failure (>100 o)
Ø A comprehensive intraoperative and postoperative plan is advised for optimal outcome
Ø Preoperative neurologic deficits should be carefully examined and recorded
Ø Severe idiopathic scoliosis, can lead to pulmonary hypertension and failure of the right ventricle
Ø Airway should be examined using line of sight approach, especially look for neck movements.
Ø Left ventricular ejection fraction of less than 50% and a forced vital capacity (FVC) of less than 25% of predicted,
contraindicates elective surgery in patients with DMD.
Ø Areas of optimisation mainly include nutritional status,anaemia, underlying reversible obstructive pulmonary
component and cardiac status.
Ø Planning and management for large volume haemorrhage throughout the case is necessary.
Ø Because of concerns about spinal cord ischemia, there is now less emphasis on induced hypotension.
Ø Spinal cord monitoring,position related problems, hypothermia and venous air embolism are some of the
intraoperative concerns.
Ø Specialised spinal cord function monitoring can be achieved by measuring evoked potentials, which is now the
standard of care.
Definition Congenital:
Scoliosis is an abnormal lateral curvature of spinal column Neuromuscular (cerebral palsy, spinal cord trauma, spinal
occurring in 2-3% of population. It is defined as a complex muscular atrophy, spina bifida, muscular dystrophy, and
deformity of the spine resulting in lateral curvature and others), and
rotation of the vertebrae as well as a deformity of the rib
cage, with concomitant secondary involvement of respiratory, Idiopathic the most common form, (65% -70% of cases).1,2,3
cardiovascular and neurologic systems.1 [Table 1]
Classification based on etiology Manifests in childhood or early adolescence and progresses

more commonly in females, with need for surgical correction
It is classified as: eight times as often than their male counterparts.

Anaesthesia for scoliosis correction 98 Anju Grewal
Usually the lateral curvature is towards right (right convex) likelihood of other comorbidities or congenital conditions e.g.
and commonly involves 7-10 vertebrae. However, if the of the spinal cord (20%), genitourinary system (20-33%), and
curvature is left-sided (left convex) there is an increased cardiac conditions (10 -15%)).1-3
Idiopathic (70%) Neuromuscular Congenital Traumatic Syndromes Neoplastic Infection

(15%) Vertebral Vertebral
anomalies fractures
Early onset Cerebral palsy Rib Radiation Marfan’s Primary Tuberculosis

(infantile) anomalies tumours
Late onset Myopathies Spinal Surgery Rheumatoid Secondary Osteomyelitis

(juvenile / e.g., Duchenne dysraphism arthritis tumours
adolescent)
Severe Poliomyelitis Associated Osteogenesis

curves occur with renal imperfecta
predominantly in Syringomyelia and cardiac Mucopo
girls. defects lysaccharide
25% have mitral disorders
valve prolapse.
Friedreich’s High Neuro-
ataxia incidence fibromatosis
of cord
tethering
Table 1: Classification of scoliosis aetiology
Determination of Severity of curve with Implications To determine the Cobb’s Angle, perpendicular lines are drawn
from the outer surfaces of the upper and lower, maximally
Severity of scoliosis is usually measured using the Cobb’s angle.
The Cobb angle is a measure of the greatest curvature of the tilted, vertebrae. The angle formed by these intersecting
spine.Surgery is indicated when the Cobb’s angle exceeds 50o perpendiculars determines the Cobb angle.
in the thoracic spine and 40o in the lumbar spine. 1-3
Calculation of Cobb’s angle

As the curvature increases, rotation progresses, and the defect due to scoliosis worsens the respiratory weakness
chest cavity becomes narrowed resulting in a restrictive lung associated with neuromuscular disease.1-4
defect.3 More severe curves result in a restrictive lung defect
and dyspnoea on exertion (>65 o). In patients with idiopathic Uncorrected progression leads to respiratory failure,
scoliosis, pulmonary function may remain normal until the pulmonary hypertension and right heart failure (>100 o).1
curvature reaches 65 degrees. However, in patients with If untreated, idiopathic scoliosis is often fatal in the fourth or
congenital and neuromuscular causes of scoliosis, pulmonary fifth decades of life as a result of pulmonary hypertension or
dysfunction is likely to occur at lesser angles as the restrictive respiratory failure.4
Cobb’s angle Clinical manifestations
(Degrees)
<10 No symptoms
>25 Increase in pulmonary artery pressure
>40 Consider surgical intervention
>70 Significant decrease in lung volume
>100 Dyspnea on exertion
>120 Alveolar hypoventilation, chronic respiratory failure
Table 2: Severity of scoliosis and clinical correlation
Surgical Approaches team to outline a comprehensive intraoperative and

postoperative plan for optimal outcome keeping the
The aim of spinal deformity surgery is to correct the curve and pertinent issues stated above.
fuse the spine, improving posture and halting the progression
of pulmonary dysfunction. The approach may be posterior, B. A detailed history comprising of present issues, exercise
anterior or combined depending on the cause and severity tolerance and past medical history are pertinent to elicit
of the curvature. progression of respiratory function, cardiac, neurological
and any other pre-existing comorbidities Evaluate the
Anaesthetic / Perioperative Issues1-8 location and degree of spinal curvature, etiology of
• Restrictive pulmonary dysfunction with cor pulmonale scoliosis.
• Underlying comorbidities especially neuromuscular C. A physical exam of cardiorespiratory system should
disorders determine presence of dyspnea, increased work of
• Extensive surgical related complications breathing, tachypnea, rales, wheezing, or signs of right
heart failure.
P Positioning
P Intraoperative spinal cord monitoring and effect of D. Preoperative neurologic deficits, if any, should be
anaesthetic agents carefully examined and recorded.
P Hypothermia E. Based on the severity of the curve and the degree of
P Blood loss and coagulopathy respiratory impairment and other organ involvement,
P Visual loss the following preoperative laboratory studies should be
considered:
P Air embolism
P` Postoperative Pain 1. Chest radiograph & Pulmonary Function testing
2. Electrocardiogram
Preoperative Evaluation
3. Echocardiogram
A. A thorough preoperative evaluation should focus on 4. Arterial blood gases
assessment of neurological status and extent of organ
5. Coagulation Studies: Platelet count, Prothrombin time
dysfunction which occurs secondary to the advanced
(PT) and Partial thromboplastin time (PTT)
curvature. It should also enable the interdisciplinary

6. Electrolyte panel • Reversible conditions should therefore be optimised
7. Liver function test prior to surgery.1-8
Pre-operative Concerns Cardiac function
• Respiratory system involvement Cardiac function is an important consideration in certain

cases. In few rare cases of severe idiopathic scoliosis, regional
• CVS involvement
hypoventilation caused by abnormal diaphragm movement
• Assessment and documentation of neurologic status and chronic hypercarbia and hypoxemia from advanced
• Airway assessment pulmonary disease can lead to pulmonary hypertension
• Anticipation and preparation for blood loss and failure of the right ventricle. However patients with non-
idiopathic scoliosis associated with neuromuscular diseases
Respiratory system such as Duchenne muscular dystrophy and long chain
• When the Cobb Angle exceeds 65 degrees, respiratory acetyl carnation deficiency, will have dilated cardiomyopathy
function is likely compromised. secondary to their primary disease. A history of significant
exercise intolerance or physical examination showing
• Evaluation should be focused on assessing presence
evidence of jugular vein distension, hepatic congestion
and severity of pulmonary dysfunction from restrictive
or lower extremity oedema should prompt evaluation of
lung disease. Severity is determined by speed of onset,
cardiac function with echocardiography. Investigators
underlying cause of scoliosis, especially association
have questioned the efficacy of resting echocardiography
of neuromuscular disease, degree of curvature and
and indeed opined on the justification to have a stress
associated comorbidities.
echocardiography. 1-8
• Clinical signs and symptoms of significant restrictive
respiratory impairment include dyspnoea with activity or Airway Assessment
at rest and inability to cough or clear secretions. Exercise
Airway should be examined using line of sight approach. In
tolerance may be reduced even if lung volumes are
particular, neck movement should be examined for range of
normal mainly due to reduced chest wall compliance.
movement, neurological compromise and instability.7
• Pulmonary function testing (PFTs) may demonstrate
the characteristic pattern of restrictive lung disease Special considerations of Non-idiopathic scoliosis1-8
(decreased vital capacity, functional residual capacity,
These are secondary to the complex comorbidities related
and total lung volume). The greatest reduction is in vital
to their underlying disease process. Often, these patients
capacity. PFTs characteristically show decreased forced
have received specialised care with ongoing evaluation,
expiratory volume in one second (FEV1), decreased
which must be obtained and reviewed prior to surgery. Three
forced vital capacity (FVC) with a normal FEV1/FVC ratio.
more common forms of non-idiopathic scoliosis are Cerebral
Total lung capacity (TLC) is also decreased in patients
palsy, Duchene muscular dystrophy (DMD) & Mitochondrial
with restrictive pulmonary disease. Residual volume is
diseases.
generally maintained in these patients.
• The alterations in lung volumes are caused by changes Cerebral palsy is a non-progressive neurologic disease of
in chest wall compliance and the abnormal thoracic cage foetal and neonatal brain development that presents with
geometry altering the resting position of the thoracic movement limitation and spastic paralysis often resulting
cage, rather than parenchymal changes or lower airway in scoliosis. Varying degrees of cognitive impairment is the
obstruction. major challenge posed by patients with cerebral palsy limiting
• Lung parenchyma may be impaired in congenital or their ability to cooperate through the perioperative period.
infantile type. The primary abnormality in pulmonary gas
Duchene muscular dystrophy (DMD) is a genetic disorder
exchange is ventilation perfusion maldistribution.
leading to progressive muscle degeneration presenting
• As the scoliotic deformity progresses, the work of with symptoms of proximal muscle weakness and
breathing increases and alveolar hypoventilation pseudohypertrophy beginning in early childhood and
predominates. Therefore, these patients may develop advancing to skeletal deformity (including scoliosis), paralysis
hypoxemia, hypercapnia, secondary electrolyte and cardiorespiratory failure. Hence close attention should be
aberrations, and progress to pulmonary hypertension paid to factors like acidosis, hypoxaemia, hypercarbia, and
and respiratory failure. hypothermia that increase pulmonary vascular resistance,

and exacerbate right heart strain. Morris, proposed that need for invasive cardiovascular monitoring, urinary
left ventricular ejection fraction of less than 50% and a catheterization, neurophysiological monitoring,
forced vital capacity (FVC) of less than 25% of predicted, postoperative analgesic regimes and the wake-up test.
is contraindicated elective surgery in patients with DMD. 3,9 Patients and families may benefit from talking to patients
who have been through the procedure.1-8
Succinylcholine should be avoided as it may cause
rhabdomyolysis and hyperkalemic cardiac arrest in these Preparation and anticipated management for
group of patients whilst they also exhibit sensitivity to non- Haemorrhage1-3, 5
depolarizers.
• Scoliosis correction often requires a large incision with
Mitochondrial diseases are a set of conditions that cause removal of vertebral bone at multiple levels and can take
multiorgan dysfunction from inadequate cellular energy, many hours.
caused by defects in mitochondrial metabolism, and can
affect every body system, in some cases causing profound • Due to the large area of decorticated bone exposed in
neuromuscular disease leading to scoliosis spinal surgery, the blood loss may be extensive.
Preoperative Preparation • In prone positioning, the vertebral veins become

engorged from abdominal pressure and can contribute
Scoliosis correction is always an elective procedure, hence to major blood loss (>50% of blood volume) and
optimisation measures should be mandatorily undertaken for the development of both consumptive and dilutional
the benefit of patients with significant comorbidities. coagulopathy.
Areas of Optimisation mainly include • Blood loss is related to length of procedure and number
of segments fused. The 24 hour blood loss has been
P Nutritional status calculated at about 200 ml/segment fused. Patients
P Anaemia, with neuromuscular disease may be particularly at risk
P Underlying reversible obstructive pulmonary because they often have longer procedures with more
component or infection, incentive spirometry, segments fused, they have osteopenic bone which bleed
P Cardiac status especially volume status, heart more and requires sublaminar wiring, rather than laminar
failure and blood pressure control. hooks, prolonging the procedure. They may also have
• The pre-existing worsened baseline respiratory status subclinical coagulation abnormalities.
is unlikely to improve during or immediately after • Loss of up to one half of a patient’s blood volume or
scoliosis correction and may make intraoperative and more is not unexpected and planning for large volume
postoperative ventilation challenging. haemorrhage throughout the case is necessary. This
• Significant postoperative atelectasis should be may include preoperative iron supplementation or
anticipated, and in severe cases of scoliosis secondary erythropoietin for patients who are found to be anaemic
to neuromuscular causes, controlled ventilation prior to surgery.
postoperatively may be required due to respiratory • The healthy teen with idiopathic scoliosis usually will not
muscle involvement, hence logistic issues of arranging require transfusion in the operating room, but case-end
a bed in ICU in consultation with intensivist should be hemoglobin is usually as low as 7–8gm/dl. Children with
dealt with. other etiologies of scoliosis will almost always require
• Finally, for intrathoracic approaches to correction, lung intraoperative blood transfusion.
isolation using a double lumen tube, bronchial blocker, • Autologous blood donation may be considered in
or endobronchial intubation may be required. institutions equipped with this capability. Intraoperative
• In addition, arrangement for blood products, intensive acute normovolaemic haemodilution is a technique used
care services and adequate preparation for autologous occasionally in adult patients in which 2-3 units of blood
pre-donation, monitoring devices etc should be instituted are removed at the beginning of the operation and an
in advance. equal volume of colloid or three times the volume of
crystalloid are infused into the patient making blood
• It is also pertinent to counsel the patient and relatives lost during the operation more dilute. At the conclusion
as a multidisciplinary team regarding the procedure, of the operation, the blood removed at the beginning is

transfused back into the patient. Cell salvage techniques normothermia. One is placed on the upper extremities
(e.g. a Cell Saver machine, which suctions blood lost to and one on the lower extremities below the buttocks. A
be processed and available for transfusion) should be rapid IV/ blood warmer cum infuser should also be set up.
considered.
5. Extra care is taken when positioning these patients in
• Induced hypotension is a pharmacological technique the prone position to compulsively avoid compression of
that aims to maintain systolic blood pressure at or near eyes/face and abdomen/genitalia, and to maintain neutral
80mm Hg. Some centres have utilised this technique extremity position, particularly avoiding hyperextension
to reduce the amount of bleeding during an extensive of the shoulders, compression of axilla, ulnar nerves at
operation such as scoliosis correction. It is presumed elbow and lateral cutaneous nerves in the upper thigh.
that a lower perfusion pressure will lead to decreased
blood loss during the surgery. However, this technique 6. Any increase in abdominal pressure can compromise
is associated with complications such as post-operative venous return via the inferior vena cava. This may raise
visual loss and anterior spinal ischaemia leading to pressure in the epidural veins resulting in increased
postoperative paralysis, and therefore should be avoided operative blood loss.
in any patient with a high risk of complications from a 7. Pressure points should be well padded (elbows, pelvis,
relatively decreased blood flow to vital organs (kidneys, knees, ankles). The eyes should be protected and
eyes, brain, heart). checked frequently throughout surgery to make sure
Intraoperative Concerns there is no external pressure.
• Spinal Cord monitoring (SSEP MEPs/wake up) 8. Specialised tables (e.g. the Allen table) can be helpful
and positioning is indeed a team responsibility. In addition
• Position related problems (prone)
the endotracheal tube and intravenous lines should be
• Hypothermia well secured and monitored for movement during the
• Venous air embolism case. Careful attention to avoid placing any pressure
on the eyes during the operation is critical.
Positioning and Monitoring Devices1-3,5,-8
Neurologic Monitoring1-8
1. In addition to standard monitoring like ECG, NIBP, pulse
oximetry, temperature, and capnography, an arterial • Neurologic injury may occur from mechanical injury
catheter for blood pressure monitoring, lab draws and to the spinal cord or nerves during instrumentation,
pulse pressure variation monitoring or cardiac output excessive distraction of the cord during rod insertion, or
monitoring (e.g.LidCO) is important which can provide compromised perfusion of the spinal cord.
more detailed information about haemodynamic status • The goal of intraoperative neuromonitoring is to identify
and help guide resuscitation This is ideally placed in the disruption in nerve signals quickly so that surgical
upper extremity to allow for easy access to the cannula adjustments can be made before the final spinal column
during surgery. BIS (EEG) monitoring is reassuring configuration is set.
when using TIVA rather than volatile anaesthesia.
• Scoliosis correction for congenital kyphosis,
Transesophageal echocardiography (TEE) may be used
neurofibromatosis, skeletal dysplasias and postinfectious
in complex non idiopathic scoliosis corrective surgeries.
scoliosis carry higher neurologic risk.
2. Two wide bore peripheral IV access and a central • Neurological injury can be due to:
access may be useful for administration of fluid /blood ᴑ Direct contusion of the cord by implant or
& blood products, vasoactive infusions, (to trend central instrument.
venous pressure although the absolute central pressure
ᴑ Reduction of spinal cord blood flow by stretching
is always inaccurate due to positioning of the patient),
or compression of vessels or direct interruption of
and for postoperative care. Patients who are anticipated
radicular blood flow.
to require intensive care unit admission postoperatively
should have a central line inserted for surgery. ᴑ Distraction injury of the spinal cord
ᴑ Epidural haematoma.
3. A urinary catheter is used to monitor urine output.
• The areas of the cord most vulnerable to ischaemic injury
4. Two forced air warming blankets are used to maintain are the motor pathways supplied by anterior spinal artery.

Specialised spinal cord function monitoring can be achieved anesthetic in the presence of nitrous oxide is compatible
by measuring evoked potentials which is now the standard with adequate monitoring of SSEPs. However, there is a
of care. These are created by stimulating a peripheral nerve high degree of inter-individual variability of response, and
and measuring signals generated in the somatosensory the overall quality of the SSEP is superior in the absence
cortex (somatosensory evoked potentials – SSEPs) or of volatile anesthetics and nitrous oxide. Intravenous
stimulating near the motor cortex and measuring signals agents have minimal effects on cortical SSEPs, except
at the target muscle (motor evoked potentials – MEPs). etomidate and ketamine, which actually increase SSEP
Intraoperative monitoring of these pathways allows for signal amplitude. Continuous infusion of propofol 100-
continuous assessment of the entire signal transduction 200 mcg/kg/min is well tolerated.
pathway including cortex, spinal cord, and peripheral nerves, • Muscle relaxants improve SSEP recording because
and allows the surgeon to make adjustments in real time they suppress EMG activity and provide a “cleaner”
during the operation if signals change. background, however NMB will of course obliterate
MEPs.
Good communication between the neurophysiology team,
anesthesiologists and surgeons is critically important, • High doses of continuously infused opioids are
tailoring the administered anesthetics to those known to compatible with SSEP monitoring, but bolus doses of
least affect the quality of electrophysiological monitoring.1-3 opioids and other sedatives should be avoided during
critical stages of surgery to eliminate transient effects
1. Somatosensory Evoked Potential monitoring allows on the SSEP that may be confused with spinal cord
continuous assessment of the integrity of the ascending/ compromise.
dorsal spinal cord columns by extracting and averaging • Anesthetic Effects on MEPs: MEPs are extremely
the very low amplitude signal (microvolt range) of sensitive to the inhibitory effects of volatile anesthetics.
EEG activity in response to electrical stimulation of the Doses as low as 0.25-0.5 MAC can suppress synaptic
upper extremity (control signals) and lower extremities transmission. Nitrous oxide, although less suppressive
(monitoring dorsal cord integrity and function). than other inhaled agents, demonstrates a synergistic
2. Motor Evoked Potentials monitor the ischemia-sensitive effect on amplitude depression when combined with
ventral grey matter of the descending /anterior columns other anesthetics. Because of the potential for signal
of the spinal cord, by electrically stimulating the motor disruption with volatile anaesthetics, cases with SSEP
cortex trans-cranially, and recording the induced motor or MEP monitoring most commonly are done with a total
activity distally. MEPs are checked intermittently by the intravenous anaesthetic (TIVA) technique. In order to
neurophysiologist throughout the case, but have the assess the depth of anaesthesia more adequately, and
advantage of providing instant feedback, as no averaging avoid intraoperative awareness in the absence of MAC
is required. Additionally, the amplitude of MEPs is much values based on end-tidal anaesthetic, a Bispectral Index
higher than those of SSEPs (in the millivolt range as or BIS monitor should be used during a TIVA.
compared to the microvolt range). There are other factors that influence signal transduction
and it is critical that the depth of anaesthesia be
3. Anesthetic agents and physiologic perturbations may constantly maintained throughout the procedure. Hypoxia,
interfere with SSEP and MEP signals: hypercarbia, hypothermia and hypotension must be
• Effect of anesthetic agents on SSEP: Volatile anesthetics avoided. Thus during the spinal fusion, a physiologic
produce a dose-dependent increase in latency and and pharmacologic steady state should be maintained to
decrease in amplitude. Up to 0.5-1 MAC of a volatile effectively use SSEPs and MEPs. 1-3

Parameter Effect
Hypothermia or Hyperthermia ↓
Anemia ↓
Hypotension ↓
Hypoxia ↓
Hypocarbia ↓
Alterations in physiologic parameters that alter SSEPs and MEPs
Agent Amplitude Latency
Halothane ↓ ↑
Desflurane ↓ ↑
Isoflurane ↓ ↑
Sevoflurane ↓ ↑
Nitrous oxide ↓ ↔
Barbiturates ↓ ↑
Etomidate ↑ ↔
Ketamine ↑ ↔
Midazolam ↓ ↔
Opioids ↔ ↔
Propofol ↔/↓ ↔
Anesthetic agents that alter the sensory and motor EPs
Any intraoperative neurophysiologic changes (increased prior to distraction to allow ample time for physiologic
latency, decreased amplitude, or complete loss of waveform) optimization (Reversal of induced hypotension and
should be immediately reported to the anesthesiologist normalization of MAP, hemoglobin, temperature, etc.).
and surgeon. The team (anesthesiologist, surgeon and Although patient characteristics and anatomy differ, a
neurophysiologist) should then decide how to address the general guideline for this stage of the procedure is that
changes. the MAP should be maintained between 65-75 mmHg
in standard risk cases and 75-85 mmHg in high-risk
Surgical Distraction of the Spine cases.
1) After surgical exposure and placement of anchoring 2) What to do if Neurophysiologic signals change? 1-3
hardware, the surgeon will begin to distract, or
straighten, the spine. This is a high-risk time for • Announce the change to the surgeon and OR staff
neurophysiologic compromise. The surgeon should • Determine by asking the electrophysiologist:
notify the anesthesiologist approximately 15 minutes
ᴑ When did the change occur?

ᴑ What was the change? remifentanil or sedatives that maintain responsiveness like
ᴑ Increased latency? Decreased amplitude? Complete dexmedetomidine may also be employed.
loss?
Although confirmation of function is reassuring, loss of
ᴑ Change in MEPs, SSEPs or both? function may already be irreversible. The single window of
ᴑ Where is the signal change? observation does not allow correlation of loss of function with
surgical events.
• Determine if anesthetic management (change
in anesthetic gas administration, bolus IV drug Hazards and disadvantages include confounding of results by
administration) was coincident in time and therefore anesthetics which may impact cognition, risk of inadvertent
might be responsible. If so, try to correct (reduce gas extubation during movement in prone position, air embolism
concentration, etc.) during deep inspiration, dislodgement of instrumentation due
of violent movements or injury3.
• Determine if a change in hemodynamics, specifically
hypotension, is coincident with the change in monitoring. ᴑ Clonus test can be used prior to wake-up test. It
If so, correct. can be normally elicited in patients with intact spinal
reflexes and lack of central inhibition and can be
3) Management of neurophysiologic signals change while performed when a neurologically normal patient is
surgeons address their contribution to new spinal cord just emerging from general anesthesia. If clonus
dysfunction: is present, spinal cord integrity is assumed and if
• Administer 100% oxygen absent, full wake-up test if performed. However the
window of opportunity is very small and absence of
• Increase the spinal cord perfusion pressure using a mean
clonus is not a reliable injury. 1-3, 10
arterial pressure of at least 75 mmHg. Initiate infusion of
dopamine if required to do so. ᴑ Aborting procedure, in which the distracting rods are
• Optimize hemoglobin/hematocrit and coagulation status. removed and the back is closed as expeditiously as
• Turn off volatile anesthetics and nitrous oxide, if possible.
administered, and convert to TIVA ᴑ Administration of methylprednisolone 30 mg/kg IV
• If signals do not improve, discuss the following options (limited data to support efficacy).
with the surgeons, cognizant that after the anesthetic
and physiologic parameters have been optimized, the ᴑ Imaging of the spine under the same general
ultimate management is their responsibility: anesthetic to rule out spinal cord compression due
to an epidural hematoma. Note that this can only
ᴑ Wake-up test, in which the patient is allowed to effectively be accomplished with a CT myelogram.
arouse to demonstrate neurologic function, then the
surgery is resumed. Anesthetic Technique
The most basic intraoperative test of nerve function is the A balanced General anesthesia with tracheal intubation
wake-up test. Although not routinely used, awareness of (GETA) is facilitated with standard Intravenous induction
the technique is important for historical reasons and for use and an armoured flexometallic endotracheal tube, keeping
in settings where neuromonitoring may not be available. in mind the probability of difficult airway issues with DMD.
In this test, the patient is awakened after correction rod Succinylcholine is avoided especially in DMD. A maintenance
placement to assess basic lower extremity nerve function. technique using non-depolarising relaxant, moderate to high
If neurological function is deemed intact, the patient’s dose opioid, and sub MAC volatile agent or propofol infusion
anaesthetic is deepened and the operation completed. In along with multimodal analgesia is usually preferred.
order to be reliable, the patient must be able to follow simple
Postoperative Issues and complications1-8
motor commands. Anaesthetic technique should allow for
rapid wake-up during and after the operation, and may be • Postoperative Concerns
achieved with careful titration of an opioid-based general • Pain management
anaesthesia. If the patient does not respond during the wake-
• Pulmonary function & need for Postop mechanical
up test due to excessive opioid administration, then gradual
ventilation
titration of naloxone until the patient is responsive to verbal
commands may be necessary. Rapid-acting opioids such as • Bleeding & coagulation abnormalities

• Hyponatremia – due to inappropriate ADH secretion prone or in steep Trendelenberg position for
• Postoperative visual loss extended periods.
Post operative pulmonary complication P It occurs in two distinct forms—ischaemic optic
neuropathy (ION) and central retinal artery
P postoperative pulmonary complications can occur occlusion (CRAO).
in scoliosis correction and are more likely in more P ION may be anterior (ischaemia of the optic nerve
severe disease or syndromic patients. near the orbit) or posterior (ischemia of the optic
P While scoliosis correction may prevent further tract towards the occiput) with posterior ION
decline in respiratory status, it is not likely to occurring three times as frequently.
improve baseline function particularly in the P ION is associated with blood loss > 1000mL or
immediate postoperative period. 45% of estimated blood volume, operations lasting
P A patient with a preoperative vital capacity or FEV1 > 6 hours, preoperative anaemia, intraoperative
< 40% of expected may require postoperative hypotension, and intraoperative haematocrit < 30.
controlled ventilation, while a VC or FEV1 ≥ 70% P Periorbital oedema from high volume crystalloid
should have adequate pulmonary reserve to allow resuscitation may also contribute to ION. CRAO
for immediate postoperative extubation. occurs from direct compression of the eye causing
P Respiratory status should be optimised retinal ischemia. To prevent CRAO any direct
postoperatively because atelectasis, pressure on the eye must be avoided.1-5
hypoventilation, secretion retention, Consideration of Non Scoliotic surgery for Scoliotic
immobilisation, and analgesic medications can all patients1-8
worsen underlying pulmonary disease. Patients
should be managed in a high dependency or • Patients with scoliosis often present for procedures
specialised postoperative area familiar with spinal unrelated to scoliosis correction with several significant
corrective surgery. implications for anaesthesia care.
• Postoperative pain management after scoliosis surgery • When patients with scoliosis are anaesthetized and
can be challenging due to the large skin incisions and positioned for surgery, careful attention must be paid
multiple osteotomies. to pressure points to avoid the development of nerve
injuries and skin ulceration.
P Optimizing pain control for patient satisfaction
• Extra padding and support may be necessary to
and prevention of respiratory complications from
accommodate these patients whose spinal curvature
hypoventilation is an important consideration.
may prevent usual positioning on a flat operating room
P A multimodal approach to analgesia using table.
acetaminophen (paracetamol), NSAIDs, gabapentin,
• Epidural and spinal drug placement in patients with
ketamine, opioids and other available analgesics
lumbar or thoracic scoliosis presenting for procedures
may improve outcomes.
other than scoliosis repair can be particularly challenging.
P Patient-controlled analgesia has been reported to If possible, an area of the spine that has minimal
improve patient satisfaction. abnormal curvature but still provides adequate coverage
P Intrathecal opioids or intraoperative epidural for anesthesia or pain control should be selected for
placement may also be considered, but must be epidural placement. If this is not possible, then epidural
weighed against the risk of pruritus in the case of or spinal placement may still be attempted but patients
intrathecal opioids and hypotension and impaired should be aware of the possibility of multiple attempts
postoperative neurologic examination in the case and increased risk of accidental dural puncture. When
of epidural catheter placement. attempting neuraxial anesthesia in a patient with scoliosis,
P Another rare but potentially devastating the trajectory of spinal curvature should be delineated
postoperative complication from scoliosis by tracing the spinous processes around the desired
correction that deserves attention is postoperative level of approach. The intervertebral space is then often
visual loss (POVL). POVL is rare in paediatric larger more laterally in the direction of the curvature
patients but can occur in any operation and is away from midline (toward the convexity). If available,
more common in operations where patients are ultrasound may provide useful information about the

best approach to the epidural or intrathecal space. Even Gibson PR. Anaesthesia for the correction of scoliosis in
after successful placement, spread of medication into the children. Anaesth Intensive Care. 2004;32:548-559.
epidural space may be unpredictable and often patchy or
one-sided. Post operatively, epidural anaesthesia may Anand H. Kulkarni, Ambareesha M. Scoliosis and Anaesthetic
cause confusion when assessing neurological function Considerations. Indian Journal of Anaesthesia 2007; 51 (6)
and is now rarely used for this reason. : 486-495
Conclusion
Savini Wijesingha, Carolyn Smith. considerations in spinal
Modern perioperative care has enabled surgery in patients deformity surgery. Orthopaedics and Trauma 2017; 31:6:
previously considered unsuitable. Because of concerns about 422-424
spinal cord ischemia there is now less emphasis on induced
hypotension to reduce blood loss and allogeneic transfusion Entwistle MA, Patel D. Scoliosis surgery in children.
requirements with increased emphasis on antifibrinolytic Continuing education in anaesthesia. Crit Care Pain 2006;
therapy and cell salvage. The postoperative course of 6: 13e6.
patients has been improved by multi-modal postoperative
Sharma A, et al. Anaesthesia for spinal surgery. Anaesthesia
pain therapy. The success of this surgery requires a
and intensive care medicine (2015), http:// dx.doi.
dedicated team approach
org/10.1016/j.mpaic.2014.12.002
References
Guidelines for the Anesthetic Management of Patients with
Michael A Entwistle, Davandra Patel Scoliosis surgery in Scoliosis Undergoing Posterior Spinal Fusion Surgery. Lucile
children. Continuing Education in Anaesthesia, Critical Care Packard Children’s Hospital Stanford
& Pain | Volume 6 Number 1 2006 doi 10.1093/bjaceaccp/
mki063 Morris P. Duchenne muscular dystrophy: a challenge for the
anaesthetist. Paediatr Anaesth 1997; 7: 1-4.
J. Matthew Kynes, Faye M. Evans. Surgical correction of
scoliosis: anaesthetic considerations. ATOTW 318 – Surgical Owen J. The application of intraoperative monitoring during
Correction of Scoliosis (10th July 2015) www.wfsahq.org surgery for spinal deformity. Spine 1999; 24:2649-2780.

MCQ
1. Respiratory function is compromised when cobb’s 4.Postop controlled ventilation is required if preop vital
angle exceeds(degree) capacity or FEV1___ of expected
A.65 A.<40
B.40 B.<60
C.25 C.>40
D.70 D.>60
2.In patients with DMD, elective surgery is contraindicated 5.Direct compression of eyes causes CRAO
if FVC is less than A.True
B.False
A.25% predicted
B.30% predicted
C.10% predicted
D.45% predicted
3.To maintain spinal cord perfusion, MAP should be

atleast ___mmHg
A.60
B.75
C.80
D.65
5.True 4.A 3.B 2.A 1.A
ANSWERS:

10 PANCREATIC MALIGNANCY WITH OBSTRUCTIVE
JAUNDICE FOR WHIPPLE’S PROCEDURE
Professor, Akilandeswari M
SRIHER.
Chennai
Key points
Ø Obstructive jaundice in pancreatic malignancy predisposes to coagulopathy, infection and renal dysfunction.
Ø The optimization of perioperative fluid therapy is crucial to improve pulmonary function, tissue oxygenation,
gastrointestinal motility, and wound healing
Ø Thoracic epidural anesthesia and analgesia facilitates recovery in the postoperative period and prevents
respiratory complications
Ø Implementation of enhanced recovery protocols in the perioperative period aid successful postoperative outcomes
Pancreatic ductal adenocarcinoma accounts for over 90% whipple’s procedure, which involves the resection of the
of all the pancreatic malignancies and is the second most proximal pancreas along with the distal stomach, duodenum,
common digestive-system cancer after colorectal cancer. distal bile duct and gall bladder. The intestinal continuity
The incidence of pancreatic cancer in India is 0.5–2.4 is restored via a gastrojejunostomy, hepaticojejunostomy
per 100,000 men and 0.2–1.8 per100,000 in women. The and pancreatic jejunostomy. Distal pancreatectomy along
tumour occurs predominantly in the head of pancreas (60- with splenectomy is done for lesions in the tail of pancreas.
70%), while 20 to 25% are found in the body/tail and the Hence, the pancreatic resection surgery constitutes major
reminder involve the whole organ. They are often diagnosed abdominal procedure that demands enhanced perioperative
late and the five year survival rate after curative resection care in terms of patient assessment, preparation and
varies between 10-30%. intraoperative management.
Clinical presentation Obstructive jaundice pathophysiology and perioperative

implications
Patients with pancreatic cancer are usually more than 65
years of age, habituated to smoking and diabetic. Chronic Jaundice is noted with tumours involving the periampullary
recurrent pancreatitis, obesity and genetic mutations are region and the head of pancreas. The inadequate biliary
other factors that increase the risk for pancreatic cancer. drainage results in cholangitis and retention of bile acids
lead to hepatocellular damage. The risk for postoperative
The symptoms include asthenia, weight loss, jaundice, complications such as renal failure, sepsis, haemorrhage
epigastric pain, abdominal pain and steatorrhea. Vomiting and mortality is more in patients with obstructive jaundice.
secondary to gastric outlet obstruction can be present. The
jaundice is usually progressive and painless in nature due Bacterial translocation and sepsis
to obstruction of the bile duct by the tumour located in the
head and body of pancreas. Steatorrhea is due to the loss The bile salts prevent bacterial proliferation and promotes
of the pancreas’s ability to secrete fat-digesting enzymes clearance in the intestine. The sphincter of Oddi presents
or to blockage of the main pancreatic duct. Unexplained, a barrier to retrograde bacterial translocation under normal
superficial thrombophlebitis reflects the hypercoagulable physiological conditions. In obstructive jaundice, this
state that frequently accompanies pancreatic cancer. defence mechanism is lost and bacterial translocation
occurs. Patients who underwent ERCP and sphincterotomy
The diagnosis is by imaging modalities -CT, endoscopic demonstrated microbial colonisation of 100%, that was
ultrasound, ERCP and MRCP. The surgical treatment is polymicrobial in nature.

Pancreatic malignancy with obstructive jaun- 110 Akilandeswari M
dice for Whipple’s procedure
Renal failure is endogenous activation of opioids in jaundiced patients
that results in pruritus. The MAC awake of desflurane is
The renal failure in jaundiced patients is due to decreased
reduced in obstructive jaundice and is inversely related
renal blood flow secondary to hypovolemia, depressed
to the concentration of serum bilirubin levels. The use
cardiac function, and reduced response to vasoactive
of isoflurane is associated with significant hypotension
drugs. Renal vasoconstriction occurs as a result of
when compared to non jaundiced patients. The defective
Systemic Inflammatory Response Syndrome (SIRS) from
serotoninergic neurotransmission in the brain contributes
endotoxins released from the translocated intestinal flora.
to the increased sensitivity to inhalational anesthetics. The
Fasting, inadequate fluid therapy in the perioperative
duration of neuromuscular blockade with rocuronium is
period, hypovolemia due to blood loss, fluid shifts and
prolonged without any change in the onset time of blockade.
hypotension in the perioperative period worsen renal
function in the postoperative period. The most important Preoperative risk assessment and optimisation
preventive measure to reduce the risk of renal dysfunction
The objective of preanesthetic evaluation is to optimise
is, overnight intravenous fluid therapy to maintain adequate
the coexisting medical illness and the problems unique
intravascular volume and vigorous treatment of hypotension
to the surgical pathology. Jaundice, malnutrition, renal
in the intraoperative period. Mannitol and dopamine have
dysfunction, endotoxemia, thromboembolism, and
limited role in the prevention of renal failure and is not
postoperative pulmonary complications are concerns
indicated.
unique to pancreatic carcinoma that needs appropriate
Cardiac function preoperative evaluation and optimization for favourable
postoperative outcome.
The vascular tone is depressed and the response to
vasopressors are minimal. Bile acids have direct effects on A complete history, physical, laboratory examinations,
myocardial conduction and contraction. They exert negative and a detailed assessment of cardiological, respiratory,
chronotropic effects, prolong PR interval and decrease neurological, gastrointestinal, and renal systems should
myocardial contraction by alteration of membrane currents. be performed. Diabetic patients should be evaluated for
Elevated levels of atrial natriuretic polypeptide depresses associated microvascular and macrovascular complications
the myocardial function and decreases peripheral vascular such as nephropathy, peripheral neuropathy, retinopathy,
resistance. Hence, there is exaggerated hypotension to diabetic autonomic neuropathy, and cardiovascular disease.
volume depletion, blood loss, neuraxial blockade and HbA1c levels below 7% are optimal and preoperative switch
induction agents such as propofol. over to insulin is recommended in patients treated with oral
hypoglycemic agents.
Coagulation
• Cardiovascular assessment should be based
Hypercoagulability in pancreatic cancer is due to increased
on the presence of clinical risk factors, presence
platelet adhesiveness and aggregation induced by the
of active cardiac conditions, and the patient’s
tumor cells, formation of microthrombi from circulating
functional capacity. Echocardiogram, baseline
carcinoma mucins and production of procoagulant factors.
ECG is indicated for all and stress cardiac imaging
The jaundiced patients have coexisting coagulopathy due
should be considered in patients with abnormalities
to defective synthesis of Vitamin K dependent coagulation
on their resting ECG.
factors.
• Pulmonary function testing is done in case of
Effect on drugs active pulmonary disease, wheezing or dyspnea
on exertion, in heavy smokers with active cough,
Patients with obstructive jaundice have varying levels of
in elderly (age > 70), and morbidly obese patients.
hepatic dysfunction that affects the uptake, metabolism and
biliary excretion of drugs. Changes in hepatic blood flow • Nutritional assessment: Loss of 10% of body weight
during surgery can further alter the drug disposition in the in the last 6 months and albumin values lower
intraoperative period. The dose of etomidate is reduced in than 3g/dL indicates malnutrition. These patients
obstructive jaundice and titrated doses of propofol are given should be provided with nutritional support for at
to prevent profound hypotension during induction. There least 2 weeks prior to surgery. Immunonutrition

is initiated in patients who are malnourished and targets to improve oxygen delivery. The use of dynamic
without evidence of sepsis. The enteral feeds parameters such as stroke volume variation, pulse pressure
are supplemented with arginine, glutamine and variation, esophageal doppler flow guided fluid therapy.
omega 3 fatty acids for 5-7 day to attenuate the Isotonic balanced crystalloids are used in the perioperative
inflammatory response. period for volume replacement and maintenance therapy.
Preoperative hydration with 1-1.5 ml/kg/hr is recommended
• Preoperative anemia is treated with iron,folic acid
in patients with jaundice posted for surgical resection. The
and vitamin supplements.
combined use of other targets- mean arterial pressure
• Preoperative endoscopic biliary drainage should (MAP) ≥ 65 mmHg, urinary output > 0.5 ml/kg/h, oxygen
not be carried out routinely in patients with a serum venous saturation ≥ 70%, lactate levels < 3 mmol/L and
bilirubin concentration less than 250 µmol/L.Vitamin optimal cardiac index in the intraoperative period would
K 10 mg IV for 3 days is given for replenishment of impact positive clinical outcome. Colloids are not safe as
Vit K dependent coagulation factors in patients with they increase the risk of bleeding, renal injury, need for
hyperbilirubinemia. renal replacement therapy and cumulative effects.
• Fractionated low-molecular-weight heparin
Intraoperative glucose control is achieved with insulin
(LMWH) is initiated 12 hrs before surgery.
infusion coupled with periodic monitoring of glucose to
• Cessation of alcohol and smoking for 4 weeks prevent hypoglycaemia and hyperglycemia (target 110-
before surgery should be recommended. 180mg/dl).
• Mechanical bowel preparation prior to surgery is Normothermia during surgery prevents surgical site infection,
not indicated. coagulopathy and delayed recovery from anesthesia. The
• Intravenous hydration with isotonic crystalloids must use of forced-air warming blankets together with fluid-
be initiated in patients with obstructive jaundice. warming systems facilitate normothermia as, whipple’s
procedure is associated with major fluid shifts, evaporative
• Preoperative carbohydrate drinks are recommended
loss and prolonged surgical duration. The transfusion
in patients without diabetes. Intake of clear fluids up
thresholds for RBC should be individualised based on the
to 2 hours before anaesthesia is allowed.
cardiac and pulmonary status, although 7-9gms/dl is the
• Antimicrobial prophylaxis should be used in a target for low risk group of patients.
single-dose manner initiated 30–60 minutes before
Mechanical prophylaxis- compression stockings and
skin incision.
intermittent pneumatic compression is recommended
Intraoperative management in the intraoperative and postoperative period, until the
risk of bleeding is diminished and LMWH is initiated. A
The combination of general anaesthesia and mid thoracic
multimodal approach for pain relief along with epidural
epidural anaesthesia is the standard technique of choice
in the postoperative period with supportive therapy for
for this surgery. Thoracic epidural provides excellent pain
breathing improves recovery. Early mobilisation should be
relief, attenuates the catabolic response to abdominal
encouraged from the first postoperative day as a part of
surgery, lowers the incidence of pulmonary complications,
enhanced recovery after surgery. Enteral feeding should be
decreases the cardiac metabolic demand and reduces the
commenced as soon as 12 hours following surgery. Chest
risk of thromboembolic complications. The risk of tumour
physiotherapy and deep breathing exercises help to prevent
recurrence has been reduced with institution of neural
pulmonary complications.
blockade by local anesthetics. Mechanical ventilation
during surgery should involve the application of a protective The management of patients with pancreatic malignancy
ventilation strategy - lower tidal volumes < 8 mL/kg, PEEP for surgical resecion requires preoperative evaluation and
= 6-12 mmHg and recruitment manoeuvres. optimization. The standard of intraoperative care planned,
should provide optimal pain relief, excellent surgical
Goal-directed hemodynamic therapy (GDHT) enables
conditions and facilitate fast tracking for enhanced recovery
rational use of fluids, inotropes, vasopressors and red
following the major abdominal surgery.
blood cell (RBC) transfusion according to hemodynamic

References 3. Obstructive jaundice and perioperative management.
Acta AnaesthesiologicaTaiwanica 52 (2014) 22-29
1. Guidelines for Perioperative Care for
Pancreaticoduodenectomy:Enhanced Recovery After 4. Perioperative Fluid Therapy for Major
Surgery (ERAS_) Society Recommendations World J Surgery. Anesthesiology 2019;130(5):825-32
Surg (2013) 37:240–58
2. Anaesthetic perioperative management of patients

with pancreatic cancer. World J Gastroenterol 2014
March 7; 20(9): 2304-20

MCQ
1. Peak incidence of adenocarcinoma is after 50 years of 4. The most common cause of death in the postoperative
age period following Whipple’s procedure is:
a) True a) Myocardial infarction

b) False b) Intraperitoneal haemorrhage
c) Pulmonary embolism
2. Major benefits of a neuraxial block in a Whipple d) Pneumonia
procedure include all the following except,
5. Which of the following have been shown to be risk
a) Decreases the incidence of atelectasis factors for development of adenocarcinoma pancreas?
b) Leads to earlier return of GI function
c) Decreases the risk of urinary retention a) Cigarette smoking
d) Reduces the risk of pulmonary embolism or deep- b) Coffee drinking
vein thrombosis c) Adult-onset diabetes mellitus
d) Prior gastrectomy
3. What is the 5-year survival rate after a whipple’s
surgery?
a) 30-35%
b) 20-25%
c) 50-55%
d) 5-10%
5.D 4.B 3.B 2.C 1.A
ANSWERS:

11 ANAESTHESIA FOR NEONATAL EMERGENCIES
Professor and HOD, Anila Malde

Lokmanya Tilak Municipal Medical College and General Hospital
Mumbai
Key points
Ø Neonates undergoing emergency operations present several difficult challenges for the anaesthesiologist
Ø The anaesthetic considerations in neonatal surgical emergencies are based on the physiological immaturity of
various systems, poor tolerance of different anaesthetic drugs and associated congenital anomalies and effects
Ø Many surgical emergencies in the neonate are life threatening and are frequently accompanied by multiple organ
system failure
Ø Common causes of intestinal obstruction in neonatal period are duodenal, jejunal or ileal atresia, Meckel’s
diverticulum, meconium ileus, necrotising enterocolitis, malrotation with volvulus, Hirschprungs disease, and
anorectal malformation
Ø Most of the disorders previously considered as neonatal emergencies, now no longer need emergent surgery due
to new technology and methods of treating sick neonates
Ø The main goal is the titration of anaesthetics to desired effects and careful monitoring of the cardiorespiratory
status
Ø Muscle relaxation is typically employed to facilitate surgical exposure and abdominal closure
Ø Meticulous attention regarding fluid management, blood loss, temperature control and analgesia is essential
Ø The use of regional anaesthesia has been shown to be safe and effective
Ø Multidisciplinary team work (between the health care team, including the surgeons, anaesthesiologists and
neonatologists), with preoperative optimization, are important to ensure best possible care of the neonate.
Introduction pressure is poorly maintained thus leading to lung

collapse, especially under general anaesthesia.
This chapter outlines the basics of anatomy, physiology,
Lesser amount of type I fibers in respiratory muscles
pharmacology, suggested techniques, monitoring methods,
make them more prone for fatigue. Alveolar
regimens for fluid management and anaesthetic considerations
ventilation is 130 ml/kg/min for neonate versus
in common neonatal emergencies.
60 ml/kg/min for adults to meet increased oxygen
General Considerations consumption and carbon dioxide production.Foetal
Respiratory System hemoglobin which is present up to 3 months has
higher affinity for oxygen. Anaemia sufficient to
• Anatomical differences: Neonates and infants have
jeopardise oxygen carrying capacity of the blood
a proportionately larger head and tongue, narrow
is possible if the haemoglobin concentration is less
nasal passages, an anterior and cephalad larynx, a
than 13 g/dl in the newborn.
long epiglottis, and a short trachea and neck. They
are obligate nasal breathers. The cricoid cartilage • Control of breathing:
is the narrowest part. They are prone to dangerous
tracheal oedema. o Response to Hypoxemia in Infants: During the first
2 to 3 weeks of age, both full-term and premature
• Physiological differences: The airway and chest wall infants in a warm environment respond to hypoxemia
are highly compliant, so the negative intrathoracic

Anaesthesia for Neonatal Emergencies 116 Anila Malde
(15% oxygen) with a transient increase followed more dependent on heart rate. Parasympathetic
by sustained decreased in ventilation. In infants innervation develops early compared to sympathetic
born at 32 to 37 weeks gestation, the initial period innervation, leading to increased incidence of
of transient hyperpnoea is abolished in a cool bradycardia in neonates.
environment, indicating the importance of maintaining
a neutral thermal environment. By 3 weeks after birth, o Arterial blood pressure increases with age.
hypoxemia induces sustained hyperventilation, as in o Many factors like hypoxia, hypercapnia, acidosis,
older children and adults. hypothermia, anaesthesia-induced changes in
o Premature infants continue to show a biphasic peripheral or pulmonary vascular tone, prematurity
response to hypoxemia even at 25 days after and infection, can lead to increase in the pulmonary
birth. Newborn infants respond to hypercapnia by artery pressure up to systemic levels. This can
increasing ventilation but less so than do older cause reopening of the intracardiac shunts.
infants. The slope of the CO2 response curve CNS
increases appreciably with gestational age as well
as with postnatal age. Unlike adults, in newborn o Blood brain barrier is immature; nerves are thinner
infants breathing 15% oxygen, the CO2 response with less myelination in the neonates; CSF volume
curve decreases in slope and shifts to the right. is relatively high in infants requiring higher drug
volume. Changes in blood flow, pressure, and
o Incidence of periodic breathing (in which breathing osmolality are associated with the development
is interposed with repetitive short apnoeic spells of intraventricular haemorrhage (IVH) in preterm
lasting 5 to 10 seconds without desaturation) was newborns.
reported to be 78% in full-term, and 93% in preterm
infants. o In neonates and infants (under 1 year), the spinal
cord (ends at the level of L3) and dural sac (ends
o Apnoea of Prematurity and Hypoxia: Central apnoea at S2-S4), are located more caudal than in the
of infancy is defined as unexplained cessation of adults. Therefore there is increased risk of trauma
breathing for 20 seconds or longer or a shorter to the spinal cord and inadvertent puncture of dura.
respiratory pause associated with bradycardia Lower approach to the epidural space is favoured.
(heart rate <100), cyanosis, or pallor. Apnoea is The intercristal line is found at L5-S1 interspace
common in preterm infants and may be related in prematures and neonates. The vertebral
to an immature respiratory control mechanism. column forms a single shallow anteriorly concave
Risk factors for postoperative apnoea include, low curve, extending from the C1 to L5 at birth. Due
gestational age at birth, anaemia, hypothermia, to cartilaginous structure of bones and vertebrae,
sepsis, and neurological abnormalities. Therefore there is decreased resistance to penetration of
careful monitoring in the postoperative period is the needle during insertion, which can cause
required. Both theophylline (10 mg/kg) and caffeine direct trauma to the ossification centre in the bone
have been effective in reducing apnoeic spells in compromising further growth. Therefore excessive
preterm infants. force should be avoided.
CVS Liver
o Cardiac calcium stores are reduced making o Functional maturity of the liver is incomplete at
neonates more susceptible to myocardial birth. Due to limited glycogen stores there is
depression by potent anaesthetic agents. tendency towards hypoglycaemia.
o There is intolerance to any degree of
o Neonatal myocardium has higher percentage of
hypoglycemia, due to their very limited
noncontractile protein, making it stiff and non-
ketogenesis and lipolysis capability to create
compliant.
energy from alternate sources.
o It has limited ability to increase the cardiac output o Due to decreased synthetic capacity of liver,
by increasing stroke volume. Stroke volume is plasma levels of albumin and coagulation factors
therefore relatively fixed making cardiac output are low in full-term newborns (and are even lower

in preterm infants). This leads to greater levels • Warming of skin disinfectant solutions decreases the
of unbound drug and increased coagulopathy heat los through evaporation.
(e.g., the need for vitamin K at birth). Vitamin K is
usually given to all newborns. • Heat lost from radiation is decreased with the use of an
incubator during transport.
Kidney
• Keeping the infant in an incubator, covered with
o GFR, tubular mechanisms, concentrating, and
blankets, minimizes heat lost through convection.
diluting capacity are not well developed in infants.
Fluid and Electrolytes Pharmacology
Neonates have higher fluid requirement due to higher • Larger body water content, lesser proteins and fats,
insensible fluid loss, larger surface area, immature skin, and immature hepatic and renal function alters drug
higher metabolism. There are two peaks in the occurrence pharmacology in neonates. Initial drug requirement
of neonatal hypocalcemia. Neonates who are not breast fed may be high but duration may be prolonged and
are supplemented with 1ml/kg 10% Ca Gluconate, 8 hourly. effects may be severe.
Temperature regulation • Because of a smaller lung functional residual

capacity, higher minute ventilation-to-FRC ratio with
Large surface area to body mass ratio, insufficient body relatively higher blood flow to vessel-rich organs,
fat for insulation, inability to shiver makes neonates both induction and emergence from anaesthesia are
more susceptible to hypothermia. They rely primarily on more rapid. Neonates require lower concentrations
non-shivering thermogenesis in which brown fat is used. of volatile anaesthetics than infants. The blood
Metabolism of brown fat is severely limited in premature pressure of neonates and infants tends to be
infants and in sick neonates who are deficient in fat stores. more sensitive to volatile anaesthetics, probably
because of not fully developed compensatory
Mechanisms of Heat Loss in Neutral Thermal Environments
mechanisms (e.g, vasoconstriction, tachycardia)
(by Percent):
and an immature myocardium that is very sensitive
Radiation- 39%, convection- 34%, evaporation- 24%, and to myocardial depressants.
by conduction- 3%.23
• Intravenous induction is used most commonly in
Hypothermia is a serious problem that has been associated emergency.
with delayed awakening from anaesthesia, altered drug
 Thiopentone sodium: Reduced clearance and
responses, cardiac irritability, bradycardia, respiratory
prolonged elimination half-life of 19 hours in
depression, increased pulmonary vascular resistance,
neonates compared with 6-12 hours in older
metabolic acidosis, and hypoglycemia. To minimize oxygen
children. Termination of effect occurs through
consumption, the neonate must be in a neutral thermal
redistribution of the drug in muscle and fat;
environment.
thiopental should be used in reduced doses (2 to
Measures to prevent heat loss: 4 mg/kg) in children and in neonates.
• For the very small neonate, operating room  Fentanyl: Because the cardiac output of neonates
temperatures must be increased is determined by the heart rate, fentanyl-induced
bradycardia may require administration of a
• Place the baby on a warming mattress, which minimizes vagolytic drug.
heat lost through conduction.
 Remifentanyl: It is a unique potent opioid in neonates.
• Heat loss may be reduced by wrapping the limbs and Unlike every other medication used in newborns,
head in wool or foil. its half-life is shorter rather than longer as in older
• Warming and humidification of inspired gases. children. This difference may in part related to the
larger volume of distribution with equivalent half-
• Warming of intravenous fluids life. Dose is - 0.25–1 µg/kg IV bolus, and infusion -
0.05–2µg/kg/min.
• Use of plastic wraps to decrease water loss through
the skin.

History and examination Monitoring
Ask for post conception and postnatal age. Check weight, cry, Precordial stethoscope, ECG, pulse oximetry, NIBP, and
tone, activity, heart rate, BP, respiratory rate, temperature temperature are minimum essential monitors. Microstream
and status of hydration. Look for cold peripheries, feeble or capnograph can give idea about circulation, respiration,
absent distal pulses and poor capillary refill. Central venous metabolism and machine related problems. It is important
pressure (CVP) if available should be noted. Also look for to identify at least one peripheral pulse site which can
evidence of respiratory distress in the form of grunting, be monitored throughout. If not, axillary artery should be
tachypnoea, laboured breathing and SpO2. In case of palpated intermittently. Monitoring of blood loss is very
important. In majority of emergencies one may need at least
abdominal emergencies, look for the degree of abdominal
one pre and post operative blood gas, Na+, K+, Ca2+( if
distension, amount of gastric tube aspiration and evidence
available), and glucose levels.
of sepsis; Check the sites for peripheral and central venous
access. Vitamin K is usually given to all newborns. Fluid therapy includes replacement of deficit fluid,
maintenance fluid as per post conception and postnatal age
Anesthetic technique and third space losses. Lactated Ringer is the fluid of choice
Awake intubation may cause intraventricular haemorrhage for intraoperative period. Dextrose is added. A minimum
haematocrit of 40 % has to be maintained. Maintenance of
in fragile, premature newborns. Neonates do not tolerate
normothermia, normoglycemia, normovolemia and normal
60 seconds of apnoea and they do require gentle puffs with
haematocrit are very essential in premature babies.
100% O2. Avoidance of hyperinflation, repeated gastric
suction and appropriate anaesthetic depth can reduce risk Post operative pain management
of regurgitation and pulmonary aspiration. Intubation can be
Paracetamol, fentanyl, local bupivacaine infiltration, caudal,
facilitated using rocuronium or atracurium. Intubation may
epidural local anaesthetics and narcotics are the mainstay
be easier with straight blade laryngoscope.
of postoperative analgesia.
Acetaminophen dosing guide—oral and rectal administration
Age Route L o a d i n g Maintenance Interval M a x i m u m Duration at max-
dose dose daily dose imum dose

28–32 weeks Oral 20 mg/kg 10–15 mg/kg 8–12 h 30 mg/kg 48 h
PCA Rectal 20 mg/kg 15 mg/kg 12 h
32–52 weeks Oral 20 mg/kg 10–15 mg/kg 6–8 h 60 mg/kg 48 h
PCA Rectal 30 mg/kg 20 mg/kg 8h
>3 months Oral 20 mg/kg 15 mg/kg 4h 90 mg/kg 72 h

Rectal 40 mg/kg 20 mg/kg 6h
Intravenous acetaminophen dosing guide
Age Loading dose M a i n t e n a n c e Dose interval Maximum daily dose
(mg/kg) dose (mg/kg) (mg/kg)

<32 weeks PCA 20 10 12 h 30
32–36 weeks PCA 20 10 8h 40
36–52 weeks PCA 20 10 6h 50
>1month 15 15 6h 60
(From: Allegaert K, Murat I, Anderson BJ. Not all intravenous paracetamol formulations are created equal. Paediatr
Anaesth.2007; 17(8):811–2.)

Acetaminophen, and particularly intravenous of a case of severe delayed respiratory depression in a
acetaminophen, should not be given at full dose for more neonate who was given 2 µg/kg caudal epidural clonidine,
than a few days because of potential toxicity. Therefore it a number of similar reports have appeared in the literature
may be prudent to delay its use until epidural or IV opioid that have resulted in an advisory to use caution when
infusions are being withdrawn on postoperative days 2 - 3. considering the use of clonidine by any route in neonates.
Epidural dexmedetomidine analgesia was also found to
Nonsteroidal Anti-inflammatory Drugs
be developmentally regulated and relatively greater in
Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are neonates in a laboratory model. These data suggest that
not currently used in neonates for analgesia due to the dexmedetomidine may be better tolerated than clonidine in
uncertainty regarding their efficacy, and potential for adverse neonates..
effects, results in an unfavorable benefit-risk ratio. They
act by inhibition of cyclooxygenase, enzymes that regulate Local anaesthetics: LAs are extensively protein bound
many cellular functions by the production of prostaglandins (>90 %), with the free, unbound fraction being the
and other substances. Prostaglandins have multiple roles pharmacologically active fraction. Alpha-acid glycoprotein
in early development, and inhibition of their synthesis (AAG) and albumin are the most important plasma
with NSAIDs may potentially result in the disruption of the proteins that bind drug; AAG levels in blood are reduced
sleep cycle, an increased risk of pulmonary hypertension, in the neonate resulting in increased unbound fractions of
alterations in cerebral blood flow, decreased organ perfusion lidocaine and bupivacaine. Toxicity has been reported after
and renal function and disrupted thermoregulation. epidural bupivacaine infusion at doses greater than 0.3 mg/
kg/h, leading to a reduction in the recommended infusion
Fentanyl: After a single intravenous dose, the duration of rate in neonates to 0.2 mg/kg/h or less and duration of
action of fentanyl is 30–45 min. Given its high lipid solubility, infusion of 48 h.
the pharmacokinetic profile of fentanyl is context sensitive,
such that its half-life progressively increases with the EMLA is suitable for use in the neonate in single doses;
duration of the infusion. multiple doses should be limited to a maximum of
four applications per day and under close supervision
Tramadol: Clearance is reduced in the neonate, but
to avoid methemoglobinemia. Prilocaine causes
reaches 80 % of adult values by 1 month of age. No
methemoglobinemia indirectly via its primary metabolite,
relationship has been established between postmenstrual
o-toluidine. Methaemoglobin is an oxidized form of
age and O-desmethyltramadol production. As in the case
haemoglobin that has a reduced oxygen-carrying capacity.
of codeine, tramadol is metabolized by the cytochrome
Methaemoglobin reductase, the enzyme that catalyzes
enzyme CYP2D6 to its major active metabolite
reduction to haemoglobin, is also developmentally regulated,
O-desmethyltramadol, which has a 200× greater affinity for
rendering neonates susceptible to methaemoglobinemia.
the mu opioid receptor than the parent compound. CYP2D6
activity is genetically regulated, with 5–40 % of individuals CONGENITAL DIAPHRAGMATIC HERNIA (CDH)
in some populations having reduced, little, or no activity
(“slow and intermediate metabolizers”), and consequently It is a defect in the diaphragm that allows the herniation of
is less able to produce O-desmethyltramadol. This has abdominal contents into the thoracic cavity. Most commonly
led to widespread unpredictability in its analgesic effects. occurs through left postero-lateral foramen of Bockdalek.
Conversely “ultrarapid metabolizers” may experience Associated anomalies are present in 10-50% of patients
adverse effects in the form of respiratory depression from the with CDH and increases mortality. The most common of
rapid conversion to O-desmethyltramadol. CYP2D6 activity these involve the central nervous system (CNS) and the
is also developmentally regulated, with reduced activity in cardiovascular system (CVS).
the very young, which may hold implications for its use in
very young patients. The effect of CYP2D6 polymorphism Clinical features
on the efficacy and disposition of tramadol at this time is
• Cyanosis, dyspnoea, apparent dextrocardia,
unknown. Opioid side effects have been reported to be less
scaphoid abdomen, bulging chest, decreased
prominent with tramadol in neonates, although this has not
breath sounds, distant or right-displaced heart
been confirmed when equi analgesic doses were used.
sounds, and bowel sounds in the chest. Signs of
Clonidine: Neonates appear to be more susceptible to both respiratory distress (retractions, cyanosis, grunting
the effects and side effects of clonidine. Since the reporting respirations) can be evident.

• Desaturation indicates reopening of the ductus • Intrathoracic approach is usually through right
arteriosus and persistent foetal circulation. Place posterior thoracotomy for right-sided defects. After
oximeter probes at preductal (right-hand) and the abdominal contents are replaced, there may be
postductal (either foot) sites to assess for a right- a significant rise in abdominal pressure, decreased
to-left shunt at the ductus arteriosus level. Early functional residual capacity, and compression
echocardiography is indicated. of the inferior vena cava (IVC). A pulse oximeter
applied to the lower extremity is essential to
• Renal and Cranial ultrasonography should be done forewarn abdominal compartment syndrome and
to rule out associated anomalies. circulatory compromise. After reduction, an attempt
• Pulmonary hypoplasia, hypertension, immaturity, to inflate the hypoplastic lung is futile, as it is
deficiency of surfactant and antioxidant enzymes unlikely to expand and the contralateral lung may
and cardiac impairment leads to hypoxia, be damaged.
hypercarbia, acidosis, myocardial dysfunction, • Recently, a laparoscopic or thoracoscopic approach
right to left shunting and persistent foetal is being utilized. Lung separation is not done.
circulation. Right lateral decubitus position is used. Carbon
• Supranormal inflating pressures and respiratory dioxide is insufflated into the left chest, starting
rates to provide adequate tidal volume and at pressures of 5 mm Hg and flows of 0.5 L/min.
minute ventilation often results in significant Immediate decrease in tidal volumes, increase in
barotraumas and contralateral pneumothorax is CO2, and eventually desaturation are reported with
common. Acidosis, hypothermia, and elevated surgical manipulations. In children with significant
airway pressures also may contribute to sustained hypercarbia and/or pulmonary hypertension,
elevations in pulmonary vascular resistance insufflation with carbon
(PVR). Relative left ventricular (LV) hypoplasia dioxide may not be tolerated, precluding this
with an attenuated muscle mass and cavity size approach.
have been described.
Anaesthesia concerns are
• Preoperative stabilization and a delayed
surgical approach are preferred now. The 1) Hypoxaemia due to lung compression, primary
goal is to maintain adequate oxygenation and pulmonary hypoplasia, pulmonary hypertension, and high-
ventilation, and prevent iatrogenic barotrauma pressure induced iatrogenic contralateral pneumothorax.
from mechanical ventilation. Bag-mask
ventilation has to be minimized to reduce the 2) Hypotension caused by overdistention of the stomach
risk of gastric expansion. Baby should be and herniation across the midline, pulmonary hypertension
endotracheally intubated. Immediately after causing RV failure, contralateral pneumothorax, kinking of
intubation, the gut should be decompressed. major blood vessels, particularly those of the liver and both
primary and secondary myocardial dysfunction.
• Medical management consists of a)
conventional or high frequency oscillatory 3) Hypercarbia and respiratory acidosis. PaCO2 reflects
ventilation, b)permissive hypercarbia, c) the severity of the lung pathology and therefore survival.
nitric oxide and d) extracorporeal membrane An inability to reduce PaCO2 is associated with a poor
oxygenation. Some surgeons prefer to operate prognosis.
on these neonates when normal pulmonary
artery pressure is maintained for at least 24-48
hours based on echocardiography. Anaesthetic considerations
Circulatory stability, respiratory mechanics, and gas • For non-intubated patients, rapid-sequence
exchange deteriorate after surgical repair. induction using sodium thiopental or propofol
should be carried out.
Surgical consideration
• Aspirate gastric contents with nasogastric tube
• Typically, supine position with transabdominal before induction.
subcostal incision is used.

• Atropine (0.02 mg/kg iv) is given prior to induction who likely will not require prolonged ventilation or
to counteract bradycardia. anticoagulation for ECMO.
• Muscle relaxation is achieved using succinylcholine/ 3) Intrapleural analgesia.

rocuronium. If necessary to mask ventilate, avoid
high inflation pressures, as this may further dilate 4) Infiltration of local anaesthetic at incision.
the bowel. In those infants who will remain intubated 5) Paracetamol suppository
after surgery, inhalational agents and narcotics
may be used as tolerated. Muscle relaxation is Postoperative Care
typically employed to facilitate surgical exposure
and abdominal closure. • It was previously believed that pulmonary hypoplasia
was responsible for most deaths; however, it is
• Nitrous oxide is avoided in infants with CDH. now believed that potentially reversible pulmonary
Low concentrations of inhalation anaesthetics hypertension may be responsible for as much as
(sevoflurane or isoflurane) can be administered 25% of reported deaths.
and increased if the patient is haemodynamically
stable. However, they are myocardial depressants • The postoperative course, after surgical
and are avoided until the chest is decompressed. reduction of CDH, is often characterized by rapid
improvement, followed by sudden deterioration
• Venous access in the lower extremities should with profound arterial hypoxemia, hypercapnia,
be avoided because the IVC may be compressed and acidosis, resulting in death. The mechanism
after reduction of the hernia, limiting venous return. for this deterioration is the reappearance of foetal
Both preductal and postductal pulse oximeters are circulation patterns, with right-to-left shunting
applied. through the foramen ovale and ductus arteriosus.
Proper sedation is necessary, as any stressful
• A precordial stethoscope on the contralateral chest
stimulus can further exacerbate already elevated
can be used to identify a pneumothorax.
pulmonary pressures with resultant increases in
• The goals of ventilation in the OR are the same as shunt flow and further desaturation.
preoperatively, i.e. to optimize pH and pulmonary
blood flow with minimal barotrauma. Peak pressures • ECMO may be required in the perioperative period,
should not exceed 25 to 30 cm H2O. Hyperventilation because of pulmonary vascular reactivity and
is reserved to initially treat an acute episode of respiratory distress refractory to conventional or
pulmonary hypertension. If a sudden deterioration even high frequency or oscillatory ventilation.
occurs in ventilation, haemodynamic status, or TRACHEOOESOPHAGEAL FISTULA (TOF)
both, pulmonary hypertension must be quickly
differentiated from a contralateral pneumothorax, Oesophageal atresia (OA) is the most frequent congenital
because the treatment for a pneumothorax is anomaly of the oesophagus, with an approximate
needle thoracostomy and chest tube placement incidence of 1 in 4000 neonates.
rather than hyperventilation.
Gross created a classification system in 1953.
• Complications associated with hypothermia include,
increased PVR with resultant right-to-left shunting. • Type A: Oesophageal atresia without fistula or so-
Hypothermia also causes increased oxygen called pure oesophageal atresia (8%)
consumption, which may result in inadequate • Type B: Oesophageal atresia with proximal TOF
oxygen delivery and acidosis, which then further (1%)
increases PVR and worsens arterial desaturation.
• Type C: Oesophageal atresia with distal TOF (84%)
Therefore, hypothermia must be avoided.
• Type D: Oesophageal atresia with proximal and
Pain management
distal TOFs (3%)
1) Continuous fentanyl infusion. • Type E: TOF without oesophageal atresia or so-
called H-type fistula (4%)
2) Epidural placed transcaudally or through lumbar or
thoracic sites especially in those with smaller defects • Type F: Congenital oesophageal stenosis (<1%)

Associated Anomalies 8. Intravenous fluid containing an adequate glucose
concentration (i.e., 10% glucose) is administered at
VACTERL: V: Vertebral (vertebral malformations, a rate appropriate for the neonate’s gestational age
hemivertebrae); A: Anal (imperforate anus, also midgut and weight.
malrotation, Meckel’s diverticulum); C: Cardiac (VSD, PDA,
TOF, ASD, coarctation of aorta); T: Trachea (TOF); E: 9. Prophylactic broad-spectrum antibiotics (eg,
Esophagus (EA); R: Renal (renal agenesis, hydronephrosis, ampicillin, gentamicin) are intravenously
renal lobulation); L: Limb (radial aplasia, polydactyly, administered.
wrist anomalies). As many as 20% to 25% of infants with
oesophageal atresia have at least three of the lesions 10. The neonate is kept warm by using an incubator or
included in VACTERL. overhead warmer.
Clinical Presentation 11. Oxygen therapy is used as needed, to maintain

normal oxygen saturation.
Classically, the neonate with OA presents with copious,
fine, white, frothy bubbles of mucus in the mouth, nose and 12. In infants with respiratory failure, endotracheal
episodes of coughing, choking and cyanosis. intubation should be performed. If preoperative
ventilation is required, inspiratory pressures should
Diagnosis be kept to a minimum.
OA is usually diagnosed soon after birth, when an oral Risk Stratification

catheter cannot be passed beyond 10 to 12 cm into the
stomach or when the neonate exhibits cyanosis, coughing, Waterston classification and Spitz classification
and choking during oral feedings. Surgical management
Plain radiographs of the chest and abdomen will reveal Type of surgery depends on the following three factors:
coiling of a nasogastric tube in the oesophageal pouch
and possibly an air-filled stomach in the presence of a co- 1. Weight of the baby
existing TOF. In contrast, pure OA may present as an airless, 2. Overall clinical condition of neonate and
abdomen. The chest radiograph provides information about 3. Upper pouch level.
the cardiac silhouette, the location of the aortic arch and
the presence of vertebral and rib anomalies, as well as the The aim of surgery is to restore continuity of the oesophagus
presence of pulmonary infiltrates. and ligate the TOF, if present. Surgery is usually performed
on the first or second day of life, if the neonate is stable and
Preoperative Management does not require respiratory support.
1. Look for other associated anomalies. P In infants with significant associated anomalies
2. An echocardiogram is strongly recommended or sepsis, a definitive repair of an oesophageal
before surgery to identify cardiac defects and the lesion may be considered too risky, and a limited
position of the aortic arch. thoracotomy may focus on ligation of the TEF
followed by placement of a gastrostomy. In some
3. Renal ultrasound should be done. cases, such critically ill infants may be mechanically
ventilated preoperatively. In these cases, a more
4. Retrognathia is common with CHARGE syndrome,
definitive surgery may be tolerated within 24 to
so be prepared for difficult intubation.
72 hours, when the extent of other anomalies is
5. A tethered cord is usually detectable with defined, cardiovascular stability is established, and
ultrasonography in the newborn period. If present, a clear surgical plan has been defined.
one cannot plan for epidural anaesthesia.
P It may be preferable to divide the fistula and place
6. Look for signs of aspiration pneumonitis. a feeding gastrostomy in a neonate with severe
comorbidities such as a duct-dependent cardiac
7. A catheter is placed in the oesophagus to drain anomaly. Primary oesophageal repair can be
saliva, and the infant is placed prone in a head-up performed 6–12 weeks after cardiac surgery.
position.

P The ligation of a TOF is urgent, but not emergent, (e.g., the pulmonary artery or main bronchus) has
except in the setting of respiratory insufficiency not been clamped in error.
severe enough to require ventilator support,
o Division of the fistula may dramatically improve
especially in the premature infant. In this setting,
ventilation. Until this moment, it is sometimes
the presence of a TOF and poor lung compliance
necessary to operate in short 3- to 5-min. bursts,
often prevent delivery of adequate tidal volumes
relaxing lung and mediastinal retraction for 1–2
(ventilation escapes into the oesophagus and
min, when saturation descends to critical levels.
stomach via the fistula). The child should undergo
The integrity of tracheal repair can be checked by
emergency transpleural ligation of the fistula, with
instilling warm saline in the chest during a sustained
delayed division of the fistula and possible repair of
inflation, to identify an air leak by the presence of
OA at 8–10 days.
air bubbles. The anaesthetist may be asked to
P Neonates with pure OA or OA with a proximal help identify the distal end of the proximal pouch
TOF often have a long gap between proximal within the thorax by manipulating the Replogle
and distal ends of the oesophagus. A feeding tube from above. The distance from the mouth to
gastrostomy is inserted and the length of the gap the distal tip is noted. Only catheters of this length
estimated radiographically at the time of surgery. If should be used for suction in the postoperative
the gap is greater than the vertical height of three period. Once the two ends of the oesophagus are
vertebral bodies, upper pouch suction is continued approximated, the anaesthetist usually passes a
postoperatively and delayed primary closure is fine transanastomotic nasogastric tube before the
usually possible by about 12 weeks of age. If the anastomosis is fashioned, to allow enteral feeding
gap is greater than six vertebral bodies, a cervical in the postoperative period. This tube must be fixed
oesophagostomy is often fashioned and the in place, because it has a tendency to become
oesophagus repaired at a later date. Oesophageal dislodged. This tube should be clearly marked to
replacement surgery is occasionally required. preclude accidental removal postoperatively. If
there is significant tension at the anastomosis, the
P An oesophagoscopy or bronchoscopy is often neonate should remain paralyzed and the lungs
performed at the start of surgery, to provide ventilated mechanically for approximately 5 days
absolute confirmation of the diagnosis, to assess postoperatively.
the position of the fistula if present, and to exclude
multiple fistulae. o A staged procedure, initial gastrostomy with
deferred thoracotomy, may be used in babies
o The traditional approach in repair of OA/TOF is < 1 kg, those with pure OA, or with more critical
extrapleural via a right posterolateral thoracotomy associated anomalies. The survival rate in this
with the neonate placed in the lateral decubitus group is lower but in the range of 80 to 95 percent.
position with a roll under the chest to facilitate Cardiac anomalies typically, are the cause of death
surgical access. The posterior mediastinum is in these, more complicated cases.
approached via the 4th and 5th intercostal spaces
and the extrapleural route, gently compressing Traditionally, in the setting of planned delayed surgery,
the right lung. The approach is delicate and surgeons have ligated the fistula and inserted a gastrostomy
time consuming but reduces morbidity from an in the newborn. In the past, some surgeons have opted to
anastomotic leak, should one occur. exteriorize the upper pouch through an oesophagostomy,
but this approach has been widely abandoned. The
o If the child becomes unstable, a transpleural gastrostomy provides a route for enteral nutrition until
approach may be used. Dividing the azygous vein surgical repair of the atresia. In most cases, definitive repair
is necessary to find the subjacent fistula, branching is undertaken between 3 and 6 months of age, depending on
off the posterior aspect of the trachea (Type C). the infant’s status (e.g., growth and cardiorespiratory status)
The right bronchus, aorta, and (rarely) left bronchus and the opinion of the surgeon. At that time, ideally, the two
may be mistaken for this structure. Test occlusion oesophageal segments are either directly anastomosed, as
of the fistula is good practice to ensure that the right the native oesophagus allows superior function compared
lung can still be inflated and that a vital structure to an interposed bowel segment or gastric tube graft.

Over the past two decades, thoracosopic repair of the chance of aspiration. Clinically, however, this is seldom
tracheoesophageal fistula and oesophageal atresia a problem and most anaesthetists use a gaseous or
(TREAT) has emerged as an acceptable and even preferred intravenous induction, facilitating tracheal intubation with a
surgical approach to repair TOF/OA. A major advantage of non-depolarizing relaxant. Irrespective of mode of induction,
thoracoscopy is that, the fistula is visualized perpendicular ventilation by face mask should be at inflation pressures
to its insertion to the trachea, and, consequently, the exact less than 10–15 cm H2O.
site for ligation is apparent. The visual advantage also
improves mobilization of the oesophageal pouch, especially P Evaluating the upper airway via rigid or fiberoptic
in the setting of a longer gap. bronchoscopy may be an integral part of the
presurgical/intraoperative course of TOF/OA
Low birth weight babies tend to be sicker, and tolerate the repair. Finally, even with initial ideal positioning
stressors such as hypoxia and hypercarbia poorly, and of the endotracheal tube, ventilation through the
are not able to sustain prolonged duration of surgery. The fistula still occurs in some patients, this is especially
known cardiac abnormality is also considered a relative true if high peak airway pressures are required.
contraindication, considering impaired oxygenation during
thoracoscopic approach. Right aortic arch is an anomaly P Several approaches have been popularized to
where anatomy is distorted, and it is difficult to work in a position the tracheal tube, while avoiding intubating
small space during TREAT. Similarly, long gap atresia and the tracheoesophageal atresia. One popular
gap more than vertebral length, are difficult to handle at the technique is to deliberately intubate the right main
time of anastomosis. Patient is placed in semiprone position bronchus after general anaesthesia is induced, and
with placement of pad underneath the right pectoral region, then withdraw the tube until bilateral air entry is
so as to tilt chest by 15° to opposite side. Table is tilted by confirmed. This ensures the tracheal tube is below
15° in reverse Trendelenburg position. the fistula but does not prevent intubation of a large
fistula at the carina.
Anaesthetic Management
P In the unusual situation of a large fistula at the
• Selective one lung ventilation is not usually level of the carina resulting in preferential gastric
required as the surgeon can easily compress the ventilation, some authors suggest passing a 2 or
lung to access the fistula. The main anaesthetic 3Fr Fogarty embolectomy catheter through the
complications relate to- inadvertent intubation of fistula into the stomach via the rigid bronchoscope;
the fistula or preferential ventilation of the fistula the balloon of the Fogarty catheter is then inflated
causing gastric distension and desaturation. to occlude the fistula.
• Limb anomalies may make venous access and P In babies with associated significant airway
arterial cannulation difficult. abnormalities, some prefer to insert the tracheal
tube while the baby breathes spontaneously,
• If there is no tracheo-oesophageal fistula present, anaesthetized with a volatile agent. ‘Awake
then gastric distension during induction of intubation’ is seldom used because, it is difficult
anaesthesia will not occur. and distressing for the baby, associated with
• Patient should have intravenous access before significant oxygen desaturation and oropharyngeal
induction and receive 20 μg/kg atropine (minimum trauma. Increases in intracranial pressure must be
0.15 mg). The Replogle tube (tube in the upper considered in a vigorous neonate. It can contribute
oesophageal pouch) is aspirated. to the occurrence of intraventricular haemorrhage
in premature infants.
• Most advocate inhalational or intravenous
induction, according to personal preference, with Positioning the tracheal tube
muscle relaxant and gentle mask ventilation before Most fistulas lie posteriorly in the mid or low trachea. Salem
intubating the trachea. and others suggest distal positioning of the ETT, with the
Leakage of gas through the fistula may cause preferential bevel facing anteriorly and the posterior wall of the ETT
ventilation of the stomach during PPV, which will decrease occluding the fistula, but this manoeuvre is challenging to
the functional residual capacity (FRC), impair ventilation achieve and maintain. In practice, we insert the tube ‘too
and oxygenation by diaphragmatic splinting, and increase deep’, slowly withdrawing it until both lungs are ventilated.

At this point, it is possible to confirm the position of the axilla, since obstruction of the mainstem bronchus
endotracheal tube by passage of a flexible bronchoscope during surgical retraction is not uncommon. It also
through it. During surgery, inadvertent bronchial intubation helps in detection of endobronchial intubation.
is a possibility because of the low lying tip. Bilateral air entry
• Lung retraction impairs ventilation, especially in
should be confirmed after intubation and whenever the
infants with respiratory dysfunction from immature
baby is re-positioned.
lungs, pneumonia, or congenital heart disease.
Inadvertent entry of ETT into the fistula, kinking of bronchus Surgeon should intermittently release the pressure
during surgical manipulation, and lung retraction can cause to allow inflation of the right lung thereby improving
drop in oxygen saturation and end-tidal carbon dioxide oxygenation and ventilation. Close communication
(ETCO2). The surgeon must stop the procedure while the between the surgeon and anaesthesiologist is
situation is clarified. The surgeon will be able to palpate the mandatory. The surgeon must be alerted when
tip of the tube in the fistula if this is the problem. desaturation occurs but must be given reasonable
time to perform the different stages of the procedure.
Intraoperative maintenance
• Blood clots or secretions may block the ETT, and
• Nitrous oxide may distend the stomach, frequent ET suctioning may be required. Rarely,
compromising ventilation, and is best avoided. the ETT may become completely occluded by
a clot that cannot be removed by suctioning,
• Avoid high FiO2 if possible in premature neonates
necessitating immediate replacement of the tube.
at risk for retinopathy of prematurity (ROP).
Because the trachea is a soft structure in the
Use air/O2 mixture for ventilation to maintain O2
newborn, surgical manipulation may kink the airway
saturation between 90-95%. At times they require
and further obstruct ventilation. Cardiac output can
ventilation with 100% oxygen, despite the risk of
fall dramatically if surgical manoeuvres compress
the ROP. Healthy infants may tolerate spontaneous
major vessels.
ventilation, but most often neuromuscular blockade
is necessary especially once the chest is opened • Good communication and cooperation with the
and the lungs are retracted. It can be difficult to surgeon are essential. Before the closure of
obtain adequate oxygenation, ventilation and the thoracic wound the lung should be carefully
surgical conditions in a spontaneously breathing re-expanded in order to avoid unnecessary
patient during open thoracotomy. postoperative atelectasis.
• Use low PIPs to avoid gastric distension by Pain Management
gases passing through fistula. Careful adjustment
of ventilation will be necessary during surgical • Intravenous opioids are effective for intraoperative
retraction of lung or during insufflation if procedure and postoperative pain management. Generous
is done thoracoscopically. Manual ventilation doses can be used if there is definite indication for
is recommended as surgical traction can easily postoperative ventilatory support.
occlude the neonate’s soft trachea. It can be helpful
• Babies who are expected to be extubated, regional
in assessing pulmonary compliance. IPPV is
anaesthesia is advantageous to avoid opioids and
usually done by hand using a Jackson Rees circuit
the risk of postoperative respiratory depression.
at a high frequency of 30-40 per minute and low Providing there are no significant vertebral
tidal volumes. anomalies, a caudal catheter may be advanced to
• Air/O2/opioid (e.g., fentanyl 1–2 µg/kg/h), propofol T6–T7 to supplement the general anaesthetic and
or low-dose volatile technique is preferred because provide excellent postoperative analgesia without
of better hemodynamic stability. Muscle relaxation the use of opioids and to facilitate extubation.
(atracurium) is usually necessary. If epidural is Surgeon can block intercostal nerves before wound
used, GA drug requirements will be reduced. closure.
• Once satisfactory ventilation is ensured, the chest • An intrapleural catheter is another means of
is opened and the lungs are retracted. A precordial providing analgesia after open surgery, but this
stethoscope should be placed in the dependent (left) may risk local anesthetic toxicity owing to rapid
absorption from the pleural cavity.

I use multimodal approach, consisting of IV fentanyl 0.5 -1 Postoperative Considerations
µg/kg, rectal paracetamol 30 mg/kg and caudal 0.125%,
Nasopharyngeal and oropharyngeal suctioning catheters
1.25 ml/kg bupivacaine after anaesthetic induction.
should be carefully marked to avoid insertion down to the
Emergence & extubation level of the anastomosis. Oral suctioning is performed
every half hour for the first day, then every hour or more
There is a constant debate whether to extubate the patient frequently as necessary on the second day. Thereafter, it is
or to continue intubation & ventilation. Extubation has performed as needed. Head extension can put tension on
advantage that it minimizes manipulation of the anastomosis the anastomosis and should be minimized.
from the ETT. However, approximately 30% will require
reintubation for clearing of secretions. With laryngoscopy Concerns during conduct of thoracoscopic
and reintubation, there are chances of trauma to the fistula tracheoesophageal fistula
site and traction on the oesophageal repair.
• Most of the times, paediatric surgeons do not
Some full-term infants are extubated after simple ligation request for onelung ventilation as nondependent
of a TEF, but this is rare, secondary to persistent effects lung is compressed by CO2 insufflation. Neonatal
of preoperative pulmonary lesions (e.g., pneumonia, insufflators are also used to overcome the problem
immaturity, other anomalies) combined with the residual of overdistension of chest cavity.
impact of surgery and general anaesthesia. In addition, • Surgery is started with insertion of 5 mm port at
tracheomalacia or a defective tracheal wall at the site of the postaxillary line near the tip of scapula, ensuring
fistula predisposes to collapse of the airway. Treatment of proper position of first port in pleural space. Gas
postoperative pain, when combined with the host of other insufflation is started at 0.1–3 L/min flow, maintaining
cardiorespiratory problems of the newborn, often requires a 5mmHg pressure in intrapleural space. This will in
period of postoperative ventilation for at least 24 to 48 hours. turn result in an increase in pulmonary vascular
The ETT provides a means to suction and expand the lungs resistance secondary to hypoxic vasoconstriction
during the first 24 hours of greatest risk. Other advantage in the right lung. The positive pressure in the
of ventilation is that, adequate amounts of analgesia can right hemithorax will also cause a decrease in
be given. venous return, by compression of the vena cava
and may also cause direct compression of the
After repair of “long-gap” EA, tension at the anastomotic
right ventricle. Thus, reductions in cardiac output
site may predispose to oesophageal leaks. Postoperative
and blood pressure are likely to occur during the
ventilatory support for 5 to 7 days has been recommended
case. Insufflation of CO2 combined with a limited
to improve the rate of maintaining anastomotic integrity.
possibility to maintain adequate alveolar ventilation
Sedation to eliminate spontaneous ventilation (i.e., to will result in serious CO2 retention combined with
eliminate negative intrapleural pressure transmitted to the pronounced respiratory acidosis (pH 7.0).
anastomosis), should be tailored to the haemodynamic
status of the infant. If deep sedation is not tolerated, • This situation is further compounded by the fact that
neuromuscular blockade may be indicated, but immobility is the measurement of end-tidal-CO2 is notoriously
often accompanied by oedema that may lead to decreased unreliable and the CO2 tracing may even become
chest wall compliance and the need for increased positive absent during parts of the procedure. A well-
pressure to maintain adequate ventilatory support. functioning arterial line is, thus, a prerequisite in this
situation. Desaturation episodes can be considered
I take the following approach: extubate babies which the rule, and to counteract this as much as possible
are good weight, full term without CHD, and without ventilation with 100% oxygen is recommended
intraoperative cardiopulmonary complications, and are during the period of OLV.
normothermic. I continue intubation and ventilation for
babies <2Kgs, premature, hypothermic, with CHD or • The combination of hypoxia, hypercapnea and
intraoperative complications or if postoperative adequacy acidosis will add to the increase in pulmonary
of ventilation is doubtful. They are weaned from ventilatory vascular resistance caused by the atelectasis of
the right lung. Due to the substantial alterations
support when adequate gas exchange and respiratory effort
that take place both regarding haemodynamics
are demonstrated.
and gas exchange it is very useful to use cerebral

near-infrared spectroscopy (Invos) to monitor fluid resuscitation. Dehydration and hypothermia
cerebral oxygenation throughout the procedure. are usually more serious in gastroschisis, as the
Even if it is clearly possible to perform TOF repair protective hernial sac is absent.
as a thoracoscopic procedure, the combination
of neonatal anaesthesia with periods of hypoxia, • Assess the baby clinically– skin perfusion, capillary
pronounced hypercarbia, and substantial acidosis refill, heart rate (HR) and blood pressure (BP),
may raise concern regarding the risk for brain cell blood gases.
apoptosis with potential long-term cognitive and
• Fluid challenge may be required. A baby requiring
behavioural problems. This is often not tolerated in
significant volume resuscitation should be electively
sick neonates with compromised cardiorespiration.
intubated.
Transient hypoxemia and hypercarbia can occur at
the beginning of procedure due to pressure effects Concerns:
on mediastinal contents and collapse of lung.
Ventilator parameters are adjusted, maintaining o Fluid resuscitation
minute ventilation, so as to maintain normal o Prevention of heat loss
oxygenation and ventilation. o Treatment of sepsis, and
• Increase in fractional of oxygen is also done to o Protection of herniated viscera.
avoid desaturation at this time point. After few
• To maintain normal oncotic pressures, protein
minutes, after the ipsilateral lung is collapsed, no
containing solutions (5% albumin) should constitute
CO2 pressure is applied. High FiO2 along with
approximately 25% of the replacement fluid which
application of positive endexpiratory pressure may
is usually a balanced salt solution (lactated Ringer’s
be required to maintain saturation above 85%.
Endtidal carbon dioxide reading will be unreliable solution).
during this period. Arterial CO2 will be raised, and • A urine output of 1 to 2 ml/kg/hr indicates
must be noted in the setting of congenital cardiac adequate hydration. Hypovolemia is indicated
disease and pulmonary hypertension. Procedure is by haemoconcentration and metabolic acidosis.
started after a stable condition is achieved. If severe metabolic acidosis develops despite
ABDOMINAL WALL DEFECTS fluid delivery, then sodium bicarbonate, colloids,
ventilatory support, and vasopressors may be
It includes: needed to maintain the pH >7.20.
• Gastroschisis (without cover, <5cms) and • Decompression of the stomach with an orogastric
• Omphalocele (with cover). tube or nasogastric tube (NGT) is done to prevent
regurgitation, aspiration pneumonia, and further
Latter is divided into exomphalus major (10-12 cms,
bowel distension due to swallowed air.
includes liver, with poorly developed abdominal and
thoracic cavities and pulmonary hypoplasia) and minor • Gastroschisis requires urgent repair. Single stage
(5-8 cms). surgery with reduction of the bowel and closure
• Prematurity and small for gestational age is more of the abdominal wall defect may be possible for
common with gastroschisis. Associated anomalies exomphalos minor. But exomphalos major and
are more common with omphalocele, hence gastroschisis generally require staged surgery as
preoperative cardiac evaluation is must. ‘Abdominal compartment syndrome’ (ACS) may
occur if the abdominal contents are reduced under
• Exomphalus major is associated with a scaphoid pressure, particularly in exomphalos major if the
abdomen and small thorax. Respiratory distress abdominal cavity is small.
may present with signs of increased work of
breathing i.e. tachypnoea, tachycardia, and • Controlled rapid sequence induction is done.
nasal flaring or apnoea. Distressed infants may Nitrous oxide is avoided as it distends the bowel
desaturate easily. and interferes with reduction of hernia. The inspired
oxygen concentration must be adjusted to maintain
• Gastroschisis and ruptured exomphalus major oxygen saturation between 95% and 97%.
may present with significant fluid loss requiring

• Atracurium is the muscle relaxant of choice as it is altered drug metabolism and excretion. Decreased
eliminated by Hoffmann’s degradation. The liberal diaphragmatic excursion, lung compression and
use of muscle relaxants provides optimal surgical decreased pulmonary compliance results in
conditions for closure of the defect. impaired ventilation. During abdominal closure, the
anaesthesiologist must monitor airway pressures
• Low to moderate concentrations of volatile and watch for decreased pulmonary compliance.
anaesthetics are administered to avoid hypotension.
• The surgeon and the anaesthesiologist should
• Serial intraoperative glucose monitoring is cooperate to assess the feasibility of a primary
indicated as hypoglycaemia can occur in infants closure. Increases in intragastric pressure
with Beckwith-Wiedemann syndrome. measured through a gastrostomy tube >20 mmHg,
• Fluid therapy consists of 5% to 10% dextrose in increases in central venous pressure (CVP) of >4
0.2% saline at the maintenance rates and lactated mmHg above baseline and failure of saphenous IV
Ringer’s solution (8 to 15 ml/kg, or more, per hour) line (if in situ) fluid to flow by gravity were frequently
for third-space loss. Extreme clinical vigilance and associated with reductions in venous return and
intensive monitoring are recommended. Blood cardiac index, requiring surgical decompression of
loss should be replaced with warmed blood and the abdomen.
hemoglobin is maintained at approximately 10-12 • Forceful closure of the abdominal wall will also
g/dl. Fresh Frozen Plasma is administered in 10 cause significant tension of the skin resulting in a
ml/kg aliquots and platelets are given if the platelet high incidence of necrosis with secondary infection.
count or coagulation screen is abnormal.
• Blood pressure and pulse oximetry measurements
• Intravenous lines are usually taken in upper limbs from a lower extremity will help identify circulatory
as abdominal distension can impair venous return problems. Lower extremity congestion and cyanosis
from the lower body. Watch for development of may also be seen if venous return from the lower
abdominal compartment syndrome (ACS) after body is impaired.
tight abdominal closure.
• It is safer to continue ventilatory support
• Intragasrtric and intravesical pressure postoperatively for large gastroschisis and
monitoring can determine the surgical course. exomphalus major.
In giant omphaloceles, due to visceroabdominal
disproportion, gradual reduction to the peritoneal CONGENITAL HYPERTROPHIC PYLORIC STENOSIS
cavity is done with a silastic silo over a several-day
period, followed by a second procedure a few days  It commonly presents between the ages of first 3 to
later for complete closure. Suggested criteria for a 6 weeks life.
staged closure include intragastric or intravesical  Cardinal features of pyloric stenosis- nonbilious
pressure >20 cmH2O, peak inspiratory pressure projectile vomiting, visible peristalsis,
>35 cmH2O, or an end-tidal carbon dioxide >50 hypochloremic, hypokalemic metabolic alkalosis,
mmHg. In either situation, postoperative ventilation with dehydration and lethargy.
will be necessary until the abdominal wall has had
time to stretch to accommodate the viscera as the  The metabolic alkalosis can cause compensatory
compliance is reduced by return of the viscera to respiratory acidosis, shift of oxygen dissociation
the peritoneum. curve to left, hypocalcaemia and convulsions.
• Tight surgical abdominal closure can result in ACS  While some potassium is lost in the vomitus, its
which includes hypotension secondary to tension concentration is generally <15 mEq/L. Of greater
on a major organ (liver) and cava. Decrease importance is the potassium loss in the urine in
in venous return not only leads to reduction in exchange for hydrogen in an effort to maintain a
cardiac output but also congestion of organs, normal serum pH. The potassium shift intracellularly
ultimately resulting in impaired perfusion. End with rising plasma pH, represent only a small portion
result is bowel necrosis, perforation, necrotizing of the plasma potassium (K+) loss. Along with
enterocolitis, acidosis, anuria, hepatic impairment, considerable hydrogen ion (H+) loss from the gastric

secretions, chloride (CI-) is also lost. The resulting in place during surgery so that air can be insufflated
hypochloremia results in maximal CI- conservation, in the stomach, to test for mucosal perforation after
with urinary CI- <20 mEq/L. Urinary Na+ cannot be the hypertrophied muscle is split.
relied on as an indirect measure of volume status.
In contrast, since all CI is reabsorbed in exchange  Due to higher incidence of postoperative apnoeic
for HCO3-, the urinary CI- concentration provides a spells, apnoea monitoring is necessary for first 12
much more accurate idea. hours.
 The following are major concerns for the INTESTINAL OBSTRUCTION

anaesthesiologist: (1) a full stomach,  One of the most common surgical emergencies
occasionally filled with contrast material can cause encountered in the neonatal period .
pulmonary aspiration; (2) metabolic alkalosis with
hypochloremia and hypokalemia; and (3) severe  Characterized by feeding intolerance, vomiting,
dehydration. and abdominal distension.
 Severely dehydrated infants should receive an initial  Common causes of intestinal obstruction in
20 ml/kg bolus of isotonic saline to re-expand the neonatal period -- duodenal, jejunal or ileal
intravascular volume. Give 5% dextrose with 0.45% atresia, Meckels diverticulum, meconium ileus,
saline as indicated by serum electrolytes and fluid necrotising enterocolitis, malrotation with volvulus,
deficits. Add potassium chloride supplementation Hirschprungs disease, and anorectal malformation.
once the urine flow is established. Surgery should
 Irrespective of type of obstruction majority have
be delayed until biochemical values reach: pH
fluid, electrolyte imbalance and abdominal
7.3-7.5, serum HCO3_ < 28-30 mEq/L, Na+ >
distension, which reduces respiratory compliance
132 mEq/L, K+ > 3.5 mEq/L, Cl- >90 mEq/L and
and venous return.
urinary Cl- >20 mEq/L with adequate preoperative
hydration. If deficits are not corrected as above,  They have to be treated like full stomach.
compensatory respiratory acidosis coupled with
residual anaesthetics may affect recovery from Atresia
GA and increase the incidence of postoperative
 They are frequently preterm or may have other
apnoea.
associated anomalies such as malrotation of the
 Once the child is satisfactorily hydrated, stomach gut, volvulus, and abdominal wall defects.
contents are thoroughly evacuated. Appropriate
 Healthy newborn infants have gastric aspirates
monitors (electrocardiogram, pulse oximeter,
that measure less than 5 ml whereas congenital
blood pressure cuff, and precordial stethoscope)
intestinal obstruction is associated with gastric
are placed. In theatre, after giving atropine, NGT
aspirates that measure greater than 30 ml.
is replaced with a fresh orogastric tube and the
stomach is sucked out in the supine and both the  Sustained vomiting (bilious or nonbilious) is the
right and left lateral positions immediately before most common symptom, occurring in approximately
induction of anaesthesia and as much of the 85% of cases.
stomach contents are removed as possible. This
suctioning technique will remove 98% of the gastric  Duodenal atresia typically presents within the
contents. This decreases the possibility of aspirating first hour of life. There is higher prevalence of
gastric contents during induction of anaesthesia. associated congenital malformation, therefore
Controlled rapid sequence induction and intubation warranting preoperative cardiology evaluation and
are done. Opioids are avoided. These patients echocardiography.
have high incidence of postoperative apnoea and  Coexisting tracheooesophageal fistula is repaired
opioids can aggravate the same. Most of the time, before correction of duodenal atresia.
local anesthetic bupivacaine (maximum dose, 1 ml/
kg of 0.25%) infiltration and rectal paracetamol  Neonates with duodenal atresia present so early in
provides sufficient analgesia. After intubation of the life, usually within the first 12 hours, so they rarely
trachea, an orogastric tube is repositioned and left are dehydrated or hypochloremic.

 An abdominal x-ray film will show the classic P Intubation for respiratory support in patients with
“double bubble” sign (i.e., dilated air-filled severe abdominal distension or sepsis may be
stomach and proximal duodenum) necessary.
Jejunoileal atresia: Anaesthetic management proceeds with decompression

of the stomach and pre-oxygenation. Avoid sedative
In jejunoileal atresia -- air-fluid levels are observed
premedication; only atropine is administered prior to
throughout the abdomen. In distal ileal obstruction, a
induction. All the patients should be considered full stomach.
barium enema may demonstrate a microcolon. Patients
Rapid-sequence induction may be used with thiopentone
are frequently premature (35%). Majority are low birth
(2-3 mg/kg) or sevoflurane in haemodynamically stable
weight. Deaths are attributed to associated malformations,
neonates with normal airway anatomy. Ventilation is done
respiratory complications, prematurity, and anastomotic
with air and oxygen avoiding nitrous oxide to minimize
complications.
intestinal distension. Muscle relaxation with suxamethonium
Investigations: CBC, electrolytes, crossmatch of blood, chest or atracurium is generally necessary to facilitate abdominal
X Ray, echocardiography to exclude endocardial cushion exploration. Use of a neuromuscular blocking agent also
defects and patent ductus arteriosus (PDA), ultrasound for decreases or avoids the need for large concentrations of
detecting renal anomalies and an annular pancreas, head potent inhalation agents, which are poorly tolerated by
ultrasound to exclude intracranial haemorrhage in premature hypovolemic neonates. Umbilical arterial lines are replaced
infants are done. Neonates tolerate surgical procedures with a peripheral arterial line so that mesenteric blood flow
best when they are metabolically and haemodynamically is not compromised.
stable.
Meconium Ileus
Goals:
 Meconium ileus (MI) accounts for 9%-33% of
P Attention should be directed to prevent or correct neonatal intestinal obstructions.
hypothermia, hypovolemia, hypoglycemia, and
hypoxemia.  It is the earliest clinical manifestation of cystic
fibrosis.
P Initial fluid requirement in these neonates is 2 to
 They usually present with abdominal distension
4 times the maintenance requirements (≥8–16
at birth, eventually progressing to failure to pass
ml/kg/hr) to ensure adequate hydration and to
meconium, bilious vomiting, and progressive
compensate for vomiting and large gastric aspirates.
abdominal distension.
Hypovolaemic shock, haemoconcentration, and
metabolic acidosis may develop with inadequate  Examination reveals dilated loops of bowel with a
resuscitation. doughy character that indent on palpation.
P Acid-base status and electrolyte levels should be  Complicated meconium ileus present at birth
monitored serially. with severe abdominal distension, sometimes
accompanied by abdominal wall erythema and
P Dopamine infusions may be required to increase oedema.
the cardiac output and improve intestinal perfusion.
A proximal small-bowel obstruction results in loss of  Abdominal distension may be severe enough to
fluids that resemble gastric juice and thus produces cause respiratory distress.
hypokalemic and hypochloremic metabolic
 Signs of peritonitis include tenderness, abdominal
alkalosis. With distal small bowel obstruction, fluid
wall oedema, distension, and clinical evidence of
losses are usually isotonic, so serum electrolytes
sepsis.
are normal until sufficient dehydration results
in metabolic acidosis, as demonstrated by  Cystic Fibrosis is characterized by the triad of
tachypnoea, low serum bicarbonate levels, and chronic obstruction and infection of the respiratory
elevated serum chloride values. tract, exocrine pancreatic insufficiency, and
elevated sweat chloride levels.
P Abdomen is scaphoid in duodenal, diffusely
distended in ileal, and the combination of two in  Diagnosis: Abdominal radiography reveals the
jejunal atresia (upper distension, lower scaphoid). following: (1) great disparity in the size of the

intestinal loops because of the configuration of the  Blood and blood products should be available in
different segments of the bowel; (2) no or few air the operating room.
fluid levels on the erect film because swallowed
air cannot layer above the thickened inspissated  Central venous pressure monitoring may improve
meconium and (3) a granular, “soap bubble” or assessment of intravascular volume status, and
“ground glass” appearance seen frequently in the fluid management; however, if there is adequate
right half of the abdomen, a finding that requires peripheral venous access, the operation should not
swallowed air bubbles to intermix within the sticky be delayed to insert the central venous pressure
meconium. When meconium ileus is suspected catheter.
based on clinical and radiographic evidence, a Anorectal Malformations
contrast barium enema may be performed with a
therapeutic Gastrografin enema.  There is high incidence of associated anomalies of
the urogenital sinus, renal agenesis, vesicoureteral
 Treatment: Perform resuscitative measures, reflux, neurogenic bladder, renal dysplasia,
including mechanical respiratory support, if megaureter, hydronephrosis, and ectopic ureter.
necessary. Initiate intravenous hydration and
gastric decompression. Evaluate and correct any  Entire spectrum of the VACTERL syndrome is
coagulation disorders, and begin empiric antibiotic common.
coverage. Surgical management is necessary in
 Decompressive colostomy is done before definitive
patients with persistent or worsening abdominal
surgery.
distension, persistent bowel obstruction, enlarging
abdominal mass, intestinal atresia, volvulus,  Echocardiography is needed to rule out associated
perforation, meconium cyst formation with peritonitis congenital heart disease.
and bowel necrosis.
 Spinal abnormalities should be ruled out before
 Management of anaesthesia: The Bishop- giving caudal anaesthesia.
Koop enterostomy is the procedure of choice.
Intraoperative management involves fluid  As they have massive abdominal distension, they
resuscitation, carefully replacing the fluid losses are to be treated like “full stomach”. Slight head up
caused by surgery and by preoperative diuresis and tilt may help in breathing.
diarrhoea (if a Gastrografin enema is attempted).
Necrotizing Enterocolitis
Adjust ongoing maintenance fluids and replace
insensible fluids lost, as well as GI losses (i.e.,  Classically occurs in small premature (80-90%)
losses from NG suction and ileostomy). Instillation and low birth weight (LBW) infants with gestational
of N -acetylcysteine via an NG tube or via ileostomy age <32 weeks and weight <1500 gm. NEC can
helps solubilize residual meconium. also occur in full-term infants on the first day of life
or months after birth.
Malrotation and Volvulus
 Term infants develop symptoms by day 2 to 3
 True neonatal emergency and surgery should
of life, whereas the extremely low birth weight
proceed as soon as possible. Delay in surgery may
(ELBW) infants are more likely to develop NEC in
result in necrosis of the entire small intestine.
the second week of life.
 These infants may have hypotension, hypovolemia,
 It most frequently involves the terminal ileum and
and electrolyte abnormalities.
proximal colon. The GI signs appear between the
 The intravascular deficits may be exacerbated by 1st and 10th days of life in more than 90% of these
the presence of barium in the gastrointestinal tract. babies.
Haematocrit may be falsely increased secondary to
 Although centred in the GIT, it is a systemic
marked intravascular volume depletion.
process primarily related to sepsis. Bowel
 Fluid and electrolyte resuscitation begins necrosis and perforation follow, and sepsis occur
preoperatively and continues during surgery. along with hyponatremia, jaundice, decreased
peripheral perfusion, haemodynamic instability,

anaemia, thrombocytopenia (50,000 to 75,000/ • RBC count: Anaemia due to prematurity, iatrogenic
mm3), coagulopathy, disseminated intravascular blood draws, haematochezia and/or a developing
coagulation, prerenal azotemia and metabolic consumptive coagulopathy.
acidosis secondary to generalized peritonitis and
hypovolemic shock. • Platelet count and coagulation study: Thrombocytopenia
(<100,000/μL), neutropenia and thrombocytopenia are
 They have coagulative or ischemic necrosis leading associated with gram-negative sepsis and platelet
to pneumatosis intestinalis and hypovolemic shock. binding by endotoxin. It is profound in severe cases that
become complicated with consumption coagulopathy.
 There is bleeding diathesis with prolonged Consumption coagulopathy is characterized by
prothrombin and partial thromboplastin time, prolonged PT, prolonged aPTT, and decreasing
decreased fibrinogen, rise in fibrin split products. fibrinogen and increasing fibrin degradation products
There is leukopenia or leukocytosis. Respiratory concentrations.
distress syndrome (RDS) is present in severe
cases. • Blood culture: Obtaining a blood culture is
recommended before beginning antibiotics.
 Abdominal radiograph may show abnormal gas
pattern, dilated loops, and thickened bowel walls 2. Serum electrolytes (Na+, K+, and Cl) are done serially
(suggesting oedema/inflammation), a fixed and at least every 6 hours depending on the acuity of the
dilated loop and sometimes scarce or absent patient’s condition.
intestinal gas, classic pneumatosis intestinalis
(characteristic train-track lucency configuration • Serum sodium: Hyponatremia is a worrisome sign that
within the bowel wall), pneumoperitoneum, portal is consistent with capillary leak and “third spacing” of
gas (appears as linear branching areas of decreased fluid within the bowel and peritoneal space. An acute
density over the liver shadow and represents air decrease (<130 mEq/l) is alarming and heightened
present in the portal venous system which is a vigilance is warranted.
poor prognostic sign) or ascites (centralized bowel • Metabolic acidosis: Low serum bicarbonate (<20
loops that appear to be floating on a background mEq/l) in a baby with a previously normal acid base
of density). Last two are better appreciated on status is also concerning. It is seen in conjunction with
ultrasonography. poor tissue perfusion, sepsis, and bowel necrosis.
Preoperative assessment 3. Arterial blood gas
Anaesthesiologist is confronted with the problems of • Depending on presentation acuity, hypoventilation and
prematurity, hypovolaemia, sepsis, acidosis, and hepatic frank apnoea, ABG can aid in the determination of the
portal gas. Preoperative respiratory status must be carefully infant’s need for respiratory support in addition to acid-
evaluated. Profound hypovolaemia from peritonitis, sepsis base status.
and massive third-space fluid losses require vigorous fluid
resuscitation with crystalloid and colloid solutions before • Acute acidosis is worrisome. Lactic acidosis results
induction of anaesthesia The preoperative assessment from decreased cardiac output (as in cardiovascular
should focus on evaluating and correcting the respiratory, collapse and shock). Tissue necrosis may also add to
circulatory, metabolic, and haematologic disorders. the observed metabolic acidosis.
One anomaly mandates a search for others. Murmurs
 Profound hypovolaemia from peritonitis, sepsis
necessitate a cardiology consult.
and massive third-space fluid losses require
Laboratory testing vigorous fluid resuscitation with crystalloid and
colloid solutions before induction of anaesthesia.
1. CBC at least every 6 hours if the patient’s clinical status Perioperative fluid administration can approach
continues to deteriorate. 150-200 ml/kg. Rapid fluid administration to preterm
• WBC count: Marked elevation or leukopenia with left neonates may cause intracranial haemorrhage or
shift. Moderate-to-profound neutropenia (absolute reopening of the ductus arteriosus with congestive
neutrophil count <1500/μL) strongly suggests heart failure.
established sepsis.

 Inotropes such as dopamine may be required P To minimize the risk of retinopathy, arterial oxygen
to maintain adequate cardiac output and bowel tensions need to be maintained at 50-70 mmHg
perfusion. intra-operatively. Hypoxia is a greater danger than
retinopathy and must be avoided.
 Blood and platelet transfusions are often necessary.
Thrombocytopenia and the associated coagulopathy P Intraoperative ventilatory settings should be
may require blood and platelet transfusions. For oriented to the maintenance of preoperative oxygen
transfusion with platelet concentrates the following tensions. The use of a continuous inline oxygen
formula is used to calculate the expected increase monitor and an air flowmeter on the anaesthetic
in platelet count: Expected increase (cells/L) = 2 machine will permit the fine control of inspired
(0.7 x 1011 x N) / Blood volume. Where the blood oxygen concentrations.
volume is given in litres and N is the number of
units of platelet concentrate administered. Using P It is advisable not to use nitrous oxide due to
85 ml/kg as the blood volume for newborns this expansion of intramural and portal gas pockets.
formula suggests that the administration of 0.18 Mural gas is composed of hydrogen, nitrogen,
unit/kg would increase the platelet count by 100 x carbon dioxide, and traces of oxygen. Due to the
109 cells/L. greater blood solubility of nitrous oxide (0.47)
relative to nitrogen (0.0122) and hydrogen (0.0149)
 The newborn has low levels of coagulation the size of bubbles could increase. This expansion
factors II, VII, IX, X, XI, and XII. Factors II, VII, could further compromise bowel blood supply.
IX, and X are all vitamin K dependent factors.
Therefore it is recommended that vitamin K be P An additional hazard of mesenteric vein gas is
administered routinely to all newborns. In the event the risk of gas embolism from the passage of gas
that coagulation needs to be restored to normal through the ductus venosus into the inferior vena
immediately, fresh plasma, fresh-frozen plasma, cava. The ductus venosus may be patent for two to
or prothrombin complex can be administered. The three weeks after birth in term infants.
administration of 10 ml/kg of fresh frozen plasma Maintenance:
or platelet concentrate will supply the minimum
haemostatic factors for most newborn haemostatic • Volatile anaesthetics can produce significant
problems. myocardial depression and hypotension particularly
in presence of sepsis and hypovolemia.
 Because of the large fluid requirements and rapid Therefore, decreased maintenance doses of
heat loss, hypothermia is a frequent. anaesthetics are needed. Fentanyl, remifentanil
Induction or ketamine combined with low-dose, inhaled
anaesthetics can provide analgesia, amnesia as
• These infants are usually on mechanical ventilation well as cardiovascular stability. Neuromuscular
prior to surgery. If not already intubated on arrival blocking agents facilitate surgical exposure.
in the operating room, full stomach precautions are Inotropic agents occasionally are needed
in order. Preoxygenation and premedication with to support the cardiovascular system when
atropine should be given prior to induction and fluid therapy alone fails to maintain adequate
laryngoscopy. Following rapid sequence induction perfusion.
an endotracheal tube should be chosen to allow
ventilation with PIPs >20 cmH2O, due to high intra- Postoperative period:
abdominal pressures and decreased pulmonary • Mechanical ventilation and cardiovascular
compliance. support are usually continued because of
• Prematurity and its problems like retinopathy abdominal distension and co-existing RDS.
(retrolental fibroplasia), Hyaline membrane disease Total parenteral nutrition is essential even after
--- requiring varying amounts of supplemental sepsis is controlled and metabolic stability is
oxygen and mechanical ventilation. established.

MYELOMENINGOCELE • Analgesia should be multimodal with small doses
of intraoperative opioids, intravenous paracetamol,
• These neonates may have feeding difficulties due and wound infiltration with local anaesthetics.
to the neurological deficit and be volume depleted
secondary to evaporative and third space losses • Preterm infants are at increased risk of postoperative
from the exposed area. Preoperative intravenous apnoea, especially after neurosurgery.
fluids may be required.
HYDROCEPHALUS
• Presence of any associated congenital anomalies • The presence of bradycardia, hypertension,
should be excluded and the degree of the and irregularities in breathing suggests critically
neurological deficit confirmed. increased ICP and requires urgent treatment.
• Open myelomeningocele should be closed within • Preoperative preparation includes planning for the
48 h of birth, since the risk of infection increases positioning of the infant, particularly if the head is
with the time the defect is exposed. large. Achieving the optimal position is essential
for tracheal intubation, which could otherwise be
• With cervical encephalocele, the neck is often
difficult due to head size.
short and rigid which can make tracheal intubation
difficult. • Induction of anaesthesia may be achieved via
either the intravenous or inhalational route.
• Earlier, tracheal intubation was recommended in the
left lateral position-- but this is not necessary if the • Oxygenation and haemodynamic stability should
spinal defect is first padded to prevent pressure from be maintained throughout and acute increases in
being applied to the layers covering the spinal cord. ICP avoided.
The head and body can be raised and supported
• The lungs should be ventilated throughout as
using foam pads. For occipital encepaloceles, the
spontaneous ventilation is contraindicated when
airway is often secured with the neonate in the left
the cranium is open.
lateral decubitus position as it is difficult to stabilize
the large CSF-filled encephalocele with the neonate • Bradycardia or other arrhythmias may occur when
supine. With anterior encephaloceles, the child may the ventricular catheter is inserted.
be positioned supine with the airway secured using
• Insertion of the distal end of the VP shunt into
orotracheal intubation.
the peritoneum requires that a passageway be
• Surgery is usually performed with the neonate in tunnelled under the skin from the head to the
the prone position. In the prone position, particular abdomen to accommodate the shunt catheter. This
attention should be paid to the eyes, which should is usually a very stimulating manoeuvre, requiring
be padded and protected from pressure. Pressure 0.5 µg/kg fentanyl. Paracetamol may be used for
on the abdomen should also be avoided to prevent postoperative analgesia. It is also helpful to infiltrate
compression of the IVC and engorgement of the abdominal wound with local anaesthetic.
the paraspinal vessels as well as to allow free
• Thermoregulation can be problematic as a large
abdominal movement with respiration. This can be
proportion of the neonate is washed with antiseptic
achieved by placing “jellies” under the chest and
prep and surgery requires a large amount of
hips.
exposure. To prevent hypothermia, the room must
• Induction of anaesthesia may be either - inhalational be warmed before the neonate arrives (≥26°C)
or intravenous. and a forced air warmer used. Central temperature
should be monitored (e.g., oesophageal) throughout
• Blood loss is usually small unless a large skin flap
surgery and the trachea extubated only if the
or a craniotomy (in the case of encephaloceles) is
neonate is normothermic.
planned. However, if brisk blood loss is anticipated
(as in the case of encephaloceles), packed red References
blood cells should be in the operating room at the
time of skin incision. 1. Malde AD and Virkar N. General consideration in
emergency neonatal and pediatric surgeries. In:

Editors: In: Gandhi MN, Malde AD, Kudalkar AG, 7. Spaeth JP, Lam JE. The Extremely Premature Infant
Karnik HS, Eds. Practical Approach To Anaesthesia (Micropremie) and Common Neonatal Emergencies.
For Emergency Surgery. New Delhi, Mumbai, In: Coté CJ, Lerman J, Anderso BJ, Eds. Coté
Panama City, London: Jaypee Brothers Medical and Lerman’s A Practice of Anesthesia for Infants
Publishers (P) Limited; 2011: PP 303-320. ISBN 978- and Children, sixth edition. Elsevier https://t.me/
93-5025-070-9 Anesthesia_Books).
2. Malde AD. Anaesthetic management of neonatal 8. Morton NS, Fairgrieve R, Moores A & Wallace E.
thoracic surgeries. In: Gandhi MN, Malde AD, Anesthesia for the Full -Term and Ex-Premature
Kudalkar AG, Karnik HS, Eds. Practical Approach Infant. In: Gregory GA and Andropoulos DB, Eds.
To Anaesthesia For Emergency Surgery. New Delhi, Gregory’s Pediatric Anesthesia, fifth edition. Wiley
Mumbai, Panama City, London: Jaypee Brothers and Blackwell, John Wiley & Sons Ltd. 2012
Medical Publishers (P) Limited; 2011: PP 321-344.
ISBN 978-93-5025-070-9. 9. Lönnqvist PA. Management of the Neonate:
Anesthetic Considerations. In: Bissonnette B Ed.
3. Malde AD, Pethkar T and Tandekar A. Anaesthesia Pediatric Anesthesia Basic Principles—State of the
for neonatal and pediatric abdominal emergencies. Art—Future. Shelton, Connecticut: People’s Medical
In: Gandhi MN, Malde AD, Kudalkar AG, Karnik Publishing House—USA; 2011.
HS, Eds. Practical Approach To Anaesthesia For
Emergency Surgery. New Delhi, Mumbai, Panama 10. Ramos CT and Kim PCW. Management of the
City, London: Jaypee Brothers Medical Publishers Neonate: Surgical Considerations. In: Bissonnette
(P) Limited; 2011: PP 345-365. ISBN 978-93-5025- B Ed. Pediatric Anesthesia Basic Principles—State
070-9. of the Art—Future. Shelton, Connecticut: People’s
Medical Publishing House—USA; 2011.
4. Malde AD. Anesthesia for neonate with tracheo-
esophageal fistula. How I do it?” In: RACE 2019 11. Howard RF. Pain Assessment and Management.
(Ramachandra Anesthesia Continuing Education), In: Lerman J Ed.Neonatal Anesthesia. New York,
Chennai, CME book. Springer; 2015: 383-400.
5. Brett CM and Davis PJ. Anesthesia for General 12. Davidson AJ, Nandi R, and Carden SM. Howard
Surgery in the Neonate. In Davis PJ, Cladis FP, Eds. RF. Anesthesia for the Neonate: Neurosurgery
Smith’s Anesthesia for Infants and Children, Ninth and Ophthalmology. In: Lerman J Ed.Neonatal
Edition. Philadelphia: Elsevier Inc; 2017: PP 597- Anesthesia. New York, Springer; 2015: 271-290.
603. 13. Allegaert K, Murat I, Anderson BJ. Not all intravenous
6. Cross K, Smith J, and Walker IA. Thoracoabdominal paracetamol formulations are created equal. Paediatr
and General Surgery. In: Lerman J Ed, Neonatal Anaesth.2007; 17:811–2.
anesthesia. New York Heidelberg Dordrecht London:
Springer; 2015: 232-237.

MCQ
1. Physiological changes in neonate include all except 4. The most common form of TEF is
A. Type E
a. Lesser type 1 respiratory muscle fibre b. Type B
b. Alveolar ventilation is 60ml/kg/min c. Type C
c. Fetal haemoglobin persists till 3 months of life d. Type D
d. Highly compliant chestwall and airway
5. Fluid management in neonates-FALSE statement is
2. Following are the measures to prevent heat loss in
infants except a. Lactated Ringer is the fluid of choice for
intraoperative period
a. Warming the operating room prevent heat loss by b. A minimum haematocrit of 60 % has to be
convection maintained
b. Placing the baby on a warming mattress minimizes c. Use of 10% dextrose is recommended to prevent
heat loss through conduction. hypoglycaemia
c. Humidification of gases reduce heat loss through d. A urine output of 1 to 2 ml/kg/hr indicates adequate
evaporation hydration
d. Heat loss from radiation is decreased by use of
double shelled isolette during transport.
3. The maximum daily dosage of acetaminophen for 28-

32 weeks PCA babies is
a. 10mg/kg
b. 20mg/kg
c. 30mg/kg
d. 40mg/kg
5.B 4.C 3.C 2.A 1.B
ANSWERS:

12 DAMAGE CONTROL RESUSCITATION IN TRAUMA
Professor and Head, Sudarsan K,

GEM Hospital & Research Centre
Coimbatore
Key points
Ø Damage control Resuscitation is the concept which focus on early and aggressive measures to prevent the lethal
triad of Hypothermia, Acidosis and Coagulopathy
Ø It is a systematic approach to the management of the trauma patient with severe injuries that starts in the
emergency room and continues through the operating room and the intensive care unit
Ø Survival risk following trauma is maximum for traumatic brain injury and closely followed by major hemorrhage
and exsanguination
Ø Damage control part zero is the earliest phase of the damage control process which occurs in the pre-hospital
setting and continues into the emergency department
Ø Early blood transfusion and reduced crystalloid administration is advised to prevent dilutional coagulopathy
Ø Balanced transfusion is practiced to prevent consumptive loss of coagulation factors
Ø Permissive hypotension and prevention of hypothermia are very important to prevent further blood loss and
decreases incidence of mortality
Ø Sensitive measures of the adequacy of cellular oxygenation are the base deficit and serum lactate
Ø The main focus of Damage control surgery is rapid control of hemorrhage, and to continue with ongoing
resuscitation
Introduction then specifically linked to patients who were hemorrhaging,

hypothermic, and coagulopathic. This understanding allowed
Massive hemorrhage accounts for nearly 30-40% all fatalities for the first article in 1993 by Rotondo and Schwab specifically
in trauma victims. Statistically speaking, survival risk following adapting the term “damage control”
trauma is maximum for traumatic brain injury and closely
followed by major hemorrhage and exsanguination. Massive Damage control is a U.S. Navy term defined as “The capacity
hemorrhage remains the leading cause of preventable deaths of a ship to absorb damage and maintain mission integrity.”
in major trauma. Damage control resuscitation(DCR) is the
strategy developed to specifically address the conditions that DCR primarily has its origins in the military’s experience of
worsens the outcome following trauma. management of major haemorrhage during recent conflicts
in Afghanistan and Iraq in 2007. When applied to surgery
History and critically ill patients, damage control surgery (DCS)
incorporates fundamentals which include arresting surgical
Surgeons have utilized the concept of damage control hemorrhage, containing gastrointestinal spillage, inserting
surgery for years, and controlling hemorrhage with packing surgical sponges and applying a temporary abdominal
over the bleeding spot is over a century old. Pringle described closure. This sequence is followed by immediate transfer to
this technique in patients with substantial hepatic trauma as the intensive care unit with subsequent re warming, correction
early as initial parts of 20th century. The U.S. military did not of coagulopathy and hemodynamic stabilization. Return to
encourage this during World War II and the Vietnam War. the operating theatre is then pursued 6–48 hours later for
Thereby the war casualties following massive trauma was a planned re-exploration that includes definitive repair and
substantially higher. Subsequent studies were repeated by primary closure if possible. In essence, a typical operative
Feliciano and colleagues in 1981 and they found that hepatic sequence is interrupted by completing only the most crucial
packing increased survival by 90%. This technique was aspects during the first phase.

Damage Control Resuscitation in trauma 138 Sudarsan K
Rationale Essential Components of damage control Resuscitation
Damage control resuscitation (DCR) is a systematic approach 1. Early recognition of the problem
to the management of the trauma patient with severe injuries 2. Early initiation of Massive transfusion protocol including
that starts in the emergency room and continues through the blood product transfusions
operating room and the intensive care unit. 3. Reduced crystalloid fluid administration
4. Permissive hypotension in selected populations
DCR aims to maintain circulating volume, control haemorrhage 5. Immediate hemorrhage control (Damage control surgery
and correct the ‘lethal triad’ of “Coagulopathy, Acidosis and or Angiographic)
Hypothermia” until definitive intervention is undertaken. The 6. Continued Intensive care management in restoring
natural extension of Damage Control Surgery has been blood volume and correcting Coagulopathy, Acidosis
damage control resuscitation (DCR) and Hypothermia.
7. Plan a definitive surgery once stable in 24 to 36 hours.
Indications for Damage Control Resuscitation
Anatomic Parameters Physiologic Parameters Laboratory Parameters
• Estimated Injury severity score >36 • Weak or Absent radial pulse • Lactate >2.5mmol/L
• Penetrating chest/abdominal injury • Core body temperature <35C • Platelet Count <90,000/ml
• Open Pelvic fracture • Syst BP <100mm Hg • Fibrinogen >1g/dl
• Long bone open fracture with head in- • Heart Rate > 100 beats/mt • PT > 16 secs
jury • PaO2/FiO2 < 250 • INR >1.5
• Major Crush injury • Urine output <50ml/hour • Hb < 10
• pH <7.2
• Base deficit <6
Early recognition or Damage Control Part 0 be used early in the resuscitation of bleeding trauma patients.
In CRASH-2 trial, 1g of TXA given as an early bolus followed
It is vital to understand that the initial resuscitation of a by an infusion of 1g over the ensuing 8 hours was associated
bleeding trauma patient can have a tremendous impact with an absolute risk reduction of 1.5%.
on survival. Therefore the early recognition of ongoing
bleeding and prompt decision regarding the sequence of Important elements include
the resuscitation events to follow will have direct implication
on the outcome. P ABC resuscitation
P Permissive hypotension
Damage control part zero is the earliest phase of the damage
P Limitation of crystalloid with early use of blood and blood
control process. It occurs in the pre-hospital setting and
products
continues into the emergency department. The emphasis
is on injury pattern recognition (to identify patients likely to P Early use of Tranexamic Acid (TXA)
benefit from damage control), followed by DCR and rapid Early initiation of Massive Transfusion Protocol
transfer to theatre of identified patients.(2)
DCR focus specifically on restoration of venous return
Blood products and Tranexamic acid (TXA) are increasingly to the right heart before the patient’s physiologic reserve
used in the pre-hospital environment and may be widely is exhausted in concert with expedient correction and
available to paramedic crews in some areas of the UK. subsequent prevention of coagulopathies by hemostatic
Tranexamic acid (TXA) is an anti-fibrinolytic agent that can resuscitation with plasma and platelets.

Massive Transfusion is defined when either fresh frozen plasma (FFP) and platelets in approximately
a 1:1:1 ratio. This is known as balanced transfusion,
1) Total blood volume is replaced within 24 hours, administration of packed red blood cells being balanced
2) 50% of total blood volume is replaced within 3 hours, or with coagulation factor delivery. Without this, dilution
3) Rapid bleeding rate is documented or observed. of coagulation factors will exacerbate consumptive
loss; this has the potential to rapidly result in a spiral
Rapid bleeding rate in adults can be defined as more than of coagulopathy and worsening blood loss. Whilst
4 units of red blood cells (RBCs) transfused within 4 hours such protocols have been found to reduce morbidity
with active major bleeding or more than 150 mL/minute of and mortality, the requirement for such large amounts
blood loss. of clotting products and the exact composition of this
Local protocols will vary but hemostatic resuscitation transfusion regime is difficult to achieve in many of the
aims to deliver a mixture of red blood cells (RBCs), Indian Primary and secondary centers
Stanford Massive Transfusion Protocol 2009
Reproduced with permission from IJA, Vol.58, Issue 5, 2014

Reduced crystalloid fluid administration even when controlling other major problems associated with
trauma.
Although crystalloids have its own significant role in a
bleeding victim, when it comes to a situation where the Hypothermia can be caused by the trauma itself or as a result
individual requires Damage Control Resuscitation, excessive of various resuscitation efforts.
crystalloid administration is associated with hypothermia,
coagulopathy and worst clinical outcome. It is reasonable to Normal central thermoregulation is altered, and the shivering
restrict fluid boluses to patients who lose their radial pulse or response is blocked. At the same time, the metabolic activity
are demonstrating signs of abnormal end-organ perfusion. of tissues begins to slow, resulting in decreased heat
production.
Crystalloids can cause a dilutional coagulopathy and do little
for the oxygen carrying capacity needed to correct anaerobic During early resuscitation efforts massive transfusion of cold
metabolism and the oxygen debt associated with shock. IV fluids was found to be one of the major offenders. Also
The use of room temperature or cold IV fluids can also be during the efforts of Damage control Surgery there remains
implicated as a major cause for hypothermia. Also, because plenty of opportunity to lose core body temperature from
of its higher concentration of chloride, crystalloids have been open abdomen during laparotomy.
associated with hyperchloremic acidosis and the worsening Hypothermia worsens coagulation abnormalities through
of trauma patient’s existing acidosis. several mechanisms. The early coagulopathy of trauma is a
As a result of the pathologic changes associated with trauma, well-recognized entity that is present at the time of admission
capillary permeability increases causing a loss of osmotic in more than 25% of injured patients with a base deficit
pressure and a loss of fluid to the interstitial and intracellular greater than 6.
space. Isotonic, hypotonic, and colloid solutions given post The possible mechanisms worsening coagulopathy following
injury have been shown to leak and cause edema with only hypothermia include
a fraction remaining within the intravascular system. This
fluid shift can have profound systemic consequences adding 1) Direct action on platelets decreasing the responsive-
further insult to organs already compromised by the initial ness of trauma induced platelet activation
injury. 2) Induces reversible platelet sequestration in liver and
spleen
One interesting option for maintaining limited volume
resuscitation is hypertonic saline (HTS), which has been a 3) Disturbances in enzyme activity thereby reducing the
research focus for resuscitation efforts for several decades. activity of enzyme related clotting factors XI and XII.
4) Hypothermia alters fibrinolysis and decreases Throm-
Permissive hypotension boxane B2 production.
The concept of permissive hypotension is to keep the blood Therefore, the effect of hypothermia on coagulation
pressure low enough to avoid exacerbating haemorrhage takes place through several distinct mechanisms. Thus
by hydrostatic clot disruption whilst maintaining adequate hypothermia related coagulopathy is difficult to treat with
end organ perfusion. Permissive hypotension and restrictive standard resuscitation techniques.
fluid administration are therefore reciprocal components
of this approach. initial fluid administration is delayed or Several active re-warming techniques have been attempted
minimized and, less aggressive resuscitative end points are with varied success rates which include, forced air warmers,
used. In practical terms, this means targeting systolic blood heating blankets, body cavity lavage with warm fluids, warm
pressures of 70–90 or 50 mmHg mean arterial pressure. IV fluids, and blood warmers.
This approximately equates to aiming for the restoration of
Acidosis
a palpable radial pulse. Such an approach decreases both
the severity and incidence of dilutional coagulopathy, and as Metabolic acidosis is the predominant defect resulting from
such compliments a strategy of haemostatic resuscitation. persistent hypoperfusion. The systemic effects of acidosis
worsen the myocardial performance of already compromised
Prevention of Hypothermia
cardiovascular system. Acidosis below 7.2 is associated with
In general, prognosis is directly related to the degree of grossly reduced myocardial contractility and cardiac output,
hypothermia, with a 100% mortality observed in patients resulting in worsening of hypotension, bradycardia, cardiac
who present with a core body temperature under 32.8°C, arrhythmias, and hypoperfusion to liver and spleen. Acidosis

acts synergistically along with hypothermia in worsening the Summary
coagulation abnormality thereby posing significant problems
in bleeding trauma victim. Damage control Resuscitation is the concept adapted from
U.S. Navy services which focus on early and aggressive
Serum Lactate and Base deficit measures to prevent the lethal triad of Hypothermia, Acidosis
and Coagulopathy. This strategy starts well in advance
Sensitive measures of the adequacy of cellular oxygenation from the time of transfer at the site of injury then continues
are the base deficit and serum lactate. The base deficit is through the Emergency department, Operating Department,
a measure of the number of millimoles of base required to Intensive care unit until resuscitation is complete and the
correct the pH of a liter of whole blood to 7.40, and its normal victim is stabilized. Although this strategy has immense scope
value is -3 to +3. This determination is readily available as it for further study and refinement but shows great promise in
can be measured on a blood gas analysis, and base deficit outcome for major trauma victims.
is a useful guide to the adequacy of resuscitation efforts in
the early stages. References
Serum Lactate is a byproduct of anaerobic metabolism and a 1). Chad.G.Ball, MD.,M.Sc., Damage control resuscitation:
fairly specific marker for tissue hypoperfusion. It has a shorter history, theory and technique, Can J Surg, Vol. 57 , No.
half life of around 3 hours. Serial measurements of lactate 1, February 2014
offer better prognostic value for resuscitation than an isolated
value. The drawbacks include: the delay in processing the 2). C. M. Lamb, P. MacGoey, A. P. Navarro and A. J. Brooks,
result values and need to take the sample from central vein Damage control surgery in the era of damage control
or arterial line to obtain more reliable result. It is also useful resuscitation; BritishJournalof Anaesthesia113(2):
to remember that the values would normally be higher in 242–9(2014)
patients with cirrhosis or other major liver diseases. 3). M. Giannoudi • P. Harwood; Damage control
Damage Control Surgery resuscitation: lessons learned; Eur J Trauma Emerg
Surg (2016) 42:273–282
The main focus of Damage control surgery is rapid control
of hemorrhage, and to continue with ongoing resuscitation. 4). Juan C. Duchesne, MD, FACS, FCCP, Norman E.
Minimal surgical intervention should include short surgical McSwain, Jr., MD, FACS, Bryan A. Cotton, MD, FACS,
hemostasis procedures. John P. Hunt, MD, MPH, FACS, Jeff Dellavolpe, MD,
Kelly Lafaro, MD, MPH, Alan B. Marr, MD, FACS,
Other important factors to consider include prevention of Damage Control Resuscitation: The New Face of
hypothermia, containment of spillage of gastrointestinal Damage Control; The Journal of TRAUMA® Injury,
and uro genital contents in to the peritoneum. Once surgical Infection, and Critical Care • Volume 69, Number 4,
haemostasis is achieved, patient should be transferred back October 2010
to intensive care unit to continue further resuscitation and
prevention of the hypothermia, acidosis and coagulopathy.

Damage Control Resuscitation 142 Sudarsan K
MCQ
1. Not a component of damage control resuscitation 4. Not a Cause of hypothermia in a bleeding trauma victim
a) Early initiation of massive transfusion protocol a) Alteration of Central thermoregulation

b) Increased administration of intravenous fluids b) Shivering response is affected
c) Permissive hypotension in selected populations c) Resuscitation with cold IV fluids
d) Immediate hemorrhage control d) Coagulopathy
2. Lethal triad does not include 5. Systemic effects of metabolic acidosis include
a) Hypothermia
b) Hypovolemia a) Hypotension
c) Acidosis b) Worsening coagulopathy
d) Coagulopathy c) Bradycardia
d) All of the above
3. Initial resuscitation of a bleeding trauma victim occurs in
a) Pre-hospital setting
b) Emergency room
c) Triage room
d) Operation room
5.D 4.D 3.A 2.B 1.B
ANSWERS:

FOCUS SESSIONS
13 PERIOPERATIVE PHARMACOLOGICAL RISK REDUCTION STRATEGIES IN
PATIENTS WITH MYOCARDIAL INFARCTION
Professor and HOD Ranjith B Karthekeyan

Department of Cardiac Anesthesiology
SRIHER
Key points
Ø Perioperative myocardial infarction occurs in up to 6.2% of surgeries

Ø There are 2 distinct identities responsible for the development of myocardial ischemia: the first is acute coronary
syndrome and the second is as a result of prolonged myocardial oxygen supply-demand imbalance in the presence
of stable CAD
Ø The major determinants of myocardial oxygen consumption are myocardial contractility and ventricular wall
tension
Ø Beta blockers and statins are to be continued on the day of surgery in patients who are already on treatment
Ø Continuation of P2Y12 inhibitor treatment should be considered for 4 weeks after BMS implantation and for 3–12
months after DES implantation, unless the risk of life-threatening surgical bleeding on this agent is unacceptably
high
Ø Diuretics for hypertension should be continued to the day of surgery and resumed orally when possible
Introduction acute coronary syndrome (ACS), also known as Type 1

myocardial infarction (MI), and the second is as a result of
Perioperative cardiovascular complications are a source of prolonged myocardial oxygen supply-demand imbalance in
morbidity and mortality for more than 200 million patients the presence of stable CAD (Type 2 MI) – the presentation
worldwide who undergo non-cardiac surgery each year. and determinants of which is given below (Figure 1).
In large cohorts and randomized trials, perioperative
myocardial infarction (MI) occurs in up to 6.2% of surgeries. Induction of anesthesia, surgical trauma, bleeding,
In addition, patients with ischemic heart disease undergoing anemia, hypoxia, and post-operative pain lead to surges in
noncardiac surgery are at an increased risk for perioperative catecholamines, cortisol production, and a hypercoaguable
myocardial complications including perioperative ischemia, state. Tachycardia and elevations in blood pressure
infarction, cardiac failure and dysrhythmias, all associated increase coronary artery sheer stress and can precipitate
with increased morbidity and mortality. coronary plaque destabilization, plaque rupture, coronary
thrombosis, and Type 1 MI. Imbalances in myocardial
The number of patients with coronary artery disease oxygen supply and demand from tachycardia, hypotension,
(CAD), who are on medical treatment or have already hypoxia, or anemia in the setting of stable CAD leads to
undergone stent placement or a coronary artery bypass Type 2 MI. (1,2)
graft and require surgery, is on the rise. The degree of the
As shown in figure 1, the major determinants of myocardial
coronary occlusion, the volume of the affected ischemic
oxygen consumption are myocardial contractility and
myocardium, extent of collateral circulation, pre-existing
ventricular wall tension and the myocardial oxygen delivery
myocardial metabolic rate, genetic factors, and the intrinsic
equals the product of arterial oxygen content and coronary
survival capacities of the myocytes collectively determine
blood flow.
the specific clinical presentation of myocardial ischemia.
The pharmacological agents used perioperatively act on
Pathophysiology the varied determinants as above and help in optimizing the
supply-demand ratio to the ischemic myocardium.
The pathogenesis of cardiovascular events in the operative
period is complex .There are 2 distinct identities responsible Varied practices across institutions is being carried out
for the development of myocardial ischemia: the first is on starting and discontinuing of drugs perioperatively.

Perioperative pharmacological risk reduction 146 Ranjith B Karthekeyan
strategies in patients with myocardial infarction
However the recommendations and best medical practices • Initiating beta blockers in the perioperative setting
are mentioned below. as an approach to reduce perioperative risk is of
uncertain benefit in those with a long-term indication
Recommendations on perioperative therapy – with focus but no other RCRI risk factors (IIb)
on drugs and pharmacological aspects (3- 5).
• It may be reasonable to begin perioperative beta
The points below are a summary and taken from the blockers long enough in advance to assess safety
clinical practice guideline of the AHA and ESC/ESA. The and tolerability, preferably >1 d before surgery (IIb)
class of recommendation for the following is written within
parenthesis. • Beta-blocker therapy should not be started on the
day of surgery (III).
Beta blockers
ESC recommendation
ACC AHA recommendation
• Peri-operative continuation of betablockers is
• Beta blockers to be continued in patients who are recommended in patients currently receiving
on treatment (I b) medication (I)
• Management of beta blockers therapy after surgery • Pre-operative initiation of betablockers may be
must be done by clinical circumstances (IIa). In considered in patients scheduled for high-risk
patients with intermediate- or high-risk preoperative surgery and who have 2 (or more) clinical risk
tests, it may be reasonable to begin beta blockers factors or ASA status ≥ 3 (IIb)
(IIb)
• Pre-operative initiation of betablockers may be
• In patients with more than 3 RCRI factors, it may be considered in patients who have known IHD or
reasonable to begin beta blockers before surgery myocardial ischaemia (IIb)
(IIb)

• When oral beta-blockade is initiated in patients who • If ACE inhibitors or ARBs are held before surgery, it
undergo non-cardiac surgery, the use of atenolol or is reasonable to restart as soon as clinically feasible
bisoprolol as a first choice may be considered (IIb) postoperatively (IIa)
• Initiation of peri-operative high dose beta-blockers ESC recommendation

without titration is not recommended (III)
• Continuation of ACEIs or ARBs, under close
• Pre-operative initiation of betablockers is not monitoring, should be considered during non-
recommended in patients scheduled for low-risk cardiac surgery in stable patients with heart failure
surgery(III) and LV systolic dysfunction (IIa)
Perioperative statin therapy • Initiation of ACEIs or ARBs should be considered

at least 1 week before surgery in cardiac-
ACC AHA recommendation
stable patients with heart failure and LV systolic
• Continue statins in patients currently taking the dysfunction (IIa)
drug (I B)
• Transient discontinuation of ACEIs or ARBs before
• Perioperative initiation of statin use is reasonable in non-cardiac surgery in hypertensive patients should
patients undergoing vascular surgery (IIa) be considered (IIa)
• Perioperative initiation of statins may be considered Antiplatelet agents

in patients with a clinical risk factor who are
undergoing elevated-risk procedures (IIb) AHA
ESC recommendation • Continue dual antiplatelet therapy (DAPT) in

patients undergoing urgent noncardiac surgery
• Peri-operative continuation of statins is
recommended, favouring statins with a long half- during the first 4 to 6 weeks after BMS or DES
life or extended-release formulation (I) implantation, unless the risk of bleeding outweighs
the benefit of stent thrombosis prevention (I)
• Pre-operative initiation of statin therapy should be
considered in patients undergoing vascular surgery, • In patients with stents undergoing surgery that
ideally at least 2 weeks before surgery (IIa) requires discontinuation of P2Y12 inhibitors, continue
aspirin and restart the P2Y12 platelet receptor–
Alpha-2 agonists
inhibitor as soon as possible after surgery (I)
AHA
• Management of perioperative antiplatelet therapy
• Alpha-2 agonists are not recommended for
should be determined by consensus of treating
prevention of cardiac events (III).
clinicians and the patient (I)
ESC
• In patients undergoing nonemergency/nonurgent
• Alpha2 receptor agonists reduce post-ganglionic
noncardiac surgery without prior coronary stenting,
noradrenaline output and might therefore reduce
it may be reasonable to continue aspirin when the
the catecholamine surge during surgery. In the
risk of increased cardiac events outweighs the risk
international Peri-Operative Ischemic Evaluation
of increased bleeding (II)
2 (POISE-2) trial, clonidine increased the risk of
clinically important hypotension and non-fatal • Initiation or continuation of aspirin is not beneficial
cardiac arrest. Therefore, alpha 2 receptor agonists in patients undergoing elective noncardiac non
should not be administered to patients undergoing carotid surgery who have not had previous coronary
non-cardiac surgery. stenting (III)
ACE inhibitors
ESC
ACC/ AHA recommendation
• It is recommended that aspirin be continued for
• Continuation of ACE inhibitors or ARBs is
4 weeks after BMS implantation and for 3–12
reasonable perioperatively (IIa)

months after DES implantation, unless the risk the continuation or introduction of heart rate-
of life-threatening surgical bleeding on aspirin is reducing calcium channel blockers may be
unacceptably high (I) considered in patients who do not tolerate beta-
blockers
• Continuation of aspirin, in patients previously thus
treated, may be considered in the perioperative • Calcium channel blockers should be continued
period, and should be based on an individual during non-cardiac surgery in patients with
decision that depends on the perioperative vasospastic angina.
bleeding risk, weighed against the risk of thrombotic
complications (IIb)B Diuretics
• Discontinuation of aspirin therapy, in patients • Diuretics for hypertension should be continued to the
previously treated with it, should be considered in day of surgery and resumed orally when possible.
those in whom haemostasis is anticipated to be If blood pressure reduction is required before oral
difficult to control during surgery (IIa)B therapy can be continued, other antihypertensive
agents may be considered
• Continuation of P2Y12 inhibitor treatment should
be considered for 4 weeks after BMS implantation • In heart failure, dosage increase should be
and for 3–12 months after DES implantation, unless considered if symptoms or signs of fluid retention are
the risk of life-threatening surgical bleeding on this present. Dosage reduction should be considered
agent is unacceptably high C in patients with hypovolaemia, hypotension, or
• In patients treated with P2Y12 inhibitors, who need electrolyte disturbances.
to undergo surgery, postponing surgery for at least 5 • Diuretic treatment, if necessary to control heart
days after cessation of ticagrelor and clopidogrel— failure should be continued to the day of surgery and
and for 7 days in the case of prasugrel—if clinically resumed orally when possible. In the perioperative
feasible,should be considered unless the patient is period, volume status in patients with heart failure
at high risk of an ischemic event(IIa) should be monitored carefully and optimized by
Role of Nitrates loop diuretics or fluids.
Nitroglycerine is well known for reversing myocardial • Special attention should be given to patients
ischaemia. The effect of perioperative intravenous nitroglycerine taking diuretics and patients prone to developing
on perioperative ischaemia is a debate and no effect arrhythmias. Any electrolyte disturbance especially
has been demonstrated on the incidence of myocardial hypokalemia and hypomagnesaemia should be
infarction or cardiac death. Also perioperative use of corrected in due time before surgery. Acute pre-
nitroglycerine may pose a significant haemodynamic risk to operative repletion in asymptomatic patients may
patients, since decreased pre-load may lead to tachycardia be associated with more risks than benefits. Thus,
and hypotension. minor asymptomatic electrolyte disturbances
should not delay acute surgery.
Calcium Channel Blockers
Novel approaches to reduce perioperative cardiovascular
• The effect of calcium channel blockers on the events in high-risk patients and to manage patients who
balance between myocardial oxygen supply and develop post-operative myocardial injury are currently
demand makes them theoretically suitable for risk- being studied. Intensive medical management prior to non-
reduction strategies. It is necessary to distinguish cardiac surgery has shown to reduce cardiovascular events.
between dihydropyridines, which do not act directly However, ongoing trials have to refine our understanding
on heart rate, and diltiazem or verapamil, which of perioperative cardiovascular events and determine
lower the heart rate. Although heart rate-reducing management of myocardial injury after non-cardiac surgery.
calcium channel blockers are not indicated in Ongoing studies and treatment strategies are mentioned in
patients with heart failure and systolic dysfunction, Table 1 (6).

High Intensity Statin Lowering the Risk of Operative Complications Using Atorvastatin Loading
Dose (LOAD) (NCT01543555)
Ranolazine Pathophysiology and Prevention of Perioperative Myocardial Injury
Ischemic Preconditioning Preconditioning Shields Against Vascular Events in Surgery (SAVES)
Prevention of Myocardial Injury in Non-cardiac Surgery (PIXIE)
Combination Therapy (ACEi, Beta- Optimization of Pre-surgical Testing With an Intensive Multifactorial
Blocker, Statin) Intervention to Minimize Cardiovascular Events in Orthopedic Surgery
Post-operative Management of Perioperative Cardiovascular Events
Ticagrelor Study of Ticagrelor Versus Aspirin Treatment in Patients With Myocardial
Injury Post Major Non-cardiac Surgery (INTREPID)
Dabigatran Management of Myocardial Injury After Noncardiac Surgery Trial (MANAGE)
Table 1: Studies on Prevention of Perioperative Cardiovascular Events
Conclusion 3. Fleisher, L. A., Fleischmann, K. E., Auerbach, A. D.,

Barnason, S. A., Beckman, J. A., Bozkurt, B., et al.
Perioperative myocardial ischaemia is an important entity (2015). 2014 ACC/AHA guideline on perioperative
with prognostic implications. Preoperatively, patients cardiovascular evaluation and management of
should have their perioperative risk stratified and optimised patients undergoing noncardiac surgery JACC Vol .
when time permits. Intraoperative management consists 64e 77- 137.
of appropriate monitoring and anaesthetic technique,
preventing myocardial oxygen supply-demand imbalances 4. Kristensen, S. D., Knuuti, J., Saraste, A., Anker, S.,
and follow risk reduction strategies. Bøtker, H. E., De Hert, S., Ford, I., et al. (2014). 2014 ESC/
ESA Guidelines on non-cardiac surgery: Cardiovascular
References assessment and management. European Journal of
1. Smit, M., Coetzee, A. R., & Lochner, A. (2019). Anaesthesiology, 31(10), 517–573.
The Pathophysiology of Myocardial Ischemia and 5. Priebe, H.-J. (2011). Preoperative cardiac
Perioperative Myocardial Infarction. Journal of management of the patient for non-cardiac surgery:
Cardiothoracic and Vascular Anesthesia. An individualized and evidence-based approach.
2. Sellers, D., Srinivas, C., & Djaiani, G. (2018). British Journal of Anaesthesia, 107(1), 83–96.
Cardiovascular complications after non-cardiac 6. Smilowitz, N. R., & Berger, J. S. (2016). Perioperative
surgery. Anaesthesia, 73 Suppl 1, 34–42. Management to Reduce Cardiovascular Events.
Circulation, 133(11), 1125–1130.

MCQ
1) Major determinants of myocardial oxygen consumption 4) Following is true regarding diuretics except
are
a) Diuretics for hypertension should be continued to
a) Myocardial contractility and preload the day of surgery
b) Myocardial contractility and afterload b) Dosage need not be changed in heart failure if signs
c) Myocardial contractility and ventricular wall tension of fluid overload are present
d) Myocardial contractility and hear rate c) Hypokalemia and hypomagnesaemia should be
corrected
2) Recommendation on Preoperative therapy are true d) Volume status in heart failure should be monitored
except carefully and optimised
a) Beta blockers to be continued in those who are on 5) Recommendation for antiplatelets

treatment
b ) In patients with more than 3 RCRI factors a) To continue dual antiplatelets in patients undergoing
reasonable to start beta blockers on day of surgery urgent non cardiac surgery during the first 4-6 wks
b) Reasonable to begin perioperative beta blockers after BMS or DES
earlier b) In those with stents, undergoing surgery requiring
d) Beta blockers should not be started on the day of discontinuation of P2Y12 inhibitors, aspirin too can
surgery be withheld
c) In patients undergoing non emergency surgery
3) Following is true regarding role of nitrates except without prior coronary stenting, its advisable to
continue aspirin.
a) Effect of periop nitroglycerine on periop ischemia is d) Initiation or continuation of aspirin is not beneficial in
a debate those undergoing elective non cardiac non carotid
b) No effect has been demonstrated on the incidence surgery without prior history of stenting.
of myocardial infarction
c) Periop use of nitroglycerine does not pose any
haemodynamic risk
d) Well known for reversing myocardial ischemia
5.B 4.B 3.C 2.B 1.C
ANSWERS:

14 HISTORY OF DEVELOPMENT OF ANESTHESIA PRACTICE
Associate Professor of Anesthesia David B Waisel

Harvard Medical School
Boston
Goals with public health services in which the physician practice of

anesthesiology is respected.
1) To articulate common problems faced by the develop-
ment of the profession of anesthesiology in a country Inadequate ability to participate in the professional
or medical system. atmosphere of physicians (committee work, professional
societies etc) because of time or prejudice reinforces an
2) To understand how these common problems were unfair reputation.
overcome or exacerbated by attempts to resolve these
problems in the United States. Other nations faced similar problems as they developed.
This lecture will look at the problems anesthesiologists face
The medical practice of anesthesia has developed into a when developing professional status and how these issues
respected specialty for physicians in a number of countries were wisely or poorly addressed in the United States.5 These
over the past 90 years. In some areas, however, this difficulties were in part addressed by development of powerful
development is ongoing. It has been suggested that Indian training programs, opportunities to show surgeons what a
anesthesiologists have not received the professional and physician anesthesiologist could do, particularly in war time,
financial respect they deserve.1,2 Studies report 17%-20% changes in practice, and remuneration requirements, and
of Indian anesthesiologists being unsatisfied with their successful interactions with the state in terms of regulations.
profession.3,4
References
One of the primary issues is that a growing profession is
often judged by its weakest members, not its strongest. • Kar Sk. Social conditions and compromises bone by
That is to say, medical students, nurses, surgeons etc anesthesiologists in India. Diversity and Equality in
judge the profession by rare slipshod and undedicated Health and Care 2016;13(3): 215-215.
anesthesiologists with the bare minimum of education who is
• Kapoor MC. Empowering anesthesiologists. J
trying to make money and not by a dedicated and honorable
Anaesthesiol Clin Pharmacol 2015;31(3): 291–292.
anesthesiologist, who prioritizes their patient by holding
themselves to the highest standards of education, patient • Shetti AN, Karigar SL, Mustilwar RG. Assessment of
advocacy and professional care. job satisfaction dn qualify of lie among practicing Indian
anesthesiologists. Anesth Essays R 2018;12(2): 302-8.
Another common problem is lack of rigor and oversight
by sanctioning bodies of training programs or individual • Bakshi SG et al. Work-related stress: A surgery of
physicians. Inadequate oversight and rigor help create a Indian anesthesiologists. Anaesthesiol Clin Pharmacol
poor reputation for anesthesiologists. 2017;33(1): 86–91.
• Waisel DB. The role of World War II and the European
Other problems include remuneration patterns such as, who
Theatre of Operations in the
pays the anesthesiologist (insurance, hospital, surgeon,
patient), how fees are determined, and how much they get • development of anesthesiology as a physician specialty
paid. Inequities still exist in private insurances in countries in the USA. Anesthesiology 2001;94:907-14.

15 DEXMEDETOMIDINE IN NORA
Associate Professor of Anesthesia Keira Mason

Harvard Medical School
Boston
Dexmedetomidine (DEX) is a selective alpha 2 agonist prolong analgesia, increase the sensory blockade and
which binds to the alpha 2 receptor with a 1600 time affinity spare additional motor blockade. In children, DEX, although
over the alpha1 receptor. Approved by the Food and not approved, can be used with success for sedation for
Drug Administration in 1999 for no longer than 24 hour radiological imaging studies.
administration to intubated adults, it was later approved in
2010 for adult sedation in areas outside the operating room At higher doses, bradycardia, hypotension and hypertension
and intensive care unit (ICU). Recently approved in Europe should be anticipated. The hemodynamic fluctuations
for adult sedation in the ICU only, DEX may offer the following with high dose DEX are related to the biphasic effect of
benefits in the ICU:
DEX- with drops in blood pressure at serum concentrations
• Decreased agitation as compared to benzodiazepine less than 1 mcg/liter and elevations in blood pressure with
induced sedation serum concentrations above 1 mcg/liter. These shifts, in
the literature, have been shown to be largely of no clinical
• Decreased mortality in the intubated post-coronary
significance as they have not necessitated pharmacologic
artery bypass graft (CABG) patient
intervention. DEX is a unique sedative because it does
• Decreased intubation days as compared to not affect the medulla, conferring sedation via the locus
benzodiazepine sedation ceruleus, triggering the natural sleep pathway. Studies have
• Improved hemodynamic stability as compared demonstrated that DEX simulates Stage 2 and 3 of Non-
to narcotic or benzodiazepine sedation following Rapid Eye Movement Sleep. It has been shown to be useful
CABG surgery. The hemodynamic stability following for providing sedation for electroencephalograms, preserving
CABG surgery is likely due to the observed spike activity in a natural sleep state. Animal models suggest
decrease of up to 70% serum norepinephrine and that DEX may spare apoptosis. Definitive studies in humans
epinephrine levels with low doses of DEX. have not been done, although an ICU study on the intubated
DEX has also been used for regional anesthesia, with brain injured adult has demonstrated that DEX may preserve
meta-analysis suggesting that epidural administration can cognitive function more than propofol.

16 SEPSIS - CURRENT UPDATE
Associate in Anesthesiology & Critical Care Medicine Chinyere Egbuta

Boston Children’s Hospital
 The Surviving Sepsis Campaign published their for difference in ICU length of stay (LOS) (mean
initial clinical practice guidelines for the management difference –1.51 days; 95% CI, –3.65 to 0.62; low
of severe sepsis and septic shock in 2004. quality).
 Updated versions of the guidelines were published  Performance improvement efforts for sepsis are
in 2008, 2012 and most recently in 2016 following associated with improved patient outcomes. Sepsis
the convening of the Third International Consensus performance improvement programs should optimally
Definitions Task Force (SEPSIS-3) assembled by have multi-professional representation. Successful
the SCCM and the European Society of Intensive programs should include, protocol development and
Care Medicine. implementation, targeted metrics to be evaluated,
data collection, and ongoing feedback to facilitate
 In the 2016 guidelines, SEPSIS is redefined by the continuous performance improvement.
taskforce as:
 Sepsis Screening = Earlier Recognition of Sepsis
A life-threatening organ dysfunction caused by a =Timely Therapy
dysregulated host response to infection.
*Sepsis screening has been associated with
 Resuscitation from sepsis-induced hypoperfusion, at decreased mortality in several studies.
least 30 mL/kg of IV crystalloid fluid be given within
the first 3 hours (strong recommendation, low quality  Diagnosis: Appropriate routine microbiologic
of evidence). cultures (including blood) should be obtained
before starting antimicrobial therapy in patients
 After initial fluid resuscitation, additional fluids with suspected sepsis or septic shock ONLY if
should be guided by frequent reassessment of doing so, results in no substantial delay in the start
hemodynamic status of antimicrobials.
 Reassessment: Heart rate, blood pressure, arterial  Treatment: Administration of IV antimicrobials should
oxygen saturation, respiratory rate, temperature, be initiated as soon as possible after recognition
urine output, and others; as well as other and within one hour for both sepsis and septic
noninvasive or invasive monitoring, as available. shock.
 MAP: Targeting a MAP of 65 versus 85, showed no *Empiric broad-spectrum therapy with one or
difference in mortality but did show an increase in more antimicrobials for patients presenting
arrhythmias with targeting a MAP of 85. with sepsis or septic shock to cover all likely
pathogens (Bacterial, Fungal, Viral).
 CVP: A static measurement of CVP could not help
predict response to fluid challenge. *Narrow once, pathogen identification and
sensitivities are established and/or adequate
 Lactate: Five randomized controlled trials
clinical improvement is noted.
(647 patients) have evaluated lactate-guided
resuscitation of patients with septic shock. A *The guidelines recommend against sustained
significant reduction in mortality was seen in lactate- systemic antimicrobial prophylaxis in patients with
guided resuscitation compared to resuscitation severe inflammatory states of noninfectious origin
without lactate monitoring (RR 0.67; 95% CI, (e.g., severe pancreatitis, burn injury).
0.53–0.84; low quality). There was no evidence

Sepsis - Current Update 156 Chinyere Egbuta
*A systemic inflammatory response without infection  THIAMINE: Cofactor for metabolism of branch
does not mandate antimicrobial therapy. chained amino acids
*Combination therapy (using at least two antibiotics  Mitochondrial synthesis of ATP

of different antimicrobial classes) aimed at the  Glucose metabolism to pyruvate
most likely bacterial pathogen(s) for the initial
 Coenzyme that promotes oxidation of glyoxylate
management of septic shock is not recommended.
to carbon dioxide – prevents oxalate crystallization
 Biomarkers: The use of galactomannan and from Vitamin C metabolism
D-glucan to assist in the assessment of invasive  SEPSIS COCKTAIL: Hydrocortisone, Vitamin C
aspergillus (and a broad range of fungal pathogens) and Thiamine for the Treatment of severe Sepsis
has become well accepted. and Septic Shock.
*Measurement of serum procalcitonin is commonly  Retrospective before-after study

used in many parts of the world to assist in the  Mortality: 8.5% treatment group verse 40.4%
diagnosis of acute infection and to help define the control
duration of antimicrobial therapy.
 SOFA score: No patients in treatment group
*It is important to note that procalcitonin and all developed progressive organ failure
other biomarkers can provide only supportive and
 Decreased duration of vasopressor use: 18.3 +/-
supplemental data to clinical assessment.
9.8 hours in treatment group versus 54.9 +/- 28.4
*Decisions on initiating, altering, or hours
discontinuing antimicrobial therapy should  Treatment with combination decreases mortality
never be made solely on the basis of changes and organ dysfunction.
in any biomarker, including procalcitonin.
The Surviving Sepsis Campaign Bundle: 2018 Update
 Source Control: A specific anatomic diagnosis Hour-1 Bundle
of infection requiring emergent source control
should be identified or excluded as rapidly as  Measure lactate level. Re-measure if initial lactate
possible in patients with sepsis or septic shock, > 2mmol/L.
and that any required source control intervention
 Obtain blood cultures prior to administration of
should be implemented as quickly as possible.
antibiotics.
***HOT TOPICS
 Administer broad-spectrum antibiotic.
 VITAMIN C:
 Begin rapid administration of 30 ml/Kg crystalloid
 Cofactor for synthesis of norepinephrine, dopamine, for hypotension or lactate > 4 mmol/L.
vasopressin, cortisol
 Apply vasopressors if patient is hypotensive during
 May increase vasomotor responsiveness or after fluid resuscitation to maintain MAP > 65
 Preserves endothelial barrier and microcirculation mm Hg.
 Increases host defenses by improving macrophage
and T-cell function.

Sepsis - Current Update 157 Chinyere Egbuta
SEPSIS 3 SUMMARY:
https://pulmccm.org/critical-care-review/2016-surviving-sepsis-guidelines/ By: Jon-Emile S. Kenny

17 TRAUMATIC BRAIN INJURY - DOGMA & CONTROVERSIES
Professor Padmaja Durga

Nizam’s Institute of Medical Sciences,
Hyderabad
Key points
Ø Traumatic brain injury (TBI) is among the most common among serious, disabling neurological disorders
Ø Various classifications of TBI severity such as the Glasgow Coma Scale (GCS), the Abbreviated Injury Severity
Scale (AIS)4 and Full Outline of UnResponsiveness (FOUR) Scale have been introduced based on studies.
Assessment of severity should include the extent of pathophysiological damage and anticipated course of
recovery.
Ø During pre-hospital management, airway status, breathing and circulation should be addressed first. Hypotension
and hypoxia must be corrected to prevent secondary injury.
Ø Current recommendations do not support ICP directed measures in the field, except for hyperventilation in the
intubated patient.
Ø Emergency room management include ATLS protocol, fluid resuscitation and neurological assessment including
necessary investigations.
Ø The goals of monitoring in TBI is to identify adverse physiological changes and prevent secondary cerebral
ischemia.
Ø ICP monitoring has become a mainstay in the critical care management of patients with severe TBI. ICP/CPP
monitoring is important to maintain the cerebral blood flow.
Ø Operative therapy is indicated in patients where intra cerebral collections exert significant mass effect.
Ventriculostomy insertion is the ICP monitoring procedure of choice in adults with severe TBI. Surgical management
for ICP is controversial.
Ø Non-pharmacological methods include head elevation, prophylactic hypothermia, and airway management and
pharmacological methods include hyperosmolar solutions.
Ø Outcome assessment tools are designed to provide a global index of outcome, [e.g. Glasgow Outcome Scale
(GOS), Glasgow Outcome Scale-extended (GOS-E) , Disability Rating Scale (DRS).
Introduction primary and secondary injury, with secondary injury involving

complex biochemical cascades that lead to oxidative injury,
Traumatic brain injury (TBI) is among the most common
excitotoxicity, inflammation, cellular necrosis and apoptosis
among serious, disabling neurological disorders. The
resulting in loss of cerebral blood flow autoregulation and
consequences of trauma to the brain may result in a wide
variety of pathophysiological effects, a range of severities, and brain swelling.1 The pathophysiological changes following
a multitude of problems. It is a complex disease involving both Traumatic brain injury are summarized in table 1 below.

Traumatic brain injury - Dogma & controversies 160 Padmaja Durga
Physiological Parameter Pathophysiological Change with TBI
Cerebrovascular Changes
Cerebral Blood Flow Increased initially, then decreased
Cerebrovascular autoregulation and Autoregulation impaired

CO2-reactivity CO2-reactivity impaired in severe trauma
Cerebral vasospasm Hypoperfusion
Blood Brain Barrier BBB leakage leads to edema
Cellular injury Cerebral edema, apoptosis, necrosis, cortical spreading

depolarization
Cellular Changes
Neurochemical changes Raised intracellular [K+], calcium (Ca2+) accumulation
Cerebral glucose metabolism Initial rapid increase in glucose uptake followed by a prolonged period
of glucose metabolic depression
Energy Crisis
Free Radicals Membrane damage, inhibit glycolytic processing of glucose,

decreased ATP production
Excitotoxicity Ca2+, Na+, and K+ fluxes, increases Na+/K+-ATPase activity, blood–

brain barrier breakdown
Inflammation Obliteration of microvasculature, blood–brain barrier impairment,

edema formation
Mitochondrial dysfunction Depletion of NAD+ stores and activation of both apoptotic and
necrotic pathways, ultimately resulting in cell death
Table 1: Summary of Pathophysiological changes following TBI
Severity Scale (AIS)4 and Full Outline of UnResponsiveness (FOUR)

Scale5(Table 2) The ordinal categories of these severity
TBI severity refers to the amount of acute disruption of brain scales are sometimes combined into the broader categories
physiology or structure. Epidemiologic studies have used of mild (or minor), moderate, and severe TBI.6 Assessment
various classifications of TBI severity, such as the Glasgow of severity helps to predict the course and eventual outcome
Coma Scale (GCS),2, 3 the Abbreviated Injury Severity of the injury.

Glasgow Coma Scale (GCS)

Eye Response
4 = eyes open spontaneously
3 = eye opening to verbal command
2 = eye opening to pain
1 = no eye opening.
Motor Response
6 = obeying commands
5 = localizing pain
4 = withdrawal from pain
3 = flexion response to pain
2 = extension response to pain
1 = no motor response.
Verbal Response
5 = oriented
4 = confused
3 = inappropriate words
2 = incomprehensible sounds
1 = no verbal response.
Full Outline of UnResponsiveness (FOUR) Scale

Eye Response
4 = eyelids open or opened, tracking, or blinking to command
3 = eyelids open but no tracking
2 = eyelids closed but opens to loud voice
1 = eyelids closed but opens to pain
0 = eyelids remain closed to pain stimuli.
Motor Response
4 = thumbs up, fist, or peace sign
3 = localizing to pain
2 = flexion response to pain
1 = extension response
0 = no response to pain or generalized myoclonus status.
Brain Stem Reflexes

4 = pupil and corneal reflexes present
3 = one pupil wide and fixed
2 = pupil or corneal reflexes absent
1 = pupil and corneal reflexes absent
0 = absent pupil, corneal, or cough reflex.
Respiration
4 = regular breathing pattern
3 = Cheyne-Stokes breathing pattern
2 = irregular breathing
1 = triggering ventilator or breathing above ventilator rate
0 = apnea or breathes at ventilator rate
Table 2: Glasgow Coma Scale (GCS) and Full Outline of UnResponsiveness (FOUR) Scale

Management requires correction, in patients with acute blood on their CT
scans.
The person’s brain injury should be assessed in the context
of pathophysiologic damage and anticipated course of Acute Hospital Care
recovery to formulate treatment plans and services along the
continuum of care.1 The interaction with non-injury factors Patients with TBI who are admitted for acute hospital care
such as age and psychosocial issues, associated injuries, range from those with more severe brain injury that requires
premorbid problems, co-morbidities, and later complications intensive care management, to those who need a period of
must also be considered during the formulation of the plan. observation to recognize secondary neurological deterioration
and neurosurgical complications that may ensue, to those
Pre-hospital management with co-morbidities that require hospital care.
In the field, patients should have their airway status, Monitoring in Traumatic brain injury
breathing and circulation addressed first. Hypotension and
hypoxia in the field are proven secondary injury insults that The goal of monitoring in TBI is to identify adverse
are associated with poor outcomes, with hypotension being physiological changes, prevent secondary cerebral ischemia
considerably more detrimental than hypoxia.7. Both of these and target the therapy to deliver substrate to the salvageable
must be prevented if possible. Endotracheal intubation may neurons in the penumbra of the injured brain. CPP is MAP
be necessary in the field. Patients should have a GCS score minus ICP. ICP/CPP monitoring is important after TBI since
assessed and pupillary exam performed, if possible, by the CBF is highly dependent on CPP especially below the lower
emergency medical personnel, prior to administering any limit of cerebral autoregulation, i.e., CPP <50 mmHg.
sedation or paralytic drug 8. Even if the patient has focal or ICP monitoring
lateralizing signs, such as a decreased sensorium and an
enlarging pupil, current recommendations do not support ICP There is a clear association between (abnormally) elevated
directed measures in the field, with the possible exception ICP’s and mortality.13-16 Nevertheless, there remains some
of hyperventilation in the intubated patient in neurologic controversy regarding the efficacy of ICP monitoring based
extremis. Every effort to have TBI patients transported to therapy vs. empiric therapies for head injury (e.g. empiric
the nearest facility possessing CT scanning, neurosurgical mannitol administration) on prospective evaluation.17 Despite
expertise and ICP monitoring capabilities, should be made.8 this controversy, ICP monitoring has become a mainstay in
The spine should also be immobilized as there is a 4 to 8 the critical care management of patients with severe TBI.
percent association of cervical spine injury with TBI.9 The As per the third edition of Guidelines for the Management
Brain Trauma Foundation’s (BTF) guidelines for Pre-hospital of Severe Traumatic Brain Injury18, the indications for ICP
Management of Traumatic Brain Injury have played a role in monitoring in TBI are as follows (Table 3), but the fourth
improving emergency pre-hospital care.10 edition does not find enough evidence to support this.19
Emergency Room management Threshold for ICP
Upon arrival in the emergency room, the Advanced Trauma Though there is insufficient data to support a Level I
Life Support (ATLS) protocol, as per the American College recommendation for a threshold, treatment should be initiated
of Surgeons, should be followed. This protocol stresses with intracranial pressure (ICP) thresholds above 22 mm
on a systematic approach to trauma injury, where airway, Hg. (Level II)19. A combination of ICP values, clinical and
breathing and circulation are assessed first. In terms of fluid brain CT findings should be used to determine the need for
resuscitation, crystalloid vs. colloid remains controversial. treatment.(Level III)19 ICP elevation, presenting as a change
A large prospective randomized trial compared saline to from lower, more normal pressures must always prompt a
albumin (Saline vs. Albumin Fluid Evaluation (SAFE) study) search for a potential surgical mass lesion via a repeat head
in the intravascular resuscitation of critically ill patients CT. One can accept an ICP range of 20 –25 mm Hg if other
showed that the subgroup receiving albumin had higher ICP parameters (CPP, PbtO2, SjvO2) are acceptable.
and also mortality.11, 12 Once fluid resuscitation is addressed,
a neurologic assessment is made in terms of GCS score, Additional neuromonitoring technologies
pupillary exam and lateralizing signs. This is preferably
ICP monitoring does not provide information regarding
done prior to any sedation or paralytic being given. A lateral
C-spine and chest x-ray should be performed. A CT scan is cerebral blood flow and metabolism, which are also important
then performed as rapidly as possible in any patient with a to the pathophysiology of TBI. Though additional monitoring
suspected or confirmed loss of consciousness, skull fracture has been developed (table 4), their use is limited to selected
or abnormal neurologic/GCS exam. Any coagulopathy centers due to the expense and lack of expertise.

GCS scores post resuscitation < or = 8 with a head CT demonstrating hemorrhages, contusions, edema or
compressed basilar cisterns
Level II
GCS scores post resuscitation < or = 8 with a normal head CT and 2 of the following
• Age > 40
• Motor posturing
• Systolic blood pressure of 90 mmHg or less
Level III
When the individual cannot have continual neurologic evaluation (e.g., use of anesthesia,
pain medicine for other injuries that preclude a neurologic exam)
Table 3: Indication for ICP monitoring
Monitor Physiological Component Monitor Limitation

Monitored
ICP • Intracranial Pressure. ICP Monitor CPP is not reliable to measure CBF with
• Used to determine CPP (intraventricular, impaired autoregulation.
parenchymal)
• Surrogate measure of
CBF
CBF CBFV and ICP Transcranial Doppler • Cerebral blood flow velocity is influenced
(TCD) by factors in addition to CBF
• Reduced CBF could be to match a
decrease CMRO2
• Normal CBF with increased CMRO2
results in ischemia
• Monitors only macrovascular
disturbances not the microvascular
circulation.
Regional Blood Thermal diffusion • Cerebral hypoxia despite normal CBF
flow flowmetry (TDF) due to reduced oxygen delivery because
Laser-doppler of increased RBC transit time
flowmetry (LFD) • Microvascular edema reduces oxygen
diffusion
• Oxygen extraction fraction (OEF) may
be increased.
Cerebral Interaction between CBF and Global- Jugular Mitochondrial dysfunction can reduce cerebral
Oxygenation oxygen delivery/ consumption venous oxygen oxidative metabolism hypoxia.
detect brain hypoxia saturation Does not measure non-ischemic mechanisms
Focal -Brain Tissue implicated in the injury
oxygen(PtO2) Perturbations in brain glucose metabolism
monitor

Monitor Physiological Component Monitor Limitation

Monitored
Cerebral energy Measuring concentrations of Cerebral Measures a very small tissue
metabolism glucose, pyruvate, and lactate. microdialysis
Additional markers, such as
glutamate (excitotoxicity) and
glycerol (membrane integrity)
Detect impending ischemia /
hypoxia and to assess the
energetic state of the injured
human brain
Comprehensive Brain multimodal
monitoring of monitoring
cerebral function
Table 4: Monitoring in TBI
EEG to better outcomes. 27-29 The Brain Trauma Foundation

Guidelines for management of Severe Traumatic Brain
Continuous electroencephalography (EEG) monitoring Injury19 are summarized in Table 6.
can detect both convulsive and non-convulsive status
epilepticus, which often is an unsuspected cause for altered • Ventriculostomy insertion is the ICP monitoring procedure
consciousness and poor outcomes in patients with severe of choice in adults with severe TBI.30
TBI.20. Continuous EEG monitoring is also mandatory in the
• It permits both monitoring of pressure via transduction
monitoring of barbiturate therapy.
and also permits CSF drainage.
Surgical treatment of head injury
• It also can be recalibrated in situ. ICP transduction via
Operative therapy is indicated in patients where intra cerebral fiberoptic (Camino) or micro strain gauge (Codman)
collections exert significant mass effect. Traditionally this devices placed, provide accurate measurements31 but
has been defined as, greater than 5 mm of midline shift and at a higher cost.
compression of basilar cisterns. Numerous surgical criteria for • Parenchymal ICP monitors cannot be recalibrated
a variety of commonly seen TBI related pathologies have been during monitoring but have negligible drift. They do not
proposed.21-25(table 5) permit cerebrospinal fluid drainage. These devices are
The Early Surgery versus Initial Conservative Treatment in advantageous when ventricular ICP is not obtained or if
Patients with Traumatic Intracerebral Hemorrhage (STITCH there is obstruction in the fluid couple.
[Trauma]) is an international multi-center, patient-randomized, • Subarachnoid, subdural, and epidural monitors (fluid
parallel-group trial. 37% of 82 patients randomized to early coupled or pneumatic) are less accurate. Clinically
surgery had an unfavorable outcome, while 47% of 85 significant infections or hemorrhage associated with ICP
patients randomized to initial conservative treatment showing devices causing patient morbidity are rare and should
an absolute benefit of 10.5%.26 Decompressive craniectomy, not deter the decision to monitor ICP.
discussed in the next section for refractory ICP elevations,
remains a controversial area. Intracranial Pressure
Medical Management of Severe TBI Treatment of elevated ICP: Current therapies used for ICP
control either cause a lowering of blood pressure and thereby
Neurological damage from TBI not only occurs at the cerebral perfusion pressure (CPP) (mannitol, barbiturates)
moment of impact, but continues to evolve over the ensuing or cause cerebral vasoconstriction (hyperventilation) thereby
hours and days as secondary injury. Outcome from TBI further reduce perfusion to the brain. An ideal therapeutic
can be improved when these secondary delayed insults are intervention should effectively reduce ICP while preserving
prevented or respond to treatment. The use of evidence- or improving CPP. The algorithm for management of ICP is
based guidelines for acute TBI care has contributed given below (figure 1 and 2)

Location CT Scan Clinical Features Intervention

Epidural Any size GCS score less than 9 with Decompression as soon as
hemorrhages associated papillary dilation possible
Greater than 30 cc in volume Regardless of whether the Evacuation
patient is symptomatic
Less than 30 cc in volume and less No focal deficits Managed by close observation
than 1.5 cm in thickness, with less and serial imaging
than 5 mm midline shift
Acute subdural Greater than 1 cm in thickness or Regardless of symptoms Emergent evacuation by
hemorrhages associated with greater than 5 mm craniotomy/ craniectomy
of midline shift
Even when smaller than above Presence of neurologic deficits, Emergent evacuation by
criteria deteriorating neurologically and craniotomy/ craniectomy
those with raised intracranial
pressures.
Intracerebral Frontal or temporal contusions Comatose Treated operatively
contusions greater than 20 cc in volume with
a midline shift of 5 mm and/or
cisternal compression
Contusion greater than 50 cc Regardless of symptoms Treated operatively
Any Size Progressive neurologic Treated operatively
deterioration referable to the
contusion or resultant refractory
intracranial hypertension
Severely contused frontal lobes Medically refractory intracranial Bifrontal decompressive
with significant mass effect hypertension craniectomy
Contusions in eloquent cortex Relatively good neurologic Carefully watched, with
exam. medical treatment of ICP
elevations if needed
Depressed skull Greater than the thickness of Even if asymptomatic Operated on acutely to lower
fractures the skull with evidence of dural the risk of infection.
laceration Antibiotic therapy
No radiographic evidence of No clinical evidence of dural Non-operative management
dural penetration, no evidence penetration, no gross cosmetic (managed expectantly +
of significant intracranial deformity, no evidence of Antibiotics)
hematoma, depression less than wound infection or gross wound
1 cm thickness, no frontal sinus contamination.
involvement, pneumocephalus
Table 5: Criteria for Surgical Management

Parameter Recommendation Level

Blood Pressure and Blood pressure should be monitored and hypotension (systolic blood pressure 90 mm II
Oxygenation Hg) avoided
Oxygenation should be monitored and hypoxia (PaO2 60 mm Hg or O2 saturation 90%) III
avoided.
Indications for Intracranial pressure (ICP) should be monitored in all salvageable patients with a II
Intracranial severe traumatic brain injury (TBI; Glasgow Coma Scale [GCS] score of 3–8 after
Pressure Monitoring resuscitation) and an abnormal computed tomography (CT) scan. An abnormal CT
scan of the head is one that reveals hematomas, contusions, swelling, herniation, or
compressed basal cisterns.
ICP monitoring is indicated in patients with severe TBI with a normal CT scan if two or III
more of the following features are noted at admission: age over 40 years, unilateral or
bilateral motor posturing, or systolic blood pressure (BP) 90 mm Hg.
Cerebral Perfusion Aggressive attempts to maintain cerebral perfusion pressure (CPP) above 70 mm Hg II
Thresholds with fluids and pressors should be avoided because of the risk of adult respiratory
distress syndrome (ARDS).
CPP of less than50 mm Hg should be avoided. III
Brain Oxygen Jugular venous saturation (50%) or brain tissue oxygen tension (15 mm Hg) are III
Monitoring and treatment thresholds.
Thresholds
Hyperosmolar Mannitol is effective for control of raised intracranial pressure (ICP) at doses of 0.25 II
Therapy gm/kg to 1 g/kg body weight. Arterial hypotension (systolic blood pressure 90 mm Hg)
should be avoided.
Restrict mannitol use prior to ICP monitoring to patients with signs of transtentorial III
herniation or progressive neurological deterioration not attributable to extracranial causes.
Prophylactic Early (within 2.5 h), short-term (48 h post-injury), prophylactic hypothermia is not III B
Hypothermia recommended to improve outcomes in patients with diffuse injury
Ventilatory Prophylactic hyperventilation (PaCO2 of 25 mm Hg or less) is not recommended. II
Strategies Hyperventilation is recommended as a temporizing measure for the reduction of III
elevated intracranial pressure (ICP). Hyperventilation should be avoided during the
first 24 hours after injury when cerebral blood flow (CBF) is often critically reduced.
If hyperventilation is used, jugular venous oxygen saturation (SjO2) or brain tissue
oxygen tension (PbrO2) measurements are recommended to monitor oxygen delivery
Steroids The use of steroids is not recommended for improving outcome or reducing intracranial I
pressure (ICP). In patients with moderate or severe traumatic brain injury (TBI), high-
dose methylprednisolone is associated with increased mortality and is contraindicated.
Deep Vein Graduated compression stockings or intermittent pneumatic compression (IPC) III
Thrombosis stockings are recommended, unless lower extremity injuries prevent their use. Use
Prophylaxis should be continued until patients are ambulatory.
Low molecular weight heparin (LMWH) or low dose unfractionated heparin should be III
used in combination with mechanical prophylaxis. However, there is an increased risk
for expansion of intracranial hemorrhage.
There is insufficient evidence to support recommendations regarding the preferred
agent, dose, or timing of pharmacologic prophylaxis for deep vein thrombosis (DVT).

Parameter Recommendation Level

Anesthetics, Prophylactic administration of barbiturates to induce burst suppression EEG is not II
Analgesics, and recommended. High-dose barbiturate administration is recommended to control
Sedatives elevated ICP refractory to maximum standard medical and surgical treatment.
Hemodynamic stability is essential before and during barbiturate therapy.
Propofol is recommended for the control of ICP, but not for improvement in mortality or II
6 month outcome. High-dose propofol can produce significant morbidity
Decompressive Bifrontal DC is not recommended to improve outcomes as measured by the GOS-E IIA
craniectomy score at 6 mo post-injury in severe TBI patients with diffuse injury (without mass
lesions), and with ICP elevation to values 20 mm Hg for more than 15 min within a
1-h period that are refractory to first-tier therapies. However, this procedure has been
demonstrated to reduce ICP and to minimize days in the ICU.
A large frontotemporoparietal DC (not less than 12 x 15 cm or 15 cm diameter) is
recommended over a small frontotemporoparietal DC for reduced mortality and
improved neurologic outcomes in patients with severe TBI.
Antiseizure Prophylactic use of phenytoin or valproate is not recommended for preventing late II
Prophylaxis posttraumatic seizures (PTS). Anticonvulsants are indicated to decrease the incidence
of early PTS (within 7 days of injury). However, early PTS is not associated with worse
outcomes.
Nutrition Patients should be fed to attain full caloric replacement by day 7 post-injury. II
Infection Early tracheostomy is recommended to reduce mechanical ventilation days when II A
prophylaxis the overall benefit is thought to outweigh the complications associated with such a
procedure. However, there is no evidence that early tracheostomy reduces mortality or
the rate of nosocomial pneumonia.
The use of PI oral care is not recommended to reduce ventilator-associated pneumonia
and may cause an increased risk of acute respiratory distress syndrome.
Table 6: Brain Trauma Foundation Guidelines for management of Severe Traumatic Brain Injury

Figure 1: Algorithm for managment of intracranial hypertension following TBI

Figure 2: Rescue pathways for management of refractory intracranial hypertension
Non-pharmacological methods Mannitol:
• Elevation of the head of the bed: Elevation of the head of • Mannitol is a commonly used agent in the control of
the bed to 30 degrees promotes jugular venous drainage raised ICP following TBI.
and lowers ICP.
• Single administration is used for diagnostic procedures
• Prophylactic Hypothermia: The role of hypothermia in (e.g., CT scan) and interventions (e.g., evacuation of
the improvement of outcomes among patients suffering intracranial mass lesions) for its short term beneficial
severe head injury remains controversial. A significantly effects.
better neurologic recovery was noted in patients with
• Prolonged therapy is used for control of raised ICP.
severe TBI who were treated using mild hypothermia
(33°C for 24 hr)32 but some studies (NABIS:H)” series)33, • Works by dehydrating the brain especially areas of
34
did not show benefit. 35, 36 or was found ineffective in cerebral edema and by altering cerebral rheology.38
improving outcomes in TBI. The BTF recommendation
• It has beneficial effects on ICP, CPP, CBF, and brain
for prophylactic hypothermia is level III.37 Preventing
metabolism, and neurological outcome.
hyperthermia can lower ICP.
• Potentially serious side effects include: renal failure and
• Airway Management: In patients where ICP management pulmonary edema.
is of concern, a mechanical airway should be in place,
allowing hyperventilation and sedation/paralysis to be • Dose: Optimally given as a slow intravenous bolus.
used as needed. The recommendation of mannitol for control of raised
intracranial pressure (ICP) is doses of 0.25 gm/kg to 1
Pharmacological g/kg body weight.
Hyperosmolar agents : Mannitol and hypertonic saline (HS) • It’s effects may be augmented by other diuretics such
are the hyperosmolar agents currently in clinical use for TBI. as furosemide. The diuretic effect must be monitored.

Serial serum osmolartity should also be measured and Surgical Management of ICP
osmolarity should be kept below 320 mOsm to reduce
risk of renal failure. Arterial hypotension (systolic blood The use of decompressive unilateral or bilateral
pressure 90 mm Hg) should be avoided. (Level II)19 . craniectomy with duraplasty to treat medically refractory
ICP elevation is controversial. Various studies have
• The use of mannitol prior to ICP monitoring should be found improved outcomes and decreased mortality
restricted to patients with signs of transtentorial herniation in patients undergoing a craniectomy for refractory
or progressive neurological deterioration not attributable ICP vs. those medically managed. 47-49 But the large
to extracranial causes. (Level III)19 randomized trial DECRA(Decompressive Craniectomy
Hypertonic Saline: in Patients with Severe Traumatic Brain Injury) has
shown that adults who had undergone early bifronto
• Hypertonic saline (HS) reduces ICP primarily due to temporoparietal decompressive craniectomy (DC) for
osmotic mobilization of water across the intact blood– severe diffuse traumatic brain injury and refractory
brain barrier (BBB) which reduces cerebral water intracranial hypertension showed improvement in
content.42 It also has effects on the microcirculation. intracranial pressures but was associated with worse
scores on the Extended Glasgow Outcome.50 RESCUEicp
• HS dehydrates endothelial cells and erythrocytes which
increases the diameter of the vessels and deformability of (Randomised Evaluation of Surgery with Craniectomy for
erythrocytes and leads to plasma volume expansion with Uncontrollable Elevation of Intra-Cranial Pressure) study
improved blood flow. It also reduces leukocyte adhesion did not show benefit.51, 52 The BTF guidelines have not
in the traumatized brain. been updated after the publication of this study.
• Effective doses range between 0.1 and 1.0 mL/kg of Neuro-medical Conditions in Moderate/Severe Brain
body weight per hour, administered on a sliding scale.43 Injury
• The rebound phenomenon seen with mannitol has not There are a number of associated neuromedical problems
been reported in TBI after 3% saline administration even unique to moderate/severe TBI. (Table 7) These conditions
with multiple uses. There is a risk of central pontine often require specialized evaluation and therapeutic
myelinolysis when HS is given to patients with preexisting interventions by physicians, nurses and relevant
chronic hyponatremia but not with normonatremia interdisciplinary team disciplines.
in doses given for ICP reduction.44 It may aggravate
pulmonary edema in patients with underlying cardiac or Ongoing evaluation is often necessary to detect the delayed
pulmonary problems. development of complication such as new or expanding
space occupying intraparenchymal lesions, extra-axial
Both mannitol and HTS are effective in reducing ICP, but lesions such as subdural and epidural hematomas, and
there is a heterogeneity in the literature with regard to which hygromas, pneumocephalus or hydrocephalus. If an
agent is most efficacious. The BTF guidelines did not find individual’s neurological status worsens or plateaus,
strong evidence to make recommendations on the use, neuroimaging studies may be warranted.
concentration and method of administration of hypertonic
saline.19 A continuous infusion of 3% saline is recommended Outcome Assessment Tools in TBI
in pediatric guidelines currently for control of increased ICP
TBI outcome refers to survival status after injury and
(Level III recommendation).45 However, the choice of first line
hyperosmolar agent is left to the treating physician. to the extent of impairment and disability after there
has been an opportunity for recovery. Some outcome
Steroids: assessments are general and designed to provide a
global index of outcome, [e.g. Glasgow Outcome Scale
Steroids have not shown to be of benefit in reducing ICP
(GOS), a five-point ordinal measure of global outcome,
elevations and are not recommended for use in TBI.46
Glasgow Outcome Scale-extended (GOS-E) (table 8),
BTF guidelines recommend that use of steroids is not
Disability Rating Scale (DRS).
recommended for improving outcome or reducing intracranial
pressure (ICP).19

CARDIOPULMONARY COMPLICATIONS
Cardiac System
→ Dys autonomia, paroxysmal sympathetic hyperactivity, or hyperadrenergic syndrome (autonomic storm)

includes fever, hypertension, tachycardia, tachypnea, posturing, andhyperhydrosis (increased sweating
and flushing)
Pulmonary System:
Causes for pulmonary Dysfunction
→ Related trauma to the chest wall
→ Compromised respiratory drive
→ Dysfunctional swallow mechanism
→ Weakened cough
NEUROENDOCRINE COMPLICATIONS
→ Hypopituitarism (28%) due to differential injuries to the hypothalamus, anterior/posterior pituitary, upper
or lower portions of the pituitary stalk, and connections to other brain and brainstem structures.
Secondary endocrine effects
→ Salt and water metabolism- syndrome of inappropriate antidiuretic hormone (SIADH) and temporary or
permanent diabetes insipidus (DI)
→ Impaired Control of body temperature
→ ↓ ACTH cortisol levels
→ ↓ Glucose metabolism
→ ↓ Gonadotropin
→ ↓ Growth hormones.
IMMOBILIZATION AND DISUSE COMPLICATIONS
→ Pressure decubitus ulcers
→ Vascular complications
→ Deep venous thrombosis (DVT) and pulmonary embolus (PE)
GASTROINTESTINAL COMPLICATIONS
Delays in gastric emptying
Dysphagia and/or an inadequate swallow reflex
Table 7: Medical Conditions associated with TBI
Category Patient Status

1 Death
2 Vegetative state
3 Lower severe disability
4 Upper severe disability
5 Lower moderate disability
6 Upper moderate disability
7 Lower good recovery
8 Upper good recovery
Table 8: Extended Glasgow Outcome Scale (GOS(E))

Conclusion 9. Holly LT, Kelly DF, Counelis GJ, Blinman T, McArthur
DL, Cryer HG. Cervical spine trauma associated
TBI is a heterogeneous disease, with a multitude of
with moderate and severe head injury: incidence,
secondary injury cascades, affecting a diverse population.
risk factors, and injury characteristics. J Neurosurg.
The outcome may also be influenced by factors such as co-
2002;96(3 Suppl):285-291.
morbidities and complications, injury severity, injury type and
management. There are very few level I recommendations in 10. Watts DD, Hanfling D, Waller MA, Gilmore C, Fakhry
the management of TBI and several areas of management SM, Trask AL. An evaluation of the use of guidelines in
continue to be contentious. prehospital management of brain injury. Prehosp Emerg
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MCQ
1. The cerebral blood flow in TBI 4. Acceptable threshold for ICP in TBI
A. Increased initially, then decreased A. 20-25 mmHg

B. Decreased initially, then increased B. 10-15 mmHg
C. Remains increased C. 25-30 mmHg
D. Remaind decreased D. 5-10 mHg
2. All of the below are clinical classification to assess TBI 5. Dose of mannitol for control of ICP
severity except
A. 0.5-1 g/kg
A. GCS B. 1-2mg/kg
B. AIS C. 0.25-1g/kg
C. Marshall classification D. 0.25-1mg/kg
D. FOUR
6. All of the statements regarding TBI are true except
3. CPP is
A. Hypotension with SBP <90 mmHg must be avoided
A. CBF-ICP B. Hyperventilationshould be avoided during first 24
B. MAP-ICP hours after surgery when CBF is critically reduced
C. MAP-1/3 ICP C. Use of steroids is not recommended for improving
D. DBP-ICP the outcome
D. CPP should be maintained >70 mmHg
6.D 5.C 4.A 3.B 2.C 1.A
ANSWERS:

18 STARLING’S EQUATION – UNDERSTANDING THE PHYSIOLOGY
Professor and Unit Head Krishna HM

Kasturba Medical College,
Manipal
Key points
Ø Starling’s equation quantifies the net movement of fluid across the capillary wall in the tissues.
Ø It is the balance of the driving forces between those within the capillary and those surrounding the capillary, in the
interstitium.
Ø The microcirculations of the kidney, the lung and the brain are special cases in the use of the Starling equation.
The application of the Starling equation to the brain is different from that anywhere else in the body and has
important clinical relevance.
Ø Newer developments like invention of electron microscope and continued research, paved way towards better
understanding of the anatomical and physiological aspects of microcirculation, hence requiring a need for revision
of the Starling Equation.
Ø Revision in Starling Principle, was proposed by Michel and Weinbaum.
Ø The revision of Starling equation highlights the importance of endothelial glycocalyx in the balance of Starling
forces.
Introduction σ - Staverman’s osmotic reflection coefficient (which tells

how leaky the capillary is to the solute or protein; it varies
Starling’s equation is a mathematical equation quantifying
from 0 to 1. A value of 1 means the protein is completely
the net movement of fluid across the capillary wall in the
reflected within the capillary, thus not allowing it to escape to
tissues. It is the balance of the driving forces between those
interstitium. A value of 0 means the protein just leaks across
within the capillary and those surrounding the capillary, in the
the capillary)
interstitium. These forces are often referred to as Starling’s
forces. The equation tells us about the direction of movement Πp- plasma oncotic pressure (often denoted as Πc, capillary
between the two compartments and the net amount of fluid osmotic pressure in literature; oncotic pressure and osmotic
transfer. pressure are often used synonymously)
Classic Starling equation Πi is oncotic pressure in the interstitial space.

An alternate way of expressing it is
The conventional expression of Starling equation is
Jv = Kf [(Pc-Pi)-σ(Πc - Πi)]
Jv/A = Lp{(Pc − Pi) −σ(Πp − Πi)}
The difference here is Kf which is the constant of proportionality
Jv - net movement of fluid (positive value indicating movement
called filtration coefficient. It is the product of area of capillary
out of the circulation)
walls A and hydraulic conductivity Lp. The vascular permeability
A - surface area of the capillaries across which fluid varies between the different microcirculation systems in the body
movement is occurring (sometimes denoted as S) (more fenestrated and permeable in the glomeruli of kidneys as
Lp - hydraulic conductivity of the capillaries (which simply compared to the microcirculation of the brain). This can also be
means how permeable they are to the fluid) affected by the inflammatory mediators.
Pc - the capillary hydrostatic pressure There are 4 forces or pressures playing a role in the
movement of the fluid, as are evident from the equation. The
Pi -the interstitial hydrostatic pressure,

Starling’s Equation – Understanding the Physiology 178 Krishna HM
Table 1: Approximate values of the pressures functioning in Starling’s equation
hydrostatic pressure of the plasma in the capillaries tends together there is a minuscule net outward filtration of fluid
to move the fluid out of the capillaries. This is opposed by from most capillary beds. When this outward filtration is
the hydrostatic pressure of the interstitial fluid. The osmotic summed across all tissue capillary beds, there appears
pressure of the plasma proteins tends to draw the fluid to be only a few milliliters of outward fluid filtration per
inwards into the capillaries and is countered by the osmotic minute throughout the entire body. This fluid which has
pressure of the proteins in the interstitium. The net balance moved out of the capillaries is ultimately returned to
between these 4 pressures, hydrostatic pressure of plasma, circulation by lymphatic vessels.
interstitial hydrostatic pressure, plasma osmotic pressure and
• The microcirculations of the kidney, the lung and the brain
interstitial osmotic pressure determines the direction (from
are special cases in the use of the Starling equation.
capillary to interstitium or interstitium to capillary) and volume
of fluid movement. The typical values of these pressures are Starling equation in relation to renal microcirculation
given in Table 1.
The situation in the glomerular capillaries is unique. In the rest
of the body, the net excess of ultrafiltration over reabsorption
is 2-4 L/day. But in the glomerular capillaries the net excess
• One of the interpretations from the Starling equation is of filtration known as the glomerular filtration rate (GFR) is
that at the arterial side, the outward hydrostatic pressure 180 L/day.
gradient is larger than the inward oncotic pressure
The filtration coefficient Kf is high (due to high permeability
gradient and thus net fluid filtration is in the outward
and large surface area of the capillaries). The reflection
direction.
coefficient is high (about 1.0, which means the ultrafiltrate
• Towards the venous side of the microcirculation, the contains no proteins). The hydrostatic pressure along the
capillary hydrostatic pressure (Pc) has decreased. length of the capillaries is high. The hydrostatic pressure in
Furthermore, progressive outward movement of water the glomerular capillaries is affected by the balance between
as blood travels through the microcirculation causes afferent and efferent arteriolar constriction. Because of the
concentration of plasma proteins, thus raising the plasma large loss of fluid and the impermeability to proteins, the
oncotic pressure. Because the outward hydrostatic oncotic pressure in the glomerular capillary increases along
pressure gradient has declined and the inward oncotic its length. (This increased oncotic pressure is important in
pressure gradient has increased, there is now net fluid the reabsorption from the proximal tubule into the peritubular
resorption (or absorption). capillaries).
Starling equation in relation to pulmonary microcirculation

• Outward fluid filtration on the arterial side of the
microcirculation largely balances inward fluid filtration The pressures in the pulmonary circuit are much lower
on the venous side of the microcirculation. When added than in the systemic circulation and the pulmonary vascular

resistance is very low. The pressure is just sufficient to else in the body and has important clinical relevance (eg use
perfuse the apical areas of the lungs in the erect healthy of hypertonic mannitol solutions).
adult. The capillary hydrostatic pressure is variable because
The need to revise Starling’s equation
of the effects of gravity. The interstitial oncotic pressure is
high indicating significant leak of protein (mostly albumin) For decades, the Starling Equation seemed to be perfect
across the thin capillary walls. The reflection coefficient considering its principles of physics and mathematics. But it
is about 0.5. The net oncotic gradient is small but favors failed to explain some practical observations that were made
reabsorption. The balance of Starling forces in the lung favors in the ensuing years. There were also newer developments
reabsorption (lungs are dry to facilitate gas exchange). There like invention of electron microscope and continued research
is a small net outward movement of fluid which is equal to on fluid management (to find out whether crystalloids
the pulmonary lymph flow rate. or colloids are better) which paved way towards better
understanding of the anatomical and physiological aspects
The safety factors which prevent the formation of pulmonary
of microcirculation.
edema are increased lymph flow with increased fluid filtration,
decrease in interstitial oncotic pressure when filtration The main contradictions observed to classic Starling
increases and high interstitial compliance. Despite these, if equation were (1) there is no venous reabsorption of fluid as
the interstitium becomes filled with fluid then the pressure hypothesized by Starling equation (2) transcapillary flow rate
rises and alveolar flooding occurs. This is called the bathtub is lower than predicted by Starling equation (3) the interstitial
effect: the analogy that the tub can take a lot of fluid before it protein concentration has a minimal effect on fluid flux and
is full and suddenly overflows. It has been estimated that the (4) albumin molecules can pass freely across the large pores
capillary hydrostatic pressure can rise to three times normal between the endothelial cells of normal capillary membrane.
before alveolar flooding occurs.
So the revision in Starling Principle, proposed by Michel
Starling equation in relation to brain microcirculation and Weinbaum (independent research), is that the osmotic
pressure forces can only be applied across the endothelial
The blood brain barrier is impermeable to low molecular
glycocalyx, the molecular sieve for plasma proteins. It
weight solutes so the plasma osmotic pressure (rather
appears now that the colloid oncotic pressure difference
than plasma oncotic pressure) is the Starling force to be
which determines Jv, is no longer a trans-endothelial force
considered here. For the same reason, the brain interstitial
per se, but rather an intra-endothelial force.
osmotic pressure is also a Starling force (rather than the
oncotic pressure of the interstitial fluid). The reflection Endothelial glycocalyx
coefficient due to these solutes is used rather than the
reflection coefficient for the proteins. This reflection is very • Bennett suggested the term, ‘glycocalyx,’ in 1963 as
high for most of these water-soluble solutes. The Starling the general name for the “extracellular, sugary coating,
equation is also altered for another reason: the hydraulic wherever it may be found.”
conductivity of the cerebral capillaries is very much lower • Glycocalyx in Greek means sweet husk. It is a
than in other capillaries. The filtration coefficient is low. This meshwork of long glycosaminoglycans (GAGs or
minimizes the amount of dehydration that occurs in response mucopolysaccharides) linked to membrane bound
to changes in plasma tonicity. Hence the application of the proteins proteoglycans as well as glycosylated proteins
Starling equation to the brain is different from that anywhere glycoproteins (Figure 1).
Figure1. Structure of endothelial glycocalyx

• Glycoproteins are cell surface receptors, selectins, min in humans following acute hemorrhage, allowing the
integrins and other functionally dynamic proteins at the absorption, or ‘autoresuscitation’, of approximately 0.5 L of
cell surface. Proteoglycans play a structural role to the interstitial fluid. However, in the steady state, no absorption
glycocalyx and are made of a core protein anchored to is seen along the entire length of most capillaries, regardless
the cell membrane with long GAGs attached to them. of the Pc. Instead, fluid is removed from the interstitium
via the lymphatic system. There are notable exceptions to
• Predominant proteoglycans are the transmembrane the steady-state no-absorption rule. These tissues include
bound syndecan and the membrane bound glypican. Major the intestinal mucosa (but not the mesentery), renal and
glycosaminoglycans are heparan sulfate, chondroitin lymphatic systems. These tissues manage to keep the Πi
sulfate and hyaluronan. Glycosaminoglycans are mainly quite low such that absorption is observed.
responsible for the molecular sieve characteristic of the
glycocalyx. They form the seamless meshwork that 2) Glycocalyx filters the albumin (plasma proteins) and
bridge the luminal surfaces of one endothelium to the not the gaps between endothelium. The sub-glycoca-
next, thereby creating a semi permeable filter to large lyx space has an important role
solutes. Thus, the principal barrier that determines the
effective oncotic force for water flow across capillary Starling’s original theory assumes that Πi is substantially
endothelium is the endothelial glycocalyx. lower than Πc. This is not correct. The interstitium is packed
with proteins due to the physiological extravasation of plasma
• The endothelial glycocalyx is a key regulator of proteins, possibly through large pores located in the venular
endothelial function. It has a major role in vascular segments of capillaries, which results in Πi approaching
permeability, cell-vessel wall interactions, blood rheology, Πc. But solving the original equation with the measured
mechanotransduction, inflammation, coagulation and Πi and c values predicts a much higher filtration rate than
fibrinolysis. that measured experimentally. Furthermore, modifying Πi
experimentally only has a minor impact on filtration rate.
Revised Starling principle and equation
The discrepancies between predicted and measured filtration
The modified Starling equation is: rates are resolved by revising the Starling equation and
Jv/A = Lp {[Pc – Pi] – σ[Πc – Πsg]} replacing Πi with the osmotic pressure in a small protein-free
zone between the endothelial glycocalyx and the endothelial
where Πsg (sometimes denoted as Πg) is the colloid oncotic cells. That is:
pressure of the subglycocalyx.
Jv/A = Lp {[Pc – Pi] – σ[Πc – Πsg]}
Normally, the colloid oncotic pressure of the subglycocalyx
(Πsg) is quite low, but this force is entirely within the capillary where Πsg is the sub-glycocalyx osmotic pressure. As
such that Jv across the endothelium is a function of Pc and the osmotic pressure counteracting Πc is Πsg, and not Πi,
Pi while the colloid osmotic difference across the endothelial changes in Πi will have little impact on the filtration rate, as
glycocalyx simply retards filtration. has been observed. Πsg is almost negligible in comparison
to Πc, so the osmotic pressure gradient approaches Πc.
The major modifications to the Starling model, with the
endothelial glycocalyx central to these modifications are as The sub-glycocalyx space is maintained protein-free by the
follows: constant outward filtration of fluid as explained by the no
absorption rule and the plasma protein filtering effect of an
1) No absorption in the steady state. There is steady intact endothelial glycocalyx. The resulting ultrafiltrate flows
state filtration all along the capillaries through the sub-glycocalyx space, and then out through the
intercellular clefts via breaks in the tight junction strands. Due
Starling theorized that after being filtered out from the
to their narrow width, the velocity in the breaks is high even
arterial end of a capillary (the segment with high Pc), fluid
at low filtration rates, which prevents movement of interstitial
was then reabsorbed at the venous end (the segment with
protein back into the sub-glycocalyx space.
low Pc). However, experiments have found that while there
is an initial transient response where fluid is absorbed after 3) The endothelial glycocalyx is a determinant of hydrau-
a sudden decrease in Pc, this rapidly changes back to lic conductivity
outward filtration, even at the venous end of the capillary.
This transient absorption phase lasts approximately 15–30 The endothelial glycocalyx is also an important determinant
of hydraulic conductivity. Hydraulic conductivity (Lp) is

the ease with which water passes across the vessel wall. much less than predicted by the classical Starling forces
It is dynamically influenced by the endothelial glycocalyx due to the resistance offered by the glycocalyx layer.
and the endothelium. The endothelial glycocalyx reduces Revised Starling equation shows that the important Starling
Lp by mechanically resisting fluid flow. It also affects Lp forces are the transendothelial pressure difference and the
by a mechanotransducing shear force to the underlying plasma–subglycocalyx colloid osmotic pressure difference
endothelial cells, which respond to increased shear stress by (as against plasma-interstitial space fluid colloid osmotic
releasing nitric oxide and altering junctional proteins resulting pressure difference in classical equation). Interstitial space
in an increase in Lp. This process is physiologically relevant fluid colloid osmotic pressure is not a direct determinant of
when meeting the increased demand for metabolic substrates fluid flux across the capillaries. The clinical application of
to skeletal muscle during exercise. Endothelial cells have revised Starling principle is still unfolding.
a significant role in regulating Lp. The tight and adherens
junctions contribute to the high hydraulic resistance of the Suggested Reading
intercellular space. 1. Woodcock TE, Woodcock TM. Revised Starling equation
Summary and the glycocalyx model of transvascular fluid exchange:
an improved paradigm for prescribing intravenous fluid
Even before the structures could be identified or their therapy. British Journal of Anaesthesia 2012; 108 (3):
functions elucidated Starling hypothesized the factors 384–94. doi:10.1093/bja/aer515
governing fluid shift across the capillaries. This Starling
equation has stood the test of time and provoked research 2. Levick JR, Michel CC. Microvascular fluid exchange and
to answer the questions on optimal fluid therapy and the revised Starling principle. Cardiovascular Research
generalized inflammatory states such as sepsis. The revision 2010; 87: 198–210. doi:10.1093/cvr/cvq062
of Starling equation highlights the importance of endothelial 3. Milford EM, Reade MC. Resuscitation fluid choices to
glycocalyx in the balance of Starling forces. There is no preserve the endothelial glycocalyx. Critical Care 2019;
reabsorption of fluid at the venular end of the capillaries 23:77. https://doi.org/10.1186/s13054-019-2369-x
(steady state filtration). Fluid flux out of the capillaries is

MCQ
1. Stavermans osmotic reflection in classic starlings C. product of capillary walls and hydraulic conductivity
equation value varies between D. Difference in oncotic pressure in artery and
interstitium
A. 0-1
B. 0-0.1 3. The πsg in revised starling principle involves
C. 1-2
D. 2-3 A. colloid oncotic pressure of subglycocalyx
B. Hydaulic conductivity of capillaries
2. Kf is C. filtration coefficient
D. Net movement of fluid
A. difference between hydrostatic pressure and oncotic
pressure in artery 4. The endothelial glycocalyx is determinant of hydraulic
B. Difference between hydrostatic pressure and conductivity
oncotic pressure in interstitium
A.True
B.false
4.True 3.A 2.C 1.A
ANSWERS:

19 INTERPRETING CHEST X RAYS
Professor & Consultant Radiologist, Anupama Chandrasekaran

SRIHER,
Chennai.
Key points
Ø While reading a X ray, it is important to develop a search pattern that can be applied to every radiograph
Ø The AP view results in magnification of the anterior structures and an increase in the width of the mediastinum.
Ø Poor inspiratory film alter the apparent size of the heart and mediastinum, which may appear 10-40% larger or
wider
Ø The ideal position of the tracheostomy tube is with its tip located 1/2 to 2/3rd the distance from the stoma to the
carina.
Ø The presence of air-bronchogram is useful in making a diagnosis of consolidation, the cause depends on the
clinical presentation
Ø Meniscus sign is seen in the chest X ray of a patient with pleural effusion, on erect film
Ø Deep costophrenic sulcus sign is observed in pneumothorax, on chest X ray
Chest radiographs form a part of every anesthetist’s daily

practice. It is important to develop a search pattern that can
be applied to every radiograph. This will help in ensuring that
maximum information is obtained. A systematic and ordered
approach to chest X ray interpretation will go a long way in this
regard. It is not that experienced hands do not miss findings
on chest X rays, just that they miss fewer ones.
Before coming to actually reading an x ray and looking for

pathologies, certain essentials have to be verified:
• Patient information – Name, Age, Sex, Date of

Radiograph and if multiple X rays are available,
arrange them in chronological order
• Identify radiographic technique - AP/PA film,
inspiratory/expiratory, exposure, rotation, patient CXR: PA view
position (supine or erect)
AP view: This is usually obtained with a portable X ray unit
PA vs AP on very sick patients and infants, and is most often a supine
X ray. In this view, the scapulae are projected over the lung
PA view is the optimal view because it results in reduced
fields, the rectangular shape of the lower cervical vertebral
magnification and increases the sharpness of structures and
bodies are clearly seen, the ribs are more oblique and the
pathologies. In this view, the scapulae are projected away
clavicle is foreshortened.
from the lung fields, the inverted ‘V’ of the lower cervical spinal
laminae are clearly seen, the ribs are less oblique and the The AP view results in magnification of the anterior structures
entire length of the clavicle is seen. - the clavicle, sternum, and heart and a 15% increase in

Interpreting chest X rays 184 Anupama Chandrasekaran
the width of the mediastinum can be expected. In addition,
supine positioning widens the mediastinum and heart due to
gravitational effects. The supine position also diverts more
pulmonary blood flow to the upper lobes and redistributes
pleural fluid. Similarly, pneumothorax may be more difficult
to detect.
2
Difference in CXR image at inspiration (1)
vs expiration (2)
Exposure
A good X ray also requires adequate penetration of the patient

by radiation. In a correctly penetrated film, the thoracic spine
intervertebral disc spaces should be just visible through
CXR: AP view
the cardiac shadow. If the entire spine is clearly visible, it
Inspiratory vs Expiratory implies that it is an overpenetrated film. In such an X ray,
the lung fields appear excessively dark and lucent. Lung
Ideally, radiographs should be taken at the peak of inspiration. lesions may be masked resulting in failure to accurately
On good inspiration, the diaphragm should be found at the gauge their presence and precise extent. Another fallacy
level of the anterior ends of the 5th or 6th rib, or the posterior is that the lucent areas may raise the false possibility of a
ends of the 9th or 10th rib. Critically ill patients are usually pneumothorax or cause a pneumothorax to be missed. On
unable to maintain inspiratory hold positions. Poor inspiratory the other hand, underpenetrated films can result in relatively
film alter the apparent size of the heart and mediastinum, increased opacification of the lung fields.
which may appear 10-40% larger or wider. Crowding of lung
markings may lead to over-diagnosis of basal atelectasis, Problems with penetration have been obviated to major
lung edema etc. extent with the advent of Computed Radiography (CR) and
Digital Radiography (DR).
Centering/Rotation
In a correctly centered chest X ray , the medial ends of both

clavicles should be equidistant from the adjoining spinous
process of the dorsal vertebrae. Any asymmetry implies the
presence of rotation. The side of the hemithorax which is
closer to the film appears excessively opaque whereas the
contralateral side appears more lucent.
Once these technical parameters have been taken into

account, one can proceed with the actual interpretation of the
X rays. There is no fixed or prescribed protocol for reading
chest X rays. One can read a a X ray from the centre to
the periphery or vice-versa, or from the top to the bottom.
However, in keeping with the intention to stick to a standard
1 protocol, one useful format is as follows:

I. Position of lines, tubes and other invasive device pulmonary trunk and main pulmonary artery. The tip of this
II. Cardiac size and contour catheter should lie within 1-2 cm of the hilum.
III. Mediastinum including trachea Cardiac Size and Contour

IV. Hila Is the heart enlarged and if so, is it possible to identify
V. Lung fields individual chamber enlargement? The normal cardiothoracic
ratio is less than 50% in adults.
VI. Costophrenic angles
Mediastinum including Trachea
VII. Diaphragm
VIII. Subdiaphragmatic regions The following questions should be answered while evaluating
the mediastinum:
IX. Bones and soft tissues
Is the mediastinum widened ? There are two ways to
LINES, TUBES AND OTHER INVASIVE DEVICES subjectively assess mediastinal widening. Firstly the width of the
If present, are they correctly positioned ? If malpositioned, are mediastinum above the level of the carina should not exceed 8
there any resultant complications? Many devices are used cm. Alternatively, the mediastinum should not form more than 25
routinely for patient monitoring and support. Malpositioning of % of the width of the chest at this level. However these criteria
these tubes may occasionally be life threatening. Therefore are not absolute and sometimes a subjective assessment may
while viewing an x ray, it is essential to ensure that they are also be useful.
correctly positioned . Are there any abnormal lucencies within the mediastinum
Endotracheal and Tracheostomy tubes to suggest the presence of pneumomediastinum ? Also
check for mediastinal shift and abnormalities in contour, or
The endotracheal tube has a radioopaque line running along the presence of any mass . The normal trachea either lies
its entire length. The ideal position is with its tip 5 – 7 cm in the midline or a little to the right. This shift to the right
above the carina ( D 4-5 level), with the head in the neutral is exaggerated on expiratory radiographs. About 2/3rds of
position. The optimal width of the tube should be between one the heart normally lies to the left of the spine.
half and two thirds of the tracheal lumen. With an abnormally
Hila
low position, a right endobronchial intubation may occur
resulting in overventilation of the right lung or right upper Bilateral hila should be of the same size and density. Also
lobe collapse, with hypoventilation of the left lung. With an check their position. Usually, the left hilum lies at a higher
abnormally high placement, the tube may get extubated level than the right, though occasionally they may lie at the
with resultant vocal cord damage. Esophageal intubation is same level.
rare and can cause hypoventilated lungs with gross gastric
Lung Fields
distension.
In a correctly centred X ray, bilateral lung fields should appear
The ideal position of the tracheostomy tube is with its tip
similar. Compare the right upper, mid and lower zones with
located 1/2 to 2/3rd the distance from the stoma to the carina.
the corresponding zones on the left side. Any abnormal
Nasogastric Tube looking opacities or lucencies should be carefully evaluated.
The radioopaque tip of the tube should lie at least 8 cm within There are two important sign , the ‘Silhouette sign’ and
the stomach to reduce the risk of aspiration. the ‘Air Bronchogram’ sign which are important in the
evaluation of air space diseases.
Central venous line
Silhouette sign
Its ideal location is with its tip beyond the last venous valves
and hence its preferable location is within the superior vena An intra-thoracic radio-opacity, if in anatomic contact with a
cava. border of heart, aorta or diaphragm, will obscure that border.
An intra-thoracic lesion not anatomically contiguous with a
PA catheter border or a normal structure will not obliterate that border.
It is also known as Swan Ganz catheter. The catheter e.g. a right middle lobe collapse or consolidation will obscure
is commonly inserted via the internal jugular vein and it the right heart margin while a lingular pathology will obscure
traverses the right atrium and ventricle before entering the the left cardiac border and a lower lobe lesion will obscure
the diaphragm.

Loss of cardiac Silhouette (right) : Silhouette sign
Air Bronchogram sign Diaphragm
This commonly signifies alveolar disease with a patent Check out the contour and position. The difference in heights
bronchus (pneumonia, pulmonary edema, ARDS, etc.), but between the apices of the two hemidiaphragms should not
may be seen in partial atelectasis. On a normal radiograph, exceed 3 cm. The diaphragm should not be abnormally
the bronchi are not normally visible unless seen end on, or if flattened (seen in hyperinflation/pneumothorax) or inverted
there is bronchial wall thickening. When the alveoli no longer (considered a radiological sign of tension pneumothorax)
contain air and opacify, the air-filled bronchi passing through
Subdiaphragmatic regions
the same area may be visible as branching linear lucencies,
or air bronchograms Do not forget to look at the subdiaphragmatic regions.
The presence of any abnormal lucencies in this location
Some commonly encountered causes of opacities are : should alert one to the possibility of pneumoperitoneum or
• Atelectasis / collapse subdiaphragmatic abscess.
• Pneumonia Bones and Soft Tissues

• Pulmonary edema Look carefully at the bones especially in the setting of trauma.
• ARDS In addition to the ribs, clavicles and scapula, information
• Hemorrhage about the spine, shoulder joints and humerus may also be
• Effusion obtained if they are clearly seen or included on the film
SPECIFIC PATHOLOGIES
Pathological lucencies may represent
The following is a brief summary of the chest X ray findings
• Emphysema
in some of the commonly encountered chest pathologies
• Bulla, Cysts which are of significance to the anesthetist:
• Pneumothorax
Collapse
• Pneumomediastinum
• Subcutaneous emphysema The radiological appearances depend upon the mechanism
of collapse, degree of collapse, presence or absence of
Costophrenic Angles consolidation, and the pre-existing state of the pleura.
Is it effaced (pleural effusion) or abnormally deep and lucent Direct Signs of Collapse
(pneumothorax in the supine position)?
• Displacent of interlobar fissures - most reliable sign

• Loss of aeration resulting in increased density of
a collapsed area
• Crowding of vessels and bronchi
Consolidation right middle lobe of lung
Congestive heart failure
• Cardiomegaly
• Large hila with indistinct margins
Collapse right lung • Cephalization of blood flow
• Kerley B lines
• Peribronchial cuffing
Indirect Signs of Collapse • Consolidation due to alveolar edema
Due to compensatory changes which occur in response to • Pleural effusion
the volume loss ARDS
• Elevation of hemidiaphragm • No cardiomegaly
• Mediastinal displacement • Pleural effusion rare
• Hilar displacement – elevated in upper lobe • No Kerley B lines
collapse and depressed in lower lobe collapse • Delay in onset of any x-ray findings for at least 12
• Compensatory hyperinflation hours post-insult
Consolidation
Implies replacement of air in one or more acini by fluid or

solid material. The presence of air-bronchogram is useful
in making a diagnosis. Its causes are varied and include
pneumonia, pulmonary edema, aspiration, hemorrhage,
ARDS, etc. Clinical correlation is therefore essential to make
the diagnosis. For example, if a patient has a cough and fever,
then infection is the likely cause, whereas aspiration should
be suspected in patients with a known predisposing factor
such as a recent seizure or an episode of unconsciousness.
CCF - Kerley B lines

Between 12 – 24 hours:
• Patchy alveolar infiltrates in both lungs
Between 24 - 48 hours:
• Coalesce to produce massive air space consolidation

of both lungs
Lung Abscess
Pulmonary Embolism (PE)
Chest x rays show abnormalities in approximately half of

the patients with pulmonary embolism. Unfortunately, these
findings are most often non-specific and a high index of
clinical suspicion for the diagnosis is required.
ARDS The chest X ray findings reflect the pathophysiological

From 5 – 7 days: changes and can be divided into three broad categories:
• Clearing is frequently secondary to the effects of i) Pulmonary embolism without infarction. The findings
CPP ventilation rather than true healing may be
• Pneumonia may superimpose – difficult to impose • Normal chest x ray

but look for new focal infiltrates and pleural effusion • Focal oligemia – Westermark Sign (in X ray below,
indicated by a red circle)
More than 1 week
• Reduction in regional lung volume
• Coarse reticular interstitial disease which may lead • Plate like atelectasis
to fibrosis
Lung Abscess
The radiological findings include
• Cavitation within an area of consolidation
• Lung nodule with surrounding consolidation (in

the stage before the abscess communicates with
a bronchus)
• Cavity with an air-fluid level
Westermark Sign (circled area)

ii) Pulmonary Embolism with infarction Massive effusion can result in complete opacification
of the hemithorax.
• Pleural based, hump shaped opacity when seen
in profile (see X ray below) and faint ill-defined • Supine X ray – Veil like opacity in the affected
rounded opacity when seen en-face hemithorax through which lung markings may be seen
• Associated pleural effusion
Right pleural effusion with meniscus sign

Hump shaped opacity (arrow mark)
Pneumothorax
iii) Pulmonary embolism associated with cardiac or • Detection of a white visceral pleural line beyond
pulmonary disease – The plain radiograph findings of which lung markings are not seen
the underlying condition predominate.
• Supine pneumothorax – ‘Deep costophrenic sulcus’
Mitral Stenosis sign, and abnormal clarity and lucency along the
anterior cardiophrenic sulcus
The plain radiographic findings include
• Straightening of left heart border

• Bulge along left heart border due to enlarged left
atrial appendage (in rheumatic heart disease)
• Widened carinal angle
• ‘Double density’ of left atrial enlargement
• Valve calcification
• Findings of pulmonary edema and cardiac failure
Pleural Effusion
The appearances depend upon the quantity of fluid as well as

the position of the patient at the time that the X ray was taken.
• Erect X ray – Blunting of the costophrenic angle

followed by development of the ‘meniscus sign”.
Right pneumothorax

Pericardial Effusion
The appearances depend upon the amount of fluid and its

distribution.
• Symmetrical cardiomegaly without specific chamber

enlargement and clear lungs rather than congested
lungs – results in ‘flask’ or ‘water-bottle’ configuration
in the erect position and globular configuration in
the supine position.
Pericardial Effusion

MCQ
1. one good inspiration the diaphragm should be 4. The tip of this catheter should lie within
found at the level of the anterior ends of
a. 1-2 cm of the hilum.
a. 5th or 6th rib
b. 3-4 cm of the hilum.
b. 7th or 8th rib
c. 5 cm of the hilum.
c. 3rd or 4th rib
d. at the hilum
d. 8th or 9th rib
5. In an adult patient, the width of the mediastinum
2. The AP view results in magnification of the anteri- above the level of the carina should not exceed
or structures like mediastinum by
a. 8cm
a. 30%
b. 10cm
b. 2%
c. 12cm
c. 15%
d. 2 inches
d. 50%
3. The ideal position of the tip of endotracheal tube

should be
a. T4 vertebra body
b. T3 vertebra body
c. T5 vertebra body
d. T6 vertebra body
5. (a) 4. (a) 3. (a) 2. (c) 1. (a)

Answers

20 DEPTH OF ANESTHESIA –CONCEPTS & MONITORING
Assistant Professor, Seema Deshpande

Baltimore.
Key points
Ø Assessment of adequate depth of anesthesia is an important measure in reducing the risk of awareness
Ø Awareness has occurred when, after completion of anesthesia, an individual has explicit recall of intraoperative
events, with or without pain
Ø Intravenous and inhalation anesthetics cause memory blockade at doses considerably lower than those required
for loss of consciousness and immobility
Ø Drug-induced paralysis may be an important factor contributing to the incidence and severity of awareness
Ø For most processed EEG monitors, a value of 100 is associated with an awake state and a value of 0 indicates
an isoelectric EEG
Ø EEG-derived monitoring can be viewed as a measure of spontaneous electrical activity of the CNS whereas evoked
potentials are measures of the response to (peripheral) stimuli, and they are also affected by the neurological
pathways conveying signals from periphery to the cortex.
Ø The brainstem response is less sensitive to anesthetic drugs
Ø Evidence showing a definitive benefit of using processed EEG monitors to prevent unintended intraoperative
awareness in all patients is very limited.
Ø Measuring ETAC and maintaining it greater than 0.7 age-adjusted MAC can prevent awareness while being most
cost-conscious.
Ø Processed EEG monitors may be a useful adjunct, aside from monitoring standard clinical signs of awareness,
in patients who are at high risk for intraoperative awareness, hemodynamically unstable, or undergoing a total
intravenous anesthetic.
Unintended intraoperative awareness is a dreaded iatrogenic Intraoperative awareness requires not only consciousness,
complication of anesthetic practice. It is associated with but also memory. (1)
posttraumatic stress disorder (PTSD), has a high public
profile, increases patients’ apprehension of surgery, and Memory is classified into different types:
also the medico-legal risks associated with anesthesia. (1) 1. Explicit (or declarative) memory refers to memories
Awareness has occurred when, after completion of that can be verified as fact and are accessible to the
anesthesia, an individual has explicit recall of intraoperative conscious mind. Explicit memory has been subclassified
events, with or without pain. The greatest difficulty is in into:
detecting whether it has taken place at all. Detection of • Episodic memory, which refers to long-term memory
awareness is necessarily retrospective and depends on of personal events associated with a specific
patient recall; there may be confusion as to when in the place and context. Most studies of intraoperative
perioperative period the event being recalled took place. awareness address explicit episodic memory
Only 50% of affected patients report awareness immediately
after operation, and recall may be reported up to a month • Semantic memory, which refers to the recall of known
after anesthesia. (2) facts about the world, such as the names of objects

Depth of Anesthesia –Concepts & Monitoring 194 Seema Deshpande
2. Implicit (or nondeclarative) memory accounts for One limitation of comparing the incidence reported in
changes in behavior (skills, habits, simple forms of different studies is variation in the content of the awareness
conditioning) that result from experience, without the experiences. To address the qualitative aspect of awareness
person or animal being consciously aware that learning events, a framework was developed to classify the features of
has caused the change in behavior. Implicit memory is intraoperative awareness reports. This framework, known as
subdivided into: the Michigan Awareness Classification Instrument, is being
used by investigators working with data in the American
• Procedural memory, such as improvements in the Society of Anesthesiologists Anesthesia Awareness Registry
ability to ride a bike -priming, which occurs when a and in several large, prospective, randomized controlled trials
response interval is reduced by previous exposure on preventing awareness.
to a familiar stimulus
Michigan Awareness Classification Instrument
One of the most potent actions of general anesthetics is
memory blockade. Intravenous and inhalation anesthetics Class 0: No awareness
cause memory blockade at doses considerably lower than Class 1: Isolated auditory perceptions
those required for loss of consciousness and immobility. (1)
Class 2: Tactile perceptions (e.g., surgical manipulation
The problem of awareness first became clinically important or endotracheal tube)
during the 1940s after the introduction of curare, and the Class 3: Pain
practice of ‘balanced’ anesthesia. With administration of Class 4: Paralysis (e.g., feeling one cannot move, speak,
neuromuscular blocking agents, it was possible for patients to
or breathe)
be conscious but unable to respond to environmental stimuli.
Class 5: Paralysis and pain
In Western countries, the overall published incidence of
awareness (with or without pain) has decreased from 1.2% in An additional designation of “D” for distress is included for
the 1960s to around 0.15% in the early part of this century. (2) patient reports of fear, anxiety, suffocation, sense of doom,
sense of impending death, etc.
Collectively, multiple studies suggest that the incidence of
anesthesia awareness is approximately 1 or 2 cases in 1,000 Risk Factors for Awareness
in the general population, with high-risk cases 10 times more
Risk factors can be classified into three subgroups: patients,
common (1 case in 100). (1)
surgical procedures, and anesthetic techniques. (1)
Although the first study of the incidence of intraoperative
Patient related factors
awareness was reported by Hutchinson in 1960, Brice et
al. initiated the current era of its investigation by describing • Females
how to detect awareness. (1) Detection of awareness can be • Unexpected difficult intubation and non-supplementation
facilitated by a structured interview. The one most commonly of anesthesia
used in both research and clinical practice is based on the
• Drug resistance: Prior history of awareness (individual
Brice structured interview. (2)
genetic variability), Excessive alcohol intake, Regular
Brice structured interview (modified): Undertaken use of amphetamines, cocaine, opiates, chronic pain
immediately after anesthesia and again within the next few syndromes
days. • Poor cardiovascular reserve: EF <30%
Questions • Severe aortic stenosis ASA>4
• Life-threatening emergencies: Severe bleeding/
1) What was the last thing you remembered happening
hypovolemia
before you went to sleep?
• Severe septic shock
2) What is the first thing you remember happening on
• Cardiac arrest/peri-arrest
waking?
3) Did you dream or have any other experiences whilst Surgical Procedures
you were asleep?
• Cardiac surgery
4) What was the worst thing about your operation?
• Obstetric surgery
5) What was the next worst?

• Trauma compromise, consider the administration of
• Rigid bronchoscopy benzodiazepines or scopolamine for amnesia.
Anesthetic Technique Related 11. Supplement hypnotic agents with analgesic agents
such as opioids or local anesthetics, which may
• Unrecognized equipment failure help decrease the experience of pain in the event of
• Reduced practitioner vigilance (e.g. vaporizer empty) awareness.
• TIVA (failure of drug delivery or poor understanding of 12. Consider using a brain monitor, such as a raw or
pharmacology) processed electroencephalogram but do not try to
• Underdosing for LSCS (fears for baby) minimize the anesthetic dose based on the brain
• Choice of agents (N2O/O2 or midazolam as sole monitor because there currently is insufficient evidence
anesthetic) to support this practice.
• Light anesthesia after induction, prior to incision 13. Monitor the brain routinely if using total intravenous
• Use of neuromuscular blockers anesthesia.
Drug-induced paralysis may be an important factor 14. Evaluate known risk factors for awareness, and if
contributing to the incidence and severity of awareness. Many specific risk factors are identified, consider increasing
of the patients who were disturbed by their experiences of administered anesthetic concentration.
awareness described feelings of helplessness and an inability
to move. Thus, the use of muscle relaxants may modify the 15. Redose intravenous anesthesia when delivery of
experience of awareness and increase the likelihood of inhalation anesthesia is difficult, such as during a long
PTSD. intubation attempt or during rigid bronchoscopy.
Checklist for Preventing Awareness (1) Assessment of adequate depth of anesthesia is an

important measure in reducing the risk of awareness.
1. Check all equipment, drugs, and dosages; ensure that
drugs are clearly labeled and that infusions are running Methods of Assessment of Depth of Anesthesia
into veins.
Subjective methods
2. Consider administering an amnesic premedication.
• Autonomic changes
3. Avoid or minimize the administration of muscle • Changes in pupil diameter
relaxants. Use a peripheral nerve stimulator to guide • Isolated forearm technique
minimal required dose.
Objective methods
4. Consider using the isolated forearm technique if intense
paralysis is indicated. • EEG & derived indices
• Evoked potentials
5. Choose potent inhalation agents rather than total
intravenous anesthesia, if possible. Subjective Methods
6. Administer at least 0.5 to 0.7 minimum alveolar Autonomic Changes

concentration (MAC) of the inhalation agent.
• Hypertension, tachycardia, sweating, tearing, mydriasis
7. Set an alarm for a low anesthetic gas concentration. • Patient Response to Surgical Stimulus (PRST) Score- 4
8. Monitor anesthetic gas concentration during hemodynamic parameters- Pressure (BP), rate (HR),
cardiopulmonary bypass from the bypass machine. sweating and tearing.
• Any score >3 is considered inadequate anesthetic depth.
9. Consider alternative treatments for hypotension other
than decreasing anesthetic concentration. Disadvantages
10. If it is thought that sufficient anesthesia cannot be • These changes are also seen with intra-operative events
administered because of concern about hemodynamic like hypotension, dehydration, hypoxia, hypothermia,
hyperthermia or sudden blood loss

PRST SCORE
Index Condition Score

Increase in systolic BP <15mmHg from baseline 0
15-30mmHg from baseline 1
>30mmHg from baseline 2
Increase in Heart Rate <15 beats/min from baseline 0
15-30 beats/min from baseline 1
>30 beats/min from baseline 2
Sweating Nil 0
Skin moist 1
Visible beads of sweat 2
Tears No excess tears in open eyes 0
Excess tears in open eyes 1
Tears overflowing 2
• Drugs like inotropes etc. also lead to such hemodynamic Since patient responsiveness is a function of the central
changes while opioids & muscle relaxants suppress nervous system, monitoring brain function during anesthesia
changes. Hemodynamic response to noxious stimuli makes sense. (3)
does not necessarily signify awareness nor does lack
However, not enough attention is paid to brain function in
of hemodynamic changes guarantee unconsciousness
anesthesia practice, likely more due to technical limitations
Isolated forearm technique (IFT) than ignorance. The heart, circulatory system, blood, lungs,
and kidneys all function in ways that are easier to understand
Tourniquet inflated on an arm of patient prior to administering and measure. Examples include pulse rate, blood pressure,
intravenous muscle relaxant isolates the forearm & allows creatinine level and oxygen saturation, which are routinely
it to remain free to move in response to verbal command in used to assess and monitor their function. In comparison,
light plane of anesthesia. brain function is much more complex.
Limitations The oldest and most widely used modality of monitoring
• Nonspecific startle response may be wrongly interpreted brain function is the electroencephalography (EEG). EEG
provides data that in its raw form, has to be interpreted by
as consciousness
highly trained clinicians. Even then, the information obtained
• Higher dose of muscle relaxant required in IFT to prevent is often hindered by interpersonal variations, relatively low
movement signal to noise ratio and limited resolution to detect more
subtle changes. Nonetheless, real-time monitoring of the
• Inability to move arm despite consciousness is overall electrical activity of the brain (predominantly the
complained of by some patients. more peripheral areas of the brain that are proximal to the
There are a majority of experts in the field of awareness electrodes) can be a highly useful tool for the anesthesiologists
who believe that the isolated forearm technique is the ‘gold to objectively assess anesthesia and sedation. (3)
standard’ technique against which other monitors should EEG changes during stages of anesthesia have been
be validated. However, only 50% of patients who respond studied in detail. Figure 1 shows basic EEG waveforms of
to command with an isolated forearm can later recall doing the adult human brain in which y-axis is voltage and x-axis
so. (2) time. General pattern of EEG changes under increasing
doses of anesthesia are shown in Figure 2. As anesthetic
Objective Measures
effect increases, EEG frequency typically slows resulting in
As mentioned earlier, assessment of adequate depth of transition through frequency-based classes: Beta -> Alpha
anesthesia is important to reduce the risk of awareness. -> Theta -> Delta

With these well-established patterns, many of the currently
available brain function monitoring devices mainly use EEG
measurements to provide clinically meaningful outputs. The
difference between the monitors usually lies in the parts of
the EEG data selected, how the data are “cleaned up” and
analyzed, and how the output measures are constructed
and displayed. (3)
Awareness Monitors
In the mid-1990s, depth of anesthesia monitors were

introduced into the market with the hope that they could
decrease the risk of intraoperative awareness. Several
devices are still available, but none have been shown to be
100% effective. (4) These devices monitor brain electrical
activity by assessing electroencephalographic (EEG) activity
Fig 1: Basic EEG waveforms of the adult human brain; y-axis
from electrodes placed on the forehead. They can be divided
is voltage and x-axis time
into:
• Monitors that process
• EEG activity
• Electromyographic (EMG) activity
• Monitors that acquire evoked responses to auditory

stimuli or auditory evoked potentials (AEPs).
Once the device amplifies and converts the analog EEG

signal, proprietary algorithms are applied to the frequency,
amplitude, latency, and/or phase relationship data derived
from the raw EEG or AEP to generate a quantitative data
point (usually a digit scaled from 0 to 100). The clinician can
then use this data point to determine the effect of anesthetic
drugs on the brain.
For most processed EEG monitors, a value of 100 is

associated with an awake state and a value of 0 indicates
an isoelectric EEG.
The currently available EEG-based monitors include
1. Bispectral index (BIS; Covidien, Boulder, Colorado, USA)
2. SEDline Monitor (Masimo, Irvine, CA)
3. State and Response Entropy (SE and RE, GE Healthcare

Technologies, Helsinki, Finland)
4. Narcotrend Index (Schiller AG, Baar, Switzerland)
5. Index of consciousness monitor (Morpheus Medical,

Barcelona, Spain)
6. NeuroSENSE Monitor (NeuroWave Systems Inc,

Fig 2: General pattern of EEG changes under increasing
Cleveland Heights, OH)
doses of anesthesia.

Device Main output and Range Target Range During

Anesthesia
BIS Monitor BIS:0 (almost flat EEG activity) to 100 40-60
(awake
Sedline Patient State Index: 0 (complete EEG 25-50
suppression) to 100 (fully awake)
Narcotrend Monitor Narcotrend stage: stage A (awake) to F Stage E
(deep to profound anesthesia)
Narcotrend index: 0 (no detected electrical
activity) to 100 (awake)
E-entropy Response entropy: 0 (suppressed EEG) to 40-60
100 (fully awake)
State entropy: 0 (suppressed EEG) to 90
(awake)
NeuroSENSE WAVCNS index: 0 (flat EEG activity) to 100 40-60
(awake)
Table 1: Commonly used Brain and EEG monitoring devices, their main reported measures and ranges during anesthesia (3)
7. SNAPII (Everest Biomedical Instruments, Chesterfield,

Missouri, USA)
8. Cerebral State Monitor (Danmeter A/S, Odense,

Denmark).
9. qCON 2000 monitor (Quantium Medical, Barcelona,

Spain)
The only evoked brain electrical activity monitor is the AEP

Monitor/2 (Danmeter A/S, Odense, Denmark)
Table 1 below shows the commonly used brain and EEG

monitoring devices, their reported measures and ranges
during anesthesia
Bispectral index and intraoperative awareness
The BIS is a dimensionless numerical scale that measures

brain activity and is derived from EEG signal processing
techniques that combine bispectral analysis, power spectral
analysis, and time domain analysis using a proprietary
algorithm. (4)
The BIS index range (0 – 100) is meant to represent a

continuum corresponding to the clinical state, ranging
from an isoelectric EEG (0) to a deep hypnotic state: light/
moderate(40), general anesthesia (40 – 60), sedation (60 –
80), and awake (80 – 100). The recommended range of the
BIS index is between 40 – 60 for general anesthesia and 55
– 70 during the last 15 min of surgery. Below, figure 3 shows Fig 3: BIS Index range guidelines
the BIS index range guidelines.

To date, the BIS monitor has been the only brain function abnormal EEG activities such as epilepsy or cerebral palsy
monitor that has been studied in large randomized controlled can change the BIS values in either direction depending
trials (RCTs). Several of these trials have compared on the associated EEG pattern. Also, several medications
outcomes with BIS-guided depth of anesthetic administration including many anesthetic agents such as ketamine,
versus standard clinical practice without the use of the BIS etomidate, halothane, or ephedrine can affect BIS values,
monitor. Because the incidence of intraoperative awareness often resulting in higher values than what they should be. (3)
is low, an extremely large number of patients are needed
Another important factor affecting the reliability of brain
to achieve the statistical power necessary to determine the
monitoring indices is the age of the patient. Studies have
efficacy of the BIS for preventing intraoperative awareness.
shown that aging is associated with widespread changes in
Myles et al. published the B-Aware trial in which adult
EEG signals. Many of the currently available brain monitors
patients were randomly allocated to BIS-guided anesthesia
do not account for these age-related changes since they
or routine care in double blind fashion; this multicenter
were originally tested in healthy volunteers.
trial demonstrated that BIS-guided anesthesia reduces the
incidence of awareness in high-risk adult surgical patients A summary review of the current literature suggests that
having general anesthesia. (5) Zhang et al. found that a the BIS index is useful in providing information on depth of
BIS-guided anesthetic decreased the risk of awareness in anesthesia during TIVA and may decrease awareness in
patients undergoing a total intravenous anesthetic (TIVA) this group of patients. On the other hand, BIS monitoring
and determined that the main reason for awareness in the is not superior (and may, in fact, be inferior) in preventing
setting of TIVA was light anesthesia. (6) intraoperative awareness compared with maintaining an
ETAC greater than 0.7 age-adjusted MAC if using an inhaled
On the other hand, the B-Unaware and BAG-RECALL trials anesthetic agent for maintenance of general anesthesia. (4)
showed that alarms to prevent light anesthesia based on the
BIS (alert if 60 < BIS < 40) were not superior to alarms based Entropy
on the End Tidal Anesthetic Concentration (ETAC) (alert if
The Entropy (GE Healthcare Technologies, Waukesha, WI,
1.3 MAC < ETAC < 0.7 MAC) in preventing awareness in
USA) monitor calculates the indices by measuring irregularity
high-risk patients. Mashour et al. published the largest RCT,
in the data acquisition of EEG and frontal EMG signals.
which demonstrated that BIS is superior to clinical signs of (8) The indices consist of two separate parameters: the
awareness, but not to ETAC maintained at greater than 0.5 fast-reacting Response Entropy (RE) and the more steady
age-adjusted MAC, in preventing explicit recall in patients and robust State Entropy (SE). Highly irregular signals with
having general anesthesia. (7) varying wavelength and amplitude over time produce high
Pitfalls with BIS entropy values and indicate that the patient is an awakened
state. More ordered signals with less variation in wavelength
EEG signals are inherently “noisy,” and many factors from and amplitude over time produce low or 0 entropy values,
placement of sensors and applied pressure to interference representing suppression of brain electrical activity and a low
from other electrical devices can affect the signals. When the probability of awareness.
output measure of the brain monitoring device is affected,
SE ranges from 0 (no brain activity) to 91 (awake), reflecting
there can be incorrect assessment of the depth of anesthesia.
the cortical state of the patient. RE ranges from 0 (no brain
(3)
activity) to 100 (awake).
For example, too much muscle tone at the area of
Therefore, RE values respond to the EMG activity resulting
sensor attachment (forehead) can increase BIS values
from inadequate analgesia. SE values are always less than
(electromyography interference) while too much
or equal to RE and based on the estimated hypnotic effect
neuromuscular blockade can have the inverse effect,
of anesthetic drugs during general anesthesia because they
reducing the BIS values. Electromechanical interference
are based on the EEG signal.
from other devices (such as pacemakers, surgical navigation
systems, endoscopic devices, and electrocautery) can lead Narcotrend
to artifacts, increasing the BIS values.
The NarcotrendR (MonitorTechnik, Bad Branstedt, Germany)
Conditions associated with reduced cerebral metabolism analyzes the raw EEG data using spectral analysis to produce
such as-cardiac arrest, hypovolemia, hypotension, cerebral a number of parameters and provides an automatically
ischemia, hypoglycemia, and hypothermia-may lead to classified EEG using proprietary pattern recognition
incorrectly low BIS values. Conditions associated with algorithms.

The EEG classification scale is A (awake), B (sedated), it provides EEG suppression percentage and a measure of
C (light anesthesia), D (general anesthesia), E (general EMG activity (75-85 Hz). To date, no correlation between the
anesthesia with deep hypnosis) and F (general anesthesia Cerebral State Monitor and the incidence of intraoperative
with increasing burst suppression). The system included a awareness has been reported.
series of subclassifications resulting in a total of 14 possible
Evoked brain electrical activity monitor
substages: A, B0-2, C0-2, D0-2, E0-1 and F0-1. The A-F
scale is also translated into a dimensionless index (0 = deep Measurement of EEG response to repeated stimuli is the
general anesthesia, 100 = awake) similar to the BIS index. basis for evoked potentials. The stimulus is usually auditory—
and hence the term, auditory evoked potentials—but other
SEDline
stimuli such as visual or sensory can also be utilized. It is
SEDline (Masimo, Irvine, CA) collects data from both important to understand the fundamental difference between
hemispheres using 4 individual EEG channels. The this approach and the other EEG-based brain monitoring
consolidated measure of depth of anesthesia in SEDline is approaches described before.
called the patient state index, ranging from 100 (fully awake
While EEG-derived monitoring can be viewed as a measure
state) to 0 (complete EEG suppression), with ranges between
of spontaneous electrical activity of the central nervous
25 and 50 considered optimal during general anesthesia.
system (predominantly cortex), evoked potentials are
Patient state index algorithm combines various aspects of
measures of the response to (peripheral) stimuli, and they
EEG data such as power changes in different frequency
are also affected by the neurological pathways conveying
channels and changes in inhibition and synchronization of
signals from periphery to the cortex.
signals from different regions of brain. Another measure,
density spectral array, provides a comparison between AEP Monitor/2
the hemispheric activity and allows the clinicians to spot
asymmetries in activities between the hemispheres. AEP Monitor/2 (Danmeter A/S, Odense, Denmark) extracts
the auditory evoked potentials (AEPs) from the electrical
SNAP index responses (EEG-signal) of the brainstem by using the
auditory radiation and the auditory cortex responding to
The SNAPII (Everest Biomedical Instruments, Chesterfield,
auditory sound stimuli. The change in AEP for regarding the
MO, USA) produces an index based on a single EEG channel
anesthetic drug effect has been investigated since the 1980s.
derived from a spectral analysis of EEG activity based on
The brainstem response is less sensitive to anesthetic drugs,
low- frequency (0.1-18 Hz), high-frequency (80-420 Hz) and
whereas middle-latency AEPs as early cortical responses
a burst suppression algorithm. A mean SNAP index of 71
respond predictably to alternating of concentrations of both
represents 95% of elective surgery patients with a loss of
volatile and intravenous anesthetic drugs. The AEP response
consciousness.
with an increased concentration of anesthetic drug showed
Cerebral State Monitor/Cerebral State Index an increased latency and decreased amplitude. These
AEP signals are necessary in signal averaging techniques
The Cerebral State Monitor (Danmeter A/S, Odense, because the AEP signal is extremely low (< 1 µV). The AEP
Denmark) produces an index (0 = isoelectrical activity, 100 index (AAI) is calculated using a mathematical analysis of the
= awake) by analyzing a single EEG channel. In addition, AEP waveform and is a correlation of drug effect of general

anesthetics. The AAI ranges from 0-100 with an AAI > 50 The table below provides a list of the currently available
corresponding to the awake state and ranges from 15-25 for processed EEG-based monitors in alphabetical order.
anesthesia, lower numerical thresholds in contrast to other (9)
EEG indices.
Table: Brief Description of Currently Available Processed EEG-Based Monitors in Alphabetical Order
Monitor Features
The AEP index, the AAI, is an index relying on MLAEP and EEG signals. Bilateral click stimuli
are delivered through headphones. The EEG signals after the stimuli are discerned from
AEP Monitor/2 (Danmeter the background EEG noise and processed for MLAEPs, reflecting neural activity within the
A/S, Odense, Denmark) thalamus and primary auditory cortex. When the AEP signals are low in quality, the AAI
is derived mainly from EEG-based spectral parameters. Burst suppression ratio and EMG
data are also displayed. Two index scales: 0–60 and 0–100.
It utilizes an algorithm based on power spectral analysis, bispectral analysis, and burst
suppression data. The derivation of the BIS index is achieved through a weighted sum
BIS Monitor (Medtronic, of relevant subparameters. The BIS index scale is from 0 to 100. In addition to a single-
Minneapolis, MN) channel EEG, it also offers a bilateral sensor for assessment of asymmetry. Density
spectral arrays and spectral edge frequencies can be displayed as well as EMG activity and
burst suppression information.
The algorithm for the cerebral state index utilizes frequency domain analysis and burst
Cerebral State Monitor
suppression ratio processed with fuzzy logic methodology for inference of the index. It
(Danmeter A/S, Odense,
uses a single-channel EEG with an index scale of 0 to 100. In addition to the index, it also
Denmark)
provides measures of burst suppression percentage and EMG activity.
The algorithm uses spectral analysis to produce 2 main parameters for overall assessment
of depth of anesthesia: the SE, for depth of hypnosis (index scale, 0–100), and RE, for
Entropy Module (GE
indirect assessment of noniception/responsiveness to stimuli (derived from the frontal
Health care Technologies,
EMG; index scale, 0–91). A widening difference between SE and RE is deemed a likely
Helsinki, Finland)
indicator of inadequate anesthesia. In addition to the waveform display of SE and RE, a
burst suppression ratio is also displayed. It uses a single-channel EEG.
Monitor Features
The index of consciousness is derived via symbolic dynamics, a time domain method that
divides the EEG signals into partitions and labels each partition with symbols of 1 and 0,
depending
Index of consciousness
on mathematical determination. It is conceptually similar to entropy. This approach can
monitor (Morpheus
detect nonlinear EEG characteristics and assess levels of signal complexity. The algorithm
Medical, Barcelona, Spain)
also includes frequency domain methods and burst suppression analysis. A fuzzy logic
inference system is used in index derivation. Burst suppression and EMG information are
also displayed. Single- channel EEG with an index scale of 0 to 99.
The Narcotrend index is derived from a system developed for the visual classification of
the EEG patterns associated with stages of natural sleep. It uses burst suppression, time,
Narcotrend Monitor
and frequency domain analysis to extract the relevant EEG parameters, which are then
(MonitorTechnik, Bad
classified through plausibility testing into a total of 14 possible substages: A (awake) to F
Bramstedt, Germany)
(deep) with further subdivisions. The most recent version also provides an index from 0 to
100. Uses 1- or 2-channel EEG. Also displays EMG information.
The WAVcns index is calculated via wavelet analysis of the EEG signals in the gamma
NeuroSENSE Monitor frequency band, using a deterministic approach (a method that always produces the
(NeuroWave Systems Inc, same output for a given EEG interval). This monitor was purposefully developed for use in
Cleveland Heights, OH) anesthesia closed-loop delivery systems. It uses bilateral brain monitoring for derivation
of index with a scale of 1 to 100.

Monitor Features
The patient state index is calculated by a 4-channel EEG with an algorithm incorporating
high heterogeneity of variance at different levels of sedation/hypnosis, taking into
account anterior– posterior relationships in the brain and coherence between bilateral
SEDline Monitor (Masimo, brain regions. Burst suppression data and plausibility analysis are applied for final index
Irvine, CA) derivation. It also displays bilateral density spectral arrays, and bilateral 4 channels of
raw EEG waveforms. Scale consists of 0–100, with optimal depth between 25 and 50
(in contrast to other monitors with similar scale and recommended anesthetic depth
between 40 and 60).
The SNAP index is based on calculations involving power spectral analysis in the 0 to 18
and 80 to 420 Hz frequency ranges, called the low-frequency index and high-frequency
SNAPII Monitor (Stryker,
index, respectively, for the derivation of the single index. It claims an algorithm that
Inc, Kalamazoo, MI)
minimizes artifacts and a shorter lag time to detect patient awakening. It uses a single-
channel EEG and an index scale of 0 to 99.
The qCON index is derived from spectral analysis and burst suppression rate and
processed through an artificial neural network and fuzzy logic system. Conceptually, it has
qCON 2000 monitor similarities to the entropy approach. The qCON index is a measure of hypnosis, whereas
(Quantium Medical, the qNOX index is a measure of noniception, each similarly derived through different
Barcelona, Spain) frequencies. Both indexes range from 0 to 99. The qNOX reference scale was derived
through EEG signals in patients moving in response to nailbed pressure. Single-channel
EEG. Also displays EMG and burst suppression data.
This list is not intended to be all inclusive.
Abbreviations: AEP, auditory-evoked potential; EEG, electroencephalogram; EMG, electromyogram; MLAEP, middle-
latency AEP; RE, response entropy; SE, state entropy.
From (9): Fahy BG, Chau DF. The Technology of Processed Electroencephalogram Monitoring Devices for Assessment of
Depth of Anesthesia. Anesth Analg. 2018 Jan;126(1):111-117.
After review, it is evident that most EEG-derived brain awareness in 2006 recommended that the decision to use a
monitoring devices (with the exception of evoked potential brain function monitor be made on a case-by-case basis with
monitors) follow a relatively similar pattern that was first each patient’s anesthetic tailored to his/her comorbidities and
introduced commercially by BIS analysis, presenting their key the procedure performed.
proprietary measures within a scale of 100 (fully awake) to 0
(flat or minimal EEG activity), with the target range in general References
anesthesia usually ranging from 40 to 60. When comparison Mashour GA, Orser BA, Avidan MS. Intraoperative awareness:
is made with the standard clinical approach (which most from neurobiology to clinical practice. Anesthesiology.2011
often lacks any brain function monitoring), brain monitoring May;114(5):1218-33.
devices have advantages in terms of reduced consumption
of anesthetic agents and shortened anesthesia recovery Nick Goddard, BM BCh BA FRCA, David Smith, BM BS DM
time, while the evidence on the impact of these devices FRCA. Unintended awareness and monitoring of depth of
on reducing the risk of intraoperative awareness and other anaesthesia. Continuing Education in Anaesthesia Critical
complications is very limited. Care & Pain, Volume 13, Issue 6, December 2013, Pages
213–217
Multimodal approaches combining both sets of standard and
brain monitoring measures may be able to achieve the most Shander A, Lobel GP, Mathews DM. Brain Monitoring and the
accurate assessment of depth of anesthesia. Depth of Anesthesia: Another Goldilocks Dilemma. Anesth
Analg. 2018 Feb;126(2):705-709.
Given the lack of conclusive evidence surrounding the
brain function monitors’ ability to prevent intra-operative Stein EJ, Glick DB. Advances in awareness monitoring
awareness, practice patterns relating to their use vary technologies. Curr Opin Anaesthesiol. 2016 Dec;29(6):711-
substantially. The ASA’s Practice Advisory for intraoperative 716.

Myles PS, McNeil J, Forbes A, Chan MTV. Bispectral surgical population: a randomized comparative effectiveness
index monitoring to prevent awareness during anesthesia: trial. Anesthesiology 2012; 117:717 – 725.
the B-Aware randomized controlled trial. Lancet 2004;
363:1757–1763. Chung HS. Awareness and recall during general anesthesia.
Korean J Anesthesiol. 2014 May;66(5):339-45.
Zhang C, Xu L, Ma Y, et al. Bispectral index monitoring
prevent awareness during total intravenous anesthesia: Fahy BG, Chau DF. The Technology of Processed
a prospective, randomized, double- blinded, multicenter Electroencephalogram Monitoring Devices for Assessment
controlled trial. Chin Med J 2011; 124:3664–3669. of Depth of Anesthesia. Anesth Analg. 2018 Jan;126(1):111-
117.
Mashour GA, Shanks A, Tremper KK, et al. Prevention of
intraoperative awareness with explicit recall in an unselected

MCQ
1. Which of the following is not a part of PRST (patient 4. What should be the target ETAC(end tidal anaesthetic
response to surgical stimulus ) score? concentration) to prevent awareness?
A. Blood pressure A. 0.7 age adjusted MAC

B. Heart rate B. 1 age adjusted MAC
C. Movement C. 1.2 age adjusted MAC
D. Sweating D. 0.9 age adjusted Mac
2. When the depth of anaesthesia increases what is the 5.Which of the following is not a method of assessment
change in EEG pattern? of depth of anaesthesia?
A. beta-alpha-theta-delta A. EEG and derived indices

B. beta-delta-alpha-theta B. Autonomic changes
C. alpha-beta-theta-delta C. EMG
D. alpha-theta-delta-beta D. Evoked potentials.
3. What is the target range during anaesthesia in Sedline

monitor?
A. 40-60
B. 25-50
C. 30-60
D. 20-50
5.C 4.A 3.B 2.A 1.C
ANSWERS:

21 MONITORING INTRAOPERATIVE COAGULOPATHY
Professor, Bhavani Shankar Kodali

University of Maryland Medical Center,
Baltimore.
Key points
Ø Even with changing time and technology, a quick method to know the coagulation status during an intraoperative
hemorrhage has not been mastered yet.
Ø The conventional coagulation cascade tests (PT, INR, PTT, Fibrinogen, D Dimer products), can always be the first
step during an ongoing bleed.
Ø TEG and ROTEM measure the viscoelastic properties of clot formation.
Ø TEG documents initial fibrin formation, clot rate strengthening and fibrin-platelet bonding via GPIIb/IIIa to eventual
clot lysis.
Ø Hemosonics Quantra Analyser uses state of the art ultrasound technology to measure clot stiffness.
Ø Triad of death includes- Hypothermia, acidosis and coagulopathy.
Ø Temperature and calcium monitoring (Quad of Death) along with acid base status should be left out of clinical
coagulation monitoring.
Introduction
Coagulopathy management is changing with time and

technology. However, we have not yet mastered a quick
method of knowing coagulation status during an ongoing
hemorrhage. Most of the currently available technologies
have a processing time of 15 to 30 minutes and this may
not include transportation of blood samples to the laboratory.
Due to extended delays in obtaining results, management
of coagulopathy remains a guessing game. However, every
effort must be made to stream line the processes involved in
quick transportation, and subsequent analysis of the samples
on a priority basis.
In an ongoing bleed, the first step seems to be, a good

old-fashioned technique of collecting a red top tube with no
reagent and placing it vertically. Simultaneously, the blood
samples can be sent to the laboratory for conventional tests
such as PT, INR, PTT, Fibrinogen, D Dimer products (Fig 1).
Each one of these tests reflects a component of clotting

pathway. Platelet functionality is not routinely used in our
clinical practice to monitor coagulation. It is used specifically,
if platelet dysfunction is suspected. If the red top blood clots
in 7 to 9 min, if offers an initial estimate that coagulation
seems normal. If blood remains fluid, it seems futile to wait Figure 1: Conventional Coagulation Cascade Tests

Monitoring Intraoperative Coagulopathy 206 Bhavani Shankar Kodali
for laboratory values to show abnormal results and thus Measurement technology: TEG measures the viscoelastic
delaying management. properties of blood in vitro. It has never been popular with
hematology laboratories, as it is not capable of performing
The laboratory coagulation results obtained during ongoing multiple batch analysis. It consists of a heated (37 °C)
hemorrhage and management reflects the coagulation cuvette or cup, that holds the blood (0.36 ml) as it oscillates
status at the time of blood sampling and not, the current through an angle of 4° 45’. Each rotation lasts 10 secs, which
circumstances of the clinical case. This lag can be as much as includes a one-second rest period at the end of the excursion.
an hour and the clinicians must guess the current coagulation A pin, which is suspended freely in the blood by torsion wire,
status based on the earlier results and products transfused. is monitored for motion (figure 2). The torque of the rotating
Hence, the guessing game continues. To help us to estimate cup is transmitted to the pin once the clot starts to form.
coagulation as recent as possible, several new technologies Therefore the strength & rate of these fibrin-platelet bonds
made their way into clinical practice. affect the magnitude of pin motion. When the clot lyses, the
Thromboelastography (TEG) and ROTEM, ROTEG bonds are broken & the transfer of cup motion is diminished.
The rotation of the pin is converted by a mechanical-electrical
TEG and ROTEM measure the viscoelastic properties of clot transducer to an electrical signal that can be monitored and
formation. Basically, they measure how quickly the clot forms, recorded by a computer. Thus, TEG documents initial fibrin
how quickly it strengthens, what is the maximum strength formation, clot rate strengthening and fibrin-platelet bonding
and, if there is breakdown with decrease in the strength of via GPIIb/IIIa to eventual clot lysis (figure 2).
the clot over time.
Fig 2: TEG

Components of a Thromboelastogram (figure 2) MA as follows: G=5000MA/100-MA. An amplitude of 50mm

(normal value for whole blood) corresponds to a SEMS of
R gR time (mm, or min=mm/2) is the period of time that 5000 dyn/cm2. An increase in MA from 50mm to 67mm is
the blood was placed in the TEG until the initial fibrin equivalent to a two-fold increase in the SEMS. Therefore it
formation. Prolonged by anticoagulants and shortened by is more sensitive to small changes in the clot strength or clot
hypercoaguable conditions. breakdown than the amplitude is in millimeters.
K gMeasured (mm, or min=mm/2) from R time, until the CI gA Coagulation Index (CI) that describes patient’s overall
level of clot firmness reaches 20mm (divergence of the lines coagulation is derived from the R, K, MA and α of native or
from 2 to 20 mm). Therefore K is a measure of speed clot celite-activated whole blood tracings (CI for celite activated
strengthening. K is shortened by an increased fibrinogen blood= 0.3258R-0.1886K+0.1224MA+0.0759α-7.7922).
level, and to a lesser extent, by platelet function, and is Normal values range from -3.0 to +3.0, which is equivalent
prolonged by anticoagulants. to three standard deviations about the mean, zero. Positive
Angle α gThis angle is formed by the slope of the TEG values outside this range (CI>3) indicate that the sample is
tracing at ‘R’ from the horizontal line. Like ‘K’, it also hypercoagulable, whereas negative values outside this range
denotes the speed at which solid clots form. Angle α is also (CI<-3) indicate that the sample is hypocoagulable.
increased by increased fibrinogen levels and to a lesser LY30 & LY60 g LY30 and LY60 measure percent lysis at
extent by increased platelet function and is decreased by 30 and 60 minutes after MA is reached. Measurements are
anticoagulants. In hypocoagulable states where the clot based on the reading of the area under the TEG tracing,
amplitude never reaches 20mm (i.e. K is undefined) the angle from the time MA is measured until 30 or 60 minutes after
is more comprehensive than ‘K’ time. the MA. Therefore, when LY30 or LY60 values are high, the
MA gMaximum Amplitude (mm) is the measurement of fibrinolytic activity is high.
maximum strength of the developed clot which depends on ROTEM (Rotational Thromboelastometry):
fibrin and platelets .
ROTEM is similar to TEG with a difference that the cup rotates
G gThe actual measure of clot firmness (shear elastic modulus in TEG, whereas the needle rotates in ROTEM.
strength, SEMS) is measured in dyn/cm2 . Calculated from
Morphological configurations
Figure 3: Morphological Diagnosis and component therapy replacement. Rotem.

The diagnosis of a coagulation defect can be made from numbers or shape of the graph obtained (Fig 3)
Figure 4: shows relationship of conventional coagulation tests against TEG
Figure 5: The relationship of MA vs Platelet number

Hemosonics Quantra Analyzer
Figure 6: Sonic estimation of elasticity via Resonace
The Quantra system is based on a patented technology called SEER (Sonic Estimation of Elasticity via Resonance)
Sonorheometry. It uses state of the art ultrasound technology to measure clot stiffness (sheer modulus of elasticity) over
time using ultrasound induced resonance.
Figure 7: Functionality of Quantra System
Quantra uses a plastic cartridge with embedded reagents. The cartridge has 4 test channels that perform 4 parallel and
independent measurements using different reagent combinations in each channel. The cartridge has connection mechanism
for attaching 3 ml syringe that can contain blood for coagulation analysis.

Channel Reagents
1 Kaolin, calcium, buffers, and stabilizers
2 Kaolin, heparinase I, calcium, buffers, and stabilizers
3 Thromboplastin, polybrene, calcium, buffers, and stabilizers
4 Thromboplastin, polybrene, abciximab, calcium, buffers, and stabilizers
Table 1: The reagents used in each channel
The reagents in Channel 1 are optimized for the of residual heparin in the sample. Channel 3 is optimized
measurements of Clot Time, whereas the Channel 2 to provide measurements of clot stiffness, which combines
measures Clot Time without the effect of any potential information about platelets and fibrinogen function.
heparin in the blood sample. Clot Time provides an Finally, channel 4 is optimized to measure the Fibrinogen
indication of the functional status of the coagulation contribution to clot stiffness. Both channels 3 and 4 use
factors that lead to fibrin formation. Furthermore, Clot hexadimethrine bromide to neutralize residual heparin. The
Time and Heparinase Clot Time (channel 2) can be difference between Channel 4 and 1 can provide platelet
combined to a clot time ratio for determining the presence contribution to clot stiffness.
Figure 8: Triad of death plus Calcium monitoring during coagulation (Quad of death)
Temperature Monitoring and Ionic Calcium Measurement (QUAD of death)
Temperature and calcium along with acid base status should be left out of clinical coagulation monitoring.

MCQ
1. TEG measures all except 4. Triad of death includes all except
A. Initial fibrin formation A. Hypothermia

B. Clot rate strengthening B. Acidosis
C. Fibrin platelet bonding C. Coagulopathy
D. Platelet quantity D. Hypotension
2. MA, maximum amplitude denotes 5. Quantra system is based on
A. Speed at which solid clots form A. Ultrasound technology

B. Max strength of developed clot B. Electromagnetic waves
C. Clot firmness C. Thermal signature
D. Initial fibrin formation D. Digital waves
3. The difference between TEG and ROTEM mainly is
A. Temperature of the heated cuvette is different

B. Angle of oscillation is different
C. Cup rotates in TEG, whereas in ROTEM the needle
rotates
D. Rotation time for TEG is 10 sec, whereas im
ROTEM it is 15 sec
5.A 4.D 3.C 2.B 1.D
ANSWERS:

22 ANAESTHETIC MANAGEMENT OF BRAIN DEAD
DONOR FOR ORGAN RETRIEVAL
Lead Consultant Jayanti Shankar

Sakra World Hospital
Bangalore
Key points
Ø Transplantation of organs has evolved as the treatment of choice for patients with end-stage organ disease
Ø Brain death is often associated with marked physiological instability, which, if not managed, can lead to deterioration
in organ function before retrieval, thus preventing successful donation
Ø Anesthesiologists should familiarize themselves with the challenges during the crucial period preceding and
during the actual harvest of organs in a brain-dead donor to improve the number and quality of donor organs
Ø Increasing number of marginal donors is now being accepted
Ø Cardiac output monitoring, lung protective ventilation, fluid and nutrition balance, correction of coagulopathy,
thromboprophylaxis and temperature management are some of the principles of donor management.
Ø The aim of the Apnea test is to check for the integrity of the brainstem respiratory center at high levels of blood
carbon dioxide.
Ø Diagnosis of brain death is established and recorded by two doctors not belonging to the transplantation teams,
one of which should be a neurologist(in the absence of a neurologist, an anesthesiologist may be present).
Ø Goals of anaesthesia for organ procurement align with established ICU care of the brain dead donor as well as
abolishing spinal motor, and hemodynamic reflexes
Ø A well-managed and organised harvest will ensure good quality organs and an overall superior outcome in the
recipients
Introduction the function of donated organs. In addition, when a

neurologist or neurosurgeon is not available in the hospital,
Transplantation of organs has evolved as the treatment an anaesthesiologist (not part of the transplant team) can be
of choice for patients with end-stage organ disease. The the member of the board of medical experts for certification
donor pool predominantly consists of brain-dead donors of brain death. This places additional responsibility to gain
and therefore optimizing a potential donor is the first step in knowledge and get trained in understanding the current
the management of multiple recipients. Large percentage of concepts in organ donation.
donated organs are not used for transplant due to poor quality
of the organ. To maximize benefit to as many recipients as Scope of Topic
possible, and to facilitate efficient use of all donated organs,
it is imperative to understand the widespread physiological 1) Intra cranial events leading to brainstem death
changes that follow brainstem death. Active donor 2) Systemic physiological changes after brainstem death
resuscitation and optimum management can help to preserve
the functional integrity of the potentially transplantable organ, 3) Management of brain-dead donor
thereby resulting in a successful transplantation. • Declaration of brain death
Anaesthesiologists play a role in maintaining hemodynamics • Resuscitation and maintenance of the organ donor
and physiological stability of donors and thereby preserving • Intraoperative management during organ retrieval

Anaesthetic Management of Brain Dead 214 Jayanti Shankar
Donor for Organ Retrieval
Intra Cranial Events Leading to Brainstem Death

Acute intra cranial haemorrhage or head injury
i
Increased intra cranial pressure
i
Progressive mass effect in the brain
i
Worsening of cerebral ischemia
i
Venous engorgement
i
Brain swelling
i
Herniation through foramen magnum
i
Arterial compression
i
Tissue ischemia and infarction
Sequential physiological changes occur as different areas of the brainstem become ischemic
Brainstem ischemia progresses in a rostral-caudal fashion and mean arterial pressure rises in effort to maintain the cerebral
perfusion pressure

Systemic Physiological Changes after Brainstem Death
Cardiovascular
Brainstem injury leads to severe hemodynamic instability, the degree of which is directly related to the severity of brain injury
and resulting degree of autonomic dysfunction. It is clear that neural and humoral factors play a role.
2. Initial period of intense autonomic activity is followed 3. Unsupported brain-stem dead patients undergo systolic
by loss of sympathetic tone and massive reduction cardiac arrest within a short time. Despite maximal
in systemic vascular resistance. The secondary support, 25 % of potential donors die before their
cardiovascular collapse occurs due to profound organs can be retrieved.
vasodilatation rather than as a result of the primary
cardiac injury. Pulmonary Changes
Causes of persistent hypotension Respiratory complications associated with brain injury
Loss of central sympathetic outflow, decreased cardiac 1. Pneumonia

output, blunted haemostatic responses, severe peripheral 2. Aspiration
vasodilatation (vasoplegia), and hypovolemia caused by 3. Neurogenic pulmonary edema
diabetes insipidus. 4. Pulmonary trauma

5. Direct injury to lungs due to catecholamine surge

Reduced T3 leads to: -
6. Sympathetic stormgsystemic vasoconstrictiong increased
cardiac afterload gelevated left atrial and ventricular • Progressive loss of cardiac contractility
pressure g Increased pressure in pulmonary capillary • Depletion of high energy phosphates
bed + endothelial damage pulmonary edema.
• Increased anaerobic metabolism
7. Sympathetic stimulation (α adrenergic) and generalized • Accumulation of lactate
inflammatory responsegPulmonary capillary permeability
g pulmonary edema
8. High FiO2 and PEEP requirement gOxygen toxicity and 4. Glucose metabolism
barotrauma
A) Depletion of insulin levels
Reduced PVR gIncreased pulmonary capillary permeability
and pulmonary overflow g causes right ventricular dysfunction. i
Decrease in intracellular glucose
Endocrine Changes
i
Posterior pituitary failure is seen in 80% of cases, anterior Energy deficit
pituitary is more resistant g the main emphasis is on replacing i
vasopressin secreted by the posterior pituitary. Anaerobic metabolism, acidosis
1. Anti-diuretic hormone (posterior pituitary) B) Administering large volume of glucose containing fluids
to treat Hypernatremia (due to DI)
2. Cortisol (anterior pituitary)
3. Thyroid (anterior pituitary) i
4. Insulin and glucose (anterior pituitary) • Increased catecholamine
• Hyperosmolar state
1. Early depletion of anti-diuretic hormone (posterior
• Osmotic diuresis
pituitary stops secreting vasopressin)
• Profound hypovolemia
Development of diabetes insipidus
DIABETES INSIPIDUS Other Systems

• Inappropriate diuresis
Hepatic function g depletion of hepatic glycogen and
• Severe hypovolemia
reduction in hepatic sinusoidal perfusion.
• Hyperosmolality
• Hypernatremia Renal g hypotension leads to renal vasoconstriction.
i Prolonged renal vasoconstriction leads to acute kidney injury
2. Decrease in adrenocorticotropic hormone (ACTH) and renal failure.
from anterior lobe of pituitary
i Coagulation g tissue thromboplastin released by necrotic
Cortisol levels decrease after brainstem death brain tissue
i i
}
Impaired stress response in brain dead donors activates coagulation
3. Impaired thyroid stimulating hor- i
mone (TSH) function endothelial dysfunction
+ Disseminated intravascular coagulation (28% of donors)
impaired peripheral conversion to T4 Sick
(tetraiodothyronine) euthyroid Temperature regulation g Hypothermia due to
i state
• impairment of temperature regulation secondary to loss
Rapid decline of free T3 (triiodothyronine)
of hypothalamic control
i

• fall in metabolic rate leads to reduced heat production is essentially the absence of response to noxious stimulus
• loss of muscular activity also contributes to reduced (supraorbital pressure or pressure on the nail bed) with the
heat production exception of spinally mediated reflexes.
• loss of shivering mechanism Example of causes - Spontaneous intracranial haemorrhage,
• profound vasodilatation leads to heat loss head injury, cerebral anoxia/ischemic injury (cardiac arrest
due to asthma, asphyxiation, drug overdose, hanging,
Immune system drowning, meningitis, carbon monoxide poisoning or primary
Making the organs
Activation of endothelial cells, platelets more susceptible cardiac arrest), primary cerebral tumour.
and leukocytes to post-transplant
Rule out confounding factors - Shock/ hypotension,
host inflammatory
Upregulation of proinflammatory hypothermia, neurotoxic snake envenomation, brainstem
and immunological
mediators encephalitis, Guillain- Barre’ syndrome, Encephalopathy,
response
Severe hypophosphatemia, drugs known to alter neurologic,
neuromuscular function and electroencephalographic testing,
like anaesthetic agents, neuro-paralytic drugs.
This increase in immunogenicity renders the
transplanted organ more susceptible to the Absence of Brainstem Reflexes
recipient’s immune system and increases
likelihood of early rejection. A formal evaluation of the brainstem reflexes is undertaken
when the patient has had fixed dilated pupils and absent
cranial nerve reflexes for more than 4 hours.
Management of the Brain dead Donor (BDD)
Performance of a complete neurological examination
Appropriate management of the donor from the diagnosis of
brain death to the end of organ procurement is of paramount • Examination of the patient for response to noxious stimuli
importance. This can be divided into:
• Absent pupillary light reflex- Afferent II cranial nerve,
• Declaration of Brainstem death efferent III nerve
• Pre-procurement management • Absent corneal reflex -Afferent V nerve, efferent VII nerve
• Organ procurement procedure
• Absent reflexes in the face and maxillary region - Area
Declaration of Brain Death supplied by V cranial nerve (trigeminal)
The Transplantation of Human Organs Act, 1994 - definition • Absent oculo-cephalic reflex (doll’s eye movement)
of death: ‘Deceased person’ means a person in whom -Afferent VIII, efferent III and VI.
permanent disappearance of all evidence of life occurs-
(1). By reason of brain-stem death or (2). In a cardio- • Absent oculo-vestibular reflex- The afferent is the VIII
pulmonary sense. and efferent III and VI cranial nerves.
(Donation after circulatory arrest is beyond the scope of • Absent pharyngeal (gag) and laryngeal (cough) reflex)-
this discussion) Afferent IX and efferent X cranial nerves
Brainstem Death: ‘Brain-stem death’ means the stage at Absence of Respiratory Efforts In The Presence Of
which all functions of the brainstem have permanently and Hypercarbia - The Apnoea Test
irreversibly ceased. The aim of this test is to check for the integrity of the brainstem
Criteria for Diagnosis: Irreversible coma + Absence of respiratory center at high levels of blood carbon dioxide.
brain-stem reflexes + Apnoea When should the test be done?
Irreversible Coma After the first clinical exam, the patient should be observed
The determination of brain death requires the identification for a defined period of time for clinical manifestations that
of the proximate cause and irreversibility of coma. Coma are consistent with the diagnosis of brain death.

A 6-hour observation period is sufficient and reasonable in Indeterminate - If PCO2 is < 60 mm Hg and PCO2 increase
adults and children over the age of 2 years. is < 20 mm Hg over baseline, the result is indeterminate and
a confirmatory test can be considered or apnoea test can
Pre-requisites for the apnoea test be repeated.
• Proximate cause for unresponsive state that is Negative – observed respiration during apnoea test
incompatible with survival
• Neurological imaging to confirm diagnosis (CT/MRI etc.) Ancillary tests
• Exclusion of associated medical conditions that could When clinical examination, assessments of brainstem
account for unresponsiveness reflexes and the apnoea test are conclusive, no additional
• Exclusion of drugs causing unresponsiveness (drug testing is required to determine brain death.
overdose g wait for 5 half-lives before testing)
Indications for ancillary tests are:
• Core temperature ≥ 36.5°C or 97.7°F
• Euvolemia or positive fluid balance in the previous 6 1) Patients with cranial or cervical Examples of
hours injuries, cardiovascular instability ancillary tests-
• Normal PCO2 or arterial PCO2 ≥ 40 mm Hg 2) Severe facial trauma, otorrhagia, Electroence
eye agenesis, phalography
Steps for the apnoea test (EEG), Cerebral
3) For reassurance of family members
angiography,
Preoxygenate patient with 100% O2 for 10 to 15 minute (to and medical staff. Transcranial
ensure denitrogenation of lungs) and do a base line ABG 4) Panel of doctors is in doubt or doppler,
(try to achieve an arterial PO2 ≥ 200 mm Hg for safely disagreement of the diagnosis Radionuclide scan
conducting the test)
Diagnosis and certification
• Connect a pulse oximetry and disconnect the ventilator.
• 4- 6 l/min of O2, using a soft catheter (via endotracheal Diagnosis of brain death is established and recorded by two
tube) into the trachea at the level of carina. doctors not belonging to the transplantation teams. One must
be a specialist in neurology.
• Look closely for any respiratory movements (abdominal
or chest excursions). Certification of brainstem death requires a panel of four
• Measure arterial PO2, PCO2, and pH after approximately doctors.
8 – 10minutes later. (For every minute of apnoea PaCO2
1. Doctor in charge of the patient
rises by approximately 3 mm Hg).
• If respiratory movements are observed, the apnoea test 2. The doctor in charge of the hospital where the patient
result is negative (i.e. it does not support the clinical was treated
diagnosis of brain death).
3. An independent specialist of unspecified specialty
Terminate the test if
4. Neurologist or neurosurgeon
• Patient’s systolic blood pressure (SBP) ≤100 mmHg
(stabilize and then attempt) Amendments in the THO Act (2011) and THAO rules 2014
have allowed a surgeon/physician and an anesthetist/
• Oxygen saturation not maintained during apnoea testing
intensivist, in the event of the non-availability of neurosurgeon/
(≤85%for more than 30 s)
neurologist.
• Patient repeatedly desaturates or becomes hypotensive
during apnoea testing (ancillary tests) Clinical examination and apnoea test need to be done two
times with an interval of six hours between them. After
Interpretation
the second test the team can start counseling the family
Positive - If respiratory movements are absent and arterial regarding organ donation. The time of death is the end of
PCO2 is ≥ 60 mm Hg (option: 20 mm Hg increase in PCO2 second apnoea test.
over a baseline normal PCO2), the apnoea test result is
Form 10 should be filled and signed by the medical
positive (for brain death).
experts certifying brainstem death and all phases of the

determination of brain death should be clearly documented Pre-procurement management -Resuscitation and
in the medical record:- maintenance of the organ donor
1. Etiology and irreversibility of coma / unresponsiveness Management objectives

2. Absence of motor response to pain
3. Absence of brainstem reflexes during two separate Before declaration optimise the chances of survical
examinations separated by at least 6 hours
4. Absence of respiration with pCO2 ≥ 60 mm Hg After declaration preserve viability of potential
5. Justification for, and result of, confirmatory tests if used transplant organs
6. ORGAN SPECIFIC CONSENT FOR ORGAN DONATION
DONOR MANAGEMENT
(form 8/ form9)
1. General care
Exclusion criteria for organ donation
2. Monitoring
Infection (HIV/ Human T cell leukemia-lymphoma
virus/measles/ rabies/ adenovirus/ parvovirus/herpetic 3. Investigation
meningoencephalitis) and Active malignant disease or a
history of malignancy that poses a high risk for transmission. 4. Medical management
General Care Monitoring
 Hand Hygiene Routine monitoring includes

 Frequent turning- to prevent decubitus
 ECG, Pulse oximetry, Blood pressure–
ulcer, skin care and dressing changes
invasive,Central venous pressure
 Urinary and IV catheter care
 Core temperature, Hourly urine output
 Bronchial toilet – improves elimination of
 Echocardiography -assess fluid deficit
secretionsimproves chance of lung
 Swan-Ganz catheter/Cardiac Output monitors
donation.
for unstable donors
 Eye care – to ensure no corneal abrasions/
 Arterial and CVP lines -in the upper
ulcers  chance of corneal donation.
extremities (femoral line readings inaccurate
 Actively warm to maintain core temp 35˚C
during organ procurement surgery).
 Nasogastric tube -prevention of aspiration.
Investigation
Laboratory
 Hemoglobin, hematocrit, complete blood count, Coagulation profile

 Blood glucose,Blood urea nitrogen, serum creatinine, serum electrolytes
 Urine analysis
 Liver function test
 Screening for hepatitis B, C, hepatitis B core antigen , HIV, IgM and IgG for cytomegalovirus
Cardiac evaluation
These changes reflect
 ECG
ECG ST-T changes  Loss of vagal tone
Atrial and ventricular arrythmias  Sympathetic overactivity
 ECHO Conduction abnormalities  Myocardial infarction
 Electrolyte abnormality
 Effect of drug therapy
Imaging RACE 2020 Ramachandra Anesthesia Continuing Education
 CXR
ECG ST-T changes  Loss of vagal tone
Atrial and ventricular arrythmias  Sympathetic overactivity
 ECHO Conduction abnormalities  Myocardial infarction
 Electrolyte abnormality
Donor for Organ Retrieval  Effect of drug therapy
Imaging
 CXR
 USG for abdominal organs
Other mandatory investigations
 BLOOD GROUPING AND CROSS MATCHING

 HIV Antibody, HBSAg, HCV antibody(Risk of transmission of infection may still remain)
If the patient is hospitalized for more than 72 hours
 Cultures of blood and urine may be required, if there is evidence of infection
Additional tests for multiorgan donors Following need to be monitored every 24hourly
 Echocardiography for heart transplant  Arterial blood gas &Lactate
 Bronchoscopy for lung transplantation  Electrolytes, creatinine and blood sugar levels.
10
Medical Managament • If needed, short acting antihypertensive such as

esmolol, sodium nitroprusside, hydralazine, labetalol,
The medical management of organ donor can be broadly or nitroglycerine should be used.
divided into
Hypovolemia/Hypotension:
• Management of hemodynamics
• Management of metabolic derangement • Intravenous fluid administration is required for the
• Hormonal resuscitation management of hypovolemia.
• Temperature management • Suitable organs for transplantation should be identified
• Management of respiration in advance to plan focused management of fluid
• Hematological parameters replacement
• Nutrition management • One should check for signs of continuing haemorrhage
(external, GI, urinary, abdominal, etc.)
Management of hemodynamics
• Discontinue medications that may contribute to
Aim of cardiovascular support is to protect the heart from hypotension (e.g. antihypertensives, betablockers)
ischemia and other damage while maintaining its ability to
work efficiently and perfuse other organs Three management strategies are commonly adopted and
treatment is escalated depending on the clinical response.
Goals for management of hemodynamic status of the donor: - These strategies are:
• To maintain normovolemia and blood pressure A) Volume expansion

• Optimize cardiac output to maintain perfusion pressure B) Vasopressors, Inotropes.
of all organs C) Hormonal replacement
• Minimize use of vasoactive agents
A) Volume Expansion/Preload
Hypertension:
• Crystalloids with balanced salt content to avoid
• Due to the transient nature of autonomic storm, hypernatremia (concurrent DI), hyperchloremic acidosis
antihypertensives are usually not required. (increases renal vascular resistance, confounds base
excess)

• Dextrose - may further complicate the hyperglycemia • Norepinephrine is also commonly used
and hypothermia.
• high doses of norepinephrine>0.05 mg/kg/min should
• Colloids are to be avoided. Hydroxyethyl starches be avoided as it causes cardiac graft dysfunction
(damage renal epithelial cells and cause early graft particularly right ventricular performance, high early
dysfunction in the transplanted kidneys). and late mortality
• Albumin solutions (20%, 4%) may be considered to • Dopamine can be used as well, but has an increased
reduce the amount of volume given. incidence of arrhythmias. High doses may lead to acute
tubular necrosis in renal recipients
• Packed red cells if needed to achieve a haematocrit of
30 (to maintain oxygen delivery), avoid if not imperative • Large doses of adrenergic agents should be avoided as
they cause direct myocardial injury
The most commonly used fluids are Ringer’s lactate,
Plasmalyte-A, Ringer’s acetate, half normal saline. Arrhythmias
Monitoring for volume therapy • More commonly seen in case of longer lag between brain
death and organ removal.
• Central venous pressure -poor guide for directing
• Prevention of arrhythmia: Electrolytes, blood pressure,
resuscitation, to maintain 6-10cmH2O
fluid volume and body temperature should be carefully
• Repeat bedside echocardiography monitored and maintained within normal range.
• If arrhythmia occurs standard therapy such as Amiodarone
• Mean arterial pressure 60mmHg
or Cardioversion.
• Pulse pressure variation to determine optimal fluid status • Atropine is not useful in bradycardia. Adrenaline,
isoprenaline or pacing may be effective.
• Urine output 1-3 ml/kg/hr (in the absence of polyuria due
to diabetes insipidus or diuretics) C) Hormonal replacement
• Cardiac index >2.5 (high cardiac output state due to • Recommended in persistent hemodynamic instability and/
vasodilatory shock may be a confounder) or when ejection fraction is< 45% on echocardiography
and when heart donation is planned.
• ScvO2 >70% (low basal metabolism due to brain death
may be a confounder) • Use of methylprednisolone in supraphysiological doses
- decreases extravascular lung water, decreases levels
B) Vasopressors, Inotropes
of inflammatory markers, and increases organ retrieval
• An adequate perfusion pressure should be maintained. rates (especially lung)
• Target systolic and mean arterial pressure- >100 mm Hg • Hydrocortisone in low doses has been shown to reduce
and > 70 mmHg respectively vasopressor requirement
• Vasopressors only once hypovolemia has been
excluded/corrected. • Hormonal cocktail – vasopressin + steroid+ thyroid
hormone + insulin
• Vasopressin
Suggestions
• In pressor dose (1-2 U/hr) plays an important role
• Vasopressin up to 2.4 units/hour reduces the a) Vasopressin 1 U bolus followed by an infusion of 0.5-2.0
requirement of other inotropes. U/h (desmopressin intranasal has a selective action on
• Low-dose vasopressin to treat diabetes insipidus, aid the V2 receptors and a half-life varying from 6 to 20 h).
restoration of vascular tone, and reduce epinephrine b) Methylprednisolone: 15 mg/kg immediately after
requirement. diagnosis of brain death and 24th hourly thereafter.
• At doses >0.04mcg/mt it causes coronary, renal and Another option- 250mg followed by 100mg/hour till the
splanchnic vasoconstriction which may jeopardize organ retrieval.
cardiac, renal and hepatic function

c) Insulin infusion to maintain blood glucose between 80 • Surface warming should be done in all patients with
and 150 mg. hypothermia
• Patients with body temperature of less than 34° should
d) Thyroxin (T4) to improve hemodynamics -20 mcg bolus
be given core warming
followed by infusions of 10 mcg/h. Tri-iodothyronine (T3)
given as a 4-mcg bolus followed by an infusion of 3 mcg/h. • In such cases, inhaled gases should be warmed and
Since intravenous preparation is not available humidified by using humidifier
thyroxine (naso-gastric tube) 300-400mcg/8 hourly • Intravenous fluid should also be warmed if large volumes
instead are to be administered
Diabetes insipidus (DI): Diabetes insipidus is characterized by Respiration
• urine output of >4ml/kg/h, Valuable time is Aim of respiratory support is to maximize oxygen delivery to
lost waiting for labs
• serum sodium >145 mEq/L before initiating transplantable organs.
treatment, therefore
• serum osmolality >300mosm/kg • Respiratory passage should be clear without any
presumptive diagno-
• urinary osmolality <300 mosm/kg sis is made of urine obstruction
output is >4ml/kg for
• urine specific gravity of <1.005 2 consecutive hours. • Routine measures such as suctioning, positioning and
Desmopressin or vasopressin should be used early in the turning should be continued
management of diabetes insipidus.
• Lung protective ventilatory strategy g aim to protect lung
Desmopressin g 2-6 mcg/nasal puff;1-2 nasal puffs every while optimizing oxygenation
6-8h
• Tidal volumes 6-8ml/kg
Vasopressin g IV infusion at a dose of 0.5–2.0 U/h • Positive end-expiratory pressure of 5-10 cmH2O
• Early use of antidiuretic agents in suspected diabetes • to maintain oxygen delivery

insipidus may prevent physiological instability due to • prevention of atelectasis
hypovolemia and hypothermia.
• Lowest efficient FiO2 for PaO2 >100
• In a hypotensive patient with diabetes insipidus,
• Interstitial fluid overload should be avoided
a vasopressin infusion is a more rational choice,
as it achieves correction of both hypotension and • Oxygen saturations within normal limits
diabetes insipidus. • Normocapnia should be maintained
• Vasopressin has been demonstrated in a randomized Hematological management
trial to improve organ retrieval rates
• In case of active bleeding, the cause of bleeding should
Metabolic derangement be corrected at the earliest
• Intravenous fluids are also required to maintain normal • Anaemia g transfusion of blood
fluid volume and electrolyte balance • Worsening coagulopathy g coagulation factors and
platelets
• Doses of insulin required for maintaining glucose control
may be higher than normal Infection management
• Maintain blood sugars 80-150mg/dl • Routine use of antibiotic prophylaxis is not warranted
Temperature • Antibiotic agents (Gram staining of aspirated secretion

and positive culture)
• Prevention of hypothermia, active warming helps to
prevent hypothermia Management of nutrition
• Efforts should be made to maintain temperature >35 °C • Nutrition should be continued in patients awaiting
consent for organ donation.

• Continuing enteral feeding may help in providing • At least, three suction machines and a close watch kept
beneficial effects for organ functioning. for significant bleeding
• If heart retrieval is planned the cardiac unit may use -
Organ Procurement - Intraoperative Management for
Organ Retrieval • pulmonary artery catheter-based evaluation for
assessment and optimisation
The management of brain-dead donors needs more • A transoesophageal echocardiography to evaluate
preparation of the mind rather than any new skill. The the heart as well as volume status optimisation and
outcome of multiple recipients may hinge on crucial decisions for ruling out valvular and congenital problems
taken during the care of the donor. Organ retrieval involves
various teams coming in to harvest the allocated organs. An • Defibrillator and appropriate internal paddles to tackle
anaesthesiologist is ideally suited to create a good rapport significant arrhythmias
between the various harvest teams. Access
Pre-operative evaluation • Two large bore intravenous catheters -for rapid large-
volume intravascular fluid replacement
• Confirming the history including mode of death • Central venous catheter is recommended prior to the
• Comorbidities, Addictions start of surgery (if not present)
• Radiological studies, Blood investigations and arterial • An arterial catheter -blood pressure can be continuously
blood gases followed and managed
• Culture reports Cardiovascular and Volume status
• Apnoea test
There are multiple contributors to volume loss in the brain-
• A thorough note should be made of donor family consent dead patient.
(Form 8) and the brain death certification (Form 10)
on which the appropriate authority signatures must be Fluid shifts with interstitial accumulation can occur from
present the abdominal and/or thoracic incision made for organ
procurement
Monitoring and equipment
Evaporative losses and overt incisional blood losses also
• Electrocardiography, oximetry, capnometry, temperature occur
and urine output
Polyuria secondary to diabetes insipidus can further
• Invasive arterial and central venous pressure
contribute to hypovolemia

Inotropes and vasopressors • Positive end-expiratory pressure (positive end-expiratory
pressure of 4–8 cm of water)
Dopamine, phenylephrine, epinephrine, norepinephrine,
• Lowest feasible FiO2 to maintain PaO2 >100mmHg.
and vasopressin are common agents and provide adequate
hemodynamic support. • Proper oral and endotracheal suction and recruitment
strategies help in preserving the lung.
Vasopressin is considered by some, to be the most ideal of • Intermittent disconnection of ventilation to allow
these agents as it addresses the blood pressure as well as bronchoscopic suctions and collection of cultures and
the diabetes insipidus. Vasopressin infusion is dosed in the to facilitate dissections around the heart and lung may
range of 0.01-0.04 IU/min be needed.
Organ specific requirement Endocrine and metabolic
• The goal should be to achieve normovolemia if thoracic Goals
organs are to be harvested.
• Serum glucose <150mg/dl
• Renal function will depend on excellent optimisation of
the volume status however if lungs are being harvested • Sodium <155mEq/l
fluid restrictive approach is needed (positive balance is • Maintain Electrolyte balance
deleterious).
Cortisol (3-5 mg/kg) vs methylprednisolone (15-60 mg/kg).
• Hydroxyethyl starch (HES) is implicated in impaired
immediate renal graft function. However, in lung If sodium levels persist>155 mEq/L, 0.45% NaCl (77 mEq/L),
donors, colloid solutions are recommended to minimize can be used as a maintenance fluid.
accumulation of pulmonary oedema and deterioration
Electrolyte imbalances - hypokalaemia and low calcium and
in gas exchange
magnesium need continuous correction.
• High dose inotropic support may be deleterious as hearts
from donors who are dependent on high inotropic support Organ specific requirement
are more likely to exhibit moderate to severe myocardial Steroids
injury.
• Improved donor hemodynamics, oxygenation,
• Central venous pressure (CVP) <10 mmHg has been
procurement rates, graft and recipient survival.
shown to increase the number of hearts and lungs
available for transplantation without decreasing the • Methyl prednisolone offers benefit in procuring lung due
utilization of other organs to better oxygenation as well as offers reduction in graft
dysfunction in heart transplant. Also shown to reduce
Pulmonary
High PEEP reduces serum and intregraft cytokine expression and improved
Pulmonary goals cardiac output, triggers liver graft function.
release of vasopressin Hyperglycemia
• Lung protective ventilation
and activates the
• Tidal volumes 6-8ml/kg
renin angiotensin • A lower rate of organ suitability for transplantation and
• PEEP 8-10cm H2O
system which causes decreased renal graft survival.
• Plateau pressures <35cmH2O
vasoconstriction
• PaO2/FiO2 of more than 300 • Serum glucose control to levels <200 mg/dL - improved
and impaired organ
is desirable outcomes in pancreas transplant patients. This level
perfusion
• pH 7.35-7.45 should be maintained especially if a pancreas transplant
Organ specific requirement is planned.
If a lung harvest is planned, the BDD should receive Vasopressin

protective lung ventilation consisting of • increases the organ recovery rate and graft survival,
• Smaller tidal volume (6 ml/kg/min), periodic recruitment by decreasing plasma hyperosmolarity and improving
may be needed systemic blood pressure as well as cardiac output.

Three-drug hormone replacement therapy Additional considerations
• Triiodothyronine/levothyroxine (T3/T4), methylprednisolone, It is important to know which organs will be procured as this
and vasopressin increases the number of viable organs for can affect anaesthetic management.
transplant by>20% and improves early graft function.
Prior to heparinization, removal of indwelling central lines or
Serum sodium pulmonary artery catheters that traverse the superior vena
cava, as these vessels will be clamped prior to removal of the
• Levels>155 mEq/L showed a significantly increased rate heart. After heparin (dose of 300 units/kg) is administered,
of early graft loss the surgical teams cannulate the major arterial blood
• Hypernatremia is detrimental for the organs especially vessels; the cardiac team utilizes the ascending aorta, and
the liver probably due to accumulation of ionogenic the abdominal team utilizes the infrarenal abdominal aorta.
osmoles within liver allograft cells. Following cannulation, aortic cross-clamps are placed (one
in the chest and one in the abdomen) and then intravascular
• Transplant of these livers into recipients with normal flushing of cold solution is begun as well as topical cooling
sodium levels may promote intracellular water of the organs.
accumulation, cell lysis and death.
For lung procurement, positive pressure breaths are
Musculoskeletal and temperature regulation administered to inflate the lungs prior to removal.
Spinal reflexes remain intact even after brain death and Ventilation and monitoring may be stopped after ensuring a
therefore a long-acting neuromuscular agent is administered cardiac standstill on infusion of the preservative solutions,
to counter any movement. and there is no longer a need for further anaesthesia care
while the organs are removed in the following order: heart,
Opioids - to counteract hemodynamic response by controlling
lung, liver, pancreas, kidneys. The heart (due to its shortest
the catecholamine surge, before the incision.
allowable ischemic time of under 4 hours) is a priority and
Inhalational agents -used for their vasodilator properties the ultimate clamping time is based on the judgement of the
and their effects on ischemia-reperfusion injuries maybe cardiac team.
beneficial in these cases.
Extubation should be done in the OR.
Normothermia is recommended before and during
Time of death = neurologic determination
procurement (temperature >35°)
(SECOND APNOEA TEST), NOT when
Organ specific requirement ventilator is removed and NOT when heart
beat ceases.
Volatile anaesthetics may induce ischemic preconditioning
in hepatic and cardiac surgery and therefore some retrieval Miscellaneous
teams administer them at least during the last 30 min before
aortic clamping. Preservative solutions
Hypothermia in donor leads to delayed graft function in renal The fundamental challenge of organ preservation is the need
recipients to maintain the viability and function of the organ in the absence
of an adequate blood supply, metabolic waste removal, and
Hematologic physiologic stimulation. Apart from this, ischemia-reperfusion
injury (or IRI) remains an important risk factor for both acute
Haemoglobin concentration of 9-10 g/dL and no less than 7
rejection and long-term graft outcomes Suppression of
g/dL. Platelets and plasma should be given when clinically
metabolism has been the most established strategy in organ
significant bleeding is evident.
preservation and includes both hypothermic preservation (for
Organ specific requirement hours) and cryopreservation (for days). Organs are stored
in chilled specialized preservation solutions which prevent
Transfusion of platelets in donor may cause post-operative cellular swelling and minimize molecular changes within the
graft dysfunction in liver recipient. Other contributary factors cells. Each 10 °C drop in temperature of the organ results in
are high serum sodium and longer cold ischemia times. a 50 percent decrease of its metabolic rate, until it reaches

10 to 12 percent of normal physiological rates at 4 °C. during retrieval allows unhurried removal of organs in optimal
The University of Wisconsin (UW) solution, HTK (consisting and undamaged condition.
of histidine, tryptophan and ketoglutarate) and Celsior have
proven to be effective in preserving the harvested organs. References
Standard Criteria Donors 1. Bucce JF. Brain death and its implications for management
of the potential organ donor. Acta Anaesthesiol
• Age <60 y Scand.2009;53: 1239-1250
• If 50-59 y g no comorbidities in donors 2. Smith Martin. Physiological changes during brain stem
death- Lessons for management of the organ donor.
Extended Criteria Donors The Journal of eHeart and Lung Transplantation. 2004;
• Advanced age >60 y regardless of comorbidities 23 (9):217-224
• Long ischemia times 3. Xia VW, Braunfeld M. anesthesia management of organ

donors. Anesthesiology clinics. 2017; 35: 395-406
• Pre-existing co-morbids (eg. Stroke or aneurysm,
4. Anderson AT, Bekker P, Vageli PA. Anesthetic
hypertension, serum creatinine >1.5mg/dl)
considerations in organ procurement surgery: a narrative
• Steatosis (liver graft) review. Can J Anesth. 2015; 62: 529-539.
• Donation after cardiac death (not in India)
5. Champigneulle B, et al. Intraoperative management of
Issues due to extended criteria donations brain-dead organ donors by anesthesiologists during
an organ procurement procedure: results from a French
• Intraoperative complications
survey. BMC Anesthesiology. 2019; 19;108-114.
• example– increased hyperkalemia, post reperfusion
syndrome, intraoperative bleeding, higher chances 6. Demetrios JK et al. Medical management to optimize
of re-exploration donor organ potential: review of the literature. Can J
Anesth. 2005; 53: 820-830.
• Post operative risks
7. Finlayson D. Providing Anesthesia for Neurologically
• delayed graft function
Deceased Donors (NDD). BC Transplant. 2013.
• Immune mediated rejection
Summary 8. Pandit RA, et al. Management of Potential Organ Donor:
Indian Society of Critical Care Medicine (ISCCM) -
Goal of brainstem dead donor management - Rule of 100 Position Statement.
• Systolic BP >100 mmHg 9. S h e t t y V L , e t a l . T h e b r a i n ‑ d e a d d o n o r : A n
• Urine output > 100 ml/h anaesthesiologist’s perspective. Indian Journal of
• PaO2 >100mmHg Anaesthesia.2017;61; Issue 12; 952-956.
• Haemoglobin >100 g/l (10g/dl) 10. Kumar L. Brain death and care of the organ donor.
• Blood sugar 100 mg/dl or 100% normal Journal of Anaesthesiology Clinical Pharmacology. 2016;
32(2):146-152.
Conclusion
11. McKeown DW. Management of the heartbeating brain-
Highly specific intraoperative management is required dead organ donor. British Journal of Anaesthesia. 2012;
during organ procurement after brain death. To manage 108 (S1): 96–107.
the heart-beating brain-dead donor, the anaesthesiologist
must incorporate knowledge of the effects of brain death 12. Anwar ASMT, Lee J. Medical Management of Brain-
on each organ system as well as employ specific measures Dead Organ Donors. Acute and Critical Care. 2019;
to ensure a smooth retrieval process. Maintaining stability 34(1):14-29

MCQ
1. Not a prerequisite for apnea testing 4. Time of death in a brain dead organ donor is
a) Neurological confirmation of diagnosis(CT/MRI)
b) PaCO2 ≥40 mmHg a) Time of first apnea test
c) Core temperature of 35.6°C b) Time of second apnea test
d) Cause of unresponsive state that is incompatible c) Time of extubation
with survival d) Time of cessation of heart beat
2. Which of the following reflexes may be present in a 5. Vasopressor of choice in a brain dead organ donor
brain dead patient?
a) Noradrenaline
a) Pupillary reflex b) Adrenaline
b) Knee jerk c) Vasopressin
c) Oculocephalic reflex d) Dopamine
d) Pharyngeal reflex
3. Which of the following is the first line of management of

hypotension in a brain dead donor?
a) Intravenous fluid replacement with balanced salt

solution
b) Use of vasopressors and/ or inotropes
c) Volume expansion with colloids
d) Blood transfusion to achieve a Hct of ≥ 30
5.C 4.B 3.A 2.B 1.C
ANSWERS:

23 PREECLAMPSIA –CURRENT CONCEPTS
Sreekumar EJ Sunil T Pandya

Assistant Professor Director,
SRIHER Century Super specialty Hospital
Chennai Hyderabad.
Key points
Ø Pre-eclampsia is a leading cause for maternal mortality
Ø Classification into pre-eclampsia with or without severe symptoms
Ø Seizure prophylaxis and blood pressure control form the major modality of treatment
Ø Regional anesthesia is preferred in the absence of coagulopathies
Ø Delivery of the placenta remains the only cure for preeclampsia, but in women far from term, it has to be balanced
versus the risks of severe prematurity of the infant.
Ø Ongoing management of women with severe preeclampsia in the postoperative period should be by adequately
trained staff in the appropriately monitored setting.
Hypertensive disorders of pregnancy are only second to Classification of Hypertensive disorders

haemorrhage, as a cause of maternal death all over the
The commonly used classifications are the ACOG and the
world and in India, this accounts for around 20% of the
ISSHP classifications.
maternal deaths. Preeclampsia is a disorder of pregnancy
associated with new-onset hypertension, which occurs most Pre-eclampsia is classified as with and without severe
often after 20 weeks of gestation and frequently near term. symptoms.
2016 World Congress of the International Society for the Study of Hypertension in Pregnancy (ISSHP)
Hypertension known before pregnancy or present in the first 20 weeks:
1. Chronic hypertension
a. Essential
b. Secondary
2. White-coat hypertension
3. Masked Hypertension
Hypertension arising de novo at or after 20 weeks:
1. Transient gestational hypertension
2. Gestational hypertension
3. Pre-eclampsia∗ – de novo or superimposed on chronic hypertension

Preeclampsia –Current Concepts 230 Sunil T Pandya
ACOG CRITERIA
Hypertension Proteinuria
• Defined as systolic BP ≥140 and/or diastolic Proteinuria should be assessed by dipstick urinalysis
BP ≥90 mmHg
• If positive (≥‘1+’, 30 mg/dl) then spot urine protein/creati-
• Blood pressure should be repeated to confirm nine (P/Cr) ratio should be performed
true hypertension
• A P/Cr ratio ≥30 mg/mmol
I. if blood pressure is severe (SBP ≥160
(0.3 mg/mg) is abnormal
and/or DBP ≥110 mmHg) then the
blood pressure should be confirmed • A negative dipstick test can usually be accepted and further
within 15 min; P/Cr testing is not required at that time
II. for less severe blood pressure, repeat- • Proteinuria is not required for a diagnosis of pre-eclampsia
ed readings should be taken over a few
• Massive proteinuria (> 5 g/24 h) is associated with more
hours.
severe neonatal outcomes
ISSHP ACOG criteria (2019)
Pre-eclampsia is gestational hypertension Diagnostic Criteria for Preeclampsia

accompanied by one or more of the following
new-onset conditions at or after 20 weeks’ ges-
tation:
1. Proteinuria Blood pressure
2. Other maternal organ dysfunction, including: • Systolic BP of 140 mm Hg or more or diastolic BP of 90 mm Hg or
• Acute kidney injury (AKI) (creatinine more on two occasions at least 4 hours apart after 20 weeks of ges-
≥90 μmol/L; 1 mg/dL) tation in a woman with a previously normal BP
• Systolic BP of 160 mm Hg or more or diastolic BP of 110 mm Hg or
• Liver involvement (elevated transami-
more. (Severe hypertension can be confirmed within a short interval
nases e.g. ALT or AST>40IU/L) with or
(minutes) to facilitate timely antihypertensive therapy).
without right upper quadrant or epigas-
tric abdominal pain) and
Proteinuria
• Neurological complications (examples
include eclampsia, altered mental status, • 300 mg or more per 24 hour urine collection (or this amount extrapolat-
blindness, stroke, clonus, severe head- ed from a timed collection) or
aches, persistent visual scotomata) • Protein/creatinine ratio of 0.3 mg/dL or more or c Dipstick reading of 2+
(used only if other quantitative methods not available)
• Haematological complications (throm-
bocytopenia – platelet count below Or in the absence of proteinuria, new-onset hypertension with the new
150,000/μL, DIC, hemolysis) onset of any of the following:
• Thrombocytopenia: Platelet count less than 100,000 x 109/L
3. Uteroplacental dysfunction (such as fetal
growth restriction, abnormal umbilical artery • Renal insufficiency: Serum creatinine
Doppler wave form analysis, or stillbirth) concentrations, greater than 1.1 mg/dL or a doubling of the serum
creatinine concentration in the absence of other renal disease
• Impaired liver function: Elevated blood concentrations of liver trans-
aminases to twice normal concentration
• Pulmonary edema
• New-onset headache unresponsive to medication and not account-
ed for by alternative diagnoses or visual symptoms

Severe Features 3. Very low-density lipoprotein toxicity
• Systolic blood pressure of 160 mm Hg or more, 4. Genetic imprinting

or diastolic blood pressure of 110 mm Hg or more
on two occasions at least 4 hours apart (unless 5. Increased trophoblast apoptosis or necrosis
antihypertensive therapy is initiated before this
6. Exaggerated maternal inflammatory response to deported
time)
trophoblasts
• Thrombocytopenia (platelet count less than
100,000x109/L) 7. Imbalances of angiogenic factors
• Impaired liver function as indicated by abnormally 8. Cardiovascular response to abnormal placentation

elevated blood concentrations of liver enzymes (to
twice the upper limit normal concentration), and An astute and circumspect diagnostic approach is required
severe persistent right upper quadrant or epigastric when other corroborating signs and symptoms indicative of
pain unresponsive to medication and not accounted severe preeclampsia are missing.
for by alternative diagnoses
Clinical Presentation
• Renal insufficiency (serum creatinine concentration
Disease manifestations of severe preeclampsia occur in
more than 1.1 mg/dL or a doubling of the serum
all body systems as the result of widespread endothelial
creatinine concentration in the absence of other
dysfunction.
renal disease)
Hematologic Changes
• Pulmonary edema
• Various hematologic changes may occur in women
• New-onset headache unresponsive to medication
with preeclampsia, especially in preeclampsia with
and not accounted for by alternative diagnoses
severe features.
• Visual disturbances
• Thrombocytopenia and hemolysis may occur,
Pathophysiology and may reach severe levels as part of HELLP
syndrome. Platelet counts less than 100,000/
Several mechanisms of disease have been proposed in mm3 occur most commonly in women with severe
preeclampsia: disease or HELLP syndrome and correlate with the
severity of the disease process.
1. Chronic uteroplacental ischemia
• In contrast to normal pregnancies and other
2. Immune maladaptation hypertensive disorders, platelets are activated in
preeclampsia; subsequent platelet degranulation

is believed to account for the decreases in platelet 109/L, there is significant liver dysfunction, or there
function, and aggregation appears to account for is suspected placental abruption.
the decrease in platelet count.
• Right upper quadrant or epigastric pain is thought
• The syndrome of disseminated intravascular to be due to, periportal and focal parenchymal
coagulation (DIC) occurs in some women with necrosis, hepatic cell edema, or Glisson’s capsule
preeclampsia, generally in the setting of severe liver distension, or a combination. Spontaneous hepatic
involvement, intrauterine fetal demise, placental rupture is rare but is associated with a 32% maternal
abruption, or postpartum hemorrhage. mortality rate.
• Activation of the coagulation system is marked by Renal Changes

consumption of procoagulants, increased levels of
fibrin degradation products, and end-organ damage • The histopathologic renal changes classically
secondary to microthrombi formation. In advanced described in preeclampsia as glomerular
DIC, procoagulants (e.g., fibrinogen, platelets) endotheliosis consist of swollen, vacuolated
decrease to a level that may lead to spontaneous endothelial cells with fibrils, swollen mesangial
haemorrhage. cells, subendothelial deposits of protein reabsorbed
from the glomerular filtrate, and tubular casts.
Hepatic Changes
• Proteinuria in preeclampsia is nonselective, as
• Hepatic function may be significantly altered in a result of increased tubular permeability to most
women with preeclampsia with severe features. large-molecular-weight proteins (albumin, globulin,
transferrin, and hemoglobin).
• Alanine amino- transferase and AST may be
elevated. • Urinary calcium decreases because of an increased
tubular reabsorption of calcium.
o Aspartate amino- transferase is the
dominant transaminase released • In women with preeclampsia, contraction of the
into the peripheral circulation in liver intravascular space secondary to vasospasm leads
dysfunction due to preeclampsia and to worsening renal sodium and water retention. The
is related to periportal necrosis. The fact normal increase in renal blood flow and glomerular
that AST is increased to a greater extent filtration rate and the expected decrease in
than ALT, at least initially, may help in serum creatinine may not occur in women with
distinguishing preeclampsia from other preeclampsia, especially if the disease is severe.
potential causes of parenchymal liver
disease, in which ALT usually is higher • Preeclampsia with severe features may include
than AST. acute renal deterioration as part of the clinical
spectrum. Oliguria in severe preeclampsia is a
• Increased serum levels of LDH in preeclampsia consequence of intrarenal vasospasm with an
are caused by hepatic dysfunction (LDH derived approximate 25% reduction in glomerular filtration
from ischemic, or necrotic tissues, or both) and rate. In these patients, transient oliguria (less than
hemolysis (LDH from red blood cell destruction). 100 mL over 4 hours) is a common observation in
labour or the first 24 hours of the postpartum period.
• Increase in bilirubin secondary to significant
hemolysis may develop only in the late stages of • Plasma concentrations of uric acid normally
the disease. increase in late pregnancy, and this is thought
to be due to increased rates of fetal or placental
• Similarly, alterations in hepatic synthetic function, production, or both, decreased binding to albumin,
as reflected by abnormalities of prothrombin time, and a decrease in uric acid clearance. The serum
partial prothrombin time, and fibrinogen, usually uric acid concentration increases to a greater extent
develop in advanced preeclampsia. Evaluation in preeclampsia. The most commonly accepted
of these coagulation parameters is probably only explanation for hyperuricemia in preeclampsia,
useful when the platelet count is below 150,000 x besides increased production, is the increased

reabsorption and decreased excretion of uric acid • In addition, the interaction of various vasoactive
in the proximal renal tubules. agents, such as prostacyclin (vasodilator),
thromboxane A2 (potent vasoconstrictor), nitric
The Cardiovascular Changes in the Preclinical Phase of oxide (potent vasodilator), and endothelins (potent
Preeclampsia vasoconstrictors) results in another significant
change described in preeclampsia: intense
• In the preclinical phase of preeclampsia, vascular
vasospasm.
reactivity, hemodynamic indices, and left ventricular
(LV) properties are subtly impaired, especially • Attempts to correct the contraction of the
in those women destined to develop preterm intravascular space in preeclampsia with vigorous
preeclampsia. fluid therapy are likely to be ineffective and could
be dangerous because of the frequent capillary
o At midgestation, there is a shift toward a low
leak and decreased colloid oncotic pressure often
cardiac index, associated with a high total
associated with preeclampsia.
vascular resistance index, increased mean
arterial pressure, contracted intravascular • A pregnant heart in preeclampsia works at the
volume, and reduced venous reserve edge of its reserve, and any additional stress could
capacity. In contrast, the hemodynamic result in a significant deterioration of function and
profile of women destined to develop late- lead to overt cardiovascular and cardiopulmonary
onset preeclampsia is not well delineated, complications.
with some authors reporting a normal
cardiac index and increased total vascular • Aggressive fluid therapy may result in elevation
resistance index at midgestation, and others of the pulmonary capillary wedge pressure and
reporting a high cardiac output/ low TVR increased risk of pulmonary edema.
status.
Cardiovascular Management in Uncomplicated
o The pattern of LV dysfunction and remodeling Preeclampsia with Severe Hypertension
seen in preeclampsia is similar to that seen in
early essential hypertension in nonpregnant • Delivery of the placenta remains the only cure for
women and is indicative of afterload-induced preeclampsia, but in women far from term, it has to
impairment of subendocardial myocardial be balanced versus the risks of severe prematurity
fibers. of the infant.
o Raised biomarkers of cardiovascular • In daily practice, the antihypertensive therapy in

dysfunction, endothelial injury, and uncomplicated preeclampsia cases is not tailored
generalized oxidative stress are seen in to the specific hemodynamic pattern and cardiac
women presenting with preeclampsia. function of the woman.
o Women with both placental insufficiency • Some guidelines recommend lowering of non-
and impaired LV function were more likely to severe BP to a systolic level of 140 to 150 mmHg
develop preterm/early-onset preeclampsia, and a diastolic level of 90 to 100 mmHg, because
whereas those who also have placental of the risk of haemorrhagic stroke in the presence
insufficiency but normal or even enhanced of systolic hypertension. However, thresholds also
LV function, will be more likely to have an vary depending on the existence of comorbidities
uncomplicated pregnancy. and maternal age.
The Cardiovascular Changes at Presentation with • Proposed medications include oral labetalol,
Preeclampsia methyldopa, nifedipine or isradipine, and
some β-adrenoceptor blockers .Atenolol is not
• In addition to hypertension, women with recommended, because of its association with fetal
preeclampsia or eclampsia typically lack the growth restriction. Angiotensin- converting enzyme
hypervolemia associated with normal pregnancy; inhibitors, angiotensin receptor blockers, and
thus, hemoconcentration is a frequent finding. direct renin inhibitors are strictly contraindicated

in pregnancy because of severe fetotoxicity, o Care should be exercised when using nifedipine
particularly in the second and third trimesters. or any calcium antagonist with magnesium sulfate
because of the synergic effects of these drugs.
• There is a consensus that BP should be
expeditiously treated when it is severe, defined o Magnesium sulfate is no longer recommended as an
as sustained (>15 minutes) hypertension (≥160 antihypertensive, but it is unanimously considered
mm Hg SBP or ≥110 mm Hg DBP) attributable to the drug of choice for the prevention and treatment
the short-term complications related to this status, of eclampsia in all cases of severe preeclampsia.
such as intracerebral hemorrhage and infarction,
Pulmonary Edema
cardiopulmonary events, placental abruption, and
stillbirth. • Pulmonary edema is the most common
• The goal of antihypertensive treatment is to achieve cardiopulmonary complication of preeclampsia,
which occurs in up to 3% of women, mainly in the
a range of 140 to 150 mmHg SBP/80 to 100
peripartum or postpartum stage, and treatment is
mmHg DBP at a rate of 10 to 20 mmHg every 10
similar to that used in the non-obstetric patients.
to 20 minutes to prevent prolonged severe systolic
hypertension and its consequences on the patient. • The European Society of Cardiology 2011 guidance
• Care should be taken to avoid abrupt falls in BP, recommends intravenous nitroglycerine (glyceryl
trinitrate) as the first-line choice in treatment for
which may induce complications as a result of end-
pulmonary edema associated with preeclampsia.
organ hypoperfusion, including fetal death from
An alternative agent, sodium nitroprusside, is
placental hypoperfusion. Continuous maternal and
recommended in severe heart failure associated
fetal monitoring should be adopted until the BP is
with pulmonary edema and critical hypertension,
stable.
but it should be used only with caution and by
• The ideal antihypertensive medication should experienced clinicians.
reduce BP in a controlled manner, not lower CI,
• Intravenous furosemide is used to promote
reverse uteroplacental vascular constriction, or
venodilation and diuresis, whereas intravenous
result in adverse maternal/fetal effects.
morphine may be given as a venodilator and
• The first choice of medication differs in the major anxiolytic.
international society recommendations, mainly
• Afterload reduction using vasodilators may be
because of known safety of use in pregnancy and
necessary especially in the case of LV diastolic
historical reasons.
dysfunction, and inotropic support should be given
o The European Society of Cardiology/National in the case of LV systolic dysfunction.
Institute for Clinical Excellence recommend
• Despite the risks of aspiration, non-invasive
intravenous labetalol.
ventilation is preferred, because it provides
o Parenteral hydralazine may increase the risk of increased inspired oxygen concentration, displaces
maternal hypotension <90 mmHg SBP. Parenteral fluid from the alveoli into the pulmonary circulation,
labetalol may cause neonatal bradycardia. decreases the work of breathing, and decreases
the need/risks for tracheal intubation.
o Second-line alternatives include labetalol or
nicardipine by continuous infusion pump. Sodium • Urine output, electrolyte balance, BP, and maternal/
nitroprusside should be reserved for emergencies fetal heart rate should be closely monitored. The
after failure of both labetalol and hydralizine and woman should be positioned such that the head
used for short time periods because of cyanide is elevated and antenatal uterine displacement
and thiocyanate toxicity and increased intracranial obtained.
pressure effects with risk of worsening maternal
Invasive Hemodynamic Monitoring, Fluid Balance, and
cerebral edema.
Volume Expansion
o Methyldopa is usually stopped within 2 days of
delivery, because postpartum use is associated Some authors recommend the use of invasive hemodynamic
with an increased likelihood of depression. monitoring in the management of women with severe pre-

eclampsia to monitor fluid therapy during plasma volume changes may compromise visualization of airway
expansion, particularly in managing severe cardiac disease, landmarks during direct laryngoscopy.
pulmonary edema refractory to medical therapy, persistent
• Subglottic edema can cause airway obstruction.
oliguria unresponsive to fluid challenge, and severe
hypertension unresponsive to a parental antihypertensive. • Signs of airway obstruction include dysphonia,
hoarseness, snoring, stridor, and hypoxemia.
Central Nervous System
Pulmonary
• Although the term preeclampsia suggests that
• Plasma colloid osmotic pressure is reduced in
eclampsia is the end stage of preeclampsia, it
normal pregnancy because of decreased plasma
is more accurate to consider eclampsia as the
albumin concentration, and it is decreased even
outward manifestation of disease progression in
further in preeclamptic women.
the brain, similar to other organ involvement.
• Women with normal pregnancies have a mean
• Central nervous system manifestations include osmotic pressure of approximately 22 mm Hg in the
severe headache, hyperexcitability, hyperreflexia, third trimester and approximately 17 mm Hg during
and coma. the early postpartum period. In contrast, a study of
women with preeclampsia demonstrated a mean
• Visual disturbances can include scotoma,
colloid osmotic pressure of approximately 18 mm
amaurosis, and blurred vision.
Hg before delivery and 14 mm Hg after delivery.
• Non-invasive measurements of cerebral blood flow • Decreased colloid osmotic pressure, in combination
and resistance, along with other neuroimaging with increased vascular permeability and the loss of
approaches, suggest that the loss of cerebral intravascular fluid and protein into the interstitium,
vascular autoregulation and vascular barotrauma increases the risk for pulmonary edema.
occur with preeclampsia and eclampsia.
• Excess intravenous fluid is an important risk factor
• Hyperperfusion of the brain, particularly in the for pulmonary edema in preeclamptic patients.
setting of the endothelial dysfunction present in
preeclampsia, causes vasogenic edema. Uteroplacental Perfusion
• Uteroplacental perfusion can be impaired in

• Failure of autoregulation occurs most commonly in
pregnancies complicated by preeclampsia.
the posterior circulation, such that the changes in
the brain with severe preeclampsia/eclampsia result • In contrast to normal pregnancy, downstream
in the posterior reversible leukoencephalopathy resistance in the uteroplacental bed increases,
syndrome (PRES). diastolic flow velocity decreases, and the systolic-
to-diastolic flow velocity ratio increases.
Airway
• The systolic-to-diastolic ratio, calculated from
• In pregnant women, the internal diameter of the
Doppler ultrasonographic determination of blood
trachea is reduced because of mucosal capillary
flow velocities, reflects intrinsic arterial resistance.
engorgement.
• Pathophysiologic changes can result in fetal growth
• In women with preeclampsia, these changes can
restriction (the fetal syndrome) in some pregnancies
be exaggerated with upper airway narrowing as
complicated by severe preeclampsia.
a result of pharyngolaryngeal edema; these

Conditions Precluding Expectant Management∗

Maternal
• Uncontrolled blood pressures (persistent SBP 160 mm Hg or more or DBP 110 mm Hg or more) not re-
sponsive to antihypertensive medication
• Persistent headaches, refractory to treatment
• Epigastric pain or right upper pain unresponsive to repeat analgesics
• Visual disturbances, motor deficit or altered sensorium
• Stroke
• Myocardial infarction
• HELLP syndrome
• New or worsening renal dysfunction (serum creatinine greater than 1.1 mg/dL or twice baseline)
• Pulmonary edema
• Eclampsia
• Suspected acute placental abruption or vaginal bleeding in the absence of placenta previa
Fetal
• Abnormal fetal testing
• Fetal death
• Fetus without expectation for survival at the time of maternal diagnosis (eg, lethal anomaly, extreme pre-
maturity)
• Persistent reversed end-diastolic flow in the umbilical artery
Intrapartum Management myocarditis).
In addition to appropriate management of labor and • Although there is a relationship between toxicity and
delivery, the two main goals of management of women with plasma concentration of magnesium, with higher
preeclampsia during labor and delivery are infusion rates increasing the potential for toxicity, the
accurate magnesium concentration clinically effective
1) prevention of seizures and 2) control of hypertension. in prevention of eclampsia has not been established.
Seizures occur even with magnesium at a therapeutic
Seizure Prophylaxis
level, whereas several trials using infusion rates of
• A significant body of evidence attests to the efficacy of 1 g/hour, frequently associated with subtherapeutic
magnesium sulfate to prevent seizures in women with magnesium levels, were able to significantly reduce
preeclampsia with severe features, and eclampsia. the rate of eclampsia or recurrent convulsions.
• There is no consensus regarding, the prophylactic • The regimen generally preferred is intravenous [IV]
use of magnesium sulfate for the prevention of administration of a 4–6 g loading dose over 20–30
seizures in women with gestational hypertension or minutes, followed by a maintenance dose of 1–2 g/
preeclampsia without severe features. Magnesium hour.
sulfate is more effective than phenytoin, diazepam,
• The adverse effects of magnesium sulfate (respiratory
or nimodipine (a calcium-channel blocker used in
depression and cardiac arrest) come largely from its
clinical neurology to reduce cerebral vasospasm) in
action as a smooth muscle relaxant.
reducing eclampsia and should be considered the
drug of choice in the prevention of eclampsia in the o Deep tendon reflexes are lost at a serum
intrapartum and postpartum periods. magnesium level of 9 mg/dL (7 mEq/L),
• Benzo- diazepines and phenytoin are justified only o Respiratory depression occurs at 12 mg/dL (10
in the context of antiepileptic treatment or,when mEq/L), and
magnesium sulfate is contraindicated or unavailable
(myasthenia gravis, hypocalcemia, moderate-to- o Cardiac arrest at 30 mg/dL (25 mEq/L).
severe renal failure, cardiac ischemia, heart block, or

o Because magnesium sulfate is excreted almost places the patient at risk of significant adverse
exclusively in the urine, measuring urine output effects. In patients with mild renal failure (serum
should be part of the clinical monitoring, in addition creatinine -1.0–1.5 mg/dL) or oliguria (less than 30
to monitoring of respiration status and tendon mL urine output per hour for more than 4 hours),
reflexes. If renal function is impaired, serum the loading dose of 4–6 g should be followed by a
magnesium levels will increase quickly, which maintenance dose of only 1 gm/hour.
Antihypertensive Approach: Drugs and Thresholds for Treatment
Anesthesia Considerations • Magnesium sulfate has significant anesthetic

implications because it prolongs the duration of
• With improved techniques over the past decades, nondepolarizing muscle relaxants. However, women
regional anesthesia has become the preferred with preeclampsia who require cesarean delivery
technique for women with preeclampsia with severe should continue magnesium sulfate infusion during
features and eclampsia for labor and delivery. A the delivery. This recommendation is based on the
secondary analysis of women with preeclampsia observation that magnesium sulfate half-life is 5
with severe features in a randomized trial of low- hours and that, discontinuation of the infusion of
dose aspirin reported, that epidural anesthesia was magnesium sulfate before cesarean delivery would
not associated with an increased rate of cesarean only minimally reduce magnesium concentration at
delivery, pulmonary edema, or renal failure. the time of delivery while possibly increasing the risk
of seizure. The induction of general anesthesia and
• General anesthesia carries more risk to pregnant
the stress of delivery may even reduce the seizure
women than regional anesthesia does because of:
threshold and increase the likelihood of eclampsia in
o Risk of aspiration the immediate postpartum period, if the infusion of
magnesium sulfate is stopped during delivery.
o Failed intubation due to pharyngolaryngeal edema
and, HELLP
o Stroke secondary to increased systemic and
intracranial pressures during intubation and The syndrome of haemolysis, elevated liver enzymes,
extubation. and low platelets is a severe form of pre-eclampsia. It is
associated with increased rates of maternal morbidities,
• However, neuraxial anesthesia and analgesia are including DIC, placental abruption, pulmonary edema, acute
contraindicated in the presence of a coagulopathy renal failure, liver hemorrhage or failure, acute respiratory
because of the potential for hemorrhagic distress syndrome, sepsis, stroke, and death.
complications. Thrombocytopenia also increases the
risk of epidural hematoma. There is no consensus in Clinical management is similar to that for severe
regard to the safe lower-limit for platelet count and preeclampsia and includes intravenous magnesium sulfate
neuraxial anesthesia. for seizure prophylaxis and antihypertensive medications,

to maintain a systolic blood pressure below 160 mm Hg and References
a diastolic blood pressure below 110 mm Hg.
1. ACOG Practice Bulletin No. 202: Gestational
Postpartum management Hypertension and Preeclampsia. Obstet Gynecol.
2019;133(1):e1–25.
• Ongoing management of women with severe pre-
eclampsia should be by adequately trained staff in 2. Hofmeyr R, Matjila M, Dyer R. Preeclampsia in 2017:
the appropriately monitored setting. Obstetric and Anaesthesia Management. Best Pract
• Analgesia Res Clin Anaesthesiol. 2017 Mar 1;31(1):125–38.
• There are few studies examining different analgesic 3. Brown MA, Magee LA, Kenny LC, Karumanchi
options for women with pre-eclampsia after SA, McCarthy FP, Saito S, et al. The hypertensive
caesarean birth. disorders of pregnancy: ISSHP classification, diagnosis
• Neuraxial techniques, local anaesthetic techniques, & management recommendations for international
opioids, paracetamol and tramadol have not practice. Pregnancy Hypertens. 2018 Jul;13:291–310.
been examined to any significant degree in this
4. Dennis AT. Management of pre-eclampsia: issues for
population.
anaesthetists. Anaesthesia. 2012;67(9):1009–20.
• Non-steroidal anti-inflammatory agents are
frequently used for analgesia after childbirth. 5. Melchiorre K, Sharma R, Thilaganathan B.
• Thromboprophylaxis should be considered for all Cardiovascular Implications in Preeclampsia: An
women with pre-eclampsia, with consideration Overview. Circulation. 2014 Aug 19;130(8):703–14.
given to timing of agents in relation to neuraxial 6. Chestnut’s Obstetric Anesthesia - Principles and
anaesthesia. practice ; Fifth edition , Elsevier publications

MCQ
1. Respiratory depression with magnesium occurs at a 4. Sodium nitroprusside is not preferred due to all except
dose above ___ mg/dL
a) Thiocyanate toxicity
a) 5 b) Cerebral edema
b) 7 c) Short action
c) 10 d) Depression
d) 12
5. The half life of magnesium is ___ hrs
2. Which is not a sign of pre-eclampsia with severe features
a) 1
a) SBP > 160 mmHg b) 5
b) Platelets < 150000 x109/L c) 10
c) Pulmonary edema d) 15
d) Visual disturbances
3. The mean colloid osmotic pressure is higher in pre-

eclampsia due to vasoconstriction compared to normal
pregnancy
a) True
b) False
5.B 4.D 3.B 2.B 1.D
ANSWERS:

HOW I DO IT?
24 UNANTICIPATED DIFFICULT AIRWAY IN CATAGORY II LSCS
Professor, Bhavani Shankar Kodali

University of Maryland Medical Center,
Baltimore.
Key points
Ø Airway management can be challenging and tracheal intubation is more likely to fail. Failed intubation and
subsequent inadequate ventilation is an important cause of maternal mortality and morbidity
Ø Proper airway assessment is important. Oxygenation and ventilation are the priorities after failed intubation
Ø Optimal conditions for intubation such as correct positioning and pre-oxygenation in the patient is important
Ø Video laryngoscope may prove useful if the anesthesiologist is familiar with this technique
Ø Knowing when to abandon each step of the failed intubation drill and move on to the next is vital
Ø When both intubation and ventilation have failed, the anesthetist must cease further attempts at oxygenation by
face mask or LMA and proceed rapidly to the neck to access the upper airway
Ø Simulation exercises and teaching using airway manikins and animal models play an important role in supplementing
training in the operating theatre
Lecture Objectives: The pregnant woman presents several unique challenges

for airway management. This is because of differences in
Need for separate guidelines for difficult airway in obstetrics physiology and the surgical situation. Airway edema associated
Current Difficult Airway Algorithm for airway management in with pregnancy and labor can make pregnant airway more easily
failed intubation in obstetrics susceptible to trauma and bleeding, and thus contributing to
difficulty in intubation.
CVCI and role of emergency cricothyrotomy in obstetrics
Decreasing FRC in pregnancy and subsequent changes
Need for separate guidelines for difficult airway in in the pharyngeal space volume contributing to difficult
obstetrics intubation cannot be disregarded because of lack of authentic
studies in pregnant subjects, which are difficult to perform.

Unanticipated Difficult Airway in Catagory II LSCS 244 Bhavani Shankar Kodali
Sometimes we must rely on indirect evidence from

nonpregnant subjects. Additionally, there is a potential
conflict between the needs of the mother and the fetus.
This leads to a potential conflict between the obstetrician
and the anesthesiologist under emergent, testing, and
tense circumstances. Furthermore, the decision among
care providers can vary for a similar situation and thus,
complicating the issues further. In our practice of large
obstetric coverage, intubations that were found to be difficult
during cesarean delivery were subsequently easy few months
following delivery. This illustrates that, the circumstances
surrounding pregnancy and labor in some way affect
successful intubation.
To summarize, there are unique features in obstetric practice

that require separate guidelines:
1) Physiological changes of pregnancy do play some

role- decreased apnea time, airway changes.
2) Majority of cases in the obstetric unit are performed

under regional anesthesia and therefore a definite
pathway is necessary when encountered with difficult
airway.
3) Conflict between mother and fetus
4) Conflict between the care providers
5) Individual variation among care providers
6) Hastiness during emergent cesarean delivery
Current Difficult airway algorithm for airway management

in obstetrical failed intubation management in obstetrics
The best algorithm is your own. This is because there

are several circumstantial differences between various
institutions, in sources, manpower, and equipment.
Nonetheless, the algorithm devised must fulfill the basic
requirement that, the algorithm will help the clinicians, safely
navigate the difficult intubation scenario and protect both
the mother as well as the baby. Furthermore, algorithms
will help caution the clinicians of impending difficulty, so that
Low FRC decreases oxygen reserves during apnea preventive steps are taken before embarking on to intubation.



Reproduced from Mushambi MC , Kinsella SM, Popat M, Swales H, Ramaswamy KK, Winton AL, Quinn AC.
Obstetric Anaesthetists’ Association and Difficult Airway Society guidelines for the management of difficult and failed tracheal
intubation in obstetrics.
Anaesthesia 2015; 70: 1286 – 1306, with permission from Obstetric Anaesthetists’ Association / Difficult Airway Society’

Video laryngoscopes change the game:
At our Institution, all obstetric intubations are performed with video laryngoscope. This is a game changer in algorithms.
In the ASA algorithm of difficult airway, video laryngoscope can be applied at several steps of the algorithm to change the
direction of airway management as success might be achieved early by video laryngoscope as illustrated below.

CVCI and role of emergency cricothyrotomy in obstetrics technique rather than failing to do so. It is possible that two
lives can be preserved by timely intervention. Accuracy of
It is imperative that all anesthesiologists should be familiar identification of the land mark ‘cricothyroid membrane’ is
with cricothyrotomy. It is strongly encouraged that clinicians difficult in morbidly obese pregnant subjects. Ultrasound can
undergo simulation training to perform cricothyrotomy in the help, but how practical is this device in chaotic circumstances
setting of CVCI. It is worth taking the risk to perform this is to be seen.
Further Reading
Kodali etal Anesthesiology 2008;108:357-62
Isono Anesthesiology 2008;108:347-9.
You-Ten etal Anaesthesia 2105;70:1230-34.
Mushambi and Kinsella. BJA 2015; October 28

25 ANAESTHESIA FOR PAEDIATRIC VATS
Professor Neerja Bhardwaj

PGIMER
Chandigarh
Key points
Ø The increasing use of VATS in children has been possible due to refinements in the technique, improved
instruments and advancement in pediatric anaesthesia
Ø In infants with unilateral lung disease, oxygenation is better with healthy lung non-dependent, which is in contrast
to that in adults
Ø Infants have poor elastic properties of lungs, and their closing volume is greater than their FRC, with terminal
airway closure occurring during normal tidal ventilation
Ø Infants respond to hypoxia with a biphasic response, with an initial increase in ventilation for a minute followed by
a decrease and apnea
Ø Children with anterior mediastinal mass require special consideration. Heavy premedication or anaesthetic
induction with the loss of spontaneous ventilation can lead to total airway occlusion and an inability to provide
ventilation by mask or with a tracheal tube in place
Ø Single-lung ventilation can be provided by selective endobronchial intubation, balloon tipped bronchial blockers or
with double lumen tubes(in older children)
Introduction Effect of lateral decubitus position on ventilation and

perfusion
Thoracic surgery in children is commonly performed in
the neonatal period for repair of congenital diaphragmatic When the patient is in the upright position, both ventilation
hernia (CDH), tracheoesophageal fistula (TEF), patent and perfusion are greater in the more dependent versus
ductus arteriosus (PDA) ligation and excision of congenital the non-dependent portions of the lung. However, the
cystic adenoid malformation (CCAM). It may be performed gravitational gradient of blood flow exceeds the gradient
in older children for mediastinal masses, lung diseases, of ventilation leading to a spectrum of ventilation perfusion
decortication and excision of hydatid cyst. All these ratios (V/Q). In normal lungs, this ratio varies from 0.6 at the
procedures are now being increasingly performed using bases to 3.3 at the apices, with a mean value of 0.8. During
thoracoscopy. The increasing use of VATS in children thoracic surgery under general anaesthesia, neuromuscular
has been possible due to refinements in the technique, blockade and mechanical ventilation cause decrease in
improved instruments and advancement in paediatric functional residual capacity (FRC) of both lungs leading
anaesthesia. Therefore, the management includes a wide to ventilation perfusion (V/Q) mismatch. Compression of
range of diseases, a wide range of ages (from low birth dependent lung in the lateral decubitus position may cause
infants to full term infants) and varied surgical pathologies. atelectasis. Surgical retraction or one lung ventilation
To provide a safe and effective anaesthesia to these wide (OLV) results in collapse of the operative lung. Hypoxic
ranging ages, one needs to understand both principles and pulmonary vasoconstriction (HPV) which normally acts
physiology of neonatal and thoracic anaesthesia as well as to divert blood flow away from the underventilated lung,
one lung ventilation (OLV). The anaesthetic challenges are thereby minimizing V/Q mismatch, may be diminished
mainly related to difficulty in OLV leading to hypoxia, carbon by inhalational anaesthetic agents and other vasodilating
dioxide insufflation producing hypercarbia and the effect of drugs. These factors apply equally to patients of all age
lateral decubitus position in neonates, infants and children. groups from infants to adults. However the overall effect of

Anaesthesia for Paediatric VATS 252 Neerja Bhardwaj
the lateral decubitus position on V/Q mismatch is different in time this pressure is applied. The effect of systemic CO2
infants compared with older children and adults. absorption depends on the amount which diffuses in. The
amount of carbon dioxide that diffuses across the pleura
In adult patients with unilateral lung disease, oxygenation and into the blood stream depends on Fick’s Law according
is optimal when patient is placed in the lateral decubitus to which the diffusion of a gas across a membrane is
position with the healthy lung dependent and the diseased proportional to the area of the membrane in contact with
lung non-dependent. This is probably related to an increase the gas (A), the difference in partial pressure of the gas
in blood flow to the dependent, healthy lung and a decrease across the membrane (P1–P2), and a diffusion constant
in blood flow to non-dependent, diseased lung because of (D). The diffusion is therefore proportional to the solubility of
hydrostatic pressure gradient between the two lungs. In the gas and inversely proportional to the square root of the
infants with unilateral lung disease the reverse is true i.e. molecular weight as well as the thickness of the membrane.
oxygenation is better with healthy lung non-dependent. The The Transpulmonary pressure is the difference between
reason for this is: the alveolar and intrapleural pressure and is injurious
• Infants have a soft, easily compressible rib cage that to lung parenchyma with greater risk of acute lung injury
cannot fully support the underlying lung and ARDS as the plateau pressure rises. An increase in
intrapleural pressure causes decrease in transpulmonary
• FRC is closer to residual volume (RV) making airway pressure, allowing for a safe increase in ventilator pressures
closure likely to occur in the dependent lung even proportional to the pressure provided. An increased carbon
during tidal breathing dioxide absorption can lead to hypercarbia if the procedure
lasts for >1 h. Hypercarbia stimulates sympathetic system
• The abdominal hydrostatic pressure gradient is
resulting in an increase in heart rate and blood pressure
deficient in infants, reducing the functional advantage
and it also sensitizes the myocardium to the arrhythmogenic
of the dependent lung
effects of catecholamines with volatile anaesthetic agents.
• A reduced hydrostatic pressure gradient between Thus, it requires an increase in minute ventilation to restore
the non-dependent and dependent lungs reduces the ETCO2 to baseline. The elimination of CO2 continues for
the favorable increase in perfusion to the dependent, about 10 min after deflation leading to a difference between
ventilated lung. Increased oxygen requirement of the mean arterial and end-tidal CO2 (0.33 – 8.8 mmHg).
infants (6 to 8 ml/kg/min) compared to adults (2 to 3 ml/ These effects are magnified in children mainly because of
kg/min) coupled with a small FRC predisposes them to an increased pleural surface area to mass ratio, decreased
hypoxemia especially in the lateral decubitus position. pleural thickness and less distance between vessels and
serous surface.
Effect of CO2 insufflation
Effect of one lung ventilation (OLV)
Carbon dioxide is considered close to an ideal gas for
insufflation during minimally invasive surgery. An ideal gas Following partial lung collapse, hypoxic pulmonary
for insufflation should not support combustion, should have vasoconstriction (HPV) increases pulmonary vascular
limited systemic absorption and if absorbed should have resistance with consequent re-routing of blood to the well
limited systemic effects, should be rapidly excreted, should ventilated lung zones. This normal physiologic response
be highly soluble in blood and should produce limited to atelectasis decreases ventilation perfusion mismatching
physiological effects if intravascular embolism occurs. and improves arterial oxygenation. However, when more
In this context, carbon dioxide is the best since it meets than 70% of the lung is atelectatic (as in OLV), HPV is
most of the properties of an ideal gas. The only drawback obliterated.
with carbon dioxide is its vascular absorption across the
peritoneum. Air, oxygen and nitrous oxide all support After collapse of the operative upper lung, all the ventilation
combustion. Helium is a good gas but is expensive and if passes to the lower lung, but blood flow although reduced,
intravascular embolization occurs, its relative insolubility persists in the nonventilated lung. This blood flow does
could lead to serious cardiovascular collapse. not participate in oxygenation and represents a right to left
transpulmonary shunt which accounts for the decrease
Pneumothorax exerts its effect on various organ systems
in arterial PO2 seen during OLV. Preexisting pulmonary
by physical pressure and via systemic absorption of carbon
disease, elevation of the diaphragm, compression of
dioxide. The extent of pressure exerted depends on the
the thoracic cavity from the mediastinum and abdominal
absolute amount of intrathoracic pressure and length of

contents, rolls and packs used to facilitate positioning of the diaphragm of preterm and term infants as well as the
patient, all contribute to a disparity between ventilation and intercostal muscles contains less type 1 muscle fibers
perfusion in the ventilated lung thus increasing the shunt (slow endurance) making the respiratory muscles of
fraction still further. neonates more susceptible to fatigue.
3. Resting lung volume or functional residual capacity

The physiologic basis for haemodynamic instability during
(FRC) is determined by the static balance between the
OLV is multi-factorial. As the chest cavity is closed, rapid
outward and inward recoil pressure of the chest wall and
and excessive CO2 insufflation can create a tension
lung, respectively, and is lower in neonates than in older
pneumothorax. The resultant compression of the lungs and
subjects. Due to the poor elastic properties of infant lungs,
great vessels could decrease venous return and stroke
their closing volume is greater than their FRC, with terminal
volume with resultant hypotension. Gas insufflation can
airway closure occurring during normal tidal ventilation.
activate pulmonary stretch receptors and increase vagal
tone with consequent bradycardia and also can cause Infants apply several mechanisms to maintain and
mediastinal shifting and cardiac tamponade. dynamically increase their FRC:
Effect of normal respiratory physiology • Post-inspiratory activity of intercostal and
diaphragmatic muscles (self-recruitment
Normal respiratory physiology of neonates and infants
maneuver)
magnifies the problems produced by LDP, CO2 insufflation
and OLV. • High respiratory rates with short
expiratory times (auto-PEEP or dynamic
A. Neonates are at an increased risk of atelectasis due hyperinflation)
to the following:
• Laryngeal adduction in expiration to
1. Collateral connections between alveoli (pores of increase expiratory airway resistance
Kohn and bronchoalveolar canals of Lambert) are not (functional PEEP).
present until the first years of life increasing the risk of
C. Immature respiratory system
atelectasis in dependent lung areas.
1. The ventilatory response to hypoxia and hypercarbia
2. Production of pulmonary surfactant begins by 23 to 24
is impaired. Hypercapnia increases tidal volume (TV)
weeks’ gestational age and reaches sufficient levels
and respiratory rate (RR) in adults and children but
after about 35 weeks of gestation. Surfactant-deficient
response is attenuated in neonates. There is biphasic
lungs are characterized by poor compliance, reduced
response to hypoxia. There is an initial increase in
volume and widespread atelectasis, ventilation-
ventilation for a minute followed by a decrease and
perfusion mismatching and hypoxia.
apnea. Anaesthetic drugs further blunt the respiratory
B. Neonates are at risk of airway collapse control to both hypoxia and hypercarbia.
1. Newborn infants, especially if born premature, have 2. The anatomical dead space in infants is greater than
fewer and larger alveoli than older children and adults. older children owing to relatively large head size.
Alveolarization, i.e. the growth and development of
3. Pharynx, larynx and the bronchial tree are more
alveoli, continues into childhood and adolescence. In
compliant leading to dynamic upper airway collapse
neonates, due to fewer alveoli, there is less elastic
during forceful inspiration.
recoil and therefore an increased risk of airway collapse
on expiration. 4. Airway diameters are smaller leading to higher airflow
resistance as the resistance is inversely proportional to
2. The thorax of neonates is highly compliant and
the fourth power of the airway radius. Any secretions,
deformable. In respiratory distress, there can be
blood or presence of endotracheal tube therefore
pronounced inspiratory intercostal, sternal, and
increases the work of breathing in preterm and term
supraclavicular recessions as well as a paradox
neonates.
inspiratory inward movement of the chest wall due to
the high compliance of the thorax. In neonates, the 5. Term infants and especially preterm infants have
efficiency of the intercostal muscles is reduced as the immature antioxidative systems and are at risk of
ribs are aligned more horizontally. Additionally, the oxygen toxicity.

Anaesthetic management be given prior to ET intubation to facilitate placement of
the ETT without haemodynamic or respiratory responses.
The anaesthetic management of a child undergoing VATS Monitoring includes ECG, invasive blood pressure, oxygen
requires a thorough preoperative evaluation for associated saturation, end tidal concentration of CO2 and anaesthetic
congenital diseases particularly congenital heart disease gases, temperature, urine output and blood loss. Most
and degree of respiratory compromise. It will also identify patients require arterial cannulation for measurement of
any underlying disease or cause of airway compromise invasive blood pressure and arterial blood gases during
which can impact the anaesthetic management. One single lung ventilation (SLV) as there is a gradient between
should perform appropriate imaging and laboratory studies ETCO2 and PaCO2. Placement of a central venous catheter
before the conduct of anaesthesia depending on the clinical is not required routinely if peripheral venous access is good.
condition of the child. Blood should be arranged because In situations, where CVP placement is required, it should
thoracoscopy can convert to open thoracotomy and also be placed on the side of thoracoscopy to avoid inadvertent
there can be trauma to major vessels or bleeding due to bilateral pneumothoraces.
surgical reasons. Pulmonary function tests and ECG or
ECHO are not routinely recommended unless they are With GA and positive pressure ventilation, surgical
required based on the patient disease. visualization is poor owing to the lung coming into the
surgical field. Therefore, OLV is performed.
Children with anterior mediastinal mass require special
Maintenance of anaesthesia should be with 100% oxygen
consideration. Depending on the location of the mass and
and nitrous oxide should be avoided. Amongst the
its compression of the tracheal lumen, heavy premedication
inhalational agents, isoflurane is preferred because it causes
or anaesthetic induction with the loss of spontaneous
less attenuation of the hypoxic pulmonary vasoconstriction
ventilation can lead to total airway occlusion and an inability
(HPV). Intravenous opioids facilitate a decreased usage of
to provide ventilation by mask or with a tracheal tube in
inhaled anaesthetic agent, limiting the impairment of HPV.
place. A preoperative CT may be useful to identify this
Another option is use of total intravenous anaesthesia. A
problem. More than 50% compromise of the cross sectional
combination of general and regional anaesthesia may also
area of trachea by the mass on CT, identifies patients who
have an advantage of reducing the need for anaesthetic
are at risk of airway collapse and total airway obstruction
agent as well as provision of intraoperative and postoperative
after induction of GA. These patients would benefit from
anaesthesia.
preoperative chemo or radiotherapy to reduce the mass
size. Alternatively, maintaining spontaneous ventilation Techniques of single lung ventilation in paediatric
for intubation of airway is recommended. If there is airway patients
collapse after induction, use of rigid bronchoscopy is life-
saving. Also, these patients would require preoperative Single – lumen endotracheal tube (Selective
ECHO to rule out cardiac compression. A back up of endobronchial intubation)
cardiopulmonary bypass is also recommended.
This technique involves the intentional endobronchial
Fasting guidelines, choice of premedication (oral midazolam intubation of the non – surgical lung with a conventional
0.5mg/kg) and operating room preparation is similar to that endotracheal tube (ETT). To achieve left main – stem
for any major surgery in an infant/child. H2 antagonist like intubation, once ETT is in trachea, it is rotated 180° so
ranitidine and metoclopramide may also be used. that the bevel faces the right side and the head is turned
to the right and ETT is advanced into the bronchus till the
Anaesthetic induction techniques include either inhalation breath sounds disappear on the operative side. A fiberoptic
techniques with sevoflurane in oxygen. Intravenous bronchoscope may be passed through or alongside the ETT
anaesthetic agents can also be used if there is a patent to confirm or guide placement. When a cuffed tube is used,
intravenous access. Once adequate bag-mask ventilation the size should be 0.5 or 1 mm smaller than the uncuffed
has been demonstrated, either induction technique can tube. Also the distance from the tip of the tube to the distal
be followed by the administration of a non-depolarising cuff must be shorter than the length of the bronchus to
neuromuscular relaxant (NDMR). If there is a contraindication ensure that the cuff is entirely in the bronchus. The problems
to the use of a NMBA and controlled ventilation like in with single – lumen endotracheal tube include
presence of big cyst, intubation can be accomplished
during spontaneous ventilation. In these circumstances, • Difficulty to provide an adequate seal of the bronchus
a dose of lidocaine (1–2 mg/kg) or propofol (1 mg/kg) can which prevents the operative lung from adequately

collapsing and also does not prevent contamination of corresponds to the length of the right main-stem bronchus
the healthy lung and therefore allows the catheter to be placed so that the
balloon is entirely in the main-stem bronchus and still not
• Suctioning of the operated lung cannot be done obstructing the right upper lobe bronchus. The blue balloon
• Hypoxemia may occur due to obstruction of right upper on a yellow catheter allows easy visualization. The blocker
lobe bronchus. kit consists of a multiport adapter that allows uninterrupted
ventilation while the blocker is being placed with the FOB.
Balloon – tipped bronchial blockers The blocker also contains a nylon loop that emerges at the
tip of the blocker. The nylon loop is used to couple the FOB
The Fogarty embolectomy catheter and Arndt blocker are
to the blocker for placement into the desired bronchus. After
balloon – tipped blockers used for bronchial blockade to
successful placement, the loop can be withdrawn, and the
provide OLV in children.
lumen can be used for suction and oxygen insufflation to
Fogarty embolectomy catheters the unventilated lung. The smallest tube through which
the WEB and the FOB can be simultaneously placed is
The Fogarty embolectomy catheter is frequently used as determined by the outer diameter of the blocker catheter and
a bronchial blocker. It comes with a wire stylet that can be the FOB. However, if the ETT is too small to accommodate
curved at the distal end to allow directing the catheter tip the smallest available WEB and FOB, this blocker may be
laterally into the desired main bronchus. The blocker can placed outside the ETT.
be placed either alongside the ETT or through the ETT. To
place the blocker alongside the ETT, it is advanced through Univent tubes
the larynx by direct laryngoscopy, with the concavity facing
The Univent tube is a conventional tube with a second
forward. Once it is in the trachea, the blocker catheter tip
lumen containing a blocker that can be advanced into a
is rotated 90° to the right for right-sided placement and
bronchus and inflated. The blocker component of Univent
90° to the left for left-sided placement, before advancing
tube, does not have a lumen for the egress of gas and
the blocker into the desired main-stem bronchus. The ETT
oxygen insufflation. Also, these tubes have a much larger
is then placed into the trachea, alongside the blocker. The
cross-sectional area so that the 3.5-mm ID tube has an
catheter balloon is positioned in the proximal main-stem
external diameter of 8 mm. Therefore, it is appropriate for
bronchus under fiberoptic visual guidance.
children who are 6 years or older. The smaller Univent
In another technique the bronchus on the operative side tubes have a disproportionately high resistance to gas flow.
is intubated with an ETT. A guide wire is then advanced Also, the blocker balloon has low-volume, high-pressure
through the ETT into the bronchus. The ETT is then characteristics with a greater likelihood of causing mucosal
removed, and the blocker is advanced over the guide wire injury, even during normal inflation. Univent tubes are easy
into the bronchus. An ETT is finally reinserted into the to place and less likely to become displaced.
trachea alongside the blocker catheter. The advantage
Double-lumen tubes
of this blocker is that it can be used successfully even in
infants (size 3-F). Catheters with an open tip are preferred Conventional DLTs are available only in adult sizes (35-, 37-,
over closed-tip catheters because the lumen of the catheter 39-, and 41-F). The smallest DLT is 26-F, which may be used
facilitates lung collapse and can be used as a suction port in children as young as 8 to 10 years old. These tubes are
or for oxygen insufflation. Potential problems include relatively easy to use and offer the advantage of separation
of the two lungs and the ability to suction and oxygenate
• Dislodgment of the blocker into the trachea, with
the operative lung with continuous positive airway pressure
subsequent obstruction to ventilation
(CPAP). Left-sided tubes are preferred to right-sided DLTs
• Because the catheter balloon has low-volume, high- because of the shorter length of the right main bronchus
pressure properties, over distension of the balloon can and the risk of right upper-lobe obstruction. However these
damage or even rupture the airway. tubes are unsuitable for patients with difficult upper-airway
or abnormal tracheobronchial anatomy, children requiring
Arndt endobronchial blockers postoperative mechanical ventilation, and children less than
10 years of age. The technique of placing a DLT in children
This blocker is available in three sizes (5-, 7-, and 9-F) and
is the same as in adults. The DLT is first inserted through
can be used in children who are old enough to accommodate
the glottis with direct laryngoscopy, rotating it 90° to the
a 5.0-mm ETT. The low-pressure, high-volume balloon

left, and then advancing it only until the proximal edge of 3. Hammer GB. Pediatric thoracic anesthesia.
the cuff is past the vocal cords. The tracheal cuff is then Anesthesiology Clinics of North America 2002; 20:
inflated, and ventilation to both lungs is resumed. The FOB 153 – 80.
is then placed through the bronchial lumen and advanced
until the carina and main-stem bronchi are clearly identified. 4. Choudhry DK. Single – lung ventilation in pediatric
The FOB is then advanced into the left main-stem bronchus anesthesia. Anesthesiology Clinics of North America
just proximal to the left upper-lobe bronchi. The tracheal 2005; 23: 693 – 708.
cuff is then deflated, and the entire DLT is advanced over 5. Hammer G, Hall S, Davis PJ. Anesthesia for general
the FOB until its bronchial lumen comes into view beyond abdominal, thoracic, urologic and bariatric surgery.
the tip of the FOB. Visualization of the left upper and lower In: Motoyama EK, Davis PJ, eds. Smith’s Anesthesia
lobe bronchus ensures that the DLT is not advanced too for infants and children. Philadelphia: Mosby Elsevier,
far. Finally, the FOB is passed through the tracheal lumen 2006: 685 – 722.
to check for a carinal or subcarinal position of the bronchial
cuff and to ensure patency of the right main-stem bronchus. 6. Tobias JD. Anaesthesia for neonatal thoracic surgery.
Best Practice & Research Clinical Anaesthesiology
Postoperative recovery 2004; 18: 303 – 20.
The child takes longer to recover since CO2 takes about 10 7. Ivani G, Tonetti F, Mossetti V. Update on postoperative
min to wash out. While extubating child should be conscious analgesia in children. Minerva Anesthesiologica 2005;
with intact reflexes. He should be monitored for vital 71: 501 – 5.
parameters and pain. Pain relief can be achieved with LA
infiltration at port sites/opioids/NSAIDs/paravertebral and 8. Suresh S, Wheeler M. Practical pediatric regional
erector spinae block. Child should be given ondansetron or anesthesia. Anesthesiol Clin North America 2002; 20:
dexamethasone to prevent PONV. 83 – 113.
References 9. Fabila TS, Menghraj SJ. One lung ventilation strategies

for infants and children undergoing video assisted
1. Haynes SR, Bonner S. Anaesthesia for thoracic thoracoscopic surgery. Ind J Anaesth 2013; 57: 339
surgery in children. Paediatric Anaesthesia 2000; 10: – 4.
237 – 51.
10. Kumar K, Basker S, Jeslin L, Karthikeyan C, Matthias A.
2. Tobias JD. Anaesthesia for minimally invasive Anaesthesia for pediatric video assisted thoracoscopic
surgery in children. Best Practice & Research Clinical surgery. J Anaesthesiol Clin Pharmacol 2011; 27: 12
Anaesthesiology 2002; 16: 115 – 30. – 16.

26 ANESTHETIC MANAGEMENT OF PATIENTS WITH
COPD FOR LAPAROSCOPIC SURGERY
Professor & HOD Rajeshwari S

AIIMS
New Delhi
Key points
Ø Patients having minimally invasive surgery experience better peri-operative outcomes than patients having open
abdominal procedures
Ø Anesthetic concerns for patients undergoing laparoscopic and robotic surgery include measures to mitigate the
physiologic effects of the pneumoperitoneum, absorption of CO2 and positioning required for surgery.
Ø During robot-assisted radical cystectomy, use of a valveless trocar for pneumoperitoneum is associated with a
significantly lower plateau pressure and improvement in other respiratory parameters.
Ø Smoking should be stopped at least 8 weeks before for full benefit.
Ø Regional anesthesia in the form of epidural/spinal anesthesia may be used as sole anesthetic for brief procedures,
and to provide effective analgesia post operatively.
There are many advantages of laparoscopy, such as faster having minimally invasive surgery experience better peri-
recovery, shorter hospital stay, and earlier return to normal operative outcomes than patients having open abdominal
activities. Postoperative pain and pulmonary complications procedures. Minimally invasive surgery correlates with
are less, along with smaller incisions and scars. Minimally improved peri-operative quality of life (QoL), shorter length
invasive surgery (e.g., laparoscopic or robotic assisted of hospital stay and lower complication rates in comparison
surgery) has emerged for the treatment of several benign to open surgery.
and malignant conditions. Most intra-abdominal organs can
be approached laparoscopically. Examples are the adrenal The adoption of minimally invasive surgery also improves
glands, kidney, bladder, prostate, colon, rectum, uterus patient turnover, decreases leave from work and reduces
and stomach (Fig 1). Increasing data show that patients costs for the healthcare system.
Fig 1: Examples of laparoscopic and

robotic surgery

Anesthetic management of patients with 258 Rajeshwari S
COPD for laparoscopic surgery
Despite these advantages, there are some concerns of Thus, anesthetic concerns for patients undergoing
laparoscopic surgery. laparoscopic and robotic surgery differ from those for
patients undergoing open abdominal surgery. They
Foremost is the patho-physiological effects of include measures to mitigate the physiologic effects of the
pneumoperitoneum created to facilitate surgery. pneumoperitoneum, absorption of CO2 and positioning
Carbon dioxide (CO2) is most commonly used to create required for surgery. Some laparoscopic/robotic procedures
pneumoperitoneum. Increased intra-abdominal pressure take longer than the open alternative. This raises concerns
and CO2 absorption can cause effects on cardiovascular in patients affected by severe pulmonary disease.
and pulmonary parameters during the surgical procedure
(Fig 2). Pneumoperitoneum, by way of increased intra Special care must be given to patients with severe
abdominal pressures, affects the respiratory mechanics chronic obstructive pulmonary disease because higher
by splinting the diaphragm, increasing intra thoracic airway pressures are required to ventilate patients during
pressures and transpulmonary pressures. Increased laparoscopy, predisposing patients to bullae rupture.
intrathoracic pressures also cause reduction in venous Similarly, with the Trendelenburg position, compression
return, contributing to hypotension. In patients with chronic of the intra-abdominal organs and the undersurface
obstructive pulmonary disease (COPD), flattening of the of the diaphragm can aggravate these effects. CO2
diaphragm affects respiratory mechanics negatively. retention and respiratory acidosis easily occur due to
Pneumoperitoneum increases the intra-abdominal pressure increase in intrinsic PEEP, air trapping, V/Q mismatch
and worsens the effect of the flat diaphragm. The inability and atelectasis. Additionally, pneumothorax, pneumo-
to compensate for arterial CO2 elevation can precipitate mediastinum, hypotension, right ventricular strain and
significant acidosis, which can lead to cardiovascular failure are the possible complications that can occur during
and respiratory collapse; therefore, hyperventilation after laparoscopy and can worsen outcome. During robot-
intubation is required. If acidosis develops and cannot be assisted radical cystectomy, use of a valveless trocar for
reversed, then the procedure may need to be converted to pneumoperitoneum is associated with a significantly lower
open laparotomy. Pplat and improvement in other respiratory parameters.
Fig 2: Systemic effects of pneumoperitoneum

Effects of laparoscopy on outcome in patients with patients, with both PaCO2 > 5.9 kPa and PaO2 < 7.9 kPa
COPD predicting a worse outcome. For example, the likelihood of
PPCs increases considerably with preoperative wheezing
Galvis(1) et al reported that patients with COPD who warranting aggressive treatment with bronchodilators and
undergo laparoscopic hysterectomy have an increased risk possibly inhaled and systemic steroids in the days before
of experiencing postoperative pneumonia, reintubation, surgery. Upper respiratory infections should be ruled out
renal insufficiency and sepsis. They advocated that and treated as a cause of increased secretions and airway
anesthesiologists should consider the pulmonary disease hyper-reactivity.
status of patients when assessing preoperative risk.
Smoking should be stopped at least 8 weeks before, for full
Liao(2) et al studied the post operative course of more than
benefit.
3,900 patients with COPD undergoing cholecystectomy. The
hospital stay, ICU stay, mechanical ventilation, life support Nutritional status should be improved, as reduced albumin
measures, including vasopressors and hemodialysis, and is associated with poor outcome. Serum albumin level
rates of hospital mortality, acute respiratory failure and <35 mg/L is a strong predictor of postoperative pulmonary
pneumonia were increased in COPD patients compared complications.
with those in non-COPD patients.
Anesthesia techniques during laparoscopy
Guo(3) et al stated that major laparoscopic gastrointestinal
surgery for properly selected COPD patient was safe and General anesthesia
feasible, with short term benefits. In a series of patients
undergoing laparoscopic colonic resection, it was found Ventilation
that laproscopic approach resulted in better preservation
As mentioned above, gas insufflation up to 10-15 mm Hg
of lung function and reduced complications. Similarly, in
causes diaphragmatic and chest wall stiffening. When
patients subjected to open vs laparoscopic gastrectomy,
constant volume controlled modes are used, this translates
Chang et al found no significant differences in incidence of
into high peak airway pressures. Airway resistance increases
postoperative pulmonary complications.
due to distortion of large airways. Plateau pressures are
Inokuchi et al(4) found that post operative pulmonary more indicative of atelectasis.
complications were slightly, but not significantly less
frequent in the laparoscopic group than in the open group. ETCO2 monitoring
In a recent study Bhaskar et al(5) compared outcomes In patients with COPD undergoing cholecystectomy,
in patients with COPD undergoing open colectomy (OC) Oziyuvaci et al(6) showed that PaCO2 was significantly
or laparoscopic colectomy (LC). They found that despite higher than ETCO2 at 5 min after induction of anaesthesia,
the potential risks of laparoscopic pneumoperitoneum in and at 5 and 20 min of insufflation (P < 0.05). It was seen
the susceptible COPD population, a minimally invasive that transcutaneous CO2 , (TcPCO2) and PaCO2 did not
approach was associated with lower risk of postoperative differ significantly at 5 min after induction of anesthesia, at
respiratory complications, shorter length of stay, and 20 min of insufflation or at 5 minutes after extubation.
decrease in postoperative morbidity.
During laparoscopy, use of volume controlled ventilation
Pre op optimization resulting in high airway pressures is seen to increase
PaCO2-ETCO2 gradient due to dead space ventilation in
Risk of Postoperative Pulmonary Complications (PPCs) patients with COPD and may decrease in obese subjects
may be decreased if any reversible causes can be treated in due to recruitment.
advance. The basic physical examination findings can help
predict the risk of PPCs. The predictive value of decreased Induction of anesthesia in patients with severe COPD
breath sounds, prolonged expiration, rales, wheezes, or presents a challenge because of the risk of hemodynamic
rhonchi has been shown in general surgical and thoracic instability resulting from air trapping and elevated intrinsic
patients. Spirometry is useful to confirm the diagnosis and positive end-expiratory pressure (PEEPi). Upper airway
to assess the severity of COPD. A baseline arterial blood instrumentation (e.g., tracheal intubation) and inhalation
gas measurement may be useful in predicting high-risk of irritants (e.g., desflurane, external disinfectants) may

trigger vagally-mediated reflex bronchoconstriction thereby Laparoscopic cholecystectomy under epidural anesthesia
promoting the expiratory collapse of the peripheral airways alone or spinal anesthesia has been reported to be safe
with incomplete lung alveolar emptying. A patient with and feasible. Thoracic epidural analgesia has been used
COPD requiring a general anesthetic is likely to be at a risk effectively for laparoscopic cholecystectomy in a recent
of hemodynamic compromise on induction of anesthesia series of 34 patients with COPD Stage III/IV. The authors
and initiation of intermittent positive pressure ventilation used low pressure pneumoperitoneum (10-12 mmHg)
(IPPV). Placement of an arterial catheter should be
and concluded that COPD patients who are at a high risk
considered for both beat-to-beat blood pressure monitoring
of general anesthesia can be operated under regional
and for repeated blood gas analysis. The patients in major
anesthesia without experiencing respiratory system
surgeries with severe COPD and hypoxia, continuous
positive airway pressure during induction may be used to complications and with less post-operative pain (9). Bayrak
improve the efficacy of preoxygenation and to reduce the et al (11) concluded that laparoscopic cholecystectomy can
development of atelectasis. be safely performed for COPD patients under general and
spinal anesthesia. However, spinal anesthesia is preferred
Whenever there is evidence of increased intrinsic PEEP the over general anesthesia as it has better postoperative
following measures may be taken to reduce air trapping: analgesia and causes no impairment of pulmonary functions.
• Allowing more time for exhalation. Reducing In conclusion, it is vital to understand the pathophysiology
the respiratory rate or the Inhalation: Exhalation
of COPD especially with respect to respiratory and
ratio (typically to 1:3–1:5) allows more time for
hemodynamic changes. Super added will be the deleterious
exhalation, thus reducing the likelihood of breath
effects of increased intraabdominal pressure and
stacking.
hypercarbia due to CO2 insufflation.
• Application of PEEP. The use of external PEEP
in ventilated patients with COPD has theoretical Reduction in many adverse effects of pneumoperitoneum
benefits by keeping small airways open during late may be achieved by (10):
exhalation, so potentially reducing PEEPi.
• Optimizing preoperative intravascular fluid volume
• Treatment of bronchospasm: It should be treated status to avoid hypovolemia.
promptly either by inhaled bronchodilators or by
deepening anesthesia with propofol or increased • Utilizing slow abdominal insufflation with maximum
concentrations of inhalation anesthetics. IAP of <15 mm Hg coupled with minimized duration
of extreme patient positioning.
Regional anesthesia in COPD
• Hemodynamic monitoring with direct arterial line
In general, the use of regional anesthesia in patients with and TEE placement in selected high-risk individuals.
COPD is associated with lower incidences of composite
morbidity, pneumonia, prolonged ventilator dependence, • Placing an arterial line for monitoring of partial
and unplanned postoperative intubation (7). pressure of CO2 in patients whom ETCO2 may be
unreliable.
In 15 patients who underwent laparoscopic cholecystectomy
under spinal anesthesia with low-pressure CO2 • Applying a team-based approach among the
pneumoperitoneum, the technique was deemed as feasible preoperative consultant, anesthesiologist, and
and safe and at least as effective as general anesthesia (8). surgeon to determine the intraoperative plan to
mitigate cardiovascular risk.
Neuraxial anesthesia as sole anesthetic technique,
for laparoscopic cholecystectomy was associated with Finally, regional anesthesia in the form of epidural/
intraoperative pain referred to the shoulder, it required spinal anesthesia may be used as sole anesthetic for
anesthetic conversion in 3.4% of the cases and did not
brief procedures, and to provide effective analgesia post
demonstrate evidence of respiratory benefits for patients
operatively.
with normal pulmonary function.

References 6. Oziyuvaci E et al. The Journal of International
Medical Research 2012; 40: 1982 – 1987
1. Galvis JN et al. JSLS 2019;23:1-8
7. Hausman MA et al. Anesth Analg 2015;120:1405–12
2. Liao KM et al. International Journal of Chronic
Obstructive Pulmonary Disease 2019:14 1159– 8. Gramatica L. et al. Surg Endosc 2002; 16:472-75
1165
9. Aidyn MA. Laparosc Endosc Surg Sci 2019;26:87-
3. Guo Y et al. BioMed Research International Volume 92
2019, Article ID 8280358,
10. Bayrak M. BMC Surgery (2018) 18:65
4. Inokuchi M et al. Surg Endosc (2013) 27:2102–
11. Atkinson TM et al. Circulation 2017;135:700–710
2109
5. Bhaskar SS et al. Surg Endosc (2018) 32:1280–

1285

27 RESCUE STRATEGIES IN ARDS INCLUDING ECMO
Associate Professor Michael Mazzeffi

Baltimore.
Key points
Ø The Berlin Definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia:
• Mild - 200 mmHg < PaO2/FIO2 ≤300 mmHg with PEEP or CPAP ≥5 cmH2O
• Moderate - 100 mmHg < PaO2/FIO2 ≤200 mmHg with PEEP ≥5 cmH2O
• Severe - PaO2/FIO2 ≤100 mmHg with PEEP ≥5 cmH2O
Ø Four ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (≤40 mL/cm
H2O), positive end-expiratory pressure (≥10 cm H2O), and corrected expired volume per minute (≥10 L/min).
Ø The timing of acute onset of respiratory failure to make diagnosis of ARDS is defined as the exposure to a known
risk factor or worsening of the respiratory symptoms within one week.
Ø Common risk factors for ARDS: Sepsis – Pulmonary and non- pulmonary, trauma, aspiration, severe burns,
TRALI, pancreatitis etc
Ø Options for management of ARDS includes Airway Pressure Release Ventilation (APRV), High Frequency
Ossillatory Ventilation (HFOV) & Extra Corporeal Membrane Oxygenation (ECMO)
Ø APRV rationale - Recruits alveoli with longer time constants for filling with sustained high CPAP, has lower peak
and plateau pressures for a given tidal volume and gains gain benefits from spontaneous breathing.
Ø HFOV Rationale -Low tidal volume with controlled pressure, maintains alveoli in open state at all times, can
prevent atelectrauma and improves V/Q matching by maintaining uniform aeration of the lung
Ø VV ECMO - A membrane oxygenator temporarily takes over gas exchange for an injured lung and ultraprotective
lung ventilation allows for lung healing.
Objectives of Talk
 Define severe ARDS B. High Frequency Oscillatory Ventilation

(HFOV)
 Summarize epidemiology and outcomes for ARDS
C. Veno-Venous Extracorporeal Membrane
 Review rescue strategies for severe ARDS
Oxygenation (VV ECMO)
A. Airway Pressure Release Ventilation
(APRV)

Rescue strategies in ARDS including ECMO 264 Michael Mazzeffi
Timeline of ARDS Nomenclature and Definitions
1967
1994
2012
The Berlin Definition
JAMA. 2012; 307 (23):E1-E8

Fig 1: Chest X ray in ARDS
Fig 2: Pathophysiology of ARDS

The AECC Definition
ARDS Epidemiology
 2005 Rubenfeld et al. reported data from 18 US  Found an ALI incidence of 78.9 cases per 100,000
hospitals in King’s county in Washington state and person years and ARDS incidence of 58.7 cases
from 3 other hospitals (21 total hospitals) per 100,000 person years
 Prospective cohort study that followed all ICU  These numbers extrapolated to approximately
admissions for 1 year 190,000 ARDS cases annually in the US
ARDS Causes
Rubenfeld GD, et al. N Engl J Med 2005;353(16):1685–93

Rubenfeld Data vs. Others
Rubenfeld GD, et al. N Engl J Med 2005;353(16):1685–93
ARDS Mortality
Trends *Data from 72 studies
Zambon M, et al. Chest 2008;133(5):1120–7

ARDS Mortality Trends in US
Cochi et al. Ann Am Thorac Soc 2016;13(10): 1742-51.
ARDS International Trends
Bellani et al. JAMA Surg. 2016; 315(8): 788-800.

Case APRV – Airway Pressure Release Ventilation
• A 23 year old pregnant woman (36 wks GA) is • A novel concept in ventilation described by Downs
admitted to the ICU. She presented to the emergency and Stock in CCM 1987.
department with high fever (103 C), tachycardia,
• Concept was to provide high level CPAP
hypoxemia, and hypotension. She was intubated and
with occasional releases. Envisioned it for
started on mechanical ventilation. Her rapid influenza
spontaneously breathing patients.
test was positive for Influenza A. She was taken for
immediate C/S. • Noted that patients with ALI have “reduced
lung volumes, V/Q mismatch, tachypnea, and
• After 2 days in the ICU she has patchy bilateral increased work of breathing” Yet patients rarely
infiltrates on CXR, a P/F ratio of 60 on 100% oxygen have “decreased respiratory muscle strength or
and 20 cmH20 of PEEP, and a PCo2 of 70 mmHg impaired respiratory drive”
with a respiratory acidosis on her ABG, she has
normal cardiac function. • Hence efforts should be made to decrease their
work of breathing by increasing lung volume and
• You have attempted recruitment maneuvers, compliance. CPAP accomplishes these goals.
paralyzed the patient with cisatricurium, and
• Lung volume does not decrease below FRC
proned the patient. None of these strategies have
during normal spontaneous respiration. Only
significantly improved gas exchange. The patient has
during releases!
a pH of 7.13 and is becoming increasingly unstable.
You are unable to ventilate her or achieve adequate Rationale for APRV
oxygenation with low tidal volume ventilation (6 mL/
kg). Plateau pressures are in the 40s and driving • Lung recruitment from sustained high CPAP.
pressure in the 20s. Recruits alveoli with longer time constants for
filling.
• What further options do you have?
• APRV has lower peak and plateau pressures for a
Possibly a few… given tidal volume.
1. APRV • Gain benefits from spontaneous breathing. During

spontaneous breathing posterior portions of the
2. HFOV diaphragm move more and dependent portions of
the lung are better ventilated in supine patients.
3. ECMO
• May be better tolerated by patients and require
less sedation
APRV Mechanics of APRV
• 5 major parameters: Phigh, Thigh, Plow, Tlow, and

Fi02
• Phigh and Thigh are determinants of mean airway
pressure and oxygenation
• Difference between Phigh and Plow and
spontaneous ventilation determine ventilation and
CO2 clearance
• Generally 80-95% of time should be spent at
Phigh
• Tlow should end when expiratory flow is 50-60%
of peak to avoid atelectasis
APRV
• Phigh can be set at desired plateau pressure

Suggested APRV Settings
Stawicki et al. J Intens Care Med. 2009; 24: 215-29.
Pressure and Flow vs. Time
Stawicki et al. J Intens Care Med. 2009; 24: 215-29.
Trouble Shooting APRV
• Is CO2 clearance a problem? Generally not if the • How to wean, “Drop and Spread technique”. Slowly
patients is breathing and in fact it may improve lower Phigh and extend Thigh. Eventually you get to
because of improved V/Q matching. There is also a continuous CPAP
phenomenon of cardiac mixing where CO2 moves
toward central airways during Thigh allowing for • When Phigh is less than 20 and Thigh is greater
easier clearance during Pressure drop. than 6 can return to conventional ventilation.

Negative Aspects of APRV
• If patient is not spontaneously breathing CO2 • Will decrease preload and can lead to hypotension
clearance can become an issue. in patients who are hypovolemic. Spontaneous
breathing helps to offset this problem.
• Many of the benefits are lost if the patient is not
spontaneously breathing, is over-sedated, or
paralyzed.
Evidences for APRV
Varpula et al Key Points
 RCT of APRV vs. SIMV with pressure support

 58 patients
 After 2 to 24 hour “stabilization” period using low tidal volume AC patients were randomized.
 No differences in mortality, ventilator free days, or oxygenation indices

Putensen Data
Putensen C, et al. Am J Resp Crit Care Med 2001; 164: 43-9.
 Thirty multi-trauma patient randomly assigned to APRV vs. Pressure control ventilation (AC)
 Pig model of peritoneal sepsis (N=7)
 Following insult randomized to LTV vs. APRV
 At 48 hrs. pigs killed and evaluated
 Also looked at biomarkers of alveolar stability and permeability, lung edema, and indices of oxygenation
Roy S, et al. Shock. 2013; 39 (1): 28-38.

Roy Data
HFOV

HFOV Rationale
• Low tidal volume, controlled pressure

• Maintains alveoli in open state at all times
• Can prevent atelectrauma
• Improves V/Q matching by maintaining uniform aeration of the lung
• Non-compliant alveoli have a long time constant for filling and HFOV may help.
HFOV rationale
Stawick SP, et al. J Intens Care Med. 2009; 24: 215-29.
How HFOV Works
• Sensormedics 3100 B is the only FDA approved device for adults

• Controls include: respiratory frequency, amplitude (delta P), mean airway pressure, bias gas flow rate,
percentage inspiratory time, and Fi02
• Delta P affects TV
• Frequency is inversely related to TV
• MAP is related directly to oxygenation
Suggested HFOV Settings

HFOV Setup
HFOV
How Gas Exchange Occurs
 TV approximately 1 to 2 ml/kg
 Bulk convection plays a limited role (mostly in proximal alveoli)
 Coaxial flow exists where gas in the center of large airways flows inward and gas on the periphery flows out
 Alveolar time constant differences set up circulation of gas between alveolar segments
 Cardiac oscillations contribute to gas mixing
 Augmented diffusion can occur because of added kinetic energy from oscillations

Pillow J et al. Crit Care Med. 2005; 33 (3 suppl): S135-41.

Trouble shooting in HFOV
• Hypoxia: Increase Fi02, MAP, or percentage inspiratory time (don’t go above 50%)
• Hypercarbia: Decrease frequency, increase delta P, increase inspiratory time (don’t go above 50%), or lower ET
tube cuff
• Sub Q air: May have an air leak, need to check daily chest x-rays
ECMO
Veno-Venous ECMO
The Original ECMO Study JAMA 1979
Zapol WM, et al. JAMA. 1979;242:2193–2196.

• 90 patients with severe respiratory failure

• Multicenter trial funded by NIH
• VA ECMO
• 10% survival in both the ECLS group and control group
What has changed in 20 years? VV ECMO Concept
• Hollow fiber oxygenators vs. old silicon • A membrane oxygenator temporarily takes over
oxygenators gas exchange for an injured lung
• Ultraprotective lung ventilation allows for lung
• Centrifugal pumps vs. roller pumps
healing/rest
• Advances in cannula technology • In neonatology it is the standard for respiratory
failure with survival rates of 70% to 90%
• More compact extracorporeal systems
• Patience is critical (sometimes months!)
• Greater understanding of ARDS and major • In the worst cases lung transplant may be an
improvements in CCM option
Park P, et al. Crit Care Clin 2011; 27: 627-46.

Cannulation Oxygenator
• Most ECMO for severe ARDS will be VV ECMO • Modern oxygenators (Quadrax) cause less platelet
unless significant associated RV failure activation and consumption
• They also have thrombo-resistant coatings and
• For VV ECMO, cannulation can be single site (via RIJ)
are low resistance
or multiple via catheters in the RIJ and femoral vein
• Numerous companies make oxygenators
Circulation and Gas Exchange including (Maquet, Medos, and Novalung)
• Blood is pumped through gas exchanger via a Heat Exchanger

centrifugal pump. Modern gas exchangers are hollow
fibers coated with polymethylpentene which allows • Body temperature is maintained using a heat
diffusion of gas but not liquid. exchanger
• CO2 clearance more effective than oxygenation Optimize lung healing and recovery
because of greater solubility of CO2
• Ideal lung protection remains controversial while
• CO2 clearance can occur with flows of 10-15 ml/kg/ on ECMO (We use PCV 10/10, RR=10)
min. Oxygenation requires 50-100 ml/kg/min of flow. • Minimize sedation as much as possible, although
challenging when patient is tachypneic and
Avalon ECMO Cannula experiences “air hunger”
VV ECMO Concept • Maintain even to negative fluid balance
• PT and ambulation critical

Does VV ECMO Work for ARDS?
Combes, et al.N Engl J Med 2018; 378:1965-75.
EOLIA take home points • 28% of patients in the control group “crossed over”
to ECMO for salvage
• Powered for 20% mortality difference between
groups (40% ECMO and 60% control) • More bleeding, more transfusion, more
thrombocytopenia in ECMO group
• 60 day mortality was 35% in ECMO group and 46%
in control group • Fewer ischemic strokes in ECMO group
• HR was 0.70 (95% CI=0.47 to 1.04, P=0.07) • More days free from renal failure and vasopressors
in ECMO group

28 ANESTHESIA FOR ROBOTIC SURGERIES - PRINCIPLES AND PRACTICE
Chairperson Jayashree Sood

Dept. of Anaesthesiology, Pain and Perioperative Medicine
Sir Ganga Ram Hospital, New Delhi
Key points
Ø Robotic surgery is still an evolving field, with newer procedures being made amenable to robotic intervention
Ø The most unique feature of this system is its tele-manipulation. It was developed to overcome the limitations of
laparoscopic surgery
Ø Robotic procedures require extremes of positioning, which place the anaesthesiologist away from patient’s airway,
especially after docking
Ø It is very difficult to access the patient during surgery. Therefore it is essential to ensure that the devices are well
placed and fixed before docking
Ø Goal directed fluid therapy is advisable
Ø In case of airway edema,” leak test” is mandatory before extubation
Ø Intraoperative temperature regulation is a challenge for the anaesthesiologist
Ø The ‘learning curve’, both for the surgeon and anaesthesiologist and technicalities of docking and undocking of
robot adds significantly to the operating time
Introduction for the anaesthesiologist to understand the impact

of these changes on anaesthetic technique and
Robotic Assisted Surgery has become popular in a wide
management.
variety of surgical procedures; cardio-thoracic, urological,
gynaecological and gastro surgical. The word ‘Robot’ is • Surgeon sits at the console and views the surgical
derived from Czech word “robota” meaning ‘forced labor’ field and controls the robotic arms. The endoscope
used by Capek in his play “Rossum’s Universal Robots” transmits dual, independent optical channels which
in 1921. It is still an evolving field, with newer procedures transmit digital images on the console’s visual
being made amenable to robotic intervention. monitor. Surgeon actually looks into two separate
monitors, each eye sees through an independent
The National Aeronautics and Space Administration (NASA)
camera channel, thus creating a 3 dimensional
developed robots for use in space. The most unique feature
image.
of this system is its tele-manipulation (surgeons can perform
surgery while sitting far from the patient). • The surgeon controls the manipulators with
Robotic system (da Vinci) was developed in 1997 to two masters (levers), which attach to the index
overcome the limitations of laparoscopic surgery. It is finger and thumb of each hand, wrist movements
equipped with all the benefits of laparoscopy system, while (replicate movement of instruments at the end
all the shortcomings of laparoscopic surgery are overcome. of the robotic arm). A frequency filter eliminates
hand tremors greater than 6Hz. The hands of the
Wide range of manipulation with the robot’s arms causes surgeon are placed on the manipulator and the
lesser trauma, minimal pain and early recovery, even after hand movements are transmitted into surgical
major surgery. This is the key of its success and popularity. instrument motion. There are 3 foot pedals: to
• Robot assisted surgery differs from conservative disengage robotic motion between arms, camera
surgical techniques and therefore it is important adjustment and cautery.

Anesthesia for robotic surgeries - Principles and practice 282 Jayashree Sood
• This surgical cart (da Vinci) has 4 arms that can be • Goal directed fluid therapy is advisable. In case of
manipulated by the surgeon in a console through airway oedema (extreme head down position) leak
computer assisted control. The 4th arm is optional, test is mandatory before extubation.
it enables the surgeon to hold another instrument or
do counter traction, thus eliminating the need for a • To deal with any unfavourable event, immediate
patient side surgeon. The instruments have seven un-docking (< 60 seconds) is done to remove all
degrees of freedom. the arms so as to intervene and save the patient.
Anaesthetic Considerations • Intraoperative temperature regulation is a

challenging task for an anaesthesiologist, especially
There are several anaesthetic considerations: during robotic procedures as patient access for
heat conserving strategies is limited.
 Patient positioning
 Carboperitoneum and its physiological effects, The ‘learning curve’, both for the surgeon and
anaesthesiologist and technicalities of docking and
 Procedure duration
undocking of robot adds significantly to the operating time.
 Temperature regulation. This leads to an increased operating room stay of the
• Proper positioning and precautions during extreme patient.
position are necessary. Robotic procedures require Conclusion
positions which place the anaesthesiologist away
from patient’s airway, especially after docking. Robotic assisted surgery has a learning curve for, both, the
surgeon and the anaesthesiologist.
• Appropriate padding of the pressure points of
patients is vital to prevent neurological injury and Suggested Reading
pressure sores.
1. Ellis DB, Albrecht MA. Anesthesia for Robotic
• The assisting staffs have to be attentive to prevent Surgery. Ronald D. Miller (Ed), Miller’s Anesthesia
injury due to a robotic arm contacting the body of (9th edition), Chapter 71, Pg 2236-50.
the patient.
2. Awad H, Walker CM, Shaikh M, Dimitrova GT,
• Improper positioning and inappropriate padding of Abaza R, O’Hara J. Anesthetic considerations for
pressure points and Trendelenburg position for a robotic prostatectomy: a review of the literature. J
prolonged period of time may result in complications. Clin Anesth 2012; 24:494-504.
• Increased intracranial pressure caused due to 3. Darlong V, Kunhabdulla NP, Pandey R,

carboperitoneum and Trendelenburg position Chandralekha, Punj J, Garg R, et al. Hemodynamic
predisposes to risk of cerebral oedema. Laryngeal changes during robotic radical prostatectomy.
and facial oedema, facial purpura and subcutaneous Saudi J Anaesth 2012; 6: 213-8.
emphysema are also reported.
4. Hoshikawa Y, Tsutsumi N, Ohkoshi K, Serizawa
• As there is restricted access to patient, due to bulky S, Hamada M, Inagaki K, et al. The effect of steep
equipment, once the robot has been positioned, it Trendelenburg positioning on intraocular pressure
is very difficult to access the patient. Therefore it is and visual function during robotic-assisted radical
absolutely essential to ensure that the intravenous prostatectomy. Br J Ophthalmol 2014;98:305-8.
lines, endotracheal tube, catheter, monitoring
devices and other protective devices are well 5. Erkiliç E, Döger C, özcan A, Soykut C, Kesimci
placed and fixed before docking. No movement is E. Mask Phenomenon Following Robot-assisted
allowed after docking, or else tearing of muscles, Prostatectomy: A Rare Complication due to
internal organs and vessels can occur. Trendelenburg Position. J Anesth Clin Res 2014;
5: 431.
• Long extension of IV lines, breathing circuits and
monitoring system is required.

VIDEO SESSIONS
29 NEURAXIAL ULTRASOUND
Archana Areti Sivashanmugam T

Mahatma Gandhi Medical College and Professor
Research Institute, Puducherry Mahatma Gandhi Medical College
& Research Institute, Puducherry
Information that can be ascertained from the ultrasound imaging of the spine for successful central neuraxial blockade:
1. The midline
2. The level
3. The interlaminar space and its midpoint
4. The approximate depth
Probe to be used is the curvilinear probe set at the musculoskeletal (MSK) pre-set.
5 views are used for US imaging of spine, 2 Transverse and 3 Sagittal, all of which have distinctive signs of identification.
Transverse views
1. Spinous process view – Tower sign

Neuraxial Ultrasound 286 Sivashanmugam T
2. Interspinous process view – Cat head appearance
3. Sagittal Views
• Transverse Process view – Paramedian sagittal view– Trident sign

• Articular Process view – Paramedian sagittal view - Camel hump sign
• Interlaminar view – Paramedian Sagittal Oblique (PMSO) view - Horse Head sign


How these views are used to obtain the information needed for the Central Neuraxial Blockade
1. The midline is identified by viewing the spinous processes with the transverse spinous process view with the tower
sign. Sequentially, the spinous processes above and below are marked on the skin, by activating the centre line, the
lines joined together indicate the midline.
2. Level Identification – View used is the Paramedian sagittal oblique view(PMSO)
The probe is placed in PMSO view, on the lower back to observe the sacrum – identified as a continuous hyperechoic
white line. The probe is slid cephalad in order to observe a break in the line which represents the L5 – S1 space. From
here, subsequent spaces can be traced and marked on the skin.

3. The interlaminar space and its midpoint
This space is identified by first starting with a paramedian sagittal scan at the transverse process to identify the Trident
sign. The probe is traced medially till the sonoanatomy shows the camel hump sign to identify the articular process
view. Further medial tracing and slight oblique tilt will reveal the horse head sign which basically represent the break
between the lamina through which the posterior dura complex and anterior dura complex with the intrathecal space,
can be visualised.
Midpoint of the interlaminar space is identified by activating the centre line .
4. The approximate depth – The depth from skin to the Posterior dura complex is approximated by visualising either by
the transverse interspinous process view or the paramedian sagittal oblique view, by utilising the calipers option of the
USG which approximates the depth.
Final Skin Markings
Since 1986, after the introduction of spinal anaesthesia by August Bier, we were very successful in using the technique
through only one landmark at the skin, that is, palpation of the tip of the spinous process. Now with US guidance, we
can visualize the interlaminar space and its midpoint, we can assess the depth of the dura and identify exactly which
interlaminar space we are accessing. With all these parameters, our central neuraxial blocks becomes more objective and
precise. Hence, central neuraxial US is very useful for our everyday clinical practice.

30 DOUBLE-LUMEN TUBES AND BRONCHIAL BLOCKERS
Director Professor, Rakesh Kumar

MAMC & Lok Nayak Hospital,
New Delhi
Key points
Ø While introducing DLT’s, the operator should try to get the best possible view of laryngeal inlet and should be very
gentle
Ø Left-sided DLTs are preferred in majority of cases because the extra length of the left main bronchus makes it
easier to place the left DLT, while the shorter and unpredictable length of the right main bronchus before it gives
off the right upper lobe bronchus makes the placement of right DLT quite difficult
Ø Chest X rays and CT scans are being used to estimate the appropriate size of DLT, in addition to guiding table
using patient’s gender and height
Ø The adult 5.5mm fiberscope will not pass through the narrowest portion of any DLT
Ø The inside of the right upper lobe bronchus is the only structure in the tracheobronchial tree that has three orifices
Ø Disadvantages of using a bronchial blocker includes slow collapse of the lung, inability to suction, more chances
of dislodgement, possibility of perforation of bronchus/ parenchyma and difficult to block the right lung.
Double-lumen tubes (DLTs) and bronchial blockers (BBs) are Most of the adult lung isolations are accomplished by DLTs
devices used for lung isolation, i.e., separating the ventilation while there are only a few indications for using BBs. Out of
of one lung from the other. DLTs allow lung isolation with the DLTs as well; left-sided DLTs are preferred in majority
option of ventilating either both the lungs or any one of the of cases (Table 1). This is because the extra length of the
two lungs. On the other hand, bronchial blockers, when left main bronchus makes it easier to place the left DLT
inflated, block the bronchus they are introduced into, and while the shorter and unpredictable length of the right main
prevent ventilation beyond that bronchus. Then there are bronchus, before it gives off the right upper lobe bronchus
endotracheal tube-BB combos such as the Univent tube that makes the placement of right DLT quite difficult, especially
can be considered a BB for all practical purpose. without guidance of fiberscope (Figure 1).
Table 1: Conditions where left DLT is not the preferred choice of lung isolation; (and the preferred alternative)

Double-lumen tubes and Bronchial blockers 292 Rakesh Kumar
Fig 1: The tracheobronchial tree showing various dimensions. The left main bronchus is predictably much longer than the
right main bronchus before it gives off right upper lobe bronchus. (From Miller, 8th edition)
Double lumen tubes Choosing the correct size of DLT
As mentioned, these are the most commonly used apparatus Various methods have been used to choose the correct size
for lung isolation. The right-sided DLT incorporates a modified of DLT. These are:
cuff, or slot, on the endobronchial side to align with the
opening of the right upper lobe bronchus. 1. Chest radiographs – Since the introduction of a scale
on the side of present day x-rays, we find these enough to
Sizes available are: calculate and choose the right size of DLTs.
• Left-sided DLT (Figure 2) - 26, 28, 32, 35, 37, 39, 41F Direct measurement of the diameter of the tracheal width
• Right-sided DLT (Figure 3) - 32, 35, 37, 39, 41F from edge to edge at the interclavicular plane from the
preoperative PA chest radiograph is recommended. We also
Sizes 41, 39, 37, 35, 28 & 26F, correspond to internal measure the dimension of the bronchus to be cannulated.
diameter of each lumen of 6.5, 6, 5.5, 5, 4.5 & 4 mm
respectively. So it must be clearly understood that 2. CT Scans – Measure the left or right main stem bronchial
when one is introducing a #41 DLT, it is equivalent diameters from a CT scan. A properly sized DLT should
to introducing a #13 ETT! This should drive home the have a bronchial tip 1 to 2mm less wide than the patient’s
facts that while introducing these tubes the operator bronchial diameter to allow for the space occupied by the
should try to get the best possible view (through direct deflated bronchial cuff.
laryngoscope or videolaryngoscope) of laryngeal inlet
and should be very gentle. 3. Based on the above two a conversion table has been
recommended for predicting DLT tube size (Table 2)

Fig 2: Left Double Lumen Tube with dedicated stylet
Fig 3: Modified bronchial cuff of Right DLT with a slot to match the opening of right upper lobe bronchus
Table 2: Predicting DLT size based on chest radiograph and CT scan

Table 3: Predicting DLT size based on patient’s gender and height
4. Multidetector CT scan (MDCT) of the chest allows iv. Maintaining the force on the laryngoscope, rotate 90°
appreciation of any abnormal tracheobronchial anatomy counterclockwise (for left sided DLT) or clockwise (for
before placement of a DLT. right sided DLT)
v. Advance further until slight resistance is encountered
5. A three-dimensional image reconstruction of
(indicating that the endobronchial lumen of the tube has
tracheobronchial anatomy from the spiral CT scans combined
entered the bronchus)
with superimposed transparencies of DLTs helps choosing
the appropriate DLT. vi. Inflate both the cuffs
vii. Attach Y-connector (Figure 4) and circuit, ventilate
6. Using guiding table patient’s gender and height
viii.Note depth of insertion of DLT
Depth of Insertion of DLT
Checking the placement and positioning of LEFT DLT
In adults, depth measured at the teeth will be approximately
Clinical
12 + (Patient height in cm/10) cm or approximately 29±1cm
for every 10 cm difference in patient height from 170 cm. • Inflate the tracheal cuff with 5-10 ml and bronchial cuff
We use a simple, patient specific measurement. This is the with 2 ml of air and ventilate the lungs and look for
para-sagittal distance parallel to trachea from the angle of bilateral chest wall movements and bilateral ventilation
mouth to angle of Louis (location of tracheal carina) plus 3cm on auscultation
to reach the left main bronchus.
• Clamp the endobronchial lumen limb adapter (Figure
Recommended steps for placement of DLT 4) and ventilate
Preparation • Breath sounds should be absent on the left side of the
chest but heard on the right side of the chest
i. Pick the size chosen as per above recommendation
ii. Measure the angle of mouth to angle of Louis length • Clamp the tracheal lumen limb adapter (Figure 4) and
and add 3cm as mentioned above. Correlate it with the ventilate
expected depth of insertion as per the formula
• Breath sounds should be absent from the right side of
iii. Test and confirm competence of cuffs
the chest but heard on the left side of the chest
iv. Ensure that the stylet does not protrude beyond bronchial
tip. Troubleshooting for Clinical checking of placement of DLT
(written for Left DLT)
Placement
1) After inflating both cuffs and checking for bilateral
i. Carry out direct laryngoscopy or videolaryngoscopy breath sounds, if breath sounds are heard on left side
ii. Advance the bronchial cuff through glottis with concave only, it indicates that the tube is too far down (tracheal
curvature oriented anteriorly opening also in bronchus). Pull out the DLT.
iii. Take the stylet out once endobronchial (blue) cuff has
2) After clamping tracheal lumen,
passed beyond the vocal cords

Fig 4: Y-connector showing the adapters for the endobronchial and tracheal lumens
a. If there is persistence of breath sounds on both sides, bronchial cuff enters the left bronchus. In case it does
it indicates that the bronchial opening is still in the tra- not slide with gentle push, maybe DLT of a size small-
chea (tube should be advanced). er is needed.
b. If there is absence of breath sounds over the entire
Fiberscopic confirmation
right lung and the left upper lobe, it indicates that the
tube is too far down the left bronchus and needs to be One must understand that the adult 5.5mm fiberscope
pulled up a little. will NOT pass through the narrowest portion of ANY DLT!
c. If unilateral, only right-sided breath sounds are heard, The recommended sizes of fiberscopes are 2.8mm for
it indicates incorrect entry of the tube in the right bron- DLT # 26,28,32F and ≥3.5mm (usually 3.7mm) for DLT #
chus. The DLT needs to be reintroduced. 35,37,39,41F.
3) After unclamping the tracheal lumen and clamping the Left sided DLT (Figure 5)
bronchial lumen,
View through the Tracheal lumen: Minimally visible inflated
a. If there is absence or diminution of breath sounds, it blue bronchial cuff in the left main stem at the level of the
indicates that the tube is not far enough down and the carina; patent right bronchus. The bronchial cuff should be
bronchial cuff is occluding the distal trachea. Deflate within 5mm of the carina.
both the cuffs and push the DLT down so that the
Fig 5: In a properly placed left DLT, fiberscopy through tracheal lumen shows the border of inflated blue bronchial cuff in
the left main stem and patent right bronchus at the level of the carina (left); and fiberscopy through bronchial lumen shows
clear view of the left upper and lower lobe bronchi and the secondary carina (right) (Right image from Miller, 8th Edition).

View through Bronchial lumen: A clear view of the left secondary port, as well as a clear view of the right middle and lower
carina. The orifices of both left upper and lower lobe should lobe bronchi distally from the bronchial lumen. Going
be identified to avoid distal impaction in the left lower lobe and inside this right upper lobe with the bronchoscope should
occlusion of the left upper lobe. reveal three orifices (apical, anterior, posterior). This is the
Right-sided DLT only structure in the tracheobronchial tree that has three
orifices. In the supine patient, the takeoff of the right upper
View through Tracheal lumen: minimally visible blue bronchial lobe is normally on the lateral wall of the right mainstem
cuff in the right main stem bronchus at the level of carina; bronchus at the 3- to 4-o’clock position in relation to the
patent left main stem bronchus (as with the left sided DLT). main carina. Some DLTs have a thick white radio opaque
View through Bronchial lumen (Figure 6): A visible right line that can lead the operator into the opening for right
upper lobe bronchus, aligned with the ventilation side upper lobe bronchus.
Fig 6: Bronchial view in a properly placed right DLT - fiberscopy through bronchial lumen shows a visible right lobe bronchus
aligned with the opening for it in the DLT and a clear view of the right middle lobe bronchus (left). Going inside this right
upper lobe reveals three orifices (apical, anterior, posterior) (right). (From Miller, 8th Edition)
Bronchial Blockers (BBs) Disadvantages of using BBs
As mentioned above, bronchial blockers have a limited role • Slow collapse of the lung
in lung isolation. • Do not allow suction
• More prone for dislodgement
Advantages of using BBs • Can cause perforation of bronchus/ parenchyma
• Difficult to block right side (RUL bronchus opening is
• Useful in anticipated or unanticipated difficult airway
variable and sometimes very close to carina)
where single lumen endotracheal tube (SLT) is easier
to place Types of BBs
• Can be used in patients with abnormal tracheobronchial 1. Independent BBs

anatomy • Wire-guided - Arndt BB (Figure 7)
• Can be placed via nasal tubes • Torque controlled
• Coopdech BB (Figure 8)
• Allow selective lobar blockade (for BBs other than Arndt • Fuji uniblocker (Figure 9)
BB that loops to fiberscope, the BBs have to be directed • Cohen BB (Figure 10)
to the desired lobar bronchus over a guide wire already
• EZ blocker (Figure 11)
placed through the fiberscope).
• Fogarty embolectomy catheters used as BBs (Figure 12)

2. Torque controlled BB incorporated into single Lumen Tube
Univent (Figure 13)
Fig 7: Arndt bronchial blocker (wire-guided)
Fig 8: Coopdech bronchial blocker (torque-guided)
Fig 9: Fuji uniblocker (torque-guided)

Fig 10: Cohen tip-deflecting bronchial blocker (torque-guided)
Fig 11: E-Z bronchial blocker

Fig 12: Fogarty embolectomy catheters
Fig 13: Univent tube with incorporated torque controlled bronchial blocker
Table 4: Characteristics of some of the BBs

Generic Insertion Procedure for BBs oxygen. Place the Arndt blocker through the blocker
port; advance till you see the loop in the BODY of
• Intubate the patient with Single Lumen Tube (SLT) in adaptor (Figure 14, image on the left). Place fiberscope
the usual manner through the diaphragm of the fiberscopy port. Advance
• Lubricate the blocker and introduce it through the blocker the fiberscope into and through the loop. Couple the
port (airtight) blocker with fiberscope by unscrewing the guide wire
• Keep the cuff inside the joint connector, connect it to the port, pulling it back and snaring it (this procedure can be
endotracheal tube and continue ventilation with 100% done prior to the attachment of Arndt Multiport Adaptor
oxygen (filling lungs with oxygen helps early collapse to SLT). Advance the fiberscope with the blocker snared
after inflation of BB cuff) to it into the desired bronchus. Keeping the fiberscope
• Slide the BB down the SLT to reach near the tip of the stable, unsnare the blocker and advance it until loop is
SLT (if the total SLT length is 30cm and the length of seen distal to fiberscope and advance it further to the
the universal 15mm connector plus BB connector make bronchus.
5cm, slide BB to nearly 35cm) Univent tube
• Introduce the fiberscope through the fiberscope port
• It is a single-lumen tube with movable blocker shaft in
• Slide the BB further under fiberscope view and direct the
external lumen
BB into the desired bronchus.
• Use manual torque and the curvature of the BB near its • The available sizes are given in Table 5.
tip for torque directed BBs. Use direction control dial in
Cohen BB. Insertion procedure for Univent tube (Figure 15)
• Once in place, inflate the cuff under fiberscope vision to • Lubricate the blocker
achieve adequate seal • Withdraw it completely into the tube
• Confirm the isolation clinically • Intubate the patient in the usual manner
• For Arndt BB (Figure 14), after intubation with SLT, • Replace the angle connector with swivel connector with
replace the angle connector of SLT with Arndt Multiport fiberscope port and continue ventilation
Airway Adaptor and maintain ventilation with 100%
Fig 14: Placement of Arndt BB

Table 5: Characteristics of various sizes of Univent tubes
Fig 15: Placement of BB through Univent tube
• Introduce fiberscope and place it at the tip of the Univent • If there is difficulty in entering the desired bronchus,
tube so that the carina and both the main bronchi are turn patient’s head to the side OPPOSITE to the
clearly visible desired bronchus and try again. If this also does
not help, slip the Univent tube down and bring
• Push the blocker down and guide it under fiberscopic
monitoring using pushing and rotational movements to it close to the desired bronchus by rotating the
the bronchus of desired side Univent tube. Now slide the blocker down under
fiberscopic view.
• Once in place, inflate the cuff under fiberscope vision to
achieve adequate seal Acknowledgement: All the AMF instructors who have been
contributing to Lung Isolation Workshops and related write-
• Remove the stylet and lock the blocker in place by sliding
ups. And all those who have suffered my attempts to ‘train
the lock at the machine end of the blocker sleeve of
and teach’ them!
Univent and note the depth inserted

31 QUADRATUS LUMBORUM BLOCK AND ITS VARIATIONS
Professor Ekta Rai

Christian Medical College
Vellore
Key points
Ø The word “Quadratus lumborum” is a Latin origin word which means square loin, which refers to the shape and
location of this muscle.
Ø QL block is more advantageous and different in its action from TAP block.
Ø Ensure optimal ergonomics at all times. Ensure line of sight, needle, probe and machine are all in line.
Ø Low frequency probe is optimal for these deeper blocks. Make sure needle tip is visible throughout the procedure.
Ø Placing wedge under hip provides better view in supine position.
Ø It is a volume block, so LAST should always be kept in mind.
Introduction The quadratus lumborum (QL) muscle is an integral part of

the thoracolumbar fascia, a myofascial system that covers
The word “Quadratus lumborum” is a Latin origin word which
the posterior area of the human body, involving part of the
means square loin, a reference to the shape and location of
lower and upper limbs. The QL muscle is flattened and has
this muscle.
a quadrangular shape; along with the multifidus and erector
The quadratus lumborum (QL) block was first described as spinae muscles, the QL helps to create an antagonist force
an ultrasound-guide “posterior” transversus abdominis plane compared to the muscles of the abdomen.
(TAP) block by Blanco in 2007, approximating the double pop
TAP technique at the lumbar triangle of Petit. Sono anatomy (Fig 2)
In quadratus lumborum (QL) block, local anaesthetic (LA) is Identify the three layers of abdominal wall muscles---transversus
given at the lateral border of QL muscle. This LA spreads abdominis is traced more posteriorly until the transversus
to the paravertebral space and thus provides wide sensory aponeurosis appears. At this region, the peritoneum curves
blockade and adequate pain relief. away from the muscles from anterior to posterior and the
retroperitoneal fat lies behind the peritoneum and deep to the
TAP and QLB are very different in their actions .There are transversalis fascia.
various approaches to QL Block.
The retroperitoneal fat is generally scanty above the iliac
Transmuscular QL block approach was described by Børglum crest and more prominent closer to the iliac crest. Tilting
et al. wherein the LA was deposited between QL and psoas the probe slightly caudal into the pelvis thus improves
major muscle. The major advantages of QL Block over TAP the view of the retroperitoneal fat and the tapered end of
block are that, it has wide sensory cover (T6-L1) and it also transversus aponeurosis. QL is usually identified medial to
provides visceral pain relief in addition to sensory pain relief. the aponeurosis of transversus abdominis muscle.
Anatomy (Fig 1) Indications
The quadratus lumborum (QL) muscle resides in the deep and 1) Abdominal surgeries-
posterior, lateral and inferior areas of the spine, involving the
iliac crest, the transverse processes of the lumbar vertebrae • Laparotomies
and the 12th rib. The quadratus lumborum muscle involves • Pyloplasty
the 12th rib (internal surface) and the transverse processes • Nephrectomies
of the lumbar bodies of L1-L4, while it comes from the iliac • Abdominoplasty
crest (inner lip) and the iliolumbar ligament. • Open Prostatectomy

Quadratus lumborum block and its variations 304 DrEkta Rai
Fig 1 Gross Anatomy
Fig 1 Sonoanatomy

2) Obstretic and Gynaecological Procedures Paramedian Sagittal Oblique Approach to Anterior QL
Block
• TAH
• LSCS Position- Lateral Decubitus position
3) Iliac crest bone graft
Probe-Low-frequency convex probe
4) Hip Surgery
Placement-Probe is placed with a transverse, oblique, and
Dosage paramedian orientation approximately 3 cm lateral to the L2
spinous process.
• Calculate toxic dosage.
• 20-30 ml per side Needling-The needle is then inserted in plane from the medial
• Stay all the time within toxic levels side of the transducer and advanced laterally to enter the
interfascial plane.
Approaches
Final Tip Location- Tip lies between the quadratus lumborum
• Anterior-QL 3
and psoas major muscles in interfascial plane.
• Lateral QL1
• Posterior QL2 and Look For – Local anesthetic pushes down the PM in the
• Intramuscular--- The spread of local anesthetic varies with ultrasound image.
each approach so it is essential to choose appropriate
approach for complete analgesia post operatively. Advantage-This approach provides better safety towards
accidental injury into the peritoneal cavity than the thin
Approaches transversalis fascial layer.
Anterior QL Block (QL 3Block) Lateral QL Block (QL1Block)
Position- Lateral Decubitus Position Position- Supine position.
Probe- low-frequency convex probe
Probe- A high-frequency linear probe is attached in the area
Placement-Probe is vertically attached above the iliac crest of the triangle of Petit until the QL was confirmed.
Needling- Needle is inserted in plane from the posterior Needle Tip-The needle tip is placed at the anterolateral
edge of the convex probe through the QL in an anteromedial border of the QL at its junction of QL with transversalis fascia,
direction. and the local anesthetic is injected.
Final Tip Location-The needle tip is placed between the PM Look for- spread of the LA is deep to the transverses
muscle and the QL muscle and the local anesthetic is injected abdominis aponeurosis.
into the fascial plane.
Intramuscular QL Block
Look for - Local anesthetic pushes down the PM in the
Position -Supine position
ultrasound image.
Probe- High frequency linear probe
Placement-Probe has to be placed slightly cephalad to the

iliac crest.
Needling-The needle tip is advanced until it penetrates the

fascia and is inserted into the QL muscle. Test injection is
initially administered to verify that the local anesthetic spreads
within the QL muscle.
Adding pressure monitors to avoid possible intrafascicular

spread during administration of these blocks is recommended.
This is especially important for anterior and lateral QL blocks,

because nerves are located anterior to the QL, where the demonstrate analgesia from T7 to T12 [9]. Intramuscular QL
needle tip will be placed. block is an effective block for lower abdominal surgery such
as laparoscopy and femoro-femoral bypass
Posterior QL Block.(QL 2 Block)
Complications
Position- Supine position.
1. Infection
Probe- Low-frequency convex probe.
2. Bleeding
Needling- The posterior aspect of the QL muscle is confirmed, 3. Injury to visceral structure
and the needle tip is inserted into this aspect of the QL 4. LAST -Since higher volumes of drugs are required ,
muscle. The local anesthetic is then injected into the left careful dosing is a must to avoid LAST. Once higher
behind the QL muscle volumes are given specially in case of bilateral blocks,
patients should be shifted only after 30-60 minutes, as
peak levels of LA are seen after this time intervals.
Conclusion
Quadratus lumborum block is safe and useful for post

operative analgesia, for abdominal procedures and
orthopedic procedures. The block effect lasts for 24–48 h.
Femoral nerve block can be an unwanted block extension of
QLB 3 leading to weakness of the lower limb and thus delay
in ambulation of patients rarely.
References
Analgesia
1. R. Blanco, “TAP block under ultrasound guidance:
The lateral and posterior QL blocks may play a role in the description of a ‘non pops technique’,” Regional
conventional perioperative pain management for abdominal Anesthesia and Pain Medicine, vol. 32, supplement 1,
surgery, as the local anesthetic injected via the approach of p. 130, 2007.
the posterior QL block can more easily extend beyond the
2. Carney J, Finnerty O, Rauf J, Bergin D, Laffey JG, Mc
TAP to the thoracic paravertebral space or the thoracolumbar
Donnell JG. Studies on the spread of local anaesthetic
plane. The posterior QL block entails a broader sensory-level
solution in transversus abdominis plane blocks.
analgesic than the lateral QL block.
Anaesthesia 2011;66:1023‑30
For the anterior QL block, the local anesthetic is injected 3. Hironobu Ueshima, Hiroshi Otake, and Jui-An Lin.
between the PM muscle and the QL muscle. Considering Ultrasound-Guided Quadratus Lumborum Block: An
the branches of lumbar plexus nerves run between the PM Updated Review of Anatomy and Techniques. BioMed
and the QL, the anterior QLB may play a role in analgesia Research International Volume 2017, Article ID 2752876
not only for the trunk but for the lower extremities as well.
4. V. R. Kadam, “Ultrasound-guided quadratus lumborum
For the subcostal QL block (subtype of anterior QL block), block as a postoperative analgesic technique for
the local anesthetic injected anterior to the QL between laparotomy,” Journal of Anaesthesiology Clinical
the QL muscle and the anterior layer of the thoracolumbar Pharmacology, vol. 29,no. 4, pp. 550– 552, 2013.
fascia observed the spread in cephalad direction close to
5. R. Blanco,T.Ansari, andE.Girgis, “Quadratus
the T12 rib with anterior displacement of the anterior layer
lumborumblock for postoperative pain after caesarean
of thoracolumbar fascia. This produces reliable dermatomal
section: a randomized controlled trial,” European Journal
coverage from T6-T7 and L1-L2.
of Anaesthesiology, vol. 32, no. 11, pp. 812–818, 20`15.
The intramuscular QL block, which involves injection of the 6. A. Chakraborty, J. Goswami, and V. Patro, “Ultrasound-
local anesthetic directly into the QL muscle, has recently been guided continuous quadratus lumborum block for
described. Murouchi et al. reported that, after the lateral QL postoperative analgesia in a pediatric patient,” A & A
block, the sensory effects evaluated using a cold test may Case Reports, vol. 4, no. 3, pp. 34–36, 2015.

32 NEUROMUSCULAR MONITORING
Professor Venkatesh S
SRIHER
Chennai
Key points
Ø The current which generates a response through all nerve fibres and hence a maximal muscle contraction is
termed a maximal stimulus
Ø Traditionally, a current of 25% above the maximal stimulus is applied when stimulating a peripheral nerve: this is
termed a supramaximal stimulus
Ø The negative electrode be placed directly over the most superficial part of the nerve. The positive electrode can
then be placed in a position along the course of the nerve, usually proximally to avoid direct muscle stimulation
Ø TOF does not require the comparison of evoked responses to a control response obtained before administration
of a neuromuscular blocking drug
Ø Reversal of residual neuromuscular block can safely be achieved when the TOF count is 3 or greater.
Ø Tetanic stimulation is very sensitive and can elicit minor degrees of neuromuscular block, but is extremely painful.
Ø Post-tetanic count is useful when profound neuromuscular block is required, when movement or coughing could
have devastating effects.
Ø Small degrees of residual block may be easier to appreciate with DBS.
Ø Tactile evaluation of the DBS ratio has been shown to be more accurate than tactile evaluation of the TOF ratio.
Ø Onset and offset of block is faster in central muscles with a good blood supply. Conversely peripheral muscles,
with a relatively poor blood supply, will have a slower onset of block and a longer recovery time.
This chapter deals with the principles and patterns of or muscle group which the nerve supplies must be visible
monitoring neuromuscular function. On recovery, the or accessible to evoked response monitoring. In order
anaesthetist can assess muscle power by a variety of to stimulate a nerve, an electrical current will need to be
clinical tests, such as the ability to sustain head lift for 5 applied. The current is usually applied transcutaneously,
seconds, or the ability to hold a tongue depressor between using ECG electrodes. The chosen nerve will contain
the teeth. These are crude assessments of neuromuscular many motor nerve fibres. All of these fibres will need to be
function, and can be influenced by many factors, for stimulated in order to produce a maximal muscle contraction.
example, residual sedation or inability to follow instructions. Generating an action potential in all of the nerve fibres in a
motor nerve will require a current of sufficient magnitude
Stimulating the motor nerve and duration. Most nerve stimulators will apply a current
The degree of neuromuscular block can be assessed by for 0.1–0.3 ms, which is more than adequate. The current
applying a supramaximal stimulus to a peripheral nerve, which generates a response through all nerve fibres and
and then measuring the associated muscular response. hence a maximal muscle contraction is termed a maximal
The nerve chosen to be stimulated must fulfil a number of stimulus. Traditionally, a current of 25% above the maximal
criteria. First, it must have a motor element; second, it must stimulus is applied when stimulating a peripheral nerve: this
be close to the skin; and third, contraction in the muscle is termed a supramaximal stimulus.

Neuromuscular monitoring 308 Venkatesh S
Ideal nerve stimulator then be observed, using a single twitch at 0.1 Hz (1 twitch
every 10 s). The onset and recovery from depolarizing and
The ideal nerve stimulator should have these basic properties: non-depolarizing block monitored using single twitches have
it should be battery operated and able to deliver a constant a similar pattern, differing only in timescale as shown below
current, up to a maximum of 80 mA. This is preferable to a in figure 1a and 1b. The major limitation to this technique is
nerve stimulator that can only deliver a constant voltage. the need to measure a control twitch before administering
Current magnitude is the factor that determines whether a the neuromuscular blocking agent. Single twitches are also
nerve depolarizes or not. At a constant voltage, current will used in the post-tetanic count, but in this instance a control
vary depending on the resistance of the skin. Skin resistance twitch height is not required.
will range from 0 W to 5 kW, and is affected by such factors
as skin temperature, adequacy of electrode application,
and disease state, for example, diabetes mellitus or
chronic renal failure. Adequacy of electrical contact should
be displayed on the monitor screen. The pulse stimulus
should last no longer than 0.3 ms and be of a monophasic,
square wave type. This will ensure that a constant current
is maintained throughout the stimulus. The polarity of the
electrode leads should be indicated; it is recommended
that the negative electrode be placed directly over the most
superficial part of the nerve. The positive electrode can
then be placed in a position along the course of the nerve, Fig 1a: Single twitch response to onset and recovery from
usually proximally to avoid direct muscle stimulation. The NMDA
nerve stimulator should be capable of delivering a variety of
patterns of stimulation including: single twitch (at 1 Hz); TOF
twitch stimulation (usually 2 Hz with at least a 10 s interval
between trains); tetanic stimulation at 50 Hz for up to 5 s;
and double-burst stimulation (DBS). Good electrical contact
with the skin can be established using ECG electrodes of
the silver/silver chloride variety. The skin should always
be cleansed adequately before applying the electrodes.
The ideal stimulator would also enable monitoring of the
evoked responses. The pattern of the evoked response
generated by nerve stimulation will depend on the type of Fig 1b: Single twitch response to onset and recovery from
drug used to produce neuromuscular block, and the pattern depolarizing blocking agents
of stimulation.
Train-of-four stimulation
Pattern of nerve stimulation
The TOF pattern of twitch stimulation was developed in an
Single twitch stimulation attempt to provide a clinical tool to assess neuromuscular
block in the anaesthetized patient. The principle was to
A single square wave supramaximal stimulus is applied to
produce a pattern of stimulation that did not require the
a peripheral nerve for a period of about 0.2 ms, at regular
comparison of evoked responses to a control response
intervals, and the evoked response is observed. The twitch
obtained before administration of a neuromuscular blocking
response will only be depressed when a neuromuscular
drug. The pattern involved stimulates the ulnar nerve with
blocking agent occupies 75% of the post-synaptic nicotinic
a TOF supramaximal twitch stimuli, with a frequency of 2
receptors. Twitch depression will need to be more than 90%
Hz, that is, four stimuli each separated by 0.5 s. The TOF
in order to provide good conditions for abdominal surgery.
was then repeated every 10 s (train frequency of 0.1 Hz).
The most useful time to apply the single twitch pattern of
As well as enabling the observer to compare T1 (first twitch
nerve stimulation is at the onset of neuromuscular block.
of the TOF) to T0 (control), it also enables comparison of
Using a single twitch at 1 Hz (1 twitch every second), it is
T4 (fourth twitch of the TOF) to T1. This is known as the
possible to establish the level at which a supramaximal
TOF ratio. When a non-depolarizing agent is given, a typical
stimulus is obtained. The onset of neuromuscular block can
pattern is observed as shown in figure 2.

block, will show signs of fade, that is, the stimulated muscle
will be unable to sustain a muscular contraction. At higher
frequencies (100–200 Hz) muscular fatigue may develop,
but at a stimulation frequency of 50 Hz this should not
occur, and the degree of fade will correspond more closely
to the degree of neuromuscular block. This pattern of
stimulation is very sensitive and can elicit minor degrees
of neuromuscular block, which is potentially useful in the
postoperative recovery room. However, its use is limited by
the fact that tetanic stimulation is extremely painful. Tetanic
stimulation has complex effects on the neuromuscular
junction especially in the presence of a neuromuscular
blocking drug. Fade is thought to be an effect of a non-
depolarizing agent on the presynaptic nerve membrane.
Acetylcholine released during a tetanic stimulus into the
Fig 2: TOF response to non-depolarising and depolarizing
synaptic cleft has a positive feedback effect through its
neuromuscular blockers
actions on presynaptic receptors. These actions ensure
There is a reduction in the amplitude of the evoked that the amount of acetylcholine released from the nerve
responses, with T4 affected first, then T3, followed by T2, terminal is far greater than that which is required to
and finally T1 (Fig 2). This decrement in twitch height is generate an adequate end-plate potential and sustain a
known as fade. As the non-depolarizing block becomes tetanic contraction. In the presence of a non-depolarizing
more intense, T4 disappears followed by T3, T2, and neuromuscular blocking agent, this margin of safety is
finally T1. The reverse is true during recovery from non- greatly reduced. The competitive block at the presynaptic
depolarizing block: T1 reappears first followed by T2, T3, receptors decreases the amount of acetylcholine mobilized
and finally, T4. During onset of non-depolarizing block, T4 and released, contributing to the fade seen during tetanic
disappears at about 75% depression of T1, T3 at 80–85% stimulation. During partial depolarizing block, fade is not
depression of T1, and T2 at 90% depression. During partial observed in response to tetanic stimulation. The amplitude
non-depolarizing block, the number of twitches (TOF count) of the evoked response will be lower but the tetanic
correlates with the degree of neuromuscular block. Twitch contraction will be maintained.
suppression of 90% would equate to a TOF count of 1 or
Post-tetanic count
less. Reversal of residual neuromuscular block can safely
be achieved when the TOF count is 3 or greater. One of During profound non-depolarizing neuromuscular block,
the most useful clinical applications of the TOF ratio is in there may be no response to TOF or single twitch stimulation.
monitoring recovery from neuromuscular block. TOF ratio In such circumstances, a post-tetanic count (PTC) may be
of 0.9 or greater, is an indication of adequate reversal. useful. If a 5 s tetanic stimulus at 50 Hz is administered,
The TOF pattern is less useful in monitoring depolarizing after which no twitch response has been elicited, followed
neuromuscular block. During onset of depolarizing block, 3 s later by further single twitches at 1 Hz, there may be a
each of the four twitches is decreased equally in size, that response to single twitch stimulation. Although this pattern
is, there is no fade. This is also observed during recovery. will not be seen during very profound block, a response will
However, if larger doses of depolarizing agent are given, be seen in the early stages of recovery, before the TOF
Phase 2 block may develop which develops some of the reappears. This is known as post-tetanic facilitation. On
characteristics of a non-depolarizing block. completion of a tetanic stimulus, acetylcholine synthesis
and mobilization continue for a short period. As a result,
Tetanic stimulation
there is an increased, immediately available store of
Tetanic stimulation uses a high frequency (50–200 Hz) acetylcholine which causes an enhanced response to
supramaximal stimulus for a set time: normally 5 s. In subsequent single twitch stimulation. The number of post-
healthy skeletal muscle during normal movement, the tetanic twitches is an indication of, when the first twitch
response is maintained as a tetanic contraction. However, of the TOF will reappear. For instance, the first twitch of
on administration of a non-depolarizing neuromuscular the TOF generally returns with a PTC of 9 when using
blocking drug, the muscle, depending on the degree of atracurium or vecuronium. The main use of PTC is when

profound neuromuscular block is required, for example, ensure accurate readings, the arm and hand must be fixed
during retinal surgery, when movement or coughing could and movement of the thumb must be along the length of the
have devastating effects. It should be remembered that a transducer. This technique can be used for assessment of
tetanic stimulus, by mobilizing acetylcholine, might affect any pattern of nerve stimulation and is the gold standard. It
the neuromuscular junction of a stimulated nerve for a has the disadvantage of being cumbersome and impractical
significant time. If two PTCs are administered in quick for use in the operating theatre.
succession, the degree of neuromuscular block will be
underestimated. It is recommended that tetanic stimulation Electromyography(EMG)
should not be repeated for a period of 6 minutes. EMG is the recording of a compound action potential that
Double-burst stimulation occurs during muscular contraction, whether voluntary or
evoked. Again, the adductor pollicis and ulnar nerve are the
DBS was developed to enable the anaesthetist to detect most commonly used, although other sites in the hand have
even small degrees of neuromuscular block clinically. been advocated, for example, the hypothenar eminence or
Significant residual neuromuscular block can be assessed first dorsal interosseous muscles. Evoked action potentials
using the TOF response. However, small degrees of residual are a measurement of electrical changes that occur in
block may be easier to appreciate with DBS. In DBS, two muscle during stimulation; it is assumed that these are
short bursts of tetanus at 50 Hz, at supramaximal current equivalent to the muscular contraction that occurs after
are applied to a nerve. Typically, each burst will have three excitation–contraction coupling.
impulses lasting 0.2 ms. Each impulse is delivered every
20 ms and the two bursts are separated by 750 ms. In The stimulating electrodes are placed over the ulnar nerve.
unparalysed muscle, two separate muscle contractions of The recording electrodes must be placed carefully: one over
equal intensity will occur. In muscle partially paralysed with the muscle belly; a second, over the tendinous insertion
a nondepolarizing agent, the response to the second burst of the muscle; and a third, in a neutral site distant to the
is reduced. This is the phenomenon of fade. The ratio of the muscle. On stimulation, a number of low voltage motor
magnitude of the second stimulus to the first is known as action potentials will be generated. These can be summated
the DBS ratio. The DBS ratio has very similar properties to into a compound action potential which, because of the very
the TOF ratio. However, tactile evaluation of the DBS ratio low voltages measured, must be amplified. Recording of
has been shown to be more accurate than tactile evaluation EMG potentials has several advantages over MMG. The
of the TOF ratio. equipment needed is not as bulky and is easier to assemble.
The arm and hand do not need to be fixed as rigidly. The
Measuring evoked muscle responses EMG does, however, have a number of disadvantages. It is
particularly prone to interference, especially from diathermy.
Assessing muscle responses by visual or tactile Hand temperature and movement will adversely affect the
means is difficult. There are a number of mechanical readings to a greater degree than with MMG. Another
(mechanomyography [MMG] and acceleromyography) and potential source of inaccuracy is direct muscle stimulation.
electrical (electromyography [EMG]) methods for detecting Some of these devices are particularly prone to drift.
and measuring these evoked responses more accurately.
Acceleromyography
Mechanomyography(MMG)
Acceleromyography was developed as a more convenient
MMG is the measurement of evoked muscle tension. The method of monitoring evoked responses in the operating
most commonly studied muscle is adductor pollicis in the theatre. The principle is similar to MMG; however, instead
thumb. When the ulnar nerve is stimulated at the wrist, the of measuring force of contraction directly, acceleration
adductor pollicis contracts and causes the thumb to move. If of the contracting muscle is measured. Force can then
the thumb is stabilized and placed under a fixed amount of be calculated using Newton’s second law of motion.
tension (preload), then evoked responses can be measured Acceleration is measured by a piezoelectric ceramic
as a change in tension develops. This is achieved using a wafer that is strapped to the thumb. When the adductor
strain gauge transducer and recorder. Note that the thumb pollicis is stimulated, the thumb will move and the attached
will not move in this situation; the muscular contraction transducer will produce a voltage, which is proportional to
is said to be isometric. The evoked change in tension is its acceleration. The voltage can then be converted into an
detected by the strain gauge and transduced into an electrical signal and displayed as a twitch response. For
electrical signal, which can then be displayed. In order to accurate measurement, the accelerating digit must be free

to move. It has been established that acceleromyography Maintenance of anaesthesia
is comparable to MMG. Acceleromyography is particularly
suited to TOF measurement and most of the commercially As the diaphragm is relatively resistant to neuromuscular
available machines will enable TOF ratio monitoring. block, a more sensitive peripheral muscle such as the
adductor pollicis may not adequately reflect the degree of
Which nerve to stimulate and when? block required at this stage of anaesthesia. A central muscle
which is resistant to neuromuscular block, for example,
It must be remembered that onset and offset of block is faster orbicularis oculi, will reflect the diaphragm more closely and
in central muscles with a good blood supply, for example, should be monitored at this time. PTC and TOF monitoring
diaphragm and larynx. Conversely peripheral muscles, with are most useful during profound neuromuscular block.
a relatively poor blood supply, will have a slower onset of
block and a longer recovery time, for example, adductor Reversal and recovery
pollicis. The muscles of the upper airway and pharynx
behave as central muscles at onset; however, they are Before administering a neuromuscular antagonist, the
sensitive to neuromuscular blocking drugs and recovery is TOF count should be at least 3. At this time, monitoring
slow, mirroring the peripheral muscles. a peripheral muscle such as adductor pollicis is the best
option. The respiratory muscles are likely to have recovered
Induction of anaesthesia to a greater degree, and monitoring a peripheral muscle
provides a larger margin of safety. Hence neuromuscular
During induction of anaesthesia and tracheal intubation, monitor is one of the essential monitors which can prevent
the muscles of the larynx and jaw must be paralysed as patient morbidity.
well as the diaphragm. The orbicularis oculi is probably the
ideal muscle to monitor at this time as it is more similar to a References
central muscle: onset of block will be similar to the laryngeal
muscles and diaphragm. Single twitch or TOF stimulation • Millers anesthesia text book 8th edition
is the most valuable stimulation pattern at induction. Single • Conor D McGrath. Monitoring of neuromuscular
twitch stimulation will allow the maximal stimulation level to block. Continuing Education in Anaesthesia, Critical
be obtained. Disappearance of the TOF will correspond to Care & Pain | Volume 6;2006
optimal intubating conditions. • D. Padmaja MONITORING OF NEUROMUSCULAR
JUNCTION Indian J. Anaesth. 2002;46:279-288

BREAKFAST SESSIONS
33 VAPORIZERS
Aruna Parameswari Pankaj Kundra

Professor & HOD Dean Academic
SRIHER Professor
Chennai JIPMER, Pondicherry
Key points
Ø Vapor is the gaseous phase of a substance which is a liquid at room temperature and at atmospheric pressure.
Ø The lower the atmospheric pressure, the lower the boiling point.
Ø Two methods are used commonly to express the concentration of a gas or vapor: Partial pressure and Volumes
percent.
Ø Patient uptake and the level of anesthesia are directly related to partial pressure but only indirectly to volumes
percent.
Ø Vaporizers may incorporate a system of wicks and channels in the vaporizing chamber to improve efficiency of
vaporization and increase the output concentration of anesthetic.
Ø The partial pressure of the agent will not change with change in ambient pressure. The clinical effect of change
in ambient pressure is insignificant and the vaporizer can be used in the same way at high altitude, sea level or
under hyperbaric conditions.
Ø With significant rebreathing, only an agent analyzer can provide an accurate value of the inspired agent
concentration.
Ø Pumping effect and pressurising effects, effects of intermittent back pressure due to PPV or use of oxygen flush,
can increase vaporiser output (especially in older vaporisers)
Ø The Drager DIVA vaporizer is a measured-flow type of vaporizer. Integrated into the Zeus anesthetic machine, it
can form part of a closed anesthetic system
Introduction The purpose of the vaporizer is thus to deliver reliably an

accurate, adjustable concentration of anesthetic vapor.
Administration of inhalational anesthetics have evolved
from the Schimmelbusch masks used by William TG Morton Physics
in 1846 to the electronically controlled vaporizers of the For safe administration of inhalational agents using
current era. Vaporizers are an integral part of modern-day vaporizers, it is essential to understand the physics behind
anesthesia, allowing the delivery of safe concentrations of vaporization: vapors and gases, saturated vapor pressure,
volatile anesthetic agent. boiling point, heat of vaporization, specific heat and thermal
conductivity.
Most of the inhalational anesthetic agents in use today are
liquids under normal conditions and must be converted into Vapor and gases
vapors before they can be used.
Every substance has its unique critical temperature
A vaporizer is an instrument designed to: above which it exists only as a gas, irrespective of how
much pressure is applied to it. At or below this critical
a) facilitate the conversion of a liquid anesthetic into its temperature, it can exist in both its liquid and gaseous
vapor form and forms; the latter is called a vapor. Thus, a vapor is the
b) add a controlled amount of this vapor to the fresh gas gaseous phase of a substance which is a liquid at room
flow. temperature and atmospheric pressure.

Vaporizers 316 Pankaj Kundra
Vapor pressure However, the relationship between SVP and temperature is
non-linear (Fig 2).
When a volatile liquid is kept inside a container closed
to atmosphere, molecules of liquid break away from the
surface (due to their kinetic energy) and enter the space
above, forming a vapor. The vapor exerts a pressure on
its surroundings, which is known as vapor pressure. Some
of the molecules that have escaped while moving freely in
the gaseous state will collide with the surface of the liquid
and re-enter it. Eventually, there will occur an equilibrium in
which the number of molecules re-entering the liquid equals
the number leaving it. At this stage, the vapor pressure is at
a maximum for the temperature of the liquid and so is called
the saturated vapor pressure (SVP).
If heat is supplied to the container, the equilibrium will be

shifted so that more molecules enter the vapor phase and
the vapor pressure will rise. If heat is taken away from Fig 2: SVP increases non-linearly with temperature
the system, more molecules will enter the liquid state
and the vapor pressure will be lowered. It is meaningless, Vapor pressures of the commonly used anesthetic agents at
therefore, to talk about vapor pressure of a liquid without 20°C are shown in Table 1.
specifying the temperature. Fig. 1 illustrates the impact of
Vapor pressure depends only on the liquid and the
temperature on saturated vapor pressure
temperature
The most important factor governing vaporizer design is the

saturated vapor pressure (SVP) of the anesthetic. SVP is a
measure of the volatility of the liquid anesthetic in the carrier
gas: after equilibration between the carrier gas and the liquid
anesthetic, the concentration of highly volatile anesthetics
(e.g. isoflurane) in the gas will be higher than that of poorly
volatile anesthetics (e.g. methoxyflurane).
Anesthetics with a high SVP will require a smaller proportion

of the total gas flowing through the vaporizer to pass through
the vaporizing chamber to produce a given concentration
than will anesthetics with a low SVP.
It follows that it can be extremely dangerous to deliver

anesthetics from vaporizers for which they were not designed.
Boiling point
At a certain temperature, the boiling point, liquid molecules

can enter their vapor phase within the liquid, creating
bubbles of saturated vapor that rise to the surface and
break free. Below this temperature, any formation of
a bubble would be instantly crushed by the greater
Fig 1: Fall in Saturated Vapour Pressure of isoflurane
atmospheric pressure. Thus, boiling point of a liquid is the
with fall in temperature. Fig A shows Isoflurane at 20ºC,
temperature at which the saturated vapor pressure is equal
with a SVP of 238 mm Hg. This leads to isoflurane vapor
to the atmospheric pressure. The lower the atmospheric
concentration of 31%. In Fig B, the temperature is 10ºC, pressure, the lower the boiling point. The boiling points of
which leads to a fall in SVP of isoflurane to 150 mm Hg some commonly used anesthetic agents at sea level are
accompanied by a fall in vapor concentration to 20% shown in Table 1.

Agent Boiling point SVP (torr, Volume percent :

(°C, 760 20°C) 100% air ≈ 21% oxygen + 78% nitrogen + 1% other gases
mmHg)
Halothane 50.2 243 Although gas and vapor concentrations are most commonly
Enflurane 56.5 175 expressed in volumes percent, patient uptake and the level
Isoflurane 48.5 238 of anesthesia are directly related to partial pressure but only
Desflurane 23.5 664 indirectly to volumes percent.
Sevoflurane 58.5 160 The concentration of anesthetic vapor in a gas is given by
Table 1: Boiling point and saturated vapor pressure of the equation:
some common agents Gas concentration = Vapor pressure / Ambient pressure
Concentration of Gases For example, at 20⁰C, the concentration of gas in a sevoflurane-
Two methods are used commonly to express the concentration vaporizing chamber (assuming it is saturated) will be:
of a gas or vapor: partial pressure and volumes percent. Sevoflurane concentration = 160/760 = 21%
Partial pressure In order to give clinically useful concentrations of the agent,
A mixture of gases in a closed container will exert a pressure we dilute this with fresh gas.
on the walls of the container. The part of the pressure exerted
Minimum alveolar concentration and Minimum alveolar
by any one gas in the mixture is called the partial pressure
partial pressure (MAC and MAPP)
of that gas. The total pressure of the mixture is the sum of
the partial pressures of the constituent gases. The minimum alveolar concentration is described in terms
of volume percent. The corresponding partial pressure for
Volume percent
each MAC value is known as the minimum alveolar partial
It is the number of units of volume of a gas in relationship to a pressure and is given in Table 2.
total of 100 units of volume for the total gas mixture. Volumes
percent expresses the relative ratio of gas molecules in a Heat of vaporization
mixture, whereas partial pressure expresses an absolute Latent heat of vaporization is the number of calories
value. needed to convert 1 g of liquid to vapor, without temperature
Volume percent = Volume of gas ‘y’/Total gas volume change in the remaining liquid. Thus, the temperature of the
remaining liquid will drop as vaporization proceeds, lowering
Volume percent = Partial pressure of gas (mmHg)/
vapor pressure, unless this is prevented.
Atmospheric pressure (mmHg)
Thus, for air at sea level, Specific heat is the number of calories needed to increase
the temperature of 1 g of a substance by 10C. Manufacturers
Partial pressures : select materials for vaporizer construction with high specific
760 mm Hg ≈ 160 mm Hg oxygen + 592 mm Hg nitrogen + heats to minimize temperature changes associated with
8 mm Hg other gases vaporization.
Property Halothane Isoflurane Sevoflurane Desflurane
MAC at age 40 y (v/v%) 0.75 1.2 1.9 6.0
MAPP (mm Hg) 5.7 9.1 14.4 45.6
Table 2: Minimum alveolar concentration (MAC) and Minimum alveolar partial pressure (MAPP) of inhaled volatile
anesthetic agents. MAC x 760 mm Hg (atmospheric pressure) gives the MAPP.

Thermal conductivity -a measure of how fast a substance • Altering the efficiency of vaporization. For example,
transmits heat. High thermal conductivity is desirable in at high flow rates, the gas leaving the vaporizing
vaporizer construction. chamber will tend to be less saturated (since the gas
spends less time in the chamber), so the output of the
Factors affecting vaporizer output vaporizer will tend to fall.
Flow through the vaporizing chamber • Carrier gas composition - The composition of the
carrier gas may affect vaporizer output by: Changes
Varying the proportion of gas passing through the vaporizing
in the viscosity and density of the gas mixture affecting
chamber and bypass is the method by which vaporizer output
the proportion of the total flow that passes through the
is controlled.
vaporizing chamber. The viscosities of air and nitrous
Efficiency of vaporization/ surface area of the liquid gas oxide are lower than those of oxygen. In the variable
interface bypass vaporizers, the characteristic of the flow
splitting valve results in decreased gas flow through
The greater the surface area of the liquid anesthetic agent the vaporizing chamber, and hence reduced output,
exposed to the fresh gas, more is the vaporization of the when using air and especially nitrous oxide compared
liquid agent. Vaporizers may incorporate a system of wicks with 100% oxygen. This effect is however, not clinically
and channels in the vaporizing chamber to improve efficiency significant.
of vaporization and increase the output concentration of
anesthetic. Ambient pressure
Saturated vapor pressure is solely a function of temperature.
Temperature
Therefore, if ambient pressure is reduced, the (constant)
The SVP of an agent decreases with decreasing temperature. SVP becomes a greater proportion of the total (reduced)
Changes in agent temperature can occur for two reasons – pressure, and the output concentration (in volumes %) rises.
fluctuations in ambient temperature and the loss of the latent The change in the agent concentration in the delivered gas
heat of vaporization (the latter being exacerbated at high flow can be calculated by:
gas flow rates). As temperature decreases, the output of the Pcal
vaporizer will decrease. These problems can be overcome Agent % = Agent % x
1 cal
by Temperature stabilization and temperature compensation. P1

Temperature stabilization: Construction of the vaporizer Where agent %1 is the agent concentration at the present
using materials with high specific heat capacity and thermal ambient pressure, P1 is the present ambient pressure, Pcal is
conductivity provides a heat sink, allowing heat to move the atmospheric pressure at which vaporizer was calibrated
rapidly between the vaporizing chamber and the atmosphere. and agent %cal is the agent % delivered at the calibrated
Plenum vaporizers are made of dense metals, while the atmospheric pressure.
Oxford Miniature vaporizer (a draw-over vaporizer) uses
But the partial pressure of the agent will not change with
glycol as a heat sink.
change in ambient pressure and since it is the partial pressure
Temperature compensation: This is dealt with separately that determines level of anesthesia, the clinical effect of
under vaporizer classification. change in ambient pressure is insignificant and the vaporizer
can be used in the same way at high altitude, sea level or
Time under hyperbaric conditions.
Vaporization causes the liquid anesthetic to cool since This, however, does not apply to the desflurane Tec 6
heat is lost because of the latent heat of vaporization of the vaporizer. The Tec 6 vaporizer is pressurized to 2 atm;
anesthetic. Therefore, the output concentration will tend to there is no compensation for ambient pressure and thus
fall over time. the concentration delivered in the fresh gas flow is stable,
regardless of ambient pressure. Thus, the dial setting must
Gas flow rate
be increased to maintain partial pressure of the agent at
Changes in carrier gas flow rate may affect vaporizer output high altitudes.
by: Classification of vaporizers
• Altering the proportion of the total gas flow that passes Vaporizers are classified based on various methods. Some
through the vaporizing chamber. of the most commonly used methods are:

A) Based on regulating the output concentration E) Based on the agent specificity
- Variable bypass - Agent specific

- Measured flow - Multiple agent
- Electronic vaporizers
Method of regulating output concentration
B) Based on the method of vaporization
The vapor pressures of most anesthetic agents at room
- Flow over temperature are much greater than the partial pressure
required to produce anesthesia. To produce clinically useful
- Bubble through
concentrations, a vaporizer dilutes saturated vapor in one
- Injection of several ways. Depending on this, vaporizers can be
C) Based on the method of temperature compensation classified as:
- Mechanical thermo compensation A) Variable bypass vaporizer

- Supplied heat The gas that flows through the vaporizer is split so that some
- Electronic thermo compensation of the gas flows through the vaporizing chamber (the part
of the vaporizer that contains the liquid anesthetic agent)
D) Based on the location of the vaporizer and the remainder goes through a bypass (without passing
- Plenum through the vaporizing chamber) to the Vaporizer outlet (Fig
3). Both gas flows (flow through the vaporizing chamber
- Low Resistance
and the bypass) join downstream of the vaporizing chamber
where gas exits the vaporizer at the desired concentration.
Fig 3: Variable bypass vaporizer. Fig A shows the vaporizer in the “OFF” position. Fresh gas flows thorugh
the bypass to the vaporizer outlet. Fig B shows the vaporizer in the “ON” position. Fresh gas flows through
the bypass and through the pressure compensating labyrinth into the vaporizing chamber, where it picks up
anesthetic vapor and flows past the concentration cone to unite with fresh gas stream before exiting at the
vaporizer outlet.
Conc./Agent Halothane Enflurane Isoflurane Sevoflurane
1% 46:1 29:1 44:1 25:1
2% 22:1 14:1 21:1 12:1
3% 14:1 9:1 14:1 7:1
Table 3 : Gas flow splitting ratios for different agents
The ratio of the bypass gas flow to the vaporizing chamber the area of the gas liquid interface enhances the efficiency of
flow is called the splitting ratio. the vaporization. This can be done by using baffles or spiral
tracks to lengthen the gas pathways over the liquid. Another
Splitting ratio = Gas going through the bypass/ Gas going method is to employ wicks that have their bases in the liquid
through the vaporizing chamber anesthetic agent. The liquid moves up the wick by capillary
The splitting ratio depends on the ratio of resistance in the action. (Fig.4 a and b). The TEC vaporizers and the Aladin
two pathways. The resistance in turn depends on the size cassette vaporizer are examples for “flow over” vaporization.
of the variable (adjustable) orifice which is present at the
inlet of old vaporizers and at the outlet of modern vaporizers.
B) Measured flow vaporizers
In these vaporizers, the vaporizer heats the anesthetic agent

to a temperature above its boiling point (so it behaves as
a gas) and this is then metered into the fresh gas flow. A
measured flow is sent by a separate oxygen flow meter
to pass to the vaporizer with the output being at saturated
vapor pressure for the anesthetic agent. In order to dilute this
otherwise lethal concentration, output from that flow meter is
combined with gas passing from the main flow meter.
Some of the older Measured-flow vaporizers include Copper

kettle, Verni-trol and Metomatic vaporizers.
The modern examples of measured flow vaporizers are the

desflurane Tec 6 vaporizer and the Drager DIVA.
C) Electronic vaporizers
In these vaporizers, a computer calculates the carrier gas flow

that needs to pass through the vaporizing chamber in order
to produce the desired anesthetic gas/vapor concentration.
Aladin cassette vaporizer is an example of a vaporizer with
electronic control of flow.
Fig. 4a: Flow over Vaporizer
Another type of electronic vaporizers withdraws a calculated
Fig. 4b: Flow over Vaporizer with wicks and baffles
amount of liquid agent from the agent bottle and injects that
liquid into the breathing system or fresh gas flow. The amount 2. Bubble through
of liquid that is injected is adjusted to achieve the desired
anesthetic concentration. The carrier gas is bubbled through the liquid anesthetic
agent. (Fig 5)
Vaporization methods
3. Injection
1. Flow over
A known amount of the liquid anesthetic agent or anesthetic
A stream of carrier gas passes over the surface of the liquid vapor is injected into the fresh gas flow. Examples include
i.e. it “FLOWS OVER” the surface of the liquid. Increasing Desflurane Tec 6 vaporizer and Maquet vaporizer.

which is attached to the roof of the vaporizing chamber. The
rod is attached only at the base of the brass jacket, which has
a higher coefficient of expansion. The outer surface of the
jacket is immersed in liquid anesthetic agent in the vaporizing
chamber. As the aforementioned liquid cools, the brass jacket
contracts more than the Invar, which is pushed upwards into
the bypass, restricting the flow of gas. (Fig. 6c and 6d)
Temperature compensation times: The temperature-

compensating mechanisms of contemporary vaporizers do
not produce immediate correction of the vapor output, but
take some time. For example, the temperature compensation
time in Drager 19.n vaporizer is 6 min/ºC.
b) Supplied heat
An electric heater can be used to supply heat to a vaporizer

and maintain it at a desired constant temperature. Example:
Desflurane Tec 6 vaporizer and Maquet Vaporizer.
c) Computerized thermocompensation
Fig 5: Bubble through vaporizer
Temperature compensation is achieved by computer control.
3. Temperature compensation The Central Processing Unit receives input from multiple
Energy in the form of heat is lost as liquid is vaporized and the

liquid temperature falls. This results in fall in saturated vapor
pressure which decreases the vaporizer output. Methods
have been employed to maintain constant vapor output with
fluctuation in liquid anesthetic temperature.
a) Mechanical compensation
This is done by altering the splitting ratio as temperature

changes so that the percentage of carrier gas that is directed
through the vaporizing chamber is increased or decreased.
With fall in temperature, the thermal element restricts the
bypass flow causing more carrier gas to pass through
the vaporizing chamber and the opposite occurs as the
temperature increases.
Two types of mechanical compensation are normally used:
The first consists of two dissimilar metals or alloys (nickel and

brass) placed back to back (i.e a bimetallic strip). As the two
metals have different rates of expansion and contraction with
temperature, the device has the ability to ‘bend’(Brass has a
greater coefficient of expansion then nickel). It can therefore
be used to vary the degree of occlusion in the aperture of
the gas channel (usually the bypass) and thus alter the flow
of carrier gases through it. (Fig.6a and 6b)
In the second arrangement, the bimetallic device consists of a

central rod made of Invar, a metal alloy with a low coefficient Fig 6: Two different types of mechanical
of expansion, sitting inside a brass jacket, the top part of thermocompensation

sources including fresh gas flow rate, carrier gas composition,
set vapor concentration, liquid level and temperature in
the vaporizing chamber (sump) and controls vapor output
electronically. This is seen in Aladin cassette vaporizer,
desflurane Tec 6 vaporizer, Drager DIVA and Maquet
injection vaporizer.
4. Based on resistance
Plenum Vaporizers have high resistance and therefore

require a pressurized source to provide a flow of gas. They
are usually placed outside the breathing circuit (VOC or
“vaporizer out of circuit” configuration), on the back bar of the
anesthetic machine, downstream of the flow meters. Most of
the modern vaporizers are plenum vaporizers.
Fig 7: Elongation of the inflow channel prevents saturated
Draw-over vaporizers require a sub-atmospheric pressure
vapor from reaching the bypass
distal to the vaporizer, to ‘draw’ the fresh gas flow through.
This is typically the patient’s own respiratory effort, so they
saturated with vapor), retrogradely into the bypass channel.
require a low internal resistance. This type of vaporizer is
When the pressure subsequently falls, the forward flow
most useful when pressurized gas sources are not available.
increases the concentration of the delivered vapor. The effect
They are not as accurate as plenum vaporizers owing to
is maximal with large pressure swings, low flows and a low
such variable flow rates, but can be used within the breathing
dial setting. Modern vaporizers are relatively immune (older
circuit (VIC or “vaporizer in circuit” configuration). Examples
vaporizers are certainly not immune) due to check valves
include the ether vaporizer EMO and the OMV (Oxford
between the vaporizer outlet and the common gas outlet,
Miniature vaporizer).
smaller vaporizing chambers, or tortuous inlet chambers.
Effect of altered barometric pressure Any of these design features prevent gas which has left the
vaporizers from re-entering it. (Fig 7)
Most vaporizers are calibrated at sea level. Since they can
be used in hyperbaric chamber or at high altitudes where Pressurising effect
atmospheric pressure is low, it is important to know how
This is a decrease in concentration of the vaporizer output
they will perform when barometric pressure is changed. The
when the overall pressure (that is, both in the bypass and
ASTM (American Society of Testing and Materials) requires
the vaporizing chamber) in the vaporizer is raised. The
that the effect of changes in ambient pressure on vaporizer
mechanism is that the partial pressure of vapor generated
performance be stated in the accompanying documents.
is dependent solely on temperature, and therefore at a high
Effect of rebreathing internal pressure, the vapor forms less of the fractional
composition of the number of molecules. Consequently, when
Rebreathing causes a difference between vaporizer setting the gas expands to atmospheric pressure at the common gas
and inspired concentration. With significant rebreathing, outlet, the delivered concentration of the vapor will be less
only an agent analyzer can provide an accurate value of the than that intended. The effect is maximal with large vaporizing
inspired agent concentration. chambers at high flows and high pressures.
Effect of intermittent back pressure Hazards and safety features of contemporary vaporizers
Pumping effect Hazards
It is due to the effect of intermittent back pressure transmitted • Incorrect agent
from the breathing circuit due to positive pressure ventilation
• Tipping
or use of the oxygen flush valve. It can increase vaporizer
• Simultaneous inhaled agent administration
output. The surge in back pressure forces gas in the back bar
(which is not saturated with vapor) back into the vaporizing • Reliance on breath by breath gas analysis rather than
chamber, and the gas in the vaporizing chamber (which is preventive maintenance

• Overfilling In addition to preventing a vaporizer from being filled with
• Leaks a wrong agent, these systems may reduce the air pollution
• Electronic failure associated with filling or draining a vaporizer.
Safety features Types (Fig 8)
Important safety features include: Funnel fill system

Keyed fill system
• Keyed fillers
Quick fill system
• Low filling port
• Secured vaporizers (less ability to move them about Easy fill system
minimizes tipping) Desflurane specific filling system
• Interlocks
Vaporizer mounting systems
• Concentration dial increases output in all when rotated
counterclockwise (as seen from above) Permanent mounting
Filling systems Permanent mounting means that tools are required to

remove or install a vaporizer on the anesthesia machine.
There are a number of filling systems available. Many are
Advantages include less chances of physical damage and
designed to allow a vaporizer to be refilled only with a
leaks. Disadvantages include not having enough mounting
specific agent. Some systems are specific to one vaporizer
manufacturer only. locations to accommodate all vaporizers and difficulties in
removing a malfunctioning vaporizer.
The ASTM (American Society of Testing and Materials)
machine standard recommends that a vaporizer designed Detachable mounting
for a single agent to be fitted with a permanently attached
These are standard on most of the modern anesthesia
agent specific device to prevent accidental filling with a
machines. They allow the Vaporizer to be mounted and
wrong agent.
KEYED FILL SYSTEM SCREW FILL SYSTEM QUIK FIL SYSTEM
Fig 8: Different types of filling systems

Fig 9a: Select-a-tec mounting system. Fig 9b: Select-a-tec mounting system
Fig.9c. Select-a-tec in Datex Ohmeda
removed without the use of tools. Select-a-tec system • High MAC

(Fig 9 a, b, c) and a similar system from Drager Medical
This precludes the use of contemporary vaporizers for
are widely used and vaporizers cannot be interchanged
controlled vaporization of desflurane. The three main reasons
between these two systems.
by which the above mentioned properties are responsible
Interlock devices for this are:
Interlock (vaporizer exclusion) systems prevent more than • Exceptionally high fresh gas flows would be needed:
one vaporizer from being turned ON at a time.(Fig. 10 and 11)
High saturated vapor pressure of desflurane leads to
Unsuitability of contemporary variable bypass vaporizer increased vapor concentration which would require excess
for use of desflurane diluting gas (bypass chamber) flow to dilute the vaporizing
chamber output to clinical concentrations. For example, at
Desflurane has unique properties among the inhalational 1 atm pressure and 20ºC, 100 ml/min of fresh gas passing
anesthetic agents, namely through the vaporizing chamber would entrain 735 ml/min of
• High saturated vapor pressure (664 mmHg at 20ºC), desflurane, as opposed to 29, 46 and 47 ml/min of enflurane,
isoflurane and halothane respectively. Now to produce 1%
• Low boiling point (22.8ºC) and

Fig 10: Datex Ohmeda Interlock
Fig 11: North American Drager interlock system

desflurane at the vaporizer output, the bypass flow should be The vapor circuit originates at the desflurane sump, which
approximately 73 L/minute, in contrast to 5 L/min or lesser for contains 450 ml of desflurane and is electrically heated and
the other three anesthetic agents. This would be impractical thermostatically controlled to 39ºC. This temperature is higher
with conventional anesthesia machines. than the boiling point of desflurane, leading to vaporization of
• Excessive cooling of liquid that mechanical tempera- desflurane. At this temperature of 39ºC, the vapor pressure
ture compensation would not work: of desflurane is 1300 mm Hg or 2 atm. The sump thus serves
as a reservoir of pressurized desflurane vapor.
High rate of evaporation of desflurane (due to high SVP)
would lead to substantial anesthetic cooling. Although Downstream from the sump is the sump shut-off valve, which
the latent heat of vaporization of desflurane is equal to is closed when the vaporizer is in the ‘OFF’ position. While
other agents like halothane and isoflurane, the high MAC the agent is being heated, the sump shut-off valve remains
of desflurane leads to considerably greater amount of closed and the vaporizer cannot be turned on (as a solenoid
desflurane being vaporized over a given period. Use of locking device prevents the concentration control dial from
contemporary variable bypass vaporizers for desflurane being turned on). Once operational (sump temperature of
would lead to significant cooling of the liquid anesthetic 39ºC), the dial lock can be released. When the dial lock
with subsequent reduction in vaporizer output, as it would
is released and the vaporizer is turned on, the sump shut
be impossible to compensate for the heat loss with the
off valve opens to allow the desflurane vapor to flow to the
conventional mechanical temperature compensation devices.
pressure regulating valve.
Due to the broad range of temperatures in the clinical setting
and the steep vapor pressure-versus-temperature curve Downstream from the sump shut off valve is the pressure
(V-P curve) of desflurane, its delivery with a conventional regulating valve, the opening of which is continuously
anesthetic vaporizer would be unpredictable.
adjusted based on the output from a pressure transducer to
• Boiling of desflurane leading to uncontrolled vapor out- ensure that the pressure of the desflurane vapor entering the
put: rotary valve (R2, a variable restrictor) in the user-controlled
concentration dial is the same as the backpressure generated
At temperatures higher than 22.8ºC, desflurane boils. If an
by the fresh gas flow from the anesthesia machine flowmeters
anesthetic agent should boil inside the vaporizing chamber
into the fixed resistor (R1). The equalized pressure supplying
of the conventional anesthetic vaporizer, the output would
R1 and R2 is the working pressure, which is constant at a
become uncontrollable as the amount of vapor produced is
limited only by the heat energy available from the vaporizer fixed fresh gas flow rate. When we increase the fresh gas
because of its specific heat. flow, more backpressure is exerted on the diaphragm of
the pressure transducer and the working pressure of the
Tec 6 desflurane vaporizer vaporizer will increase. Table shows the correlation between
The Tec 6 desflurane vaporizer is specially designed to fresh gas flow rate and working pressure.
overcome the above mentioned problems.
Fresh gas flow rate (L/ Working pressure at R1
Functionally,Tec 6 is a gas vapor blender. There are 2 min) and R2 (Gauge) (Gas
independent circuits that are arranged in parallel, inside inlet pressure) in mm Hg
the vaporizer (Fig 12). One is the fresh gas circuit and the
other is the vapor circuit and both meet at the vaporizer 1 7.4
outlet. Both these circuits are interfaced pneumatically and
5 37.0
electronically through differential pressure transducers, a
control electronics system and a pressure regulating valve. 10 74.0
Fresh gas passes through a fixed resistor (R1) before joining the Table 3: Fresh gas flow rate versus working pressure in
vapor limb at the vaporizer outlet. When a constant fresh gas the Desflurane Tec 6 vaporizer
flow encounters the fixed resistor R1, a specific backpressure
proportional to the fresh gas flow rate pushes against the If we increase the dial setting at a constant fresh gas flow
diaphragm of the control differential pressure transducer, which rate, the working pressure does not change, but the opening
conveys the pressure difference between the fresh gas circuit of R2 becomes larger, allowing more vapor to pass through
and the vapor circuit to the control electronics. R2 (Table 4).

Fig 12: Schematic diagram of the TEC 6 vaporizer
Dial setting Fresh gas flow Approximate vapor consists of electronic vapor control unit housed within the
anesthesia workstation and an interchangeable Aladin agent
(vol %) rate (L/min) flow rate through R2
cassette which contains anesthetic liquid and serves as the
(ml/min)
vaporizing chamber.
1 1 10
6 1 64 The Aladin cassette is a leakproof metal box that has a
12 1 136 larger rear section filled with a synthetic material. This is
18 1 220 the vaporizing chamber and the synthetic material (which
Table 4: Dial setting versus vapor flow thorugh restrictor behaves as the wick) is formed into lamellae and interspersed
R2 in the Desflurane Tec 6 vaporizer with metal plates, so it creates a convoluted pathway to
maximize vaporization (Fig 13). The back panel has inflow
If we keep the dial setting at 6% with a fresh gas flow rate
valve, outflow valve and spring loaded mechanical ball valves
of 1 L/min, the vapor flow rate through R2 will be 64 ml/min.
to prevent agent leak during transport. The front portion has
If we now increase the fresh gas flow to 10 L/min, working
a handle, a locking system, conventional vapor specific filling
pressure will increase from 7.4 mm Hg to 74 mm Hg. As R2
system and a glass window that displays the liquid level. The
is supplied by 10 times more pressure, the vapor flow through
top of the front section houses a row of five magnets arranged
R2 will increase ten fold, that is, from 64 ml/min to 640 ml/min.
in a sequence that provides unique vapor identification of
Newer vaporizers that cassette.
Datex Ohmeda Aladin cassette vaporizer The Aladin cassettes are color keyed to their respective
anesthetic agent, and are also magnetically coded so that
The vaporizer system used in the Datex Ohmeda S/5 ADU and the Aladin system can identify which anesthetic cassette has
GE Aisys anesthesia workstation is unique in that the single been inserted. Though very different in external appearance,
electronically controlled vaporizer is designed to deliver five the functional anatomy of the Aladin cassette vaporizer is very
different inhaled anesthetics including halothane, isoflurane, similar to that of the Dräger vapor 19.n, 20.n and the GE/
enflurane, sevoflurane and desflurane. The Vaporizer system Datex-Ohmeda Tec 4, Tec 5, and Tec 7 vaporizers.

Fig 13 : Aladdin cassette cross section showing the lamellae in the larger rear section and the fill port and liquid level
window in the front portion
The Aladin system is functionally similar to these conventional A microprocessor gathers information about the agent used,
vaporizers because like them, it consists of a bypass chamber cassette temperature, flow of gas in the bypass and makes
and vaporizing chamber. When the user sets an anesthetic calculations for the amount of agent to be added to the bypass
concentration at the workstation, the fresh gas is split into two; gas to provide the desired concentration, set by the user
the bulk of the gases flowing through the bypass where the and instructs the proportional flow valve to open sufficiently
flow is measured and a smaller portion through a mechanical to provide this.
one way valve, through an electronic ‘inflow close valve’,
through the open ball valve in the back of the cassette (which Aladin 1 and Aladin 2 cassettes
opens when the cassette is plugged into the workstation) There are some differences between the originally introduced
and into the vaporizing chamber (Fig 14). Here, it picks up Aladin 1 casettes and the currently used Aladin 2 casettes
saturated vapor and leaves via the other open ball valve, an (Fig 15). Liquid level display window is bigger in Aladin 2 and
electronic ‘outflow close valve’ and a liquid flow prevention the handle has a locking lever. There is also an additional
valve to the proportional flow valve that controls the vapor liquid level sensor which gives input back to the anesthesia
output. From here, it passes to the agent flow measurement workstation via an electronic bus, which also conveys
device and into the outlet of the control unit, where it joins vaporizer temperature data.
the bypass gas in a mixing chamber.

Fig 14

Drager DIVA Vaporizer
The Drager DIVA (Direct injection of vapor anesthetic)

vaporizer (Fig.17) is a measured-flow type of vaporizer
requiring a separate air supply. Integrated into the Zeus
anesthetic machine, it can form part of a closed anesthetic
system. It utilizes closed-loop feedback control to determine
the amount of volatile agent allowed through a closing valve
into a heated vaporization chamber(Fig 18); this then passes
A either directly into the breathing system or through a mixing
chamber into the fresh gas flow. The control unit monitors
the pressure of volatile agent in the vaporizing chamber, the
fresh gas flow and the target-expired volatile concentration, to
ascertain the amount of volatile agent required to be released
to maintain the desired concentration at the patient end.
Thus, quantitative closed-system anesthesia can be realized.
Maquet vaporizer
This is an injection type vaporizer which is electronically

controlled and used exclusively with the Maquet FLOW-i
anesthesia workstations. The device has a filling port and
B electronic level indicators, but there is no concentration
Fig 15: Fig A shows Aladin cassette 1 vaporizer and Fig B control dial. An electronic interface on the anesthesia
shows Aladin cassette 2 vaporizer. workstation is used to adjust vaporizer output.
Sevoflurane and desflurane cassettes Gas from the anesthesia machine passes through the drive
gas inlet and pressurizes the anesthetic liquid storage
Sevoflurane cassettes have Quick fil system and Desflurane
container (Fig. 19). This pressure forces the liquid anesthetic
cassettes have Saf-T-Fil system (Fig 16)
agent through the vaporizer injector, which then injects the
liquid anesthetic agent into the vaporizing chamber with
a heater. The injection is controlled by microprocessor
and occurs in a pulsed, intermittent manner and the liquid
rapidly evaporates in the vaporizing chamber (there is an
evaporative surface within the chamber). Injection is done in
small increments till the desired injection volume is obtained.
This is determined by the desired anesthetic concentration
and the fresh gas flow through the vaporizer. Fresh gas
from the anesthesia workstation flows through the heated
vaporizing chamber and gets enriched with anesthetic vapor.
Downstream from the vaporizer, there is a gas analysis line
to monitor the vaporizer output. The integrity of the injection
is monitored by an optical sensor in the vaporizer. The
heating of the evaporative surface is carefully regulated to
compensate for the effect of evaporative cooling.
The vaporizer is not vulnerable to tipping as it has no wicks to

saturate and agent cannot spill into the vaporizing chamber.
Conversion of liquid to vapor for calculation of anesthetic

usage
Fig 16: Sevoflurane and Desflurane Aladin 2 cassettes According to Avogadro’s law, 1 gram molecular weight of
with “QuickFil” and “Saf-T-Fil” respectively a gas or vapor will occupy 22.4 L at standard temperature

Fig 17: DIVA (Direct injection of vapor anesthetic) vaporizer
Fig 18: Schematic drawing of the DIVA metering system

Fig 19: Maquet injection vaporizer
and pressure (760 mm Hg and 273 K). As molecular weight halothane. With contemporary anesthesia workstations, only
of isoflurane is 184.5 Da, it would occupy 22.4 L at STP. So one vaporizer can be on at any given time and it is an ASTM
1 gram of isoflurane will occupy 22.4/184.5 L or 0.12 L. At standard to have a system in place to isolate the vaporizers
20ºC (293K), 1 gram of isoflurane will occupy [(22.4/184.5) from one another and prevent gas from passing through more
x (293/273K)], which is 0.13 L than one vaporizing chamber.
One ml of liquid isoflurane weighs 1.5 g (specific gravity of Conclusion

1.5). Therefore, 1 ml of liquid isoflurane generates 0.13 x 1.5
= 0.195 L or 195 ml of vapor at 20ºC. Anesthetic vaporizers are devices which form an integral
part of everyday anesthesia delivery. Understanding the
As 1 ml of most liquid anesthetic agents produce approximately physical principles behind their design, the functioning of the
200 ml of vapor, the hourly consumption of liquid anesthetic different types of vaporizers and the safety features available
agent can be estimated by the formula: with each is important for the safe conduct of anesthesia,
prevention of mishaps as well as for troubleshooting.
Liquid consumption/h = 3 x Vaporizer dial setting (Vol %) x
Fresh gas flow rate Recommended reading
Arrangement of vaporizers 1. Chapter 6 :Vaporizers. Dorsch JA, Dorsch

In older anesthesia machines, multiple variable bypass SE.Understanding anesthesia equipment. Fifth
vaporizers can be mounted in series, with no interlock to edition. Philadelphia: Lippincott Williams and
prevent simultaneous opening of several vaporizers. This Wilkins; 2008. 122-190.
would lead to anesthetic overdose as well as contamination
2. Davey AJ. Vaporizers. In Davey AJ, Diba A,
of the downstream vaporizer output. With such a series
Editors.Ward’s Anaesthetic Equipment. Sixth
arrangement of vaporizers, it is important to place the vaporizer
edition. Edinburgh: Elsevier Saunders; 2012. 41 –
designed for a less volatile agent (low SVP) upstream and
64.
that which is highly volatile is placed downstream. So the
order of placement from flowmeter manifold to common 3. Eisenkraft JB. Anesthesia Vaporizers. In
gas outlet would be sevoflurane, enflurane, isoflurane and Ehrenwerth J, Eisenkraft JB, Berry JM,

Editors. Anesthesia equipment: Principles and 5. Young J, Kapoor V. Principles of anaesthetic
Applications. Second Edition. Philadelphia: Vaporizers. Anesth Int Care Med 2010;11:140-
Elsevier Saunders; 2013. 64-94. 143.
4. Venticinque SG, Andrews JJ. Inhaled Anesthetics: 6. Boumphrey S, Marshall N. Understanding

Delivery Systems. In Miller RD, Cohen NH, Vaporizers. CEACCP 2011; 11(6):199-203.
Eriksson LI, Fleisher LA, Wiener-Kronish JP,
Young WL, Editors. Miller’s Anesthesia. Eighth 7. Baum JA. New and alternative delivery concepts
edition. Philadelphia: Elsevier Saunders; 2015. and techniques. Best Pract Res Clin Anaesthesiol
765-780. 2005;19(3):415-428.

34 ARTERIAL BLOOD GAS INTERPRETATION
Professor Jigi Divatia

Mumbai
Key points
Ø Respiratory acid-base disorders are disorders of carbon dioxide homeostasis whereas metabolic acid-base
disorders comprise all other conditions affecting the pH
Ø Compensation for a respiratory disturbance is metabolic, and compensation for a metabolic disturbance is
respiratory
Ø On any blood gas analyser, only three parameters are measured using specific electrodes: pH, PaO2 and PaCO2
Ø Compensation tends to minimize the impact of the primary disturbance on the pH. Thus the pH returns towards
normal but never completely (except primary respiratory alkalosis)
Ø Normal AG value must be adjusted for serum albumin
Ø Widened P(A-a)O2 implies parenchymal lung disease as a cause of reduced PaO2
Ø An increased PaCO2 with widened (A-a)O2 difference is most commonly due to COPD, but can also be due to
respiratory muscle fatigue in any cause of hypoxemic respiratory failure
Ø Hypoxemia due to hypoventilation due to a non-pulmonary cause is exquisitely sensitive to oxygen therapy
Ø Hypoxemia due to predominantly low V/Q ratios also responds well to oxygen therapy, whereas that due to shunt
does not respond to conventional oxygen therapy
Ø The normal value of the normal value of the (A-a)O2D depends on the FiO2
There are essentially two indications for arterial blood gas and the appropriate management are best understood by
analysis: examining the equation for the bicarbonate–carbon dioxide
buffer system:
1. Interpretation of acid base status
2. Interpretation of status of ventilation and pulmonary H2O + CO2 ↔ H2CO3 ↔ H+ + HCO3
gas exchange
Indeed, critically ill patients often suffer from compound
Acid-Base Status acid-base and electrolyte disorders. Successful evaluation
and management of such patients requires recognition
Acid-base homeostasis is defined by the pH of blood and
of common patterns (e.g., hypokalemia and metabolic
by the conditions of the acid-base pairs that determine it.
alkalosis), and an ability to recognise one disorder from
Normally, arterial plasma pH is maintained between 7.35–
another.
7.45. The determinants of blood pH can be grouped into two
broad categories, respiratory and metabolic. Respiratory Disturbances that affect the PaCO2 primarily are called
acid-base disorders are disorders of carbon dioxide (CO2) respiratory disturbances, and those that affect the HCO3−
homeostasis whereas metabolic acid-base disorders primarily are called metabolic. Acid-base homeostasis
comprise all other conditions affecting the pH. depends on compensation for a primary disturbance.
Acid-base, electrolyte, and metabolic disturbances are Compensation for a respiratory disturbance is metabolic,
common in medicine. Disorders of the acid–base system and compensation for a metabolic disturbance is respiratory.

Arterial Blood Gas Interpretation 336 Jigi Divatia
A simple acid-base disturbance is considered to consist of as the pH. The other disorder is a compensating disorder.
the primary disturbance and its normal compensation. A Compensation tends to minimize the impact of the primary
complex acid-base disturbance consists of more than one disturbance on the pH. Thus the pH returns towards normal
primary disturbance. In order to detect complex acid-base but never completely (except primary respiratory alkalosis).
disturbances, one must be familiar with both the direction Compensation requires normally functioning kidneys and
and magnitude of normal compensation. More than lungs. The appropriate degree of compensation can be
one metabolic disturbance may coexist (e.g., metabolic predicted. Lack of appropriate compensation in time defines
acidosis and metabolic alkalosis), but only one respiratory presence of a second primary disorder.
disturbance is possible at a time.
Primary respiratory acidosis (high PCO2)
Analysis of Acid-Base status Compensatory metabolic alkalosis (high HCO3)
On any blood gas analyser, only three parameters are Primary metabolic acidosis (low HCO3)
measured using specific electrodes: pH (-logH+), PaO2 and Compensatory respiratory alkalosis (low CO2)
PaCO2. All other parameters, including HCO3, SO2, aBE, Primary respiratory alkalosis (low CO2)
sBE, etc, are derived or calculated parameters.
Compensatory metabolic acidosis (low HCO3)
Interpretation of Acid-Base Status follows a 7-Step Primary metabolic alkalosis (high HCO3)
approach Compensatory respiratory acidosis (high CO2)
1. Acidemic or Alkalemic? 3. For a respiratory disturbance, determine whether it
2. Is the primary disturbance respiratory or metabolic? is acute or chronic
3. For a respiratory disturbance, determine whether it
is acute or chronic To determine adequacy of compensation, first determine
4. For a respiratory disorder, is metabolic
• Is the respiratory disturbance Acute? (<24 hours,
compensation OK?
pH change 0.1 for every 10 change in PCO2) If so,
5. For a metabolic disturbance, is respiratory
expect a Change of 1 mEq HCO3 for every change
compensation OK?
of 10 mmHg. of PaCO2
6. For a metabolic acidosis, determine whether an
anion gap is present • If the respiratory disturbance is Chronic? (>24
7. Determine whether other metabolic disturbances co- hours, pH change < 0.1 for every 10mmHg change
exist with an anion gap acidosis. in PCO2), expect a Change of 3- 4 mEq HCO3 for
every change of 10 mmHg. of PaCO2
While evaluating for Acid- Base status remember,
4. For a respiratory disorder, is metabolic compensation
Normal range
OK?
pH = 7.35- 7.45
Compensation for Respiratory Acidosis / Alkalosis
PaCO2 =35- 45
HCO3 =22-26 • Acute Respiratory acidosis (<24 hrs)
1 Change in HCO3 for every 10 increase in PCO2
For calculation purposes, the base is
• Chronic Respiratory acidosis (>24 hrs)
7.40 for pH 4 Change in HCO3 for every 10 increase in PCO2
40 for PaCo2 • Respiratory alkalosis 1- 2 hrs
24 for HCO3 2 change in HCO3 for every 10 change in PCO2
1. Acidemic or Alkalemic? • Respiratory alkalosis >2 days

5 change in HCO3 for every 10 change in PCO2
If pH < 7.4, acidemia; if pH >7.4, alkalemia
5. For a metabolic disturbance, is respiratory
2. Which is the primary disturbance? compensation OK?
Acidosis or Alkalosis can be Respiratory or Metabolic. • Rules for compensation for a Primary Metabolic
The primary disturbance is that which is in the direction Event:Respiratory change is compensatory

• Rule of thumb There are two important pitfalls in the interpretation of the
Change of 1 mmHg of PaCO2 for each change of anion gap.
one mEq of HCO3
1) Anion gap is proportional to the plasma albumin
• Exact calculation : Winter’s Formula concentration, hypoalbuminemia (common in
• For metabolic acidosis expected PaCO2 = [(1.5 x critically ill patients) will lower the “baseline” anion
HCO3) + 8] ± 2 gap (by approximately 2.5 mmol/L for each g/
• For metabolic alkalosis dL decline in the albumin concentration).Thus,
profound hypoalbuminemia may falsely lower the
expected PaCO2 = [(0.7 x HCO3) + 21] ± 1.5
anion gap, and thus mask a high anion gap acidosis.
PaCO2 = (0.75 x HCO3) + 19 + 7.5 (if HCO3 > 40)
• Significance of estimated compensaton Corrected AG for hypoalbuminaemia is =AG
+2.5*(4.0-albumin levels)
o If compensation is as per calculation, there
is a Single acid - base disorder 2) Alkalemia increases the anion gap by causing lactate
generation and by titrating plasma buffers, most
o If compensation less than or greater than notably albumin. (Thus, in respiratory alkalosis, the
calculated expected value, there is a dual bicarbonate concentration will be low in compensation,
or multiple acid - base disorder and the anion gap may be elevated, giving a false
impression of a high anion gap metabolic acidosis by
6. For a metabolic acidosis, determine whether an anion
inspection of the electrolytes alone).
gap is present
7. Determine whether other metabolic disturbances
• If there is a Metabolic acidosis, Check the anion
co-exist with an anion gap acidosis
gap
• Does the anion gap explain the change in HCO3?
Na – (Cl + HCO3) (normal < 12)
[HCO3]+(gap- 12) =24
• If AG > 12, anion gap acidosis
• If > 24
Accumulation of unmeasured anions
o Consider additional hidden metabolic
(MUDPILES) alkalosis
M Methanol, • If < 24
o Consider a hidden non anion gap metabolic
U uraemia
acidosis
D DKA,alcoholketosis,starvation ketosis
P paraldehyde • Valid only in patients who do not have a chronic
respiratory acid base disorder
I INH
L lactates • Delta Gap
E ethylene glycol [HCO3]+(AG- 12) =24 OR 24-[HCO3] = (AG – 12)
S salicylates
o Delta HCO3 should equal the Delta AG
• If AG < 12, non-anion gap acidosis o If Delta HCO3 < delta AG it indicates
mixed high anion gap metabolic acidosis
o Loss of bicarbonate and metabolic alkalosis
o Hyperchloremic acidosis
o If delta HCO3 > delta AG then either mixed
• Normal AG value must be adjusted for serum high AG and normal AG metabolic acidosis
albumin OR mixed high AG acidosis and chronic
respiratory alkalosis with compensatory
o Add 2.5 for every 1g/dl fall in albumin
hyperchloremic acidosis
(normal albumin 4g/dl)

• Example 1  Positive Urine AG suggests Renal
Tubular Acidosis
In a 21 yr old DM anion gap is 23 and HCO3 is 18
Therefore, Oxygenation and Ventilation
18+(23-12)=29 which is > 24 There are two abnormalities in pulmonary gas exchange
indicating presence of hidden Metabolic Alkalosis
• Hypoventilation : PaCO2 > 45mmHg
Delta HCO3 (24-18) = 6 < Delta AG (23 – 12) = 11
• Hypoxemia: PaO2 < 60 mmHg
• Example 2 Relate to FiO2
A 55 yr old alcoholic with a 2 weeks of diarrhea has Quantified by (A-a )DO2, P/F ratio, Qs/Qt, etc
an AG of 17 & HCO3 of 10
The Alveolar - air equation can help determine whether
10 + (17 -12 )=15 which is less than 24 there is a defect in oxygenation
indicating a hidden metabolic Acidosis
PAO2 = PiO2 - (PaCO2 / R)
Delta HCO3 = 14 > delta AG 5
Additional non-gap acidosis due to diarrhoea where R is the respiratory quotient
PiO2 = FiO2 x (Pb - PH2O),
Delta Ratio
Pb is atmospheric pressure
Delta ratio = Increase in AG / Decrease in HCO3
PH2O is the saturated water vapour pressure at 37
• Example
degrees C
pH 7.20;PaCO2 25mmHg; HCO3 10mmol/L; Na+
PAO2 = FiO2 x (Pb - PH2O) - - (PaCO2 / R)
-131 mEq/L,K + -6.6 mEq/L, Cl- -98.3 mEq/L
Delta ratio = Increase in AG / Decrease in HCO3 R is normally 0.8, round off to 1.0
22.7 – 12 / 24 – 10 = 10.7 / 14 = 0.76 Pb at sea level is 760 mmHg
Delta ratio < 1 suggests a greater fall in HCO3 than PH2O is 47 mmHg
expected from the change in AG
PAO2 = 105; PaO2 = 100
additional metabolic acidosis (often renal failure)
Delta ratio > 2 indicates a lesser fall in HCO3 than P(A-a)O2 = 5 (breathing room air)
expected Widened P(A-a)O2 implies parenchymal lung disease
Additional metabolic alkalosis as a cause of reduced PaO2
• Urine anion gap Respiratory Failure
(Urine Na + K) – (Urine Cl) = Urine AG Definition based on ABG
o Diagnose metabolic acidosis due to renal Type 1: PaO2 < 60 mmHg

excretory failure
Type 2: PaO2 < 60 mmHg & PaCO2 > 45-50 mmHg
o NH4 most important unmeasured ion in
+
Not possible to detect these clinically, and the trend
urine
is important
o Urine NH4+ excretion is accompanied
Hypoventilation
by Cl. Negative urine AG =increased
NH4+ excretion • Increased PaCO2 = alveolar hypoventilation
o In a metabolic acidosis without a serum • Increased PaCO2 with normal (A-a)O2D = non
anion gap: parenchymal cause
 Negative Urine AG suggests • Increased PaCO2 with widened (A-a)O2D suggests
diarrhea a parenchymal cause, but may also be due to
excess CO2 generation

An increased PaCO2 with widened AaO2D s most Hypoxemia due to predominantly low V/Q ratios also
commonly due to COPD, but can also be due to respiratory responds well to oxygen therapy, whereas that due to shunt
muscle fatigue in any cause of hypoxemic respiratory failure does not respond to conventional oxygen therapy. Breathing
100% oxygen in a patient with >40% shunt is ineffective in
An increased PaCO2 with normal (A-a)O2D may be due to correcting hypoxemia; application of mechanical ventilation
and positive end expiratory pressure is required.
• Neurogenic loss of drive
• Neuromuscular weakness Measuring the Gas Transfer Defect
• Chest wall problems Aims at quantitating the degree of parenchymal
• Upper airway obstruction problem. There is no fully reliable method.
Mechanisms of hypoxemia Alveolar-arterial O2 Difference
1. Low Inspired PO2 • AaO2D = PAO2-PaO2

2. low barometric pressure • If PaO2 is 12-20 mmHg. less than PAO2 , it suggests
3. Alveolar hypoventilation a normal gas transfer ability
4. Diffusion defect • If PAO2 >12-20 mmHg more than the PaO2, there is
an abnormal gas transfer ability
5. V/Q mismatch
• However, the normal value of the normal value of
6. Intrapulmonary shunt the AaO2D depends on the FiO2
7. Extrapulmonary shunt
Shunt fraction (Qs/Qt)
The commonest mechanisms encountered in clinical
practice are 3, 5 and 6. • Needs a pulmonary artery sample
• Normal < 2-4%
Hypoxemia due to hypoventilation due to a non-pulmonary
• Will change with cardiac output
cause is exquisitely sensitive to oxygen therapy. For
• Relatively cumbersome to repeatedly perform
example, if a patient breathing room air has a PaCO2 0f
100mmHg, by the alveolar-air equation, his alveolar PO2 PaO2/FIO2
will be 40mmHg, and with a normal (A-a)O2D of 5mmHg,
the PaO2 will be about 35 mmHg. Increasing the FiO2 to • Simple to use
just 0.3 will increase the alveolar PO2 to 104mmHg, and the • Gradation of severity
PaO2 to 99mmHg. Thus dangerous hypoxia can be easily • Mild ARDS = <300
corrected, but it is essential that the case of hypoventilation • Severe ARDS = <100
is identified and corrected.
• Does not consider effect of PEEP or PaCO2

SNAP SESSIONS
35 ASPIRATION UNDER ANESTHESIA
Professor Bala Bhaskar S

Vijayanagar Institute of Medical Sciences, Bellary,
Karnataka
Key points
Ø Regurgitation and aspiration could result despite empty stomach as the stomach can receive large quantity of
secretions from saliva, stomach and the intestines
Ø The difference between the Lower Esophageal Sphincter pressure and the intragastric pressure is the “barrier
pressure”
Ø In an awake state, intrinsic airway reflexes such as coughing, the expiration reflex, laryngospasm, apnoea and
spasmodic panting offer protection against aspiration
Ø Gastric volumes >25 ml and pH < 2.5 have been demonstrated in 40–80% of fasted healthy patients.
Ø If aspiration is suspected, head is turned towards one side and the table turned head end down so that the
regurgitated particles stay in the oropharynx and further aspiration is reduced; thorough suctioning is performed
Ø Inadequate fasting and fasting times lesser than recommended are the major factors in increasing the risk of
regurgitation and aspiration in the perioperative period
Ø Depending on the patient, aspiration is a risk before induction, during induction, during mask ventilation, before
laryngoscopy, during laryngoscopy, during extubation, or after tracheal extubation
Ø Nasogastric tube(NGT) may be suctioned and removed before intubation as presence of NGT can keep the upper
and lower esophageal sphincters open or lead to reduced tone
Ø Pharmacologic agents may be administered to decrease gastric volume (either by decreasing production or by
increasing emptying), increase gastric pH, or increase LES tone
Ø Rapid Sequence Induction-Intubation(RSII) can also be an option in conditions where there is predicted difficulty
in mask ventilation (not intubation) such as edentulous patients, bearded patients, etc
Ø 30 N force is suggested as effective to prevent regurgitation of gastric contents

Ø Supraglottic airway devices (2nd generation) could be useful electively in at risk cases and also used as rescue
devices for securing airways or for intubation with endotracheal tubes in cases of difficult mask ventilation and /
or intubation in at risk cases
Pulmonary aspiration under anaesthesia refers to the Normal Physiology of Gastric Emptying
accidental but passive passage of regurgitated gastric
contents up through the esophagus, across the trachea into The stomach, which receives the ingested food empties into
the lungs. the duodenum with antral contraction, which overcomes the
resistance offered at the pylorus. The food volume and the
Normal physiological mechanisms promote forward movement secretion of hormones influences the extent of contraction
of ingested food and liquids down the gastrointestinal tract and emptying. The antral contraction is caused by gastric
and prevent retrograde movement towards esophagus. distension stimulating vagal influences, along with gastrin

Aspiration Under Anesthesia 344 Bala Bhaskar S
secretion. Acidic, hyperosmolar contents, fat and protein greater than the intragastric pressure (10 -15 mmHg in
by-products inhibit the contractions (stimulating secretin fasted patients). It thus prevents the movement of the gastric
and inhibiting gastrin). Blood glucose, at levels >8 mmol/l contents into esophagus.
also reduces emptying of caloric content. It is worth noting
The difference between the LES pressure and the
that regurgitation and aspiration could result despite empty
intragastric pressure is the “barrier pressure”. If there is
stomach as the stomach can receive large quantity of
increase in abdominal pressure, the LES pressure also
secretions from small and large intestines. Saliva contributes
increases, maintaining the protective barrier pressure. The
1ml/ kg/ h and gastric secretions, 0.6 ml/ kg/ h to gastric
esophagogastric (EG) angle also prevents reflux. If the EG
volume during fasting. Thus, stomach is never, really totally
angle is reduced as seen in morbid obesity or with gravid
empty.
uterus, reflux can be seen at lower gastric pressures. When
Transit of Ingested Food and Drinks there is decrease in barrier pressure (LES pressure decrease
or the gastric pressure increase), the gastric contents get
For the non-caloric liquids (water), gastric emptying begins refluxed into esophagus. Additional barriers to protect against
immediately and exponentially, following first-order kinetics, regurgitation are provided by the upper esophageal sphincter
without any lag. (Figure 1) It is proportional to the volume (which has a high resting pressure- up to 100 mmHg) and
present in the stomach and thus the gastro-duodenal diaphragmatic crura (tightening the lower esophagus).
pressure gradient. For caloric liquids, hyperosmolar, acidic
or fatty fluids and solids, emptying follows zero-order kinetics, Normal mechanisms preventing aspiration
which is linear but biphasic in pattern.
In an awake state, certain intrinsic airway reflexes offer
protection against aspiration after regurgitation, such as
coughing, the expiration reflex (expiration without inspiration),
laryngospasm and apnoea and spasmodic panting (rapid
shallow breathing).
Aspiration of gastric contents into Lungs
Aspiration during general anesthesia is rare in modern

practice, ranging from 1:4,000 to 1:9,000 cases. The earliest
evidence of the risks related to regurgitation, aspiration and
death was the report from Mendelson (1946) from over
44,000 pregnancies in New York. There were 66 cases
of aspiration and two deaths, the deaths being attributed
to solids being aspirated. He explained the role of acidic
contents in the bronchus for the ensuing lung damage.
Fig 1: Gastric emptying of solids and liquids (Basic Physiology The gastric volume and pH as determinants of the risk of
for Anaesthetists. David Chambers et al) dangerous aspiration manifestations were highlighted by
Roberts and Shirley (1974) who surmised that aspirated
Normal mechanisms preventing regurgitation
volumes of 25 ml (0.4 ml/kg) and more of gastric fluid, with
For aspiration to occur, the stomach contents have to cross a pH < 2.5 were dangerous. Their opinion was based solely
the lower esophageal sphincter, ascend up the esophagus on work in a single Rhesus monkey without regurgitation and
(more likely with greater volumes), cross the upper aspiration, with right main being bronchus instilled with 0.4
esophageal sphincter and enter the trachea (and aspirate into ml/kg of acid. The current and widespread mention of these
the lungs), overcoming protective airway reflexes if patient values for humans is still not supported by validated human
is awake (cough and laryngospasm). trials and in fact gastric volumes >25 ml and pH < 2.5 have
been demonstrated in 40–80% of fasted healthy patients.
The lower esophageal sphincter (LES), a 2–5 cm long barrier,
relaxes with onset of peristalsis associated with ingestion of Consequences of Aspiration
food, allowing the food material to pass through. It moves
Aspiration of large gastric particles can cause physical
upward with inspiration and downward with expiration and
obstruction of the airway along the tracheo-bronchial tree,
has a resting pressure (tone) of 20–30 mmHg, which is
or can precipitate chemical pneumonitis (affecting gas

exchange), the latter depending on volume and pH of the second generation) and endotracheal intubation. Decision
aspirate. on mechanical ventilation is based on patient’s condition.
Fibreoptic bronchoscopy is sometimes needed to drain out
In the anaesthetised state, patient develops tachycardia, or remove large particulate aspirate. Inhaled bronchodilators,
hypertension and oxygen desaturation with increase in parenteral steroids (doubtful efficacy) and antibiotic
airway pressures and bronchospasm. These may be administration (based on culture) are other measures.
revealed within 2 hrs of the event. X ray chest may show
atelectasis or infiltrates (most commonly a right lower lobe Perioperative factors influencing regurgitation and
infiltrate) and with progression of the condition, there can aspiration
be development of interstitial and pulmonary edema, with
hyaline membrane formation and destruction of lung tissue. Inadequate fasting and fasting times lesser than recommended
Adult respiratory distress syndrome (ARDS) is a risk with are the major factors in increasing the risk of regurgitation
prolonged mechanical ventilation (>24 hrs) as also further and aspiration in the perioperative period.
deterioration and death. Arterial blood gas analysis reveals The 3 normal physiological mechanisms discussed already
hypoxia and alveolar-arterial (A-a) gradient of >300 mmHg may be disturbed in the perioperative period:
on 100% O2. The 4 stages of deterioration of ARDS may
also occur (as described by Mendelson initially). • Delay in gastric emptying (reducing forward movement
of gastric contents) (table 1)
If aspiration is suspected, head is turned towards one side
and the table turned head end down so that the regurgitant • Decreased pressures across the LES (promoting
particles stay in the oropharynx and further aspiration is retrograde movement / regurgitation towards
reduced; thorough suctioning is performed. Airway patency esophagus) (table 2) and
and oxygenation are managed with careful mask ventilation
• Obtunding the protective reflexes (promoting aspiration
(positive pressure can shift the aspirate into lower airways
into lungs)
further), placement of supraglottic devices (preferably
Patient Factors Pain Anxiety and stress

Trauma
Sympathetic stimulation
Left lateral position (for non-caloric liquids) Obesity
Pregnancy
Alcohol Ingestion
Hypothyroidism
Diabetes
Pharmacological Factors Anti-muscarinics Opioids
Surgical Factors 1. Non- Elective Surgery
2. Acute or chronic, upper or lower GI pathology
3. Neurological Disease,
impaired consciousness level or sedation
4. Lithotomy position
5. Gastro-intestinal reflux
6. Hiatus Hernia
7. Intestinal obstruction
8. Pyloric stenosis
9. Vagotomy
Anaesthetic Factors 1. Light anaesthesia, unexpected response to stimulation
2. Difficult Intubation/airway
3. Depressed reflexes ass. with anaesthetic Agents
4. Gas Insufflation
Table (1): Factors Associated with delayed gastric emptying (Soreide E et al)

Drugs increasing LES tone & Drugs decreasing LES tone & Drugs with no effect on LES
Barrier Barrier
Pressure Pressure
α adrenergic agonists β adrenergic agonists Propranolol
Histamines Cimetidine, Ranitidine
Cholinergics Atropine
Neostigmine Glycopyrrolate
Edrophonium
Succinylcholine
Pancuronium Vecuronium, Atracurium
Metoprolol
Metoclopramide Opioids
Inhalational agents
Thiopentone
Dopamine
Sodium Nitroprusside
Nitroglycerine
Propofol lowers both esophageal and gastric pressure - thus, has no effect on barrier pressure
Table 2: Effects of Drugs used in perioperative period on lower esophageal tone
Under deep sedation and general anesthesia, the protective

upper airway reflexes are also obtunded and aspiration
becomes a definite risk. Because of the heterogeneity of
patients encountered in practice, it is not possible to accept
any single ‘risk’ factor for significant damage.
The anatomy of the relevant structures and the potential

passage of gastric contents is shown in the illustration. (Fig 2)
Depending on the patient, with interplay of factors discussed,

aspiration is a risk before induction, during induction, during
mask ventilation, before laryngoscopy, during laryngoscopy,
during extubation, or after tracheal extubation.
Prevention of regurgitation and aspiration
Measures required include
• Strict adherence to nil per oral instructions before

surgery
• Avoidance of excessive airway pressures during mask Fig 2: The anatomical relationship between gastro-
ventilation oesophageal area and upper airways and lungs causing risk
• Proper airway maintenance during mask ventilation of regurgitation/vomiting under anaesthesia (Soreide E et al)
• Judicious use of pharmacologic agents as
premedication
NGT may be suctioned and removed before intubation as
During anaesthesia, following proper technique of rapid presence of NGT can keep the upper and lower esophageal
sequence induction (RSI) in full stomach patients and sphincters open or lead to reduced tone. The NGT in situ can
nasogastric tube (NGT) care will reduce the risk of aspiration. also result in ineffective esophageal compression by cricoid

pressure during RSI. NGT can be repeatedly suctioned with a fast-acting relaxant, so that the time between loss of
so that the gastric volume and the pressure are reduced. consciousness and the securing of the airway with the cuffed
Proximal repositioning of NGT (in esophagus) can reduce endotracheal tube is kept minimal. The steps are:
esophageal pressure, decreasing the risk of esophageal
rupture during induction. • Adequate preoxygenation for ‘the patient’
• Starting of application of cricoid pressure
Pharmacologic agents may be administered to decrease
• Injection of a fixed induction dose of intravenous
gastric volume (either by decreasing production or by
anaesthetic agent (thiopentone), immediately followed
increasing emptying), increase gastric pH, or increase LES
by inj. succinylcholine 1-1.5 mg/kg and tracheal
tone.
intubation with a cuffed endotracheal tube without
Metoclopramide is a prokinetic benzamide, which promotes attempting positive pressure ventilation, WITH
gastric emptying by gastric peristalsis and relaxation at continued maintenance of cricoid pressure. The
the pylorus. It also increases LES tone. It is avoided in endotracheal tube position is confirmed, cuff inflated,
cases of bowel obstruction and in patients with Parkinson’s connected to anaesthetic circuit and then the cricoid
disease or depression being a dopaminergic antagonist. It pressure is released. Hence, RSII can also be an
may also be associated with extrapyramidal side-effects. option in conditions where there is predicted difficulty
Narcotics, by delaying gastric emptying, inhibit the action in mask ventilation (not intubation) such as edentulous
of metoclopramide. It is administered at a dose of 10 mg patients, bearded patients, etc.
intravenously 15-30 mins before induction of anaesthesia
Modifications of RSII
(oral 10 mg 2 h before; in children- 0.15 mg/ kg IV and 0.25
mg/kg oral, 15-30 mins and 2 hrs before induction). 1) When succinyl choline is contraindicated, non-
depolarizers can be used, such as rocuronium at 1.0
H2 receptor blockers (ranitidine, at 50 mg IV 15-30 mins
to 1.2 mg/kg or vecuronium at 0.3 mg/kg, doses which
before induction or 150-300 mg oral at least 2 h before
allow intubating conditions in less than 90 seconds.
induction, with or without 150 mg oral previous night)
The longer duration of action of these agents is a
decrease gastric acid secretions, thus increasing gastric pH.
disadvantage but the advent of sugammadex has
Antacids can neutralize the acidic contents already present
neutralized this limitation.
in the stomach.
2) For induction agents, use of titrated doses rather
Non particulate antacids such as sodium citrate are better
than dose for loss of consciousness as end point is
as compared to particulate alkali antacids, because, if
advocated by some.
they are aspirated, they can lead to chemical pneumonitis.
Antacids are administered 15-30 minutes before induction 3) Apart from thiopentone, other IV induction agents such
of general anesthesia (non particulate- Sodium citrate 0.3 M as propofol, etomidate and ketamine have also been
concentration, pH 8.4, 30 ml). effectively used for RSII.
Proton pump inhibitors (PPIs) such as omeprazole, 4) Application of gentle positive pressure (inspiratory
pantoprazole, rabeprazole, and lansoprazole (one hour pressure <20 cm H2O) in conjunction with cricoid
before induction) block H+-K+-adenosine triphosphatase pressure has been found to be useful in situations
activity at the secretory surface of the parietal cells in the where there is risk for rapid development of hypoxemia
stomach. They reduce the volume and increase the pH of (obese, pregnant, pediatric and critically ill patients);
gastric secretions. Glycopyrrolate, an anticholinergic, can in emergent situations during which preoxygenation
increase gastric pH by inhibiting vagally mediated gastric cannot be satisfactorily completed or when satisfactory
acid production. Atropine has not been found to be effective intubating conditions are not obtained fast enough
in this aspect. when non depolarizers are used.
Rapid sequence induction of Anaesthesia and intubation 5) Inhalational induction of anaesthesia, especially in
(RSII) of trachea (previously referred to as ‘crash induction’) pediatric patients: Sevoflurane can be used for this
is a common practice intended to prevent regurgitation and purpose because of favourable induction profile. It has
aspiration in at risk patients during anaesthesia. Main aim is to been used in both pediatric and in some adult patients
achieve rapid induction with a drug with fast and predictable and the advantage is the patient will be breathing
onset, and achieve rapid and optimal intubating conditions spontaneously and depth of anaesthesia can also

be modified. Sevoflurane can be administered in two Amount of force applied in Sellick’s manoeuvre: In the
ways- tidal volume induction (patients breathe normally starved supine patient, the maximum intragastric pressure is
through the facemask), and a vital capacity induction 25 mmHg. For this pressure, about 30 N force is suggested
(after exhalation to residual volume, inhalation of as effective to prevent regurgitation of gastric contents.
vital capacity breath from the facemask). The tidal Intragastric pressure beyond 40 mm Hg itself is associated
volume inductions are started with lower sevoflurane with regurgitation and can cause retching in an awake
concentrations and the vital capacity inductions are patient, increasing intra-esophageal pressure and resulting
started with higher concentrations (8%). Nitrous oxide in esophageal rupture, also prevented by 30 newtons (N) of
can hasten induction because of second gas effect force on the cricoid. Greater force (>44 N) causes cricoid
with both these techniques. occlusion, vocal cord closure, distorted laryngeal view and
difficult ventilation making intubation difficult. If ventilation
Sellick’s Manoeuvre is difficult, the upward pressure may be removed, retaining
This manoeuvre consists of applying posterior/rostral backward pressure.
pressure by the hand, on the cricoid cartilage so that the Cricoid occlusion may also occur at 20 N and 30 N but to a
upper esophagus is pressed against the cervical vertebrae lesser degree. One technique is to start with approximately
and thus prevent the regurgitation of gastric contents into 10N of force to the awake patient and once the patient loses
the oropharynx - downward pressure is exerted by the consciousness, the force can be increased to 30N until the
forefinger while the thumb and middle finger prevent lateral trachea is successfully intubated.
displacement of the cricoid ring. (Sellick’s Manoeuvre).
Being the only complete cartilaginous circular ring, cricoid It is also advised to use the drugs with minimal effect on the
is chosen to apply the pressure effectively. The results have lower esophageal tone in the perioperative period. (Table 2)
not been consistent and it is shown that cricoid pressure
Crico-tracheal injury, active vomiting, and unstable cervical
reduces LES tone and may cause the esophagus to be
spine are some contraindications to cricoid pressure.
displaced to the side rather than to be compressed, as shown
by MRI studies and also confirmed by ultrasound studies. Role of Supraglottic devices in preventing aspiration
It has even been argued that the position of the esophagus
is irrelevant because the effectiveness of cricoid pressure is The supraglottic airway devices such as 2nd generation LMAs
due to occlusion of the hypopharynx and not esophagus as have been tried in cases at risk of regurgitation and aspiration
per MRI studies. A trained assistant should apply the cricoid as they provide better seal and have additional channels for
pressure and it is claimed that faulty application of pressure is suctioning of the oesophageal and gastric contents. These
the main reason for esophagus being not being compressed could be useful electively in at risk cases and also used as
and the glottic view being distorted in some patients. rescue devices for securing airways or for intubation with
endotracheal tubes in cases of difficult mask ventilation and
/ or intubation in at risk cases. Cricoid pressure might affect
placement of the supraglottic devices.
References
1) Mendelson CL. The aspiration of stomach contents

into the lungs during obstetric anesthesia. Am J Obstet
Gynecol 1946; 52: 191–205
2) Roberts RB, Shirley MA. Reducing the risk of acid

aspiration during cesarean section. Anesth Analg
1974; 53: 859–68
3) Maltby JR. Fasting from midnight—the history behind

the dogma. Best Pract Res Clin Anaesthesiol 2006;
20: 363–78
4) Practice Guidelines for Preoperative Fasting and the

Fig 3: Compression in the backward and upward direction Use of Pharmacologic Agents to Reduce the Risk of
(Barash)

Pulmonary Aspiration: Application to Healthy Patients Incident Monitoring Study (AIMS). Anaesthesia 1999;
Undergoing Elective Procedures. An Updated Report by 54: 19–26
the American Society of Anesthesiologists Task Force
on Preoperative Fasting and the Use of Pharmacologic 7) Soreide E, Eriksson L I, Hirlekar G, Eriksson H,
Agents to Reduce the Risk of Pulmonary Aspiration. Henneberg S W, Sandin R et al. Pre-operative fasting
Anesthesiology 2017;126(3);376-93 guidelines: an update. Acta Anaesthesiol Scand 2005;
49: 1041-1047
5) Basic Physiology for Anaesthetists. David Chambers,
Christopher Huang, Gareth Matthews. Eds.2015. 8) Clinical Anesthesia. Ed.Barash et al., 8th Ed.2017,
Cambridge University Press. First Edition. pp279-83 Wolters Kluwer
6) Kluger MT, Short TG. Aspiration during anaesthesia: 9) Miller’s Anesthesia. Ed. Ronald D Miller et al., 8th Ed.
a review of 133 cases from the Australian Anaesthetic 2015, Elsevier

MCQ
1. The lower oesophageal sphincter tone is decreased 4. The recommended force during application of cricoid
following administration of pressure is
A. Opioids A. 10N
B. Metoclopramide B. 20N
C. Succinyl choline C. 30N
D. Sellick’s manoeuvre D. 40N
2. The gastric emptying time is unaltered in 5. Cricoid pressure is contraindicated in
A. Pregnancy A. Morbid obesity

B. Trauma B. Cervical spine injury
C. Ingestion of alcohol C. Unanticipated difficult airway
D. Laboring parturient D. Optimal placement of SGA device
3. The gastric emptying of liquids is determined by
A. Viscosity
B. Osmolality
C. Calorie content
D. All of the above
5.B 4.C 3.D 2.A 1.D
ANSWERS:

36 ANAPHYLAXIS : RECOGNITION AND MANAGEMENT
Controller of Examinations, Bhimeswar MV

DR.NTR University of Health Sciences,
Vijayawada
Key points
Ø The most common causes of anaphylaxis include insect bites, stings, food, medications and latex exposure
Ø Drugs that commonly cause anaphylaxis includes Beta-lactam antibiotics, Aspirin and NSAID’s
Ø The inflammatory mediators that are released during anaphylaxis increase the contraction of bronchial smooth
muscle, trigger vasodilatation, exudation of fluid from blood vessels and cardiac muscle depression
Ø The drug of choice for managing anaphylactic shock is Epinephrine
Introduction and stridor is due to upper airway obstruction secondary to

swelling. Hoarseness, pain on swallowing or cough may
Anaphylaxis is a serious allergic reaction that is rapid in also be present.
onset and may cause death. It occurs most often in young
people and females. At least 0.05%-2% of the population Cardiovascular
experience anaphylaxis at some point in life world wide.
The rates of Anaphylaxis is increasing with 20 per 100000 Bradycardia and Hypotension are associated with
per year in 1980’s to 50 per 100000 in 1990’s. The anaphylaxis. Patients with underlying coronary disease are
increase is due to food induced Anaphylaxis. Death due to at greater risk of cardiac effects of anaphylaxis. Coronary
anaphylaxis is estimated to be 0.3 to 0.7 per million. The Artery spasm, which is related to the presence of histamine
mortality rates have decreased between 1970’s to 2000’s. releasing cells in the heart, may occur with subsequent
The most common causes include insect bites, stings, food, myocardial infarction, dysrhythmia or cardiac arrest.
medications and latex exposure. Central Nervous System
Signs and Symptoms Hypotension leads to light headedness, confusion, anxiety,
The onset of anaphylaxis is between 5 to 30 minutes headache and loss of consciousness.
and the most common areas affected are skin (80-90%), Gastro Intestinal Tract
respiratory (70%), GIT (30-45%), CNS (10 -15%) and Heart
and vasculature (10-45%). Usually two or more will be These symptoms include crampy abdominal pain, diarrhoea
involved. It causes itchy rash, throat or tongue swelling, and vomiting.
shortness of breath, vomiting, light headedness and low
Causes of Anaphylaxis
blood pressure.
Anaphylaxis occur in response to any foreign substance.
Skin
The most common triggers includes, venom from insect
Generalized hives, itchiness, flushing or swelling of tongue bites and stings, food and medications. People with atopic
or throat (20%). Other features include runny nose and diseases such as asthma, eczema or allergic rhinitis are at
swelling of conjunctiva. Skin may be cyanotic. high risk of anaphylaxis.
Respiratory Food
Respiratory symptoms include shortness of breath, wheeze Many foods trigger anaphylaxis. The triggering foods vary
or stridor. The wheeze is due to spasm of bronchial muscles; in the world. In the west, ingestion or exposure to peanuts,

Anaphylaxis : Recognition and Management 352 Bhimeswar MV
wheat, nuts, shell fish, milk and eggs are the cause of Management
anaphylaxis. In the middle east, sesame is the common
cause of anaphylaxis and rice and chickpeas are the Anaphylaxis is a medical emergency which requires
common causes in Asia. Usually children can outgrow their resuscitation measures such as Airway management,
allergies. supplemental oxygen, IV fluids and monitoring.
Medication The drug of choice is Epinephrine.
Any medicine is a potential trigger. The most common are Adjuncts drugs like antihistamines and steroids are also
Beta-lactam Antibiotics (pencillin), Aspirin and NSAID’s. used.
Other common causes include chemotherapy drugs,
vaccines, protamine and herbal preparations. The patients are observed in the ICU for 24 hrs.
Some medications like vancomycin, morphine, X-ray Epinephrine

contrast directly trigger mast cell degranulation.
Epinephrine is the primary treatment for anaphylaxis. It is
Venom given intra muscularly once the diagnosis is suspected. It
may be repeated every 5-15 minutes if required. It causes
Venom from insects causes anaphylaxis in susceptible tremors, anxiety headache and palpitation.
individuals.
In patients on Beta Blockers, epinephrine may not be
Pathophysiology
effective. In such patients, IV Glucagon may be administered.
Anaphylaxis is a severe allergic reaction of rapid onset,
Epinephrine can also be given IV by using dilute epinephrine
affecting many body systems. It is due to the release of
solution. It is associated with dysrhythmia and myocardial
inflammatory mediators and cytokines from mast cells and
basophils typically due to immunological reactions. infarction.
Immunoglobulin E (IgE) binds to the antigen (foreign material Epinephrine auto injectors are also available.
that provokes the allergic reaction). The antigen bound IgE
Adjuncts
activates FceRI on mast cells and basophils. This leads to
release of inflammatory mediators like histamine. These 1. Antihistamine (H1 & H2) are commonly used but
mediators exert their effect by increasing the contraction of not supported by evidence.
bronchial smooth muscle, trigger vasodilatation, exudation
of fluid from blood vessels and cardiac muscle depression. 2. Corticosteroids: are also used as adjuncts.
Diagnosis 3. Nebulized Salbutamol: this is effective for

bronchospasm that does not resolve with
The diagnosis is based on the signs and symptoms. There
epinephrine.
is a high likelihood of anaphylaxis if any one of the following
three occurs within minutes or hours of exposure to allergen: 4. Methylene Blue is used due to its presumed effect
of relaxing smooth muscle.
1. Involvement of skin or mucosal tissue along with
respiratory difficulty or low blood pressure. Prevention
2. Two or more of the following symptoms after 1. Avoidance of the trigger of anaphylaxis is
exposure to allergen
recommended
a) Involvement of skin or mucosa
2. Desensitization by immunotherapy.
b) Respiratory difficulties
c) Hypotension Prognosis
d) GIT symptoms Usually the prognosis is good in patients where the causes
3. Hypotension after exposure to allergen are known and prompt treatment is available. Death is
usually due to respiratory (asphyxia) and cardiovascular
Asthma Syncope and Panic attacks may mimic (shock) causes.
anaphylaxis

References 3. Sampson hA, Munoz-Furlong A, Campbell RL, et
al (February 2006). The Journal of Allergy and
1. Lee, JK; Vadas, P (July 201). “Anaphylaxis : Clinical Immunology. 117 (2): 391-7.
mechanisms and management”. Clinical and
Experimental Allergy. 41 (7):923-38. 4. Simons, et al (February, 2011). The World Allergy
Organization Journal 4 (2): 13-37.
2. Khan, BQ; Kemp, SF (August 2011).
“Pathophysiology of anaphylaxis”. Current opinion
in Allergy and Clinical Immunology. 11 (4): 319-25.

MCQ
1. The most common clinical manifestation of 4. The most common cause of anaphylaxis under
anaphylaxis is anesthesia is
a) hypotension a) Chlorhexidine
b) Bronchospasm b) Co-amoxiclav
c) Oxygen desaturation c) Rocuronium
d) tachycardia d) Latex
5. The usual type of cardiac arrest with anaphylaxis is

2. What is the immediate management of anaphylaxis
once it is diagnosed under GA? a) Ventricular tachycardia
b) Ventricular fibrillation
a) 5 mg /kg Aminophylline bolus c) Pulseless electrical activity
b) 1 mg adrenaline bolus d) Atrial flutter
c) Chlorpheniramine 10 mg slow IV
d) Hydrocortisone 200 mg iv
3. What should be the immediate investigation done once

anaphylaxis is diagnosed?
a) Mast cell tryptase immediately after initial treatment

b) Mast cell tryptase 1 hr after exposure
c) Mast cell tryptase 6 hrs after exposure
d) All of the above
5.C 4.B 3.D 2.C 1.A
ANSWERS:

37 HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC)
Associate Professor Jyotsna Agarwal

Hamdard Institute of Medical Sciences and Research
New Delhi
Key points
Ø HIPEC is a highly concentrated, heated chemotherapy delivered directly in the abdomen after cytoreductive
surgery (CRS)
Ø Preoperative hypoalbuminemia is an independent predictor of major postoperative complications and has

prognostic importance.
Ø Magnesium levels may fall during HIPEC due to dilution secondary to fluid infusion and following administration
of platinumbased perfusate
Ø Delta temperature is a significant predictor of intensive care unit (ICU) stay for more than 5 days
Ø Colloids such as Hydroxyethyl Starch are avoided as they have a negative impact on the renal function and can
increase perioperative bleeding
Ø Large-volume fluid resuscitation should be avoided, and if patients are not fluid responsive, vasopressors should
be initiated early
Ø There is a potential hazard of exposure to hazardous chemotherapeutic agents in all procedures and due
precautions must be taken
Hyperthermic Intraperitoneal Chemotherapy (HIPEC) (20–1000 times greater than plasma levels) with minimal
is a technique used to treat primary peritoneal surface effects on normal tissue. This technique involves regional
malignancies and abdominal or pelvic masses with peritoneal administration of cytotoxic drugs with direct toxic effects of
metastases. Traditionally these cancers are considered hyperthermia. Commonly used drugs are mitomycinC and
to have poor prognosis, incurable with only palliative care platinum based drugs such as cisplatin, carboplatin and
possible. oxaliplatin. These have synergistic effect with heat. Other
chemotherapeutic agents such as doxorubicin, paclitaxel,
Sugarbaker, in 1988, first described the surgical removal of
5-FU and docetaxel and irinotecan are also used.
visible tumour (debulking) along with locoregional heated
chemotherapeutic drugs. It was associated with improved Bidirectional intraoperative chemotherapy involves
quality of life and median 5-year survival. concomitant intraoperative intravenous and intraperitoneal
HIPEC is a highly concentrated, heated chemotherapy chemotherapy. It provides a bidirectional diffusion gradient
delivered directly in the abdomen after cytoreductive through the cancer cells.
surgery (CRS). Chemotherapy is infused at 41-430C into
The ideal carrier solution should improve exposure of the
the peritoneal cavity by a special roller pump along with
peritoneal surface, have slow clearance from the peritoneum,
a carrier solution. Addition of HIPEC causes unique and
maintain high intraperitoneal volume and not have any
significant perioperative implications over and above those
adverse effects on the peritoneal membranes. 1.5% dextrose
of the planned extensive CRS.
isotonic peritoneal dialysis solutions are most commonly
The rationale of HIPEC is to maximize the exposure of local used. Severe hyperglycaemia and hyponatremia can be seen
tissues to high concentrations of chemotherapeutic agents with 5% dextrose based water solutions.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) 356 Jyotsna Agarwal
The procedure involves 2 stages: intraoperative events and chemotherapeutic drugs used for
HIPEC. This procedure is associated with morbidity rates
1. Exploratory laparotomy with Cytoreduction - which of 20% – 40% and mortality rates of 3%. The Peritoneal
includes exploratory laparotomy with removal of visible/ Carcinomatosis Index (PCI) is an independent predictor
macroscopic tumour. It may also involve organ removal. of both morbidity and survival. Higher PCI is a predictor of
2. Chemoperfusion - Abdominal cavity is rinsed with a poorer long term outcome. Appropriate selection of patients
heated chemotherapy solution at 41-430C intraperitoneal in order to achieve complete cytoreduction is the key to a
temperature for around 60-120 minutes. successful outcome. Patients for CRS- HIPEC should be
upto 70 years of age, amenable to medical optimization with
HIPEC can be of two types: no active cardiac conditions, peritoneal disease amenable
to complete or near complete resection and should not have
1. Closed abdominal method- This was the first technique
extra-abdominal disease.
described. The abdominal wall is sutured after laparotomy and
chemotherapy solution circulated inside peritoneum with inflow HIPEC and Anesthesia
and outflow catheters. The rise in intraabdominal pressure
and physiological changes are similar to pneumoperitoneum. Preoperative Considerations
2. Open abdominal method- The abdominal cavity is open CRS combined with HIPEC is an invasive abdominal surgical
and washed with chemotherapeutic solution. It leads to better procedure with additional intraoperative temperature changes
distribution of heat and cytotoxic solution due to manual and fluid shifts.
stirring of the abdominal contents. The anterior parietal wall Preoperative optimization of CRS HIPEC patients should be
has suboptimal exposure and there is a risk of spillage of individualized. Depends on age, BMI, comorbid diseases,
cytotoxic drugs. Open method involves heat loss and requires functional status, disease burden, malnutrition (low albumin)
an increase in the temperature of the perfusion fluid leading and preoperative anemia.
to risk of bowel scald injuries.
Preoperative investigations include all routine investigations
Physiologic changes during HIPEC required in major surgery with special focus on cardiopulmonary
CRS-HIPEC lead to a hypermetabolic state with peripheral reserve, coagulation, renal function tests and nutrition.
vasodilation. • Full blood count
Cardiovascular changes • Coagulation studies
• Serum Electrolytes
• Decrease in stroke volume
• Urea and creatinine levels
• Increase in heart rate, central venous pressure
• Nutritional status of the patient
• No significant blood pressure changes
• Preoperative albumin level
Respiratory changes • Glomerular filtration rate- help to identify patients at risk
• Increase in peak airway pressures of an acute kidney injury associated with the HIPEC
• Decrease in PaO2/FiO2 ratio • 12 lead electrocardiogram
• Increase in end-tidal CO2 levels Assessment of the functional status in these patients is vital.
Baseline two dimensional echocardiogram should be done
Renal changes
in all patients. Dynamic cardiac testing is required in patients
• Decreased perfusion to kidneys with limited cardiac reserve and where functional capacity is
• Metabolic acidosis with increased lactate difficult to assess.
Coagulation changes Preoperative hypoalbuminaemia is an independent predictor

of major postoperative complications and has prognostic
• Decrease in platelet count, increase in PT/ INR importance.
CRS-HIPEC is a complex surgery and perioperative Perioperative nutritional rehabilitation is a must for major
management depends on many factors such as patient’s cancer surgeries. Enteral nutrition preoperatively is the
preoperative health status, disease load, surgical factors, method of choice for 1-2 weeks. If not possible, preoperative

sip feed should be tried. Parenteral nutrition should be given • Ionised calcium- due to massive/significant blood loss
if enteral nutrition is not possible. and transfusion of blood and blood products
• Serum Albumin-due to loss of ascitic fluid
Preoperative incentive spirometry and respiratory muscle
training is essential for postoperative recovery, since Temperature management
this procedure is associated with increased incidence of
postoperative pulmonary complications. Maintenance of normothermia is an important anesthetic
goal.
Intraoperative management
Delta temperature = Highest temperatures - least temperature
It is known that anaesthesia and analgesia affect long term (during CRS HIPEC) is a significant predictor of intensive care
cancer outcomes. Volatile anaesthetic agents and opioids unit (ICU) stay for more than 5 days.
enhance the malignant potential of tumours, promote cell
invasion and proliferation, cause immunosuppression and During laparotomy and CRS, patients can develop
promote angiogenesis. hypothermia. Measures to prevent heat loss such as warmed
fluids, warming blankets and forced external air warmers
Propofol based total intravenous anaesthesia (TIVA) have are useful.
shown to have improved recurrence free and overall survival.
Hyperthermia occurs during HIPEC phase. Maximum
Salient intraoperative considerations in CRS-HIPEC are temperature level occurs at 60 minutes of HIPEC.
• Temperature control Hyperthermia during the HIPEC phase lead to
• Fluid management and Urine output
• Increase in the metabolic rate
• Hemodynamic stabilization
• Increase in oxygen demand, heart rate, ETCO2
• Metabolic & electrolytes balance
• Lactatemia, metabolic acidosis
• Coagulation abnormalities
• Coagulopathies
• Glycemic control
• Renal& liver dysfunction
• Pain management
• Neuropathies, seizures
Preoperative assessment should involve anticipation and
optimization of these intraoperative considerations. These changes of hyperthermia are REVERSIBLE on
temperature control.
Intraoperative Monitoring
Hyperthermia can be effectively prevented during HIPEC
• Electrocardiogram with simple measures which should be initiated before
• Noninvasive blood pressure starting HIPEC. Reduce body temperature by 1-1.5 degrees
before heated perfusate is circulated. Following measures
• Pulse oximetry
are helpful
• End tidal CO2 monitoring
• Core body temperature monitoring • Forced external air warmers at ambient temperature
• Invasive blood pressure monitoring • Cold intravenous fluids <60C
• Central venous pressure monitoring • Cooling mattress
• Cardiac output monitoring, required in high volume • Ice packs placed in the axilla, head and neck
diseases (PCI >15) • Reduction in temperature of perfusate can help as a
• Goal directed therapy (GDT) last resort.
• Arterial blood gas- periodically throughout the surgery Intraoperative fluids
to assess gas exchange, electrolyte and lactate levels
• When 5% dextrose is used as a perfusate- serum Balanced fluids are preferred. Non-lactate containing
sodium, blood glucose monitoring balanced salt solutions are preferred as increase in lactate
levels can occur in hyperthermia. Albumin is indicated in
• Magnesium levels- due to dilution secondary to fluid
preexisting hypoalbuminemia, as intraoperatively protein
infusion and following administration of platinum based
is lost in ascitic fluid and secondary to surgical dissection.
perfusate

Colloids such as HES (130/0.4) are avoided as they have is not preferred by some due to risk of development of
a negative impact on the renal function and can increase coagulopathies.
perioperative bleeding. Fluid overload is associated with
increased morbidity and dynamic hemodynamic monitoring Primary opioid based analgesia can have increased
is preferred. Early start of vasopressors is advocated to avoid respiratory complications and postoperative ventilatory
hypervolemia. support requirement. Other regional analgesia techniques
which can be used are paravertebral or subcostal transverses
Fluid replacement of around 1.6–2 L of crystalloids (balanced abdominis plane blockade.
salt solutions without lactate) is typically required per hour.
Urine output of at least 500 mL/h is desirable especially Postoperative Considerations
during Cisplatin HIPEC.
Most of the patients require ICU / HDU care in the immediate
Diuretics should be used only if urine output is inadequate postoperative period. ICU outcome depends on early
despite adequate intravascular fluid status. Furosemide, extubation, initiation of parenteral nutrition, maintenance of
mannitol, dopamine are not recommended for renal protective fluid status and hemodynamics. Nutrition promotes wound
effect. healing and early enteral feeding is recommended.
Intraoperative Urine output Large-volume fluid resuscitation should be avoided, if patients

are not fluid responsive, vasopressors should be initiated
Intraoperative measurement of urine output is used as a early. Postoperative period requires monitoring of all major
surrogate marker of renal perfusion. During HIPEC phase, organs systems, maintenance of electrolytes and acid base
maintaining optimal urine output is vital. Recommended
balance, management of coagulopathy and blood sugar
targets for urine output are up to 0.5 mL/kg/h during CRS,
control. Monitoring of lactate trends is more informative than
2–4 mL/kg/h during the HIPEC phase and 1–2 mL/kg/h
single constant value.
post HIPEC phase. Incidence of Acute Kidney Injury
(AKI) is between 21.3% to 48%. Factors associated with Coagulopathy peaks at 24 hours and usually resolves by
development of AKI are higher age, higher BMI, use of 36 days. Hyperglycemia can be present due to physiologic
preoperative pregabalin, major blood loss, hypertension, low stress and hypercatabolic state. Maintenance of adequate
intraoperative urine output and use of angiotensin II receptor analgesia is essential for rapid recovery.
antagonist.
Transient severe hypophosphatemia may be present in
Arterial Blood Gas (ABG) Optimisation first 2–3 postoperative days due to renal tubulopathy.
Transaminitis may be present with 2 to 3 fold elevation in
Serial ABGs are done before starting HIPEC and every 15
liver function tests during first 4 postoperative days. Diarrhoea
minutes during HIPEC. The pH, electrolytes, blood sugar and
lactate are monitored and continuously optimized. can occur due to digestive hypersecretion. Stress ulcer
prophylaxis and venous thromboembolism (VTE) prophylaxis
Coagulation Monitoring are required similar to any major onco-surgery.
Preoperative & perioperative periodic monitoring of DVT prophylaxis is required during the entire perioperative
coagulation parameters is done by Prothrombin time (PT), period. Dual VTE prophylaxis (chemoprophylaxis +
INR, aPTT and point of care TEG, ROTEM and activated mechanical prophylaxis) is recommended. The risk of
coagulation time (ACT). VTE can extend upto 30 postoperative days, so extended
prophylaxis (> 28 days) should be considered.
Coagulopathy depends on the duration of surgery, extent
of resection, blood loss, degree of haemodilution and Pulmonary rehabilitation with incentive spirometry, deep
hypothermia. breathing exercises, continuous positive airway pressure
and high flow nasal cannula is required for recruitment of
Pain Management
atelectatic areas and prevention of respiratory complications.
Analgesia coverage is required from T4 to lumbosacral
Systemic chemotherapeutic toxicity of HIPEC include allergic
segments. Inadequate analgesia can lead to chronic pain,
chronic fatigue and poor quality of life after surgery. reactions, cardiotoxicity, neurotoxicity, nephrotoxicity,
myelotoxicity, bowel scalds and perforation due to exposure
Intraoperative epidural analgesia can be used with local to high temperatures of infusion drug. Cisplatin can lead to
anaesthetic agents with or without opioids. Epidural analgesia autonomic dysfunction leading to hypotension can be seen

with cisplatin. Hyponatremia, hypocalcemia , hypokalemia Exposure of OR personnel to chemotherapeutic agents can
and renal magnesium wasting leading to QT prolongation be prevented during PIPEC by minimising OR personnels
can be seen with drugs such as Cisplatin and Oxaliplatin. during PIPEC, laminar flow in the OR, wearing N95 mask,
remote controlled Injection and nebulizer from outside the
ASA class higher > 3 and surgical time more than 10 hours OR and air tight capnoperitoneum.
are significant risk factors for surgical complications such as
anastomotic leaks, sepsis and pulmonary embolism. Suggested Reads
Variants similar to HIPEC 1. Solanki SL, Mukherjee S, Agarwal V, Thota RS,

Balakrishnan K, Shah SB, et al. Society of Onco-
HITHOC - CRS along with intraoperative hyperthermic Anaesthesia and Perioperative Care consensus
intrathoracic chemotherapy guidelines for perioperative management of patients for
HITAC - Hyperthermic thoracoabdominal chemotherapy. cytoreductive surgery and hyperthermic intraperitoneal
Thoracoabdominal approach for cytoreduction (removal of chemotherapy (CRS-HIPEC). Indian J Anaesth
pleural metastasis) is followed by heated chemoperfusion. 2019;63:972-87.
PIPAC- Pressurised intraperitoneal aerosolised 2. Holt NF, Agarwal J. Cancer. In: Agarwal J, Parameswari
chemotherapy. Aerosol of chemotherapeutic drug is created A, editors. Stoelting’s Anesthesia and Co-existing
with the help of a nebulizer. Therapeutic capnoperitoneum is Disease. Third South Asia Edition. Elsevier India ; 2019.
created at temperature of 37 degree C. The drug vapors are p.601- 626.
exhausted into the operating room (OR) and are scavenged 3. ATOTW 379 — Anaesthesia for Cytoreductive Surgery
through a closed system. with Hyperthermic Intraperitoneal Chemotherapy
Hyperthermic intrathoracic or thoraco-abdominal (HIPEC) (15 May 2018).
chemotherapy are used for malignancies involving pleura. 4. Yap A etal. Global OncoAnesthesia Research
These pose additional challenges of one lung ventilation, Collaboration Group. Anesthetic technique and cancer
impaired cardiac output, and postoperative derangements outcomes. Can J Anaesth 2019;66:54661.
in pulmonary function tests.
5. Gupta N, Kumar V, Garg R, Bharti SJ, Mishra S,
Occupational hazard Bhatnagar S. Anesthetic implications in hyperthermic
There is a potential hazard of exposure to hazardous intraperitoneal chemotherapy. J Anaesthesiol Clin
chemotherapeutic agents in all procedures, it is especially Pharmacol 2019;35:3-11.
significant in PIPAC. Exposure to the OR personnel 6. Sugarbaker PH. Surgical management of peritoneal
during PIPAC can lead to hair loss, headache, irritation, carcinosis: Diagnosis, prevention and treatment.
hypersensitivity and congenital malformations. Langenbecks Arch Chir 1988;373:18996.

MCQ
1. Chemotherapy is infused at …………° C into the 4. …………….Are avoided as they have negative impact
peritoneal cavity by special roller Pump along with on renal function
carrier solution
a. Ringer lactate b. Hydroxyethyl starch
a. 44-45 °C b.41-43 °C c.43-45 °C c. Plasmalyte
2. Preoperative ………… is an independent predictor of 5. ____________ is a significant predictor of ICU stay for
major postoperative complication more than 5 days
a. Hyponatremia b. Hypoalbuminemia
c. Coagulopathy
3. Recommended targets for urine output during HIPEC

phase
a. 0.5 ml/kg/hr b.1.2ml/kg/hr c.2.4 ml/kg/hr
5.Delta temperature 4.B 3.C 2.B 1.B
ANSWERS:

38 PERIOPERATIVE HYPONATREMIA - CAUSES AND TREATMENT
Professor Nibedita Pani

SCB Medical College, Preetesh Parijat (PGT)
Cuttack, Odisha
Key points
Ø Hyponatremia has been demonstrated to be an independent risk factor for increased mortality in hospital inpatients.
Ø Preoperative hyponatremia is associated with an increased risk of perioperative major coronary events, surgical
site wound infections, pneumonia, and prolonged hospital stays.
Ø TURP, Liver transplantation and craniofacial surgery in children are three surgeries that carry an independent risk
factor for developing intraoperative hyponatremia
Ø Treatment is guided by the underlying cause, speed of onset and the presence of adverse neurological signs.
Ø Current guidelines suggests that ,correction of serum sodium should not exceed 4-8 mmol/l/day in patients with
chronic hyponatremia.
Ø Too rapid correction of hyponatremia may risk permanent severe neurological damage or death.
Introduction: Causes
The presence of hyponatremia has been demonstrated Preoperative causes

to be an independent risk factor for increased mortality in
hospital inpatients. Severe hyponatremia has long been Hyponatremia sometimes is an incidental finding during
recognised to be associated with adverse outcomes. preoperative assessment, with various underlying
It is also increasingly being recognised that, even mild mechanisms. These include:
hyponatremia can be associated with patient harm, with
o Drugs :- Commonly thiazide diuretics, vincristine
even relatively minor derangements having been shown
and cyclophosphamide. Others include SSRIs,
to be associated with increased falls and fractures.
sodium valproate and haloperidol.
Preoperative hyponatremia is associated with an increased
o CNS disorders: Infection, trauma, ischemia,
risk of perioperative major coronary events, surgical site
haemorrhage and psychosis
wound infections, pneumonia, and prolonged hospital stays.
o Malignancies:- Commonly of the lung, particularly
Classification small cell carcinoma. Other tumors include; head
and neck, duodenal and pancreatic cancers.
Hyponatremia is not a disease, but rather a pathophysiologic o Pulmonary disease: Pneumonia, asthma and acute
process indicating disturbed water homeostasis. Therefore, respiratory failure.
hyponatremia should be further classified in order to provide o Renal: Mineralocorticoid deficiency, Salt losing
directions for diagnosis and treatment. enteropathy, ketonuria, bicarbonaturia with Renal
Tubular Acidosis and metabolic alkalosis, osmotic
The classification shows that hyponatremia is a very diuresis, cerebral salt wasting disease, nephrotic
heterogeneous disorder. This has complicated clinical syndrome.
studies because, “the” patient with hyponatremia does not o Infective : Acquired immune deficiency syndrome
exist. Instead, the underlying disease that is complicated o Others: Vomiting, diarrhoea, pancreatitis, cardiac
by hyponatremia usually characterizes patients with failure, cirrhosis, glucocorticoid deficiency,
hyponatremia. hypothyroidism

Perioperative Hyponatremia - 362 Nibedita Pani
Causes and Treatment
Classification Criteria Clinical limitations

Moderate(125-129 mmol) vs Absolute SNa conc. Symptoms do not always correlate
severe (<125mmol) with degree of hyponatremia
Acute vs chronic Time of development (cut off Time of development not always
48hrs) known
Symptomatic vs Presence of symptoms Many symptoms nonspecific, chronic
asymptomatic hyponatremia may be symptomatic
Hypotonic , isotonic or Measured serum osmolality Ineffective osmoles (e.g. urea,
hypertonic ethanol) are also measured
Hypovolemic, euvolemic or Clinical assessment of Clinical assessment has low sensitivity
hypervolemic volume status and specificity
Intraoperative hyponatremia is < 260 mOsmol/kg .Aim to raise Na+ by no more than 10-
12 mmol/24 hours.
Intraoperative period is associated with an increased
incidence of significant change in the volume status, Liver transplantation
electrolyte concentrations and acid base status of a patient.
During surgery, frequent preload change occurs by
Common causes include clamping of inferior vena cava, and bleeding and metabolic
Blood loss, Vomiting ,Metabolic stress, Dilutional acidosis develops during anhepatic phase and reperfusion
hyponatremia, Mannitol use, Fluid depletion with hypotonic of liver graft. These factors cause altered serum sodium
replacement, use of other diuretics (thiazide), metabolic concentration.
acidosis.
Craniofacial surgery in children
Of special note are 3 surgeries which carry an independent
Surgical stress, SIADH, erroneous fluid replacement volume
risk factor for developing intraoperative hyponatremia and
have all been suggested as possible reasons for the high
its related complications:
incidence of hyponatremia in craniofacial surgeries.
TURP
Post operative causes
Fluid overload and iso-osmolar hyponatraemia during
TURP from large volumes of irrigation fluid being absorbed • Surgical stress response aggravated by periods of
through venous sinuses. hypotension and hypovolemia and physiological
sympathetic activity, leads to a SIADH like state.
Clinical features:
• Avid water retention with associated administration
Mild to moderate- Asympyomatic,restlessness, headache,
of free water from dextrose containing or other
and tachypnoea, or a burning sensation in the face and
hypotonic solutions, puts the patients at an
hands.
increased risk for hyponatremia.
Severe - Respiratory distress, hypoxia, pulmonary oedema
,nausea, vomiting, visual disturbance (e.g. blindness, fixed • The risk of neurological symptoms post
pupils), reflex bradycardia from fluid absorption, confusion, hyponatremia, is particularly higher in children and
convulsions, and coma. premenopausal women.
Treatment Diagnostic approach
Fluid overload: Frusemide 40mg IV. Signs and symptoms

Seizures: Benzodiazepines +/- other anti-epileptics; • The symptoms and signs associated with
consider magnesium (stabilises NMDA receptors) hyponatremia relate to both, the degree of
imbalance and the time course over which the
Hyponatremia: Hypertonic saline is only indicated for
imbalance has developed. Patients in whom acute
neurological manifestations if measured serum osmolality

severe hyponatremia has developed in under 48 Euvolaemic hyponatremia - Euvolaemic
hours present with alarming neurological findings. hyponatremia is the most common category
of hyponatremia seen in hospital inpatients.
• Headache, Confusion, Agitation, Vomiting, SIADH is the most common cause of euvolaemic
Lethargy, Convulsions, Coma, Cerebral herniation hyponatremia and it is associated with many
are some of the symptoms. different disorders. If SIADH is suspected, it can
be useful to measure urine osmolality, as a urine
• Rapidly evolving severe hyponatraemia, is a
osmolality >100 mOsm/kg in the presence of
different disease entity from slowly evolving
hyponatraemia reflects inappropriate antidiuresis.
hyponatremia. Slowly evolving hyponatraemia is
frequently asymptomatic. Hypervolaemic hyponatremia - This is a situation
characterised by a paradoxical increase in total
• Non-specific symptoms generally develop, when
body sodium, but a simultaneous and proportionally
serum sodium levels drop below 120 mmol/l. These
larger increase in total body water leading to a
symptoms include fatigue, lethargy, weakness and
dilutional hyponatremia. This reduction in water
confusion. Seizures and coma are uncommon.
excretion is secondary to either an excess of ADH
Investigations secretion or an element of renal impairment limiting
the maximal excretion of free water. Underlying
• A careful history with particular reference to the pathologies include nephrotic syndrome, congestive
patient’s recent medications and fluid intake should cardiac failure (CCF) and cirrhosis (although rarely
be taken. in the absence of ascites).
• A clinical examination, looking for indicators of Management of acute hyponatremia

volume status, e.g. oedema, jugular venous
pressure. • In acute hyponatremia with severe neurological
symptoms-100 ml bolus of 3% hypertonic saline
• ABG analysis –intraoperative hyponatremia (mostly over 10 minutes. This bolus may be repeated twice
in case of TURP) is best assessed by ABG analysis if severe neurological symptoms persist.
• Radiological investigations- where indicated might • Once symptoms have resolved ,increase in serum
include: CT of brain, thorax, abdomen and pelvis. sodium rates of up to 2 mmol/l/hour, may be
• Urine osmolality and electrolytes appropriate.
• Thyroid function tests • If hypertonic saline (3% sodium chloride) is used,

very close (1-2 hourly) monitoring of plasma sodium
• Random cortisol and/or short synacthen test, should be performed to minimise chance of osmotic
demyelination syndrome.
• Lipids, and serum electrophoresis are required.
Osmotic demyelination
Management - Management is based on the
volume status of the patient and the underlying • Presentation is usually delayed by 2-5 days
pathology. So we need to classify the condition as following correction.
per the volume status
• Diagnosis may be very difficult in sedated and
Hypovolaemic hyponatremia -In hypovolaemic ventilated patients.
hyponatremia total body water, and total body
sodium are both low, but there is disproportionate • Features are varied, including: bulbar problems,
loss of sodium compared with water. This is a paraplegia, quadriplegia and locked-in syndrome
result of the increased ADH secretion seen in
hypovolaemic states causing increased water • Changes are often irreversible but re-lowering of
reabsorption. serum sodium has anecdotal efficacy in the event
of overly rapid correction.

Treatment algorithm -Hyponatremia evaluation

Treatment algorithm -Hyponatremia evaluation
Volume status assessment
TABLE 1. Differential diagnosis and treatment

TABLE 1. Differential diagnosis and treatment
CONDITION DIAGNOSIS TREATMENT

PSEUDOHYPONATREMIA
Hyperglycemia (e.g., in Elevated glucose levels (> 400 mg per dL [22.2 Insulin, intravenous fluids, isotonic
diabetic ketoacidosis) mmol per L]), elevated anion gap saline
HYPOVOLEMIC HYPONATREMIA
Cerebral salt wasting Diagnosis of exclusion (e.g., head injuries, Isotonic or hypertonic saline
intracranial hemorrhage); urinary sodium > 20
mEq per L
Diuretic use Clinical; urinary sodium > 20 mEq per L Stop diuretic therapy
Gastrointestinal Clinical; urinary sodium < 20 mEq per L Intravenous fluids
loss (e.g., diarrhea,
vomiting)
Osmotic diuresis Elevated glucose level, mannitol use Correct glucose level, stop
mannitol use
Renal tubular acidosis Urinary osmolar gap, increased urinary pH, Correct acidosis, sodium
urinary sodium > 25 mEq per L, fractional bicarbonate
excretion of bicarbonate > 15% to 20%,
hyperchloremic acidosis, decreased serum
bicarbonate level, potassium abnormalities
(type dependent)
Salt-wasting Urinary sodium > 20 mEq per L Correct underlying cause
nephropathies
Third spacing (e.g., Clinical; computed tomography Intravenous fluids, relieve

bowel obstruction, obstruction
burns)
EUVOLEMIC HYPONATREMIA
Hypothyroidism Elevated thyroid-stimulating hormone level, Thyroid replacement therapy
low free thyroxine level
Low solute intake Clinical Increase sodium intake
Nephrogenic SIADH Same as SIADH, with low vasopressin levels Fluid restriction, loop diuretics
Psychogenic polydipsia History of schizophrenia with excessive water Psychiatric therapy
intake
SIADH Decreased osmolality, urinary osmolality > Fluid restriction, consider vaptans
100 mOsm per kg, euvolemia, urinary sodium
> 20 mEq per L, absence of thyroid disorders
or hypocortisolism, normal renal function, no
diuretic use

SIADH secondary SIADH with use of causative agent Stop causative medication
to medication use
(e.g., barbiturates,
carbamazepine
[Tegretol],
chlorpropamide,
diuretics, opioids,
selective serotonin
reuptake inhibitors,
tolbutamide,
vincristine)
Water intoxication Clinical; excessive water intake Diuresis
HYPERVOLEMIC HYPONATREMIA
Heart failure Clinical (e.g., jugular venous distention, Diuretics, angiotensin-converting
edema), elevated B-type natriuretic peptide enzyme inhibitors, beta blockers
level, echocardiography, urinary sodium < 20
mEq per L
Hepatic failure/cirrhosis Elevated liver function tests, ascites, elevated Furosemide (Lasix), spironolactone
ammonia level, biopsy, urinary sodium < 20 (Aldactone), transplant
mEq per L
Nephrotic syndrome Urinary protein, urinary sodium < 20 mEq per Treat underlying cause
L
Renal failure (acute or Blood urea nitrogen–to-creatinine ratio, Correct underlying disease with
chronic) glomerular filtration rate, proteinuria, urinary angiotensin-converting enzyme
sodium > 20 mEq per L inhibitors or ARBs
• Where indicated, MRI is the imaging modality of Hypovolaemic hyponatremia

choice.
• In hypovolaemic hyponatremia, the aim is to correct
Management of chronic hyponatremia the volume deficit, as the relative water excess will
correct itself via a water diuresis once circulating
• The desired increase in serum sodium in chronic volume is restored.
hyponatremia should be 4-8 mmol/l/day, for those • Fluids such as 0.9% should be administered until
at low risk of osmotic demyelination syndrome. blood pressure is restored and the patient has
• In patient groups where the risk of osmotic clinical euvolemia.
demyelination syndrome is high, it has been • Hypovolaemic hyponatremia is almost always
suggested that an even lower goal of 4-6 mmol/l/ an example of chronic hyponatremia, so slow
day be targeted. correction should be employed.
• For patients with severe symptoms, the entire Euvolaemic hyponatremia

6mmol/l can be achieved during the first 6 hours
• Management is dictated by the underlying cause,
of therapy, with subsequent treatment delayed until
the chronicity or acuteness of the imbalance and
the next day.
the presence or absence of neurological symptoms.

Fig2.Management of severe symptomatic hyponatremia
• Water restriction of 1–1.5 l/day may be used. CONCLUSION
• Drugs that may have caused SIADH should be Hyponatremia is a condition associated with significant
discontinued and any underlying causes morbidity and mortality. Treatment is guided by the underlying
cause, speed of onset and the presence of adverse
Hypervolemic hyponatremia neurological signs. In the absence of severe neurological
• Fluid restriction is the mainstay of treatment. signs, current guidelines suggests that correction of serum
sodium should not exceed 4-8 mmol/l/day in patients with
• Strict restriction is often necessary to achieve a chronic hyponatremia. Lower rates of correction may be
negative solute-free water balance. indicated in patients with chronic hyponatremia who have
additional risk factors for osmotic demyelination. More
• Typical initial fluid restriction for a normal sized
rapid correction should only be targeted in cases where
adult should be around 1– 1.5 litres per day.
there is certainty that, the hyponatremia is acute or if the
• Loop diuretics are sometimes used to remove hyponatremia is causing severe neurological symptoms.
excess fluid with urine usually hypotonic to plasma. Too rapid correction of hyponatremia may risk permanent
severe neurological damage or death.

References : Hyponatremia and Perioperative Complications;

Division of General Internal Medicine and Primary Care,
1. Fluid and electrolyte disorders ; Miller’s textbook of Brighamand Women’sHospital ,Brigham Circle
anaesthesia ,9th edition
4.Hawkins RC. Age and gender as risk factors for
2. Ewout J. Hoorn, Robert Zietse; diagnosis and treatment hyponatremia and hypernatremia. Clin Chim Acta.
of hyponatremia:compilation of guidelines ; J AM Soc 2003;337(1-2):169-172.
Nephrol 28:1340-1349,2017
5. Crestanello JA, et al. Preoperative hyponatremia
3. Alexander A. Leung, MD; Finlay A. McAlister, MD, MSc; predicts outcomes after cardiac surgery. J Surg Res.
Selwyn O. Rogers Jr, MD, MPH; Valeria Pazo, MD; Adam 2013;181(1):60-66.
Wright, PhD; David W. Bates, MD, MSc; Preoperative

MCQ
1) Moderate hyponatremia range is ————

4) Management of acute hyponatremia with severe
a) 125-129mmol neurological symptoms
b) 120-125mmol
c) 129-135mmol a) 3% hypertonic saline over 10 minutes
d) <125mmol b) 3% hypertonic saline over 15 minutes
c) 3% hypertonic saline over 20 minutes
2) Turp syndrome mild- moderate will not commonly d) 3 % hypertonic saline over 25 minutes
include
5) Desired increase of sodium in chronic hyponatremia is
a) Hypoxia
b) Restlessness a) 3-5 mmol/l/ day
c) Headache b) 2-4 mmol/l/ day
d) Tachypnoea c) 4-6 mmol/l/day
d) 4-8 mmol/l/day
3) Symptoms and signs of associated with hyponatremia
relate to
a) Age of patient
b) Comorbids
c) Type of surgery
d) Degree of imbalance and time course
5.D 4.A 3.D 2.A 1.A
ANSWERS:

39 VENTILATION STRATEGIES DURING RIGID BRONCHOSCOPY
Professor, Neerja Bhardwaj

PGIMER,
Chandigarh.
Key points
Ø Anesthesia for rigid bronchoscopy is challenging since both anaesthetist and the endoscopist share the common
working space – airway.
Ø Rigid bronchoscopy has several advantages over flexible bronchoscopy such as better control of the airway and
ventilation,and allows simultaneous use of instruments.
Ø Patients may be of ASA III-IV physical status so appropriate history and pre-operative tests should be done.
Ø Patients who are already dyspnoeic, haemodynamically unstable or hypercarbic at rest, have increased risk of
intra and post-operative complications.
Ø When a foreign body is suspected, the pre-operative assessment should determine the location of the aspirated
foreign body
Ø Organic materials can absorb fluid and swell, oils from nuts cause localised inflammation and sharp objects can
pierce the airway.
Ø The goals to be kept in mind is to: maintain adequate depth of anesthesia, stable hemodynamics, allow rapid
recovery of reflexes and be simple to use.
Ø Some of the ventilation strategies adopted during rigid bronchoscopy are: Apneic oxygenation, Spontaneous
assisted ventilation, Controlled ventilation, Manual jet ventilation or High frequency jet ventilation (HFJV)
Ø Monitoring Tidal volume in jet ventilation is difficult, as the system is open and ambient air entrainment is
unpredictable.
Introduction Equipment
Rigid bronchoscopy allows diagnostic and therapeutic A detailed understanding of the equipment required for
procedures to be performed in the tracheobronchial performance of rigid bronchoscopy is essential and includes
tree. Providing anaesthesia for performance of rigid the following parts:
bronchoscopy is challenging and requires technical Rigid bronchoscope
expertise since both anaesthetist and the endoscopist share
the common working space – airway. Rigid bronchoscopy • It is a stainless steel, straight and hollow cylindrical
is usually done for the diagnosis and treatment of intra tube available in various sizes.
and/or extraluminal obstruction in the airway of adults and • The external diameter varies from 9mm to 14mm,
children. It is usually performed under general anaesthesia the wall thickness ranges from 2mm to 3mm and
(GA) and requires proper pre-anaesthetic assessment. the length of the adult rigid bronchoscope is usually
Rigid bronchoscopy has several advantages over flexible 40cm.
bronchoscopy such as better control of the airway and • They have a uniform diameter from proximal to
ventilation, and the ability to simultaneously use large distal end, with a small internal channel through
forceps and suction catheters. which the rigid telescope can pass.

Ventilation Strategies During Rigid Bronchoscopy 372 Neerja Bhardwaj
• The proximal end has several ports to allow • Special attention should be paid to oral cavity, jaw
passage of the telescope, suction catheters, and and neck mobility.
instruments for removal of foreign body, tumor
excision etc., and a side port for providing ventilation • Patients who are already dyspnoeic and require
and anaesthesia. supportive oxygen, or are haemodynamically
unstable and hypercarbic at rest, are at increased
• The bronchoscope has many modifications for risk of intra and post-operative complications.
placement of stents, as well as a separate channel
for optics for continuous visualization at the same • Some important factors that should be kept in mind
time. are unstable cervical spine, decreased movement
of cervical spine especially in rheumatoid patients,
Optics maxillofacial trauma, limited mouth opening and
laryngeal stenosis or obstruction.
Generally, a rigid telescope and light source are inserted
through the rigid bronchoscope which allows visualization. • When a foreign body is suspected, the pre-operative
assessment should determine the location of the
Rigid telescope aspirated foreign body whether it is in the trachea.
This can provide visualization at angles of 0, 30, 40, 50, 90, If so, there will be a risk of complete obstruction, and
135, 180 degrees. The 0 degree telescope is adequate for the patient should be taken to the theatre urgently.
visualization of trachea and main stream bronchus. • History regarding what was aspirated is also
Light source important. Organic materials can absorb fluid and
swell, oils from nuts cause localised inflammation,
This is used for optimal visualization and most commonly and sharp objects can pierce the airway.
used is a cold light source e.g. xenon and halogen lamps.
The intensity of light can be adjusted manually. • Also, find out when the aspiration occurred. Airway
oedema, granulation tissue and infection may make
Video equipment retrieval more difficult with delayed presentations.
Video imaging is achieved by attaching a single or three • The time of the last meal should be established to
chip camera head to the telescope. assess the risk of aspiration.
Accessory instruments • The airway patency should be assessed. If the

patient is in severe distress, urgent bronchoscopy
These include rigid biopsy forceps, foreign body removal
should be performed.
forceps and stent kits.
• Administration of premedication will depend
Preoperative assessment
on the condition of the patient and may
• A standard pre-operative assessment is required include antisialogogues, benzodiazepines and
before anaesthesia. Patients may be of ASA III- bronchodilators.
IV physical status so appropriate history and pre-
Monitoring
operative tests should be done.
Standard monitoring including ECG, SPO2 and NIBP is
• The pre-operative investigations include, the routine
used. ETCO2 monitoring is difficult and sporadic owing to
investigations along with the coagulation profile in
communication of the bronchoscope with the atmosphere.
patients taking anticoagulants. Pulmonary function
tests are done, if there is a clinical suspicion of Goals of anaesthesia
severe respiratory obstruction and computed axial
tomography scan if the patient has haemoptysis or In patients undergoing rigid bronchoscopy the goals of
there is suspicion of a neoplasm. anaesthesia include:
• A pre-procedural blood gas is recommended in • Adequate depth of anaesthesia to minimize bucking,

some patients for evaluating the baseline status of coughing or straining during instrumentation
the patient in terms of hypoxemia and hypercarbia. • Stable haemodynamics

• Rapid recovery of airway reflexes at the end of the 1. Apneic oxygenation
procedure.It should be simple to use and should
result in a pain-free, alert patient within a short time Some designs of rigid bronchoscopes feature a port on
after the completion of the procedure. the direct conduit orifice, allowing intermittent airway
instrumentation during apnea followed by instrument
Anaesthesia management removal, sealing the port, and positive pressure ventilation
manually delivering fresh gas via an anaesthesia circuit
The patient is placed supine with head extended by
connected to the side port. Patient is administered 100%
keeping a roll under the shoulders. Balanced anaesthesia
oxygen before start of bronchoscopy. This is followed by
consisting of hypnosis, analgesia and muscle relaxation is
recommended for rigid bronchoscopy. Anaesthesia may be a brief time for performing an intervention, followed by
induced with Propofol/thiopentone and fentanyl in adults removing the instrument from the bronchoscope, capping
and inhalational agents in children. Fentanyl boluses and the proximal end and allowing the anaesthetist to ventilate
short acting beta blocker (Esmolol) can be used to avoid and oxygenate. This cycle is repeated till the case is
pressor response. Vocal cords should be sprayed with 4% completed. This technique carries the disadvantage of
lignocaine to prevent post-operative laryngospasm as well producing respiratory acidosis due to accumulation of CO2.
as decreasing the anaesthetic requirement. Anaesthesia The PACO2 of an awake, preoxygenated adult with normal
is maintained with intravenous infusion of propofol or lungs rises at the rate of 7 mm Hg/minute for the first 10
sevoflurane. Use of short acting muscle relaxants is seconds, 2 mm Hg/min for the next 10 seconds, then 6
recommended. Target controlled infusion as part of TIVA mm Hg/minute afterwards. It also causes interruption of the
may also be used. surgical procedure as well as of anaesthesia.
Technique of intubation 2. Spontaneous assisted ventilation
Direct intubation by the rigid bronchoscope, is the most In this technique, patient is induced with IV anaesthetic
common technique used for performing bronchoscopy. The agent like thiopentone/Propofol, and anaesthesia is
rigid telescope is placed within the distal end of the rigid maintained using TIVA with Propofol and fentanyl, but no
bronchoscope. While maintaining complete visualization of muscle relaxant is administered. The rigid bronchoscope is
the distal end of the rigid bronchoscope, it is inserted into introduced and the oxygenation and anaesthesia is managed
the oral cavity. The beveled end is kept anteriorly as the by connecting the breathing circuit to the bronchoscope port
bronchoscope is advanced along the tongue. The epiglottis situated on the side of the bronchoscope. This technique
is then visualized and lifted up by the rigid bronchoscope. carries the disadvantage of requiring more anaesthetic
As the vocal cords are approached, the bronchoscope is
concentration to achieve the requisite depth of anaesthesia
rotated 90 degrees clockwise such that, the beveled end
leading to hemodynamic instability. There is also high
lies between the cords as it is passed through them. The
incidence of hypoxemia, bronchospasm and laryngospasm
bronchoscope is advanced in a rotating motion to beyond
since the anaesthetic depth is difficult to ensure. There
the level of the cricoid cartilage. The beveled tip is allowed to
is possibility of inability to deliver adequate tidal volume
rest on the posterior wall of the trachea. The same technique
because of circuit leak leading to hypoxia or awakening of
can be applied for bronchoscopy using a laryngoscope.
patient.
Techniques for ventilation
3. Controlled ventilation
Several ventilation strategies are commonly used during
rigid bronchoscopy to provide adequate oxygenation In this type of ventilation, the bronchoscope is used like an
and ventilation, while maintaining appropriate depth of endotracheal tube for positive pressure ventilation. Silastic
anaesthesia to minimize cough and movement and ensure caps are used on ports of rigid scope and packing of the
patient comfort. The ventilation strategies utilized during oropharynx is done to minimize the leak. As these patients
performance of rigid bronchoscopy include: are given muscle relaxants there is a risk of hypoxia and
awakening of the patient if there is considerable circuit leak
1. Apneic oxygenation when connected to ventilator. Hence, manual ventilation with
2. Spontaneous assisted ventilation bag may be needed in many cases with careful observation
3. Controlled ventilation (closed system) of chest expansion. The limitations of this technique are:
operator judgement and fatigue, lack of control of fraction
4. Manual jet ventilation
of inspired oxygen concentration (FiO2) with high flow rate
5. High frequency jet ventilation (HFJV)
and inappropriate delivery of inhalational agents.

4. Jet ventilation to assess minute ventilation and airway pressures,
potentially leading to an increased risk of iatrogenic
The term jet ventilation is used to describe a rapid flow pneumothorax due to dynamic hyperinflation distal
of compressed gas delivered via a nozzle. This stream to a stenotic airway.
of gas is delivered at high pressure (0.3 – 3 bar). Low-
frequency jet ventilation provides effective ventilation and o Automated jet ventilation
oxygenation of the patient, while allowing the free passage
of bronchoscopic instruments. P Automated jet ventilation uses a commercially
available ventilator to deliver oxygen, often at
o Manual jet ventilation supraphysiologic respiratory rates, via a rigid
catheter.
P This technique was originally described by Sanders
in 1967. There is a hand operated valve which is P It frees the anaesthesiologist from providing
connected to 100% oxygen and the pressure is ventilation and allowing him to focus on other
delivered at 50 pounds per square inch (psi) or less aspects of management.
with respiratory rate between 10 and 14 breaths/
min. P Increased respiratory rate delivery produces a
motionless procedural field which allows fine
P In children and infants, the starting driving pressure movements of the surgeon.
should be approximately 0.5 psi, adjusted according
to chest expansion. Respiratory rate and duration P It can achieve adequate oxygenation and ventilation
of breath is governed by chest inflation and oxygen at very low airway pressures. The ventilator is set
saturation. for driving pressure, frequency, inspiratory time and
FIO2.
P The jet ventilation is applied by using a narrow
bore cannula which is attached to the side of the P To begin with, ventilator is set at a driving pressure
bronchoscope, or a long cannula along the long of 12-18 psi, RR of 60, with an inspiratory time of
axis of the airway may be used, with the tip going 25%. Further adjustments are made based on the
deep in the bronchoscope. The tip of the nozzle requirement. The efficacy of ventilation is assessed
should be aligned along the axis of the airway to be by chest wall ri`se which may be just visible or
effective and avoid gastric distension. by keeping hand on the patient’s chest, the chest
P The gas source is high pressure oxygen, which is should come to resting position between breaths.
passed through the pressure reducing valves to Patients with restrictive lung disease, poor chest
produce the desired chest expansion and maintain wall compliance, obesity and patients with airway
necessary oxygenation. stenosis may be difficult to ventilate by automated
jet ventilator and require adjustment of ventilator
P A jet frequency of 8–10/min, is sufficient to allow settings.
time for exhalation and prevents air trapping and
barotrauma. P Problems include hypoxia, hypercarbia, atelectasis
(due to low TV and low mean airway pressures).
P Standard monitoring is used during jet ventilation.
The atelectasis can be reversed by endotracheal
Monitoring of tidal volume (VT) becomes difficult
intubation and IPPV with PEEP after bronchoscope
because the system is open and ambient air
removal.
entrainment is unpredictable.
P Periodic CO2 and blood gas measurement or P Monitoring TV is difficult as the system is open and
transcutaneous capnography may be used ambient air entrainment is unpredictable.
to assess ventilation. Airway pressure can be P Peak pressure should be maintained below 35 cm
monitored using a catheter placed in the distal H2O.
trachea. Peak pressure should be below 35 cm of
water. Common complications of jet ventilation
P Although adequate oxygenation can usually be These include hypercarbia, hypoxia and hypotension.
obtained easily, it has the limitation of not being able

References foreign body removal. Pediatr Anesth 2013; 23:
1048 – 53.
1. Pathak V, Welsby I, Mahmood K, Wahidi
M, MacIntyre N, Shofer S. Ventilation and 4. Putz L, Mayne A, Dincq AS. Jet ventilation during
anesthetic approaches for rigid bronchoscopy. Ann rigid bronchoscopy in adults: A focused review.
Am Thorac Soc 2014; 11: 628 – 34. BioMed Res Int 2016; Article ID 4234861.
2. Pawlowski J. Anesthetic considerations for 5. Batra H, Yarmus L. Indications and complications

interventional pulmonary procedures. Curr Opin of rigid bronchoscopy. Expert Rev Res med DOI:
Anesthesiol 2013; 26: 6 – 12. 10.1080/17476348.2018.1473037.
3. Cai Y, Li W, Chen K. Efficacy and safety 6. Chadha M, Kulshrestha M, Biyani A. Anaesthesia

of spontaneous ventilation technique using for bronchoscopy. Ind J Anaesth 2015; 59: 565 –
dexmedetomidine for rigid bronchoscopic airway 73.

MCQ
1. Rigid bronchoscopy has a uniform diameter from 4. The pressure at which gas is delivered via jet ventilation
proximal to distal end
A.0.3-3 bar
A.True B.0.4-4 bar
B.false C.0.2-2 bar
D.0.5-5 bar
2. Gas use for light source is cold light source (eg:xenon
and halogen lamps) 5. Jet frequency of 8-10/min is sufficient to allow time for
exhalation and prevets air trapping and barotraumas
A.true
B.False A.True
B.False
3. During apneic oxygenation PACO2 increases at a rate
of __mmHg/min
A.7
B.10
C.2
D.6
5.True 4.A 3.A 2.True 1.True
ANSWERS:

40 MALIGNANT HYPERTHERMIA
Associate Professor, Vishnu Mahesh Babu

Rangaraya Medical College,
Kakinada.
Key points
Ø Malignant hyperthermia (MH) is a potentially lethal genetic disorder of muscle hyper metabolism triggered by
exposure to volatile anaesthetic agents and succinylcholine
Ø MH occurs in all ethnic groups in all parts of the world. Reactions occur more frequently in males than females
Ø Mutations encoding for abnormal RYR1 or DHP receptors have been found in a majority of MHS patients
Ø A previous apparently uneventful general anaesthetic does not exclude the possibility of a malignant hyperthermia
reaction to subsequent exposure
Ø Activated charcoal filters are an efficient way to reduce the concentration of volatile agents in inspired gases
during an MH reaction
Ø Dantrolene reverses the acute hypermetabolic process within minutes
Ø The goal is to suspect, diagnose and start immediate treatment for MH and promote optimum care to minimize
mortality and morbidity
Introduction Pathophysiology
Malignant hyperthermia is a potentially lethal genetic MH-susceptible (MHS) patients have genetic skeletal muscle
disorder of muscle hyper metabolism triggered by exposure receptor abnormalities that allow excessive myoplasmic
to volatile anaesthetic agents and Succinylcholine. It has calcium accumulation in the presence of certain anaesthetic
multiple inheritance patterns, including autosomal dominant, triggering agents. During an episode of MH, the clinical
autosomal recessive and unclassified; penetrance and manifestations occur as a result of calcium overload within
expression are extremely variable.1,2,3,4 the skeletal muscle cell that leads to sustained muscular
contraction and breakdown (rhabdomyolysis), cellular
Incidence
hypermetabolism, anaerobic metabolism, acidosis, and
1. Overall incidence is estimated to be 1:10,000 in their sequelae.
children, much higher than that reported for adults. Normal muscle physiology
MH episodes have been estimated to occur in
the general population in 1:100,000 administered Depolarization spreads throughout the muscle cell
anaesthetics .5 via the transverse tubule system, which activates
dihydropyridine (DHP) receptors located within the
2. This is probably an underestimate because t-tubule membrane. These receptors are coupled
unrecognized, mild, or atypical reactions occur due to ryanodine receptors (RYR1), which regulate the
to variable penetrance of the autosomal dominant passage of calcium from the sarcoplasmic reticulum
inherited trait. into the intracellular space. 8, 9. Calcium combines
Epidemiology with troponin to cross-link actin and myosin, resulting
in muscle cell contraction. Reuptake of calcium by
MH occurs in all ethnic groups in all parts of the world.
the sarco(endo)plasmic reticulum calcium ATPase
Reactions occur more frequently in males than females
(SERCA) leads to muscle cell relaxation.
(2:1)6,7

Malignant Hyperthermia 378 Vishnu Mahesh Babu
Malignant hyperthermia physiology Non-triggering Drugs for Malignant Hyperthermia
• Mutations encoding for abnormal RYR1 or DHP o Barbiturates

receptors have been found in a majority of MHS o Propofol
patients. Exposure to triggering agents in these o Etomidate
patients may lead to unregulated passage of o Benzodiazepines
calcium from the sarcoplasmic reticulum into o Opioids
the intracellular space, leading to an acute MH o Droperidol
crisis10,11,12,13 o Non depolarizing muscle relaxants
o Anticholinesterases
• The unregulated accumulation of myoplasmic o Anticholinergics
calcium causes sustained muscle contraction. o Sympathomimetics
Accelerated levels of aerobic metabolism sustain o Local Anaesthetics ( esters & amides)
the muscle for a time, but produce carbon dioxide o Alpha 2-Agonists (Clonidine & Dexmedetomidine)
and cellular acidosis, and deplete oxygen and o Nitrous Oxide ( only non - triggering inhalational
adenosine triphosphate 14,15 agent )
• This causes the early signs of MH: hypercarbia Clinical Features
(respiratory acidosis), tachycardia, and in some
cases, visible muscle rigidity. A change to anaerobic Timing of presentation
metabolism worsens acidosis with the production of
lactate, resulting in a mixed respiratory & metabolic The initial signs of MH may occur soon after induction with
acidosis. general anaesthetic triggering agents (ie, volatile agents
and/or succinylcholine) or any time during the maintenance
• Once energy stores are depleted, rhabdomyolysis phase of the anaesthetic. Some cases will appear within
occurs and results in hyperkalemia and minutes after the cessation of the anesthetic agent .18
myoglobinuria. Clinically evident hyperkalemia
(ie, electrocardiogram [ECG] changes) from Sequence of clinical signs
rhabdomyolysis may occur early in some patients, The most reliable initial clinical sign heralding the
especially those with large muscle mass. development of acute MH is an unexplained increase
• Over time, sustained muscle contraction generates in end tidal CO2, in mechanically ventilated patients,
more heat than the body is able to dissipate. or as tachypnea or breathing over the ventilator in
Hyperthermia may occur immediately or may be spontaneously breathing patients.
delayed following the initial onset of symptoms. The signs and symptoms
• In some unusual cases, core body temperature Not all of these need to be present to initiate treatment and
rises as much as 1°C every few minutes. not all occur in this order
Accelerated hyperthermia (above 41.5°C
[106.7°F]) is associated with a marked increase in Early
carbon dioxide production and increased oxygen
o Prolonged masseter spasm
consumption and can cause widespread vital
organ dysfunction. These extremely high body o Inappropriately raised end tidal carbon dioxide
temperatures are associated with the development o Inappropriate tachypnoea during spontaneous
of disseminated intravascular coagulation, a poor ventilation
prognostic indicator and often terminal event .16 o Inappropriate tachycardia
MH triggers o Cardiac arrhythmias – particularly ventricular
ectopic beats
1) Volatile anesthetic agents(eg, Halothane, Enflurane,
Isoflurane, Sevoflurane, Desflurane) with or without Intermediate
administration of succinylcholine 17 o Rapid rise in temperature (0.5 degrees C per 15
2) Succinylcholine (with or without volatile agent) minutes)

o Progressive respiratory and later metabolic acidosis Generalized muscle rigidity
o Hyperkalaemia
o Profuse sweating Generalized muscle rigidity (ie, sustained contracture) in
o Cardiovascular instability the presence of neuromuscular blockade is considered
o Decreased oxygen saturation pathognomonic for MH, provided other confirmatory signs of
o Skin mottling hypermetabolism are also present.
o Generalised muscular rigidity unresponsive to non- Masseter muscle rigidity
depolarising muscle relaxant
Masseter muscle rigidity (MMR) in the context of MH is
Late defined as jaw muscle tightness after administration of a
o Cola -coloured urine (myoglobinuria) triggering agent, usually succinylcholine, in the absence of
temporomandibular joint dysfunction or myotonia. Severe
o Generalised skeletal muscle rigidity
MMR (ie, inability to manually open the patient’s mouth)
o Grossly raised serum Creatinine Kinase (CK) after succinylcholine may indicate development of MH.19
o Coagulopathy ( Prolonged bleeding)
Mild MMR following succinylcholine is of no particular
o Irregular heart rate
concern, as long as it terminates within approximately one
o Cardiac Arrest minute and is not associated with generalized rigidity.
Differential Diagnosis Arrhythmias
o Inadequate anaesthesia/ machine malfunction Patients with MH frequently develop sinus tachycardia.
o Sepsis or infection They can also exhibit peaked T waves and arrhythmias (ie,
o Thyroid Storm ventricular ectopy, tachycardia or fibrillation) due to sudden
acute hyperkalemia.
o Pheochromocytoma
o Serotonin Syndrome Hyperthermia
o Recreational drug use (Amphetamines , Cocaine )
Although it may occur at any point in the clinical course of
o Malignant neuroleptic syndrome (MNS) MH, hyperthermia is often a later sign of MH and is often
o Intracerebral infection or haemorrhage absent when the diagnosis is initially suspected. Higher
o Inadvertent overheating maximum temperatures correlate with a higher likelihood
of all complications of MH events. Malignant Hyperthermia
An arterial blood gas is the most useful investigation to Association of the United States (MHAUS) recommends
perform. that core temperature (eg, esophageal, tympanic, rectal)
should be monitored for general anaesthetics lasting more
Clinical signs
than 30 minutes.20
Hypercarbia
Myoglobinuria
The most consistent presenting manifestation of MH is
Brownish cola, or tea-colored urine indicates the presence
hypercarbia, signaled by an increase in end-tidal carbon
of myoglobinuria, which is due to rhabdomyolysis, and
dioxide (ETCO2), that is resistant to increases in minute
peaks about 14 hours after an acute MH episode.
ventilation, and that is not caused by hypoventilation or
CO2 absorption (eg, during laparoscopy)

Prevalence of clinical signs during Malignant Hyperthermia episode 21
Clinical sign Percentage with sign

Hypercarbia 92.2
Sinus tachycardia 72.9
Rapidly increasing Temp 64.7
Elevated Temp 52.2
Generalised muscular rigidity 40.8
Tachypnea 27.1
Masseter spasm 26.7
Sweating 17.6
Cola-coloured urine 13.7
Cyanosis 9.4
Ventricular Tachycardia 3.7
Excessive bleeding 2.7
Ventricular fibrillation 2.4
Laboratory findings Clinical Indicators for Use in Determining the Malignant

Hyperthermia (MH) Raw Score22 (MH GRADING SCALE)
o Mixed metabolic and respiratory acidosis
o Hyperkalemia Process I: Rigidity
o Elevated serum creatine kinase ( CK; typically > Indicator Points
20,000 u/l)
o Myoglobinuria o Generalized muscular rigidity (in absence of shivering
due to hypothermia, or during or immediately following
o Disseminated intravascular coagulation
emergence from inhalational general anesthesia)
Diagnosis 15
MH should be strongly suspected when the end-tidal carbon o Masseter spasm shortly following succinylcholine
dioxide (ETCO2) increases despite a compensatory increase administration 15
in minute ventilation. The diagnosis is further supported by
Process II: Muscle Breakdown
muscle rigidity (generalized or prolonged masseter muscle
rigidity [MMR]) or an otherwise unexplained metabolic Indicator Points
acidosis.
o Elevated creatine kinase >20,000 IU after anesthetic
There is no confirmatory test for MH during an acute event.
that included succinylcholine 15
The diagnosis must be considered in all patients with clinical
signs who have received triggering agents, regardless of o Elevated creatine kinase >10,000 IU after anesthetic
family history or prior experience with anaesthesia. Over without succinylcholine 15
90 percent of patients developing acute MH episodes have
negative family histories for MH, and over half have had o Cola- colored urine in perioperative period 10
uneventful general anaesthetics in the past .6 Following an o Myoglobin in urine >60 g/L 5
acute event, the likelihood that a clinical event represented
o Myoglobin in serum >170 g/L Blood/plasma/serum K+ > 6
a true MH episode can be estimated using the MH clinical
mEq/L (in absence of renal failure)
grading scale.
3

Process III: Respiratory Acidosis Process V: Cardiac Involvement
Indicator Points Indicator Points
o PETCO >55 mmHg with appropriately controlled o Inappropriate sinus tachycardia 3

2
ventilation 15 o Ventricular tachycardia or ventricular fibrillation
o Arterial PaCO >60 mmHg with appropriately controlled 3
2
o ventilation 15 Other indicators that are not part of a single process
o PETCO >60 mmHg with spontaneous ventilation
2 Indicator Points
15
o Arterial PaCO >65 mmHg with spontaneous ventilation o Arterial base excess more negative than 8 mEq/L
2
15 10
o Inappropriate hypercarbia (in anesthesiologist’s judgment) o Arterial pH <7.25 10

15 o Rapid reversal of MH signs of metabolic and/or respiratory
o Inappropriate tachypnea 10 acidosis with iv dantrolene 5
Process IV: Temperature Increase Double-counting
Indicator Points If more than one indicator represents a single process,

count only the indicator with the highest score.
o Inappropriately rapid increase in temperature (in Application of this rule prevents double-counting
anesthesiologist’s judgment) 15 when one clinical process has more than one clinical
manifestation.
o Inappropriately increased temperature > 38.8°C (101.8F)
in the perioperative period (in anesthesiologist’s Exception: the score for any relevant indicators in the
judgment) 10 final category “other indicators” should be added to
the total score without regard to double- counting.
Interpreting the raw score: MH rank and qualitative likelihood
Raw Score Range MH Rank Description of Likelihood
0 1 Almost never
39 2 Unlikely
1019 3 Somewhat less than likely
2034 4 Somewhat greater than likely
3549 5 Very likely
50+ 6 Almost certain

Acute Management of suspected MH is not needed. Because it is hyper concentrated, blood
concentrations will be achieved faster in patients
Treatment for MH must be initiated immediately when the
with acute MH, with less of a sterile water volume
following occur in the absence of a persuasive alternative
load than the older form. Ryanodex contains a small,
diagnosis:
clinically irrelevant amount of Mannitol (125 mg per
• Rising end-tidal carbon dioxide (ETCO2) despite vial). The ease of use, shortened preparation time, lack
compensatory increase in minute ventilation of Mannitol, and faster effective blood concentrations
achieved with use of Ryanodex makes it the obvious
• One or more of the other clinical signs of MH (ie, choice for treating acute MH.
muscle rigidity [generalized or prolonged masseter
muscle rigidity (MMR)]), hyperthermia, tachycardia, Symptomatic treatment
or electrocardiogram (ECG) changes consistent
with hyperkalemia (eg, peaked T waves, premature • Abort or conclude surgery as soon as possible (if
ventricular contractions [PVCs], ventricular tachycardia anaesthesia is necessary, use only i.v hypnotics-TIVA).
or fibrillation. • Hyperventilate with 100% Oxygen at > 10 L / min.
• Initiate active cooling (iced saline 15 ml /kg IV every 10
Initial Steps min, gastric lavage with iced saline , surface cooling)
if temperature > 39 deg C or less if rising rapidly. Stop
1) Call for help and the MH cart
cooling when temperature < 38 deg C.
2) Notify the surgeon • Consider sodium bicarbonate treatment (1-2 mEq /kg)
3) Optimize oxygenation and ventilation for severe academia.
4) Discontinue triggering agents • Treat hyperkalemia ( Calcium chloride 5-10 mg /kg IV
Calcium gluconate 30 mg/kg or regular Insulin (0.1 unit /
5) Administer Dantrolene .
kg ) in 1 ml/ kg of 50% Dextrose or 0.5 mg/ kg Dextrose
P Administration of an initial bolus dose of 2.5 mg/kg of any percent Glucose formulation.
IV Dantrolene will achieve therapeutic blood levels.23 • For refractory hyperkalemia , consider beta- agonist (
e.g.,albuterol), Kayexalate, dialysis (ECMO if cardiac
P The end-tidal carbon dioxide (ETCO2) will usually arrest )
decrease as Dantrolene takes effect; in most cases, • Maintain urine output (hydration, Mannitol 0.25 g /kg i.v,
Dantrolene reverses the acute hypermetabolic process Furosemide 0.5-1 mg/ kg IV).
within minutes. However, some patients, especially • For persistent and rising serum CK & K+ , alkalinize
muscular males, may require dantrolene doses >10 urine with bicarbonate infusion at 1 mEq /kg /hr for
mg/kg intravenous (IV) during an acute event. . presumed imminent myoglobinuria.
P MHAUS recommends re-dosing dantrolene (1mg/kg • Treat cardiac dysrhythmias ( Procainamide 15 mg/ kg
following the initial 2.5 mg/kg bolus) as frequently as IV, Lignocaine 2 mg / kg IV follow PALS guidelines)
needed (every 5-10 min) until the patient responds with • Place peripheral arterial line and central venous
a decrease in ETCO2, decreased muscle rigidity, and/ catheter.
or lowered heart rate. may require a cumulative dose • Check ABG every 15 minutes until abnormalities are
in excess of 10 mg / kg. Prevent recrudescence, with corrected.
Dantrolene 1 mg /kg iv every 6 hours for 72 hours. • Monitor in an intensive care setting for at least 24 hours.
P Available preparations: There are two types Follow-up of Patients with MH or Masseter Muscle
of Dantrolene preparations. Rigidity
• The older conventional formulation is supplied as a 1. Medical-alert bracelet; patient and first degree relatives
lyophilized powder in a 20 mg vial, containing sodium must be assumed to have MH susceptibility
hydroxide to maintain pH of 9 to 10 and 3 g of Mannitol, 2. Refer patient to MH diagnostic centre.
which can cause fluid volume and electrolyte
complications. Each 20 mg vial requires mixing with 60 3. Review family history for adverse anaesthetic events or
mL of sterile water; warming will enhance its solubility. suggestion of heritable myopathy.
• A newer Dantrolene formulation (Ryanodex), which 4. For severe rhabdomyolysis -consider evaluation for
is dissolved rapidly, is supplied in 250 mg vials, dystrophies.
reconstituted with only 5 mL of sterile water, and warming 5. Consider Temporomandibular Joint disorder.

AAGBI ( Association of Anaesthetists of Great Britain and Ireland) has given certain guidelines , as shown below, regarding
the management of MH.


There are currently only three disorders that have been 5. Brady JE, Sun LS, Rosenberg H, Li G. Prevalence of
clearly linked with MH: malignant hyperthermia due to anesthesia in New York
State, 2001-2005. AnesthAnalg 2009; 109:1162.
P Central core disease
P King-Denborough syndrome and 6. Larach MG, Gronert GA, Allen GC, et al. Clinical
presentation, treatment, and complications of malignant
P Evans myopathy.
hyperthermia in North America from 1987 to 2006.
A rare subset of MH-susceptible patients can develop MH AnesthAnalg 2010; 110:498.
to non-anaesthetic triggers such as vigorous exercise, heat
7. Rosenberg H, Davis M, James D, et al. Malignant
and anxiety. Dantrolene produces muscle weakness, vein
hyperthermia. Orphanet J Rare Dis 2007; 2:21.
irritation , nausea , blurred vision and diarrhoea.
Once MH susceptibility is identified or suspected, a non- 8. O’Sullivan GH, McIntosh JM, Heffron JJ. Abnormal
triggering anaesthetic plan must be initiated, starting with uptake and release of Ca2+ ions from human malignant
elimination of triggering agents and thorough preparation of hyperthermia-susceptible sarcoplasmic reticulum.
the anaesthesia machine to minimize even traces of volatile BiochemPharmacol 2001; 61:1479.
agents. 9. Berchtold MW, Brinkmeier H, Müntener M. Calcium ion
The anaesthesia machine must be flushed with high-flow in skeletal muscle: its crucial role for muscle function,
oxygen for the recommended length of time (from 20 min plasticity, and disease. Physiol Rev 2000; 80:1215.
to > 100 min) specific to each machine. Activated Charcoal
10. Ohnishi ST, Taylor S, Gronert GA. Calcium-induced
filters can also be added to the inspiratory & expiratory
Ca2+ release from sarcoplasmic reticulum of pigs
ports of the anaesthesia machine to remove volatile agents.
susceptible to malignant hyperthermia. The effects of
The anaesthesia machine requires flushing with high fresh
halothane and dantrolene. FEBS Lett 1983; 161:103
gas flow ( >10 L /min ) for 90 seconds prior to adding the
activated charcoal filters. 11. Struk A, Lehmann-Horn F, Melzer W. Voltage-
dependent calcium release in human malignant
Definitive diagnosis requires muscle biopsy for the Caffeine-
hyperthermia muscle fibers. Biophys J 1998; 75:2402
Halothane contracture test (CHCT); however the CHCT has
a specificity of approximately 80% and a negative result 12. Vilven J, Coronado R. Opening of dihydropyridine
does not completely rule out MH. calcium channels in skeletal muscle membranes by
RYR Genetic testing is also done to see for RYR-1 mutations inositol trisphosphate. Nature 1988; 336:587.
to identify MH –susceptible individuals. 13. Quane KA, Healy JM, Keating KE, et al. Mutations in
Conclusion the ryanodine receptor gene in central core disease
and malignant hyperthermia. Nat Genet 1993; 5:51.
Our goal is to suspect, diagnose and start immediate
treatment for MH and promote optimum care to minimize 14. Gronert GA, Theye RA. Halothane-induced porcine
mortality and morbidity. malignant hyperthermia: metabolic and hemodynamic
changes. Anesthesiology 1976; 44:36.
References
15. Mickelson JR, Louis CF. Malignant hyperthermia:
1. Denborough M. Malignant hyperthermia. Lancet 1998; excitation-contraction coupling, Ca2+ release channel,
352:1131. and cell Ca2+ regulation defects. Physiol Rev 1996;
2. Rosenberg H, Fletcher JE. International Malignant 76:537
Hyperthermia Workshop and Symposium, Hiroshima, 16. Nelson TE. Porcine malignant hyperthermia: critical
Japan, July 16-19, 1994. 82, 803-805. 1995. temperatures for in vivo and in vitro responses.
3. MacLennan DH, Phillips MS. Malignant hyperthermia. Anesthesiology 1990; 73:449).
Science 1992; 256:789. 17. Larach MG, Gronert GA, Allen GC, et al. Clinical
4. Wappler F. Malignant hyperthermia. Eur J Anaesthesiol presentation, treatment, and complications of malignant
2001; 18:632.) hyperthermia in North America from 1987 to 2006.
AnesthAnalg 2010; 110:498

18. Litman RS, Flood CD, Kaplan RF, et al. Postoperative hyperthermia in North America from 1987 to 2006
malignant hyperthermia: an analysis of cases from .Anesth Analg 2010;110:498
the North American Malignant Hyperthermia Registry.
Anesthesiology 2008; 109:825. 22. Larach MG, Localio AR, Allen GC, Denborough MA,
Ellis FR, Gronert GA, Kaplan RF, Muldoon SM, Nelson
19. Larach MG, Localio AR, Allen GC, et al. A clinical TE, Ørding H, Rosenberg H, Waud BE, Wedel DJ: A
grading scale to predict malignant hyperthermia clinical grading scale to predict malignant hyperthermia
susceptibility. Anesthesiology 1994; 80:771. susceptibility. Anesthesiology 1994; 80: 774-775.
20. http://www.mhaus.org/healthcare-professionals/ 23. Flewellen EH, Nelson TE, Jones WP, et al. Dantrolene
mhaus-recommendations/temperature-monitoring dose response in awake man: implications for
(Accessed on May 21, 2015. management of malignant hyperthermia. Anesthesiology
1983; 59:275.
21. Larach M.G, Gronert L.G, Allen G.C et.al .Clinical
presentation, treatment and complications of malignant 24. http://www.mhaus.org/ (Accessed on October 24,
2019).

MCQ
1. Early signs of malignant hyperthermia includes all except 4. Clinical indicators for determining malignant hyperthermia
RAW score are all except
a. masseter spasm
b. myogloginuria a. PETCo2>55mm of Hg with controlled ventilation
c. increase in etCo2 b. Arterial pCo2 of >65mm of Hg
d. inappropriate tachycardia c. PETCo2 >45mm of Hg with spontaneous ventilation
d. inappropriatetachypnoea
2. The maximum dose of dantrolene for malignant
hyperthermia as per AAGBI guidelines is 5. One of the following statement is false about RYANODEX
preparation
a. 5mg/kg
b. 10mg/kg a. warming enhances solubility
c. 15mg/kg b. Dissolves rapidly with 5ml of sterile water
d. 20mg/kg c. Contains very low mannitol
d. Available in 250mg vials
3. Which of the following is not associated with malignant
hyperthermia
a. Central core disease

b. King-Denborough syndrome
c. Evans myopathy
d. Duchenne muscular dystrophy
5.A 4.C 3.D 2.B 1.B
ANSWERS:

41 EXTRAJUNCTIONAL RECEPTORS AND THEIR IMPLICATIONS
Professor of Anaesthesiology, Selvakumar R

Madurai Medical College,
Madurai.
Key points
Ø The acetylcholine receptors formed of 5 sub-unit proteins are arranged like staves of a barrel into a cylindrical
receptor with a central pore for ion channeling
Ø Before and shortly after birth, all the immature γ sub-unit containing Ach receptors are converted to the mature €
sub-unit containing receptors due to a growth factor called ARIA
Ø Denervation of muscle causes fetal type of receptors to appear extra-junctionally, within 24 hours of denervation
Ø The immature receptors are metabolically unstable with short half-life, have a smaller single channel conductance
and 2-10 fold longer mean channel open time than mature receptors
Ø The hyperkalemic response occurs 48-72 hours after an acute burns injury and may persist up to 2 years post-
burns
Ø Attenuation of this potassium release by using a small dose of non-depolarizer will not be effective
Introduction Post-Junctional Nicotinic Acetylcholine Receptors
The neuronal signal travels via the length of the axon The nicotinic Ach receptors are synthesized in the muscle
and reach the neural endings. On reaching there, the cells and are anchored to the end plate membrane by a
neuronal action potential initiates various cyclical events special 43-kd protein known as rapsyn. The receptors, formed
which ultimately lead to release of the neuro-transmitter, of 5 sub-unit proteins are arranged like staves of a barrel into
Acetylcholine. Once the Acetylcholine is released from the a cylindrical receptor with a central pore for ion channeling.
nerve ending, it travels the synaptic cleft and reaches the post- These sub-units are designated as α, β, δ, € or γ. There are
junctional muscle membrane. On the surface of the muscle two α sub-units and one from each of the other subunits.
membrane, adjacent to the nerve ending, lot of post-junctional The receptor protein complex passes entirely through the
Acetylcholine (Ach) receptors are situated. The released membrane and protrudes beyond the extra-cellular surface
Ach molecules bind with these post-junctional nicotinic Ach of the membrane and into the cytoplasm. The binding site for
receptors to elicit a response. An end plate action potential
the Ach molecule is on each of the α subunit and these are
is generated which is propagated over the entire muscle to
the sites of competition between the receptor agonists and
cause opening of the sodium channels situated over the
antagonists. Agonists and antagonists are attracted to the
muscle membrane. Once the depolarization happens over
binding site and either may occupy the site ,which is located
the muscle membrane, calcium is released from the T tubules
near the cysteine residues(unique to α –chain) at amino acid
which goes and binds with the Actin-Myosin filaments. This
positions 192-193 of the α sub-unit.
calcium binding causes the Actin-Myosin filaments to slide
and causes muscle contraction. The entire event of action The α sub-unit is the smallest of the five and is made up
potential generation and propagation depends upon the of 437 aminoacids. At rest, the receptor is closed i.e the
binding of Ach molecules to the post-junctional receptors in
membrane domains lining the hole in the centre touch
the neuromuscular junction. When the properties of these
each other at one point to prevent passage of ions. When
receptors change due to some pathological states, the
two acetylcholine molecules bind to each α sub-unit
behavior of the neuromuscular transmission also changes.
simultaneously, a conformational change in the protein

Extrajunctional Receptors and their 390 Selvakumar R
Implications
occurs and a passageway is created between the inside Characteristics of Fetal type (extra-junctional) receptors
and outside of the cell. Passage through the receptor is
The differences in the protein structure of the two varieties
non-selective and the movement of the ions is determined
of receptors namely junctional and extra-junctional cause
by their electrical and concentration gradients. Sodium driven
significant qualitative variations among the responses of
by a favourable concentration and electrical gradient moves
individual patients to relaxants and seem to be responsible
inside of the cell whereas potassium exits the cell.
for the anomalous results that are observed in conditions
Types of Nicotinic Acetylcholine Receptors like denervated state, sepsis or burns. The changes in
subunit composition (γ versus €) in the receptor confer
Junctional and Extra-junctional Receptors changes in electro physiologic, pharmacologic and metabolic
characteristics. The mature receptors are metabolically
There are many types of nicotinic receptors but muscle
stable, with half-life approximating 2 weeks, whereas the
contains only two types of varieties. During fetal development,
immature receptor has a metabolic half-life of less than 24
fetal types of receptors are found all over the muscle
hours. Immature fetal type of receptors have a smaller single
membrane. These receptors have a γ sub-unit instead of
channel conductance and 2-10 fold longer mean channel
an € sub-unit between both α sub units. As the innervation
open time than mature receptors. The changes in sub-unit
appears, it produces clustering of receptors in the end plate
composition may also alter the sensitivity or affinity or both
area of the membrane, just beneath the contact with the
of the receptor for specific ligands.
nerve. And it induces a change in receptor type at the end
plate from the fetal type (with γ sub-unit) to the adult type Depolarizing or agonist drugs such as succinylcholine and
(with € sub-unit). The end plate starts throwing many folds acetylcholine depolarize the immature receptors more easily,
and increases in complexity under the influence of a nerve resulting in cation fluxes. One tenth to one hundredth doses
contact. Just before and shortly after birth, all the immature γ necessary for the mature receptors can effect depolarization
sub-unit containing Ach receptors are converted to the mature in the fetal type receptors. The potency of non-depolarizers is
€ sub-unit containing receptors. Although the mechanism of reduced, demonstrated as a resistance to those drugs. This
this change is unclear, a neuregulin (growth factor) called resistance is due to the decreased affinity of the receptors
ARIA( for Ach receptor inducing activity) seems to play a role. and to the upregulation of immature receptors all over the
muscle membrane.
Even though the receptor type in end plate region changes,
some of the fetal type receptors persist over the muscle Significance of prolonged opening time of sodium
membrane extra junctionally. But the number of these channels
receptors is very less in normal conditions. In humans, the
The main difference between junctional and extra-junctional
conversion from fetal to adult type of receptors is almost
receptors is the opening time of the sodium channels of the
complete by birth, but the final architecture is not present
receptors. The extra-junctional type remains open for a long
until the end of the first year of life. Maintenance of large
time, compared to mature receptors when agonists attach
density gradient between junctional and extra-junctional
with them. After denervation, the upregulation of receptors
areas depends on the presence of innervation. Denervation
to immature type occurs after 24-48 hours. The channels
of the muscle causes loss of adult type receptors at the
opened by the attachment of agonists remain open for a long
junction and the increase in fetal type receptors elsewhere
time allowing large amount of potassium to escape into the
on the muscle membrane.
blood stream. If a large part of the muscle surface consists
Effect of denervation of a muscle of upregulated immature channels, the amount of potassium
released into the blood will be very high and may prove to be
The normal distribution of receptors is maintained on the dangerous. As the affinity for the non-depolarizers diminish
surface of the muscle fibres by the nerve activity. If the in this situation, attenuation of this hyperkalemic response by
incoming nerve impulses cease completely, as occurs with giving a small dose of non-depolarizer will not be as effective
denervation, or to lesser extent, if this traffic diminishes as in normal persons.
significantly, more fetal type of receptors (γ type) will
appear extra-junctionally as the normal inhibition to their Clinical implications of presence of extra-junctional
proliferation, the presence of activity at the nerve ending receptors
is removed. This phenomenon starts within 24 hours
1) Succinylcholine, on its administration in normal
following denervation.
individuals produce a rise of 0.5 -1 mEq/L of serum

Implications
potassium level. But in certain conditions like of tetanus or to facilitate intubation may prove to be
denervation, immobility, sepsis & post-burns, this dangerous.
response become exaggerated and dangerous
arrhythmias can be induced because of resulting 7) The upregulation and spread of extra-junctional
hyperkalemia. receptors also occur in burns related injury. The
hyperkalemic response occurs 48-72 hours after
2) This upregulation of receptors also leads to increased an acute burns injury and may persist up to 2 years
sensitivity to agonists and resistance to competitive post-burns. The upregulation not only occurs over the
antagonists. involved muscles but all over the body if the burns
area exceeds 15% of total body surface area. But
3) Even prolonged use of non-depolarizers in ICU leads there are case reports, in which even lesser surface
to upregulation of these receptors. This situation being area of burns injury causing lethal hyperkalemia. So
called as chemical denervation also leads to increased it’s better to withhold the use of succinylcholine in the
sensitivity to agonists. airway management of post-burns cases.
4) The co-administration of muscle relaxants in Conclusion
association with another pathological condition
that upregulates Ach receptors (post-burns & The presence of upregulated extra-junctional receptors is
immobilization) can magnify the increase in the Ach the reason for the exaggerated response to agonists and
receptors even further over and above that caused by resistance to non-depolarizing muscle relaxants in certain
the pathological condition alone. pathological states. They also cause excessive release
of potassium when succinylcholine is used for airway
5) A period of immobilization also leads to a condition management. Attenuation of this potassium release by
similar to denervation. Although the nerve itself is not using a small dose of non-depolarizer will not be effective as
anatomically severed during this time, the immobilized the sensitivity for the non-depolarizer is decreased. Better
muscle behaves as if it were denervated. Within 3-5 understanding of the mechanism behind these changes help
days of immobilization, the muscle fibres become us to manage these cases effectively and safely.
atrophied and the NMJ begins to show degenerative
changes. Although there is no associated apparent References
disruption of nerve function, the biochemical feature of
classic denervation and upregulation of Ach receptors 1. Succinylcholine induced Hyperkalemia in acquired
and spread of receptors beyond NMJ is observed. pathologic states-etiologic factors and molecular
mechanisms J.A.Jeevendra Martyn & Martina Richsfeld
6) Infection with Clostridium tetani also results in the –Anaesthesiology V(104) Jan 2006
condition similar to denervation of muscles causing
paralysis of muscles. Even though the nerves are 2. Current concepts in Neuro-muscular transmission-
intact, the exotoxin released by Cl.tetani produces M.J.Fagerlund & L.L.eriksson-British Journal of
paralyses by binding to cleavage proteins that control Anaesthesia 103 (1)-2009
the release of Ach, leading to muscle paralysis and 3. Neuromuscular physiology and pharmacology-
a denervation like state. As upgradation of Ach J.A.Jeevendra Martyn.
receptors occur here also, the sensitivity to agonists
increase, leading to lethal hyperkalemia. Thus the use 4. Wylie and Churchill-Davidson’s “A practice of
of succinylcholine either to prevent muscle spasms Anaesthesia”.

Implications
MCQ
1. Acetylcholine receptors formed of ……………. Proteins 4. Hyperkalemic response occurs ………..after an acute
are arranged like staves of a barrel into cylindrical burns injury
receptor with central pore for loss channeling
a. 24-48 hrs b. 48-72 hrs c. > 72 hrs
a. 3 Subunits B. 4 Subunits c. 5 Subunits
5. All the immature gamma sub unit containing Ach
2. Denervation of muscle causes fetal type of receptors to receptors are converted to mature ɛ Sub-unit due to
appear extra-junctionally within…………….. growth factor called ______
a.12 hrs B. 48 hrs c. 24 hrs
3. Succinylcholine administration in normal individuals

produce a rise of …………mEq/L and Sr.Potassium
level
a. 0.5-1 b. 1-1.5 c.1.5-2
5.ARIA 4.B 3.A 2.C 1.C
ANSWERS:
42 PRINCIPLES OF TEMPERATURE MONITORING
Harish Babu Ravulapalli Ramkumar Dhanasekaran

Associate Professor Associate Professor,
Narayana super speciality hospital, Nellore. SRIHER, Chennai
Key points
Ø Regulation of core temperature is achieved by means of behavioral and autonomic mechanisms that balance heat
production and heat loss, which are largely controlled by the hypothalamus.
Ø Thermoregulation has three components: Afferent thermal sensing ,central integration and efferent response.
Ø The most important efferent autonomic responses are sweating, arteriovenous shunt vasoconstriction and
shivering.
Ø Shivering doubles heat production but can increase metabolic activity by up to 600% in adults.
Ø Non-shivering thermogenesis doubles heat production in infants. It is mediated via β3 adrenergic receptors located
in brown fat.
Ø The zeroth law allows temperature to be defined.
Ø The four core temperature monitoring sites (e.g., tympanic membrane, nasopharynx, pulmonary artery, and
esophagus) remain useful even during cardiopulmonary bypass.
Ø During anesthesia, hypothermia can cause physiological derangement and may increase perioperative morbidity.
Ø The consequences of perioperative hypothermia can be- increased blood loss, surgical wound infection, increased
recovery time and length of postoperative stay, delay in drug metabolism and shivering, thus causing patient
discomfort.
Ø Prevention of hypothermia can be by passive or active warming methods.
Ø Prevention of hypo or hyperthermia is likely a superior approach to treatment.
Introduction Conversely, hyperthermia also can occur within the

perioperative environment, indicating that heat production
People normally are able to maintain core body temperature exceeds heat loss. Although hypothermia is more
(core temperature) within narrow physiological limits. common than hyperthermia in the perioperative period,
Regulation of core temperature is achieved by means hyperthermia (core temperature greater than 38 degree)
of behavioral and autonomic mechanisms that actively is more dangerous than a comparable degree of cooling.
balance heat production and heat loss. These mechanisms Hyperthermia can result from excessive covering of patients
are controlled largely by the hypothalamus [1–3]. [9], extremely warm operating room temperatures, a febrile
Anesthetic agents, opioids, and sedatives inhibit behavior response [10, 11], or uncontrolled metabolism as occurs
and autonomic responses, leaving patients essentially during malignant hyperthermia crises.
poikilothermic. Thus when patients are exposed to cool
ambient operating room environments, mild-to-moderate Normal thermoregulation
hypothermia is the usual result. Although hypothermia may
provide protection against ischemia [4, 5], there is ample Normal core body temperature varies by at least 1°C
clinical evidence showing that even mild perioperative based on circadian and menstrual cycles.[12] But at any
hypothermia causes multiple physiologic derangements given time, core temperature is tightly regulated, to within
and leads to adverse outcomes [6–8]. a few tenths of a degree during the day with slightly more
variability at night.[13]

Principles of Temperature Monitoring 394 Ramkumar Dhanasekaran
Harish Babu Ravulapalli
Regulation of temperature in human beings
Thermoregulation has three components: in the spinal cord. The hypothalamus acts to maintain core
temperature to within ~0.2°C of 37.0°C. Thermoregulatory
• Afferent thermal sensing
responses are quiescent within this range, but any deviation
• Central integration outside of this, will invoke thermoregulatory responses to
• Efferent response conserve or release heat as appropriate.
• Afferent thermal sensing
Efferent response
80% of input originates from core tissues, with the remainder
• Neuronal
coming from peripheral tissue. The following five anatomical
• Hormonal: catecholamine and thyroid hormones
areas contribute 20 % each to afferent input:
Mechanisms to preserve and increase heat [18,19,20]
• Brain
• Hypothalamus • Behavioral patterns: seek shelter, increase clothing,
• Spinal cord curl up
• Deep thoracic and abdominal tissue
• Ingestion of food
• Skin
• Increase activity
The hypothalamus is said to produce an integrated body • Vasoconstriction and piloerection
temperature in response to information from sensory
• Shivering
receptors (primarily cold receptors). The most important
efferent autonomic responses are sweating, arteriovenous • Non-shivering thermogenesis
shunt vasoconstriction, and shivering. Behavioral responses
Cutaneous vasoconstriction: via a1 (alpha one) receptors
(any volitional responses) are by far the strongest defences,
acting on arterioles, reduces heat loss caused by radiation
but not usually available to surgical patients.
and convection. A countercurrent exchange mechanism
Temperature-sensitive neurons (14, 15, 16, 17) transfers heat from the warm arterial blood going to the
limbs, to the cold venous blood returning.
Cold receptors fire continuously, the rate of which
increases with a decrease in temperature. Transmission Shivering doubles heat production but can increase metabolic
occurs through Ad (delta) myelinated fibres. activity by up to 600% in adults.
Warm receptors are quiescent at normothermia and Non-shivering thermogenesis doubles heat production
increase their firing rate in response to an increase in in infants, but probably has little significance in adults. It
temperature. Transmission is through unmyelinated C fibres. is mediated via beta three adrenergic receptors located in
brown fat.
Central integration
Brown fat is more abundant in infants and is located between
Most of the central integration takes place in the
the scapula, at the nape of the neck and along the great
hypothalamus, with only limited afferent integration occurring

vessels. It contains many mitochondria (giving its colour), Non-electrical techniques
which increase lipid oxidation to generate ATP production
and heat. An uncoupling protein called UCP1 short-circuits Mercury-in-glass thermometers – It has a slow response
the process by uncoupling oxidative phosphorylation. time and are now considered neither safe nor convenient
to use. Bimetallic strips, where two dissimilar metals with
Mechanisms to decrease heat and allow dissipation different coefficients of expansion are bonded together and
their relative movements cause bending of a coil attached
• Behavioral to a pointer, are found in theatre temperature gauges.
• Decrease activity Alongside these may be found bourdon gauges, where a
• Vasodilatation hollow tube extends when the gas inside it expands and a
• Sweating: a cholinergic impulse response pointer or sensor indicates temperature.
• Hyperventilation
Electrical techniques
Temperature monitoring and perioperative
thermoregulation Electrical means of measuring temperature rely on four
principal devices: the resistance thermometer, thermistor,
Body temperature is not homogeneous. Deep thoracic,
thermocouple, and infrared tympanic thermometer.
abdominal, and central nervous system (i.e., core)
temperatures usually are 2 to 4°C cooler than the arms and Resistance thermometer
legs and much of the skin surface is yet cooler. Unlike core
temperature, which is tightly regulated, skin temperature
varies markedly as a function of environmental exposure;
temperature of peripheral tissues (mostly the arms and
legs) depends on current exposure, exposure history,
core temperature, and thermoregulatory vasomotion. Core
temperature, while by no means completely characterizes
body heat content and distribution, is the best single
indicator of thermal status in humans.
Physics behind temperature measurement
Temperature is a measure of the average translational
kinetic energy associated with the disordered motion of
atoms and molecules. The property of matter determines,
in which direction heat energy will flow, when an object is in The basic principle of this technique is that a metal wire’s
contact with another object of a different temperature. resistance to current, increases with temperature linearly.
The most commonly used metal is platinum and the wire
The zeroth law of thermodynamics states that, if two
is incorporated in a Wheatstone bridge circuit to give very
systems are, at the same time in thermal equilibrium with
accurate measurement of temperature.
a third system, they are in thermal equilibrium with each
other. The zeroth law allows temperature to be defined. The Thermistor
‘triple point’ is the only point at which all three states can
exist at the same temperature and pressure.
Another law that relates temperature and its transmission is
the Stefan–Boltzmann law. This refers to the concept of a
black body, i.e. an ideal object that emits an equal amount
of infrared energy as that given to it; so the hotter an object
gets the more energy, it emits as infrared energy.
Measurement of temperature can be divided into: non-
electrical and electrical techniques.
Non-electrical techniques rely on the physical properties of
substances.

The thermistor is a metal oxide semiconductor. As absolute temperatures given in degrees celsius to kelvin,
thermistors change temperature, there is an exponential you must add 273.15.
decline in resistance. However, in commercial applications
where a narrow range is required, the output is often Fahrenheit
linearized by the device. They are very accurate with 0.1° - Fahrenheit used the mercury thermometer to develop this
0.2°C increments possible. temperature scale. The zero point was set using a mixture
Thermocouple of sodium chloride and ice. According to this scale, water
boiled at 212°F, ice melted at 32°F, and body temperature
was assumed to be 100°F.
Monitoring sites [22]
The core thermal compartment is composed of highly

perfused tissues whose temperature is uniform and high
compared with the rest of the body. Core temperature
monitoring (e.g., tympanic membrane, pulmonary artery,
distal esophagus, and nasopharynx) is used to monitor
intraoperative hypothermia, prevent overheating, and
facilitate detection of malignant hyperthermia. Because
these sites are not necessarily available or convenient, a
variety of “near-core” sites are also used clinically. These
include the mouth, axilla, bladder, rectum, and skin surface.
Thermocouples are based on the fact that junctions of two Each has distinct limitations but can be used clinically in
different metals produce a small voltage or current change appropriate circumstances[22].
in response to temperature. This is commonly known as
the Seebeck effect. The junctions in clinical temperature Temperature probes incorporated into esophageal
measurement are usually copper and constantan (copper stethoscopes must be positioned at the point of maximal
with 40% nickel). This combination will produce a voltage heart sounds, or even more distally, to provide accurate
change of 40 mV per oC. These devices are highly accurate readings. Modern tympanic thermocouples are soft and
and available in very small sizes. pliable.
Infrared tympanic thermometer Nasopharyngeal probes should be inserted at least a few

centimeters past the nares to obtain core temperature;
This is a device which measures radiant infrared (an
nasopharyngeal temperature are probably only accurate in
application of the Boltzmann constant), commonly from the
patients who are not breathing through their nostrils. Blood
ear drum, which is detected by a thermopile (a collection of
temperature can be measured using a thermistor attached
thermocouples). This signal is then converted within around
to a pulmonary flotation catheter (Schwan-Ganz catheter).
5 s into a temperature reading which is very accurate for
Measuring blood temperature in the pulmonary circulation
core temperature.
is the best estimate of core temperature but this is a very
Measures of temperature invasive technique. It can also be used to measure cardiac
output using thermodilution.
Kelvin
Skin-surface temperatures are considerably lower than
One kelvin is equal to 1/273.16 of the thermodynamic triple
core temperature; forehead skin temperature, for example,
point of water. A change in temperature of 1 K is equal
is typically 2°C cooler than core. Perhaps surprisingly, even
in magnitude to that of 1 °C. Kelvin must be used when
the intense vasodilation associated with sweating and the
performing calculations with temperature.
intense vasoconstriction associated with shivering, slightly
Celsius/centigrade alter the core-to-forehead temperature gradient. The 1−2°C
ambient temperature differences usually observed during
Celsius (formerly called the degree centigrade) is a surgery thus have little effect on the core-to-forehead
common measure of temperature in which a change of 1 temperature gradient. Forehead skin temperature is thus a
°C is equal in magnitude to a change of 1 K. To convert

Different Types of temperature monitoring: a) Nasopharyngeal probe b) Skin probe

c) Tympanic temperature probe, d) Temporal artery thermometry, e) Bladder probe,
f) Esophageal stethoscope with temperature sensor
surprisingly accurate measure of core temperature so long bypass. In contrast, rectal temperatures lag behind those
as a +2°C compensation is included. measured in core sites. Consequently, rectal temperature
is considered an “intermediate” temperature in deliberately
The four core temperature monitoring sites (e.g., cooled patients. During cardiac surgery, the adequacy of
tympanic membrane, nasopharynx, pulmonary artery, and rewarming is best evaluated by considering both “core” and
esophagus) remain useful even during cardiopulmonary “intermediate” temperatures.

Site Uses Limitations
Close to internal carotid Adjusts slowly to rapid changes in cerebral temperature.

Nasopharynx
artery Placement can cause nasal bleeding
Pulmonary Mixed Venous blood Affected by CPB. Decreased for several minutes after
artery temperature receiving cold cardioplegic solutions
Decreased by suctioning on nasogastric tube. Affected by

Convenient, close to ventilation through endotracheal tubes. Affected by CPB. Not
Esophageal
heart and great vessels recommended by the AHA for monitoring during therapeutic
hypothermia.
Accuracy is dependent on urine output/flow rate.

Better reflector of core Affected by intra-abdominal surgeries. Unreliable during
Bladder
temperature than rectal. CPB. Not recommended by the AHA for monitoring of anuric
patients during therapeutic hypothermia
Decreased by air currents.† Affected by changes in

skin temperature on the head and face.† Response to
Closest to Core temperature change is delayed by cerumen or dried blood in
Tympanic (Hypothalamus) via the auditory canal† Probes are difficult to place correctly.*†
internal carotid artery Placement may perforate the tympanic membrane.† Not
recommended by the AHA for monitoring during therapeutic
hypothermia
Changes occur more slowly. Can become lodged in fecal

Reflects peripheral
Rectal matter. Not recommended by the AHA for monitoring during
tissue.
therapeutic hypothermia
Useful in neonates – Can have 2°C difference from core. Changes more slowly
indicate temperature during induction of hypothermia and with rewarming. Not
Skin
gradients & cutaneous recommended by the AHA for monitoring during therapeutic
vascular tone hypothermia
Takes 15 minutes to equilibrate. Affected by Blood Pressure

Axilla convenient
cuff. Must be placed over axillary artery.
Table 1: Sites of Temperature monitoring.
(CPB, Cardiopulmonary Bypass; AHA, American Heart Association; * denotes measured by infrared; † denotes measured
by thermocouple).

Redistribution of heat after induction of anesthesia
Intra-operative Hypothermia [24,25] Etiology
During anaesthesia, hypothermia may be defined as a 1. Abolished behavioral responses

core body temperature less than 36°C. This can cause 2. Increased heat loss through mechanisms
physiological derangement in the operating theatre and mentioned below.
in recovery, and may increase perioperative morbidity. 3. Cooling effect of cold anesthetic gases and
Both general and regional anaesthesia have been shown intravenous fluids
to reduce core body temperatures with losses of 0.5–1°C
within the first hour, due to redistribution of heat from the 4. Widened interthreshold range. Heat production falls
core to the periphery, and a further loss of 0.3°C/hour as anesthetic agents alter hypothalamic function.
thereafter. It should be noted that a 1000 ml bag of fluid at The lowering of the hypothermic threshold is related
room temperature could reduce body temperature by 0.5°C to MAC. The interthreshold range widens so that
thermoregulatory responses are not triggered until
The effects of hypothermia are proportional to the change core temperature has deviated much further than
in temperature. Metabolic rate is reduced by up to 10% for normal from 37°C.
every 1°C fall in body temperature. There is a reduction
in cardiac output and an increase in hemoglobin oxygen 5. Reduced metabolic heat production (15-40%),
affinity. This leads to a decrease in tissue oxygen delivery. particularly by:
Significant hypothermia is associated with metabolic • Reduced muscle activity
acidosis, oliguria, altered platelet and clotting function and • Decreased brain metabolism
reduced hepatic blood flow with slower drug metabolism.
The MAC of inhalational agents is reduced and muscle Induction of general anaesthesia typically results in a 1°C
relaxants have a prolonged effect. Postoperative shivering fall in core temperature within the first 30 minutes. Changes
increases oxygen consumption and myocardial work. There in core temperature are due to redistribution at this early
may also be an increased incidence of wound breakdown stage. As a result, the core compartment cools and expands,
and infection. while the peripheral compartment warms and contracts.

Thermoregulatory response thresholds - The autonomic thermoregulatory response thresholds in normal conditions,
during warming of the face/hands/feet or under general anesthesia.
Action of anesthetic drugs on thermoregulatory defense mechanisms

Patterns of hypothermia during regional anesthesia compartment, and patients with cool peripheries
will suffer a greater degree of core hypothermia.
Perioperative hypothermia during regional anaesthesia can
be as severe as that seen with general anaesthesia, because • Neonates and infants have a much larger core
it also significantly impairs thermoregulatory responses. compartment than adults, as it extends closer to the
body surface.
• Central effect. Loss of afferent input from cold
receptors impairs the central thermoregulatory • Body morphology. Obese patients tend to have
response. warmer peripheries, as the adipose tissue acts as a
thermal insulator resulting in vasodilatation.
• Redistribution. Blockade of sympathetic
vasoconstriction causing redistribution hypothermia Linear Phase
in the lower half of the body, means that the initial
temperature drop will be about half that seen with This begins at the start of surgery, as the patient is exposed
GA. Blockade of motor nerves impairs shivering. to cold cleaning fluids and cool air flow in the theatre. Heat
loss exceeds heat production and most surgeries do not
• Lack of core temperature plateau because of extend past the linear phase.
blocked vasoconstriction
• Radiation contributes the most (40%) and is
Patterns of hypothermia during general anesthesia proportional to environment/core, temperature
difference to the power of four.
• Convection contributes up to 30% and is

proportional to air velocity
• Conduction contributes up to 5% and is proportional

to the difference in surface temperatures
• Evaporation contributes up to 15% and occurs

from cleaning fluids, skin, respiratory and wound.
A laparotomy can contribute up to 50% of the total.
• Respiratory contributes 10% (8% evaporation of

water; 2% heating of air) and is enhanced by the
cooling effect of cold anesthetic gases.
• Cold intravenous fluids.
Plateau Phase
Following the induction of anaesthesia, core
hypothermia occurs in three stages; Once core temperature falls below the thermoregulatory
1. Redistribution threshold, peripheral vasoconstriction increases and acts
2. Linear phase to limit the heat loss from the core department. When
3. Plateau phase core heat production equals heat loss to the peripheral
compartment, core temperature reaches a plateau. Patients
Redistribution
with an autonomic neuropathy (diabetics) have impaired
This accounts for the largest drop in core temperature of sympathetic vasoconstriction and are unable to establish a
the three stages. Vasodilatation causes redistribution of core plateau in phase 3.
heat from core to periphery. Body heat content remains
Consequences of perioperative hypothermia
unchanged.
Hypothermia affects over 60% of patients intraoperatively,
Factors affecting redistribution
and its effects are noteworthy. It adversely impacts
• Patients initial heat content. More heat will be blood loss, infection risk, and cardiac events, potentially
transferred from the warm core to a cold peripheral increasing length of hospital stay. It also slows anesthetic

drug metabolism and may alter pharmacodynamics, thus core temperature than skin temperature. However, core
contributing to increased post anesthesia care unit (PACU) normothermia does not guarantee that shivering will not
recovery time. occur. Fortunately, vasoconstriction and hypothermia
usually resolve by postoperative day one.
Blood loss [26, 27]
Cardiac events [32,33]
In a recent large retrospective study of non-cardiac
surgeries published in 2015, transfusion requirements Studies are inconsistent in determining whether, the
increased in proportion to the decrease in temperature and increased risk of myocardial infarction is due to shivering
the increased duration of hypothermia. Potential causes for or stress hormones. Physiologic responses to hypothermia
increased blood loss include hypothermia-induced platelet in nonsurgical patients include vasoconstriction and
dysfunction and coagulation cascade enzyme dysfunction. sympathetic nervous system stimulation leading to increased
epinephrine, norepinephrine, blood pressure, and heart
Surgical wound infection rate; however, stress hormones in surgical patients seem to
Mild hypothermia has been associated with increased risk respond differently. The difference between intraoperative
of surgical wound infection ,due to vasoconstriction and and postoperative stress hormone levels may suggest that,
change in oxygen tension. At 34.5 ℃, thermoregulation leads a time lag exists between stressful stimuli and hormone
to peripheral vasoconstriction. When this occurs, oxygen response. Alternatively, anesthetics may attenuate the
delivery to subcutaneous tissues decreases, impairing the stress response and protect the myocardium. This would be
strength of the collagen lattice that supports the healing consistent with the risk of myocardial infarction increasing
scar. Decreased oxygen delivery also impairs chemotaxis, and occurring postoperatively instead of intraoperatively.
phagocytosis, and antibody production by white blood cells Prevention and treatment of hypothermia [34,35]
and the immune system.
Hypothermia treatment involves minimizing cold exposure
Length of hospital stay and PACU recovery time [28] while providing heat sources, such as heat transfer systems,
PACU discharge times are also impacted by hypothermia. to equalize heat loss.
Discharge from the PACU was observed to significantly Heat transfer systems may be passive or active.
increase by 40 min in hypothermic patients based on a
modified Aldrete scoring system. Passive warming methods include passive insulation,
environmental warming, and closed or semi-closed
Drug metabolism [29,30] anesthesia systems.
Mild hypothermia impairs temperature-sensitive Active warming requires heat transfer to the patient through
enzymes that metabolize and clear anesthetic drugs, warmed fluids, circuit humidification, radiant heaters, forced
thus increasing their duration of action. The effect on or convective air warmers, infrared lights or circulating
potency differs, depending on the drug. The durations of hot water systems. A combination of these methods is
action of midazolam, morphine, propofol, and several likely most effective in practice; however, prevention of
non-depolarizing neuromuscular blocking agents (e.g., hypothermia is likely a superior approach to treatment.
vecuronium, rocuronium, atracurium) are prolonged
due to the pharmacokinetic effect of hypothermia. The Passive warming
twitch tension starts to decrease 16% per 1℃ once the
temperature of the adductor pollicis muscle is below 35.2 • Passive warming methods, including environmental
℃. With moderate hypothermia to 30℃, morphine also has heating and passive insulation, minimize but do not
decreased potency, clearance, and volume of distribution; eliminate heat loss.
although, its concentration is elevated in the plasma and • The operating room temperature is the most critical
cerebral spinal fluid. Notably, the efficacy of neostigmine factor influencing heat loss.
and naloxone seems to be preserved during hypothermia. • Heat loss increases as the difference between
the skin and environment grows. Consequently,
Shivering and thermal discomfort [31]
the simplest method to reduce heat loss is raising
If a patient is hypothermic, there is an increased incidence of ambient temperature.
thermal discomfort, oxygen consumption, vasoconstriction, • Thermal insulation may be accomplished through
and shivering. Shivering is four times more dependent on mass or reflective covering. Surgical drapes and

System Effects of Hypothermia
34°C - Vasoconstriction & Increased afterload

32°C - Myocardial depression, irritability
Cardiovascular 31 °C - Conduction abnormalities
30°C - ventricular ectopics
28°C - ventricular fibrillation, Angina
Impaired Hypoxic Pulmonary Vasoconstriction

Decreased CO2 Production
Respiratory
Left side shift of ODC curve
Diminished ventilator response to hypoxic and hypercarbia
34°C - decreased Cerebral Metabolic Rate

Neurological 33°C - Obtundation, delayed emergence from anesthesia
30 °C - Coma, papillary dilation
Problems of increased blood viscosity (Ischemia & thromboembolism)

Hematalogical Thrombocytopathy and thrombocytopenia
Impaired coagulation
Metabolic Hyperglycemia (catecholamine release & inhibition of insulin release)
Renal Cold diuresis (impaired sodium absorption)
Hepatic Impaired clearance of drugs
Table 2: Effects of Hypothermia on Organ System Function.
blankets are common examples, and covering

patients with blankets is a standard practice.
Unfortunately, effective covering of the body
surface is often not feasible in the intra-operative
setting making passive methods ineffective to
prevent hypothermia.
Active warming
Active warming is required in most situations to maintain
normothermia.
Methods include- warming of intravenous fluids, cutaneous
warming, pharmacologic vasoconstriction, and intravenous
nutrients. Of these choices, cutaneous warming (e.g.,
forced air warming, electrical resistance, circulating hot
water device) is the most widely used.
Cutaneous warming
• Likely the most common warming system, forced air
warming is effective, safe, relatively inexpensive,
easy to use [45,49], and superior to many other
warming systems[50,51].
• Forced air warmers were initially utilized to treat

postoperative hypothermia before they were
introduced for intraoperative warming.

• In this method, warmed air is forced into a • The whole Ecotherm range is manufactured from
receptacle, commonly a two-layer blanket, which a reflective plastic film bonded with a soft, but very
lies in direct contact with a large surface area of the strong non-woven fabric.
body. The forced air escapes through pores of the
blanket material creating a warm microclimate over • It can be used with diathermy/ image intensifiers
the area of contact. and x-ray.
• Heat transfer is dependent on both the amount Warming intravenous fluids

of surface area covered and the temperature
difference between the skin and blanket.
Consequently, the effectiveness is dependent upon
utilization of a properly shaped warming blanket,
appropriate placement on the body, and selection
of a high warming temperature.
Ecotherm passive insulators
• These include water baths, conductive warming with

metal, countercurrent heat exchange, microwave
technology, and forced-air warming.
• All systems provide a range of flow velocities and
temperatures with built-in prevention technologies
for excessive warming and air detection.
• However, while 42 ℃ is considered safe for blood
administration, the safe upper limit is not well
defined.
Conclusion
Core body temperature is normally tightly regulated. During

perioperative period, anesthetic induced impairment of
normal thermoregulatory control, and the resulting core-to-
peripheral redistribution of body heat is the primary cause
of hypothermia, which can lead to poor clinical outcomes.
As per current guidelines, body temperature should be
measured in patients having general anesthesia exceeding
30 minutes in duration, and in patients having major
operations under neuraxial anesthesia. Prevention of hypo
• The Ecotherm range of products are passive or hyperthermia is likely a superior approach to treatment.
insulators, that work by preventing heat loss due to
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Sessler DI. Effect of postoperative skin-surface

MCQ
1. Transmission of cold sensation occurs through 4. Which of the following is not a site of core temperature ?
_________ nerve fibres
a. Tympanic membrane
a. unmyelinated C b. Esophageal Stethoscope
b. A delta c. Pulmonary artery
c. both a & b d. Rectum
d. A gamma
5. Body temperature should be monitored in patients
2. False about non shivering Thermogenesis undergoing general anesthesia exceeding _________
minutes in duration
a. It is mediated via beta three adrenergic receptors
located in brown fat a. 45
b. Brown fat is more abundant in infants and is located b. 60
between the scapula, at the nape of the neck c. 30
c. It contains many sarcoplasmic reticulam (giving d. 120
brown color)
d. It has little significance in adults
3. The principle of Seebeck effect is used in
a. Thermister
b. Infra red thermometer
c. Thermocouple
d. None
5.C 4.D 3.C 2.C 1.B
ANSWERS:

43 CELIAC PLEXUS BLOCK
Associate Professor Arul Murugan

SRIHER
Chennai
Key points
Ø The celiac plexus is comprised of three pairs of ganglia: the celiac ganglia, superior mesenteric ganglia, and
aorticorenal ganglia. Several abdominal organs receive autonomic innervation through the celiac plexus
Ø Celiac plexus is located at the antero-lateral aspect of the first lumbar vertebral body
Ø Celiac plexus block is used for relief of intractable pain from non-pelvic intra-abdominal organs
Ø Before the procedure, intravenous fluids are required pre-block to reduce the risk of hypotension after the
procedure
Introduction • The upper abdominal organs receive their

parasympathetic supply from the left and right
The celiac plexus block (CPB) has been in practice for
more than 100 years, as a method of providing surgical vagal trunks, which pass through the celiac plexus
anesthesia to the upper abdomen. In the past two decades, but do not connect there.
as multimodal approach for pain management, celiac Indications
plexus block is now being used as an adjunct to managing
intractable abdominal pain, due to various causes. For relief of intractable pain from non-pelvic intra-abdominal
The celiac plexus is comprised of three pairs of ganglia: organs.
the celiac ganglia, superior mesenteric ganglia, and • Acute pain - may be performed during surgery for
aorticorenal ganglia. Several abdominal organs receive
postoperative pain relief.
autonomic innervation through the celiac plexus. The celiac
plexus block aims to target the afferent nociceptive fibers • Chronic pain - useful for any condition that causes
and is suitable to be used as both a diagnostic as well as a chronic severe upper abdominal visceral pain - e.g.
therapeutic tool for managing intraabdominal pain. chronic pancreatitis.
Anatomy
• Cancer pain - upper abdominal organ cancer
The celiac plexus is also known as the solar plexus. It is pain, and is frequently used for carcinoma of the
the main junction for autonomic nerves supplying the upper pancreas: diagnostic local anaesthetic block,
abdominal organs (liver, gall bladder, spleen, stomach, followed by neurolytic block.
pancreas, kidneys, small bowel, and 2/3 of the large bowel).
The celiac plexus proper consists of the celiac ganglia with Contraindications
a network of interconnecting fibers. The ganglia lie on each
• Bleeding and infection risks
side of L1 (aorta lying posteriorly, pancreas anteriorly and
inferior vena cava laterally). • Where the source of the pain is no longer being
Sympathetic supply transmitted through the autonomic nerves.
• Greater splanchnic nerve (T5/6 to T9/10) Lesser • It is dangerous to perform the block in the presence
splanchnic nerve (T10/11) Least splanchnic nerve of a large aortic aneurysm.
(T11/12)

Celiac Plexus Block 410 Arul Murugan
Technique Percutaneous Technique
The block can be performed in various ways: The most commonly used method for celiac plexus block
traditional landmark technique, surgical, percutaneous, involves the posterior approach with the percutaneous
ultrasonographic, fluoroscopic, computed tomography insertion of needles directed toward the celiac plexus.
(CT)-guided, and endoscopic ultrasonographic (EUS). The patient is placed in a prone position and needles are
Before the procedure, intravenous fluids are required pre- inserted bilaterally slightly below the inferior ribs (T12) at
block to reduce the risk of hypotension after the procedure. points approximately 6 to 8 cm from the midline [Figure 1].
Fig 1: Landmark for needle insertion
Radiographic guidance is typically used to direct the needles advances past the vertebral body, it should be inserted an
towards the celiac plexus, which is located at the antero- additional 1-2 cm, or until the dense wall of aorta is identified
lateral aspect of the first lumbar vertebral body. The celiac by pulsatile transmissions through the length of the needle.
plexus consists of a network of neural ganglia surrounding On the right side, the needle can be inserted another 1-2 cm
the aorta. On the left side (aortic side), once the needle beyond the anterior plane of the vertebral body (Figure 2).
Fig 2

Prior to the injection of drug, the needle is aspirated to rule even though its advantage over traditional percutaneous
out the presence of cerebrospinal fluid, blood, or urine. method is often debated. Fluoroscopy is commonly used to
The needle position is then confirmed with the injection of assist in the correct placement of needles and for confirming
a radio contrast agent. It is important to ensure that there appropriate spread of injected solution to the targeted area.
is no spread of radio contrast to the epidural or intrathecal Others have advocated the use of CT imaging for greater
spaces, psoas muscle (which encases the lumbar plexus), accuracy, especially given the possibility of anatomic
nerve roots, and vascular structures, especially the aortic distortions with tumor spread.
wall. Then 10 ml of local anaesthetic is injected on each
The needle entry point is just below the tip of the 12th rib,
side. If there are no neurologic deficits after 10 minutes, 10
and using fluoroscopic screening in two planes, the needle
ml of neurolytic agent (absolute alcohol) is injected on each
is advanced until it hits the side of the L1 vertebra. The
side to spread to the celiac plexus. This can have an effect
needle is withdrawn slightly and then redirected forwards
for 3-6 months duration.
until it is in the area of the celiac plexus, avoiding the aorta
Radiographic Technique and inferior vena cava. Radio contrast agent is injected to
confirm the correct placement of the needle, and then the
The use of radiographic guidance to perform the celiac appropriate drug is injected.
plexus by posterior approach is also commonly practiced
As the block causes dilatation of the upper abdominal • Upper abdominal organ puncture with abscess/cyst
vessels, it leads to venous pooling causing hypotension. formation.
This can be exacerbated by pre-existing dehydration.
• Paraplegia from injecting phenol into the arteries
Hence, the patient has to be hydrated well with intravenous
that supply the spinal cord (prevented by checking
fluid, before performing the block.
the needle position with radio contrast agent).
Complications
• Sexual dysfunction (injected solution spreads to the
• Severe hypotension may result, even after unilateral sympathetic chain bilaterally).
block.
• Intramuscular injection into the psoas muscle.
• Bleeding due to aorta or inferior vena cava injury
• Lumbar nerve root irritation (injected solution tracks
by the needle.
backwards towards the lumbar plexus).
• Intravascular injection (should be prevented by
checking the needle position with radio contrast
agent).

References Further Reading:
• Anaesthesia UK https://www.anaesthesiauk.com/ • Hadzic’s Textbook of Regional Anesthesia and

Acute Pain Management, Second Edition
• Sankalp Sehgal, Ahmed Ghaleb, Neurolytic celiac
plexus block for pancreatic cancer pain: A review • Treatment of Chronic Pain by Interventional
of literature Indian Journal of Pain. September- Approaches: the AMERICAN ACADEMY of PAIN
December 2013 | Vol 27 | Issue 3 MEDICINE Textbook on Patient Management
• Lawrence M.M., Hayek S.M., Goldner J.D. (2013) • Atlas of Sonoanatomy for Regional Anesthesia and
Celiac Plexus, Splanchnic Nerve Block, and Pain Medicine
Neurolysis. In: Deer T. et al. (eds) Comprehensive
Treatment of Chronic Pain by Medical, Interventional,
and Integrative Approaches. Springer, New York,
NY

MCQ
1. Celiac plexus block is NOT indicated for
a) Chronic upper abdominal visceral pain

b) Pain due to Spinal metastasis
c) Pain due to Carcinoma of pancreas
2. Contraindication for Celiac plexus block
a) Carcinoma of pancreas
b) Liver Cirrhosis with coagulopathy
c) Acute Necrotizing Pancreatitis
3. Sympathetic supply of Celiac plexus
a) Greater and Lesser splanchnic nerves

b) Least splanchnic nerve
c) All of the above
3.C 2.B 1.B
ANSWERS:

20/20
44 INTRAOPERATIVE FLUID THERAPY - CLINICAL PEARLS
Professor Lakshmi Kumar

Amrita Institute of Medical Sciences & Research Centre
Kochi
Key points
Ø The goal of IV fluid administration is to restore and maintain tissue fluid and electrolyte homeostasis, while avoiding
salt and water excess.
Ø The fluids in the body are distributed in the intravascular, extravascular and interstitial compartment
Ø Surgical losses should be replaced as per the judgement of the anaesthesiologist.
Ø Balanced salt solutions that contain a buffer are considered as optimal for perioperative fluid replacement.
Ø Early uses of small doses of vasopressors ,can help maintain restrictive strategy.
Ø Abdominal plane blocks are effective analgesic options in minimally invasive surgery and decreases hypotension
associated with epidurals.
Ø Restrictive fluid strategy resulted in shorter ICU stay, lesser ileus and improved outcomes.
Ø GDT use is reserved for high risk patients and may be safer with advanced hemodynamic monitoring such as TEE
or PICCO.
Ø Colloids can be used judiciously to enhance the restrictive fluid policies during surgery.
Ø Achieving optimal IV fluid therapy improves perioperative outcomes
Introduction remainder of the extracellular space occurs at the vascular

endothelial barrier as described by Starling.
The fluids in the body are distributed in the intravascular,
extravascular and interstitial compartment. Conventional The fluid components of the blood are contained within the
teaching that, the administration of crystalloids distributes vessels of the microcirculation mainly by the inward pull of
fluids equally between all three compartments has been colloid osmotic pressure (COP), produced by the protein
challenged. The distribution of colloids may be marginally content of the plasma. This opposes the high outward
higher (1.6 to 2 times) in the intravascular as compared to hydrostatic pressure, which tends to push plasma out of
the extravascular compartment. the vessels and into the interstitium. Both the hydrostatic
and colloid osmotic pressure in the interstitium is low. The
Composition of body fluids net result of these forces is, a small outward leak of fluid
Water constitutes about 60 % lean body mass, which and protein from the vasculature to the interstitium which
amounts to 42 L in a 70 Kg adult male. Two thirds of this is continually returned to the blood .In the ECF, Na+ is
is intracellular (28L) and 14L constitutes the extracellular the principal cation and Cl- the anion. In contrast, in the
fluid that can be divided into interstitial fluid (11L) and intracellular compartment, K+ is the major cation and PO4-
plasma (3 L).The capillary endothelium is freely permeable the principal anion, with a high protein content. Osmotic
to water, anions, cations, and other soluble substances equilibrium is preserved, as the membrane is impermeable
such as glucose but, is impermeable to protein and other to ions in health. TBW is maintained by balances in thirst,
large molecules. Fluid shifts between the intravascular and renin-angiotensin and atrial natriuretic peptide.

Intraoperative Fluid Therapy - Clinical Pearls 418 Lakshmi Kumar
What are consequences of extra fluid administration? Sterofundin (Ringerfundin). Of all ,Plasmalyte is
the most physiologic with plasma, as the chloride
• Healthy vascular endothelium is coated by
and sodium content are closest to normal. This is
transmembrane syndecans and membrane-bound
increasingly being used in patients with end organ
glypicans containing, heparan sulfate and chondroitin
disease. Preliminary use suggests that, the acetate
sulfate side chains, which together constitute the
buffer may be safe for liver and renal disease
endothelial glycocalyx.
patients.
• Bound plasma proteins, solubilized
What are the recommendations for fluid administration?
glycosaminoglycans, and hyaluronic acid constitute
the glycocalyx of the endothelial surface layer • Normally, insensible fluid losses are replaced by free
(ESL), which is subject to periodic constitution and water absorption from the gastrointestinal tract.
degradation.
• In a fasted patient, whose GIT replacement may be
• The glycocalyx seems to act as a molecular filter, inadequate, this will present as dehydration which
retaining proteins and increasing the oncotic pressure can be corrected by administration of crystalloids.
within the endothelial surface layer. This is the rationale in the administration of fluid
• The commonest cause for disruption of the deficit in preoperative patients.
glycocalyx is iatrogenic hypervolemia associated with • Blood and losses of fluid with protein, affect the
perioperative transfusion. This results in the release intravascular compartment.
of atrial natriuretic peptide and denudation of the
ESL, resulting in fluid movement in to the interstitial • The common belief is that, crystalloids when
space. given as a replacement equilibrate between the
intravascular and interstitial spaces ,and fluids
• Despite growing evidence on allowing fluids as close
like colloids may preferentially remain in the
to the surgery, concerns on preponement of surgical
intravascular space. Physiologic fluid shifting from
times, leads to longer durations of fasting and can
the vessel toward the interstitial space across an
lead to preoperative fluid deficits and even electrolyte
intact vascular barrier, contains only small amounts
imbalances prior to surgery.
of proteins. It does not cause interstitial edema as
• Surgery carries a risk of per-operative losses in long as it can be quantitatively managed by the
addition to on going insensible losses. lymphatic system.
What is the right choice of fluid? • Major surgery causes a deficit of 3-6L in the
perioperative fluid balance which lasts for up to
• In the current understanding, balanced salt solutions
72 hours after trauma or surgery. The common
that contain a buffer (bicarbonate, acetate, lactate or
explanation for this phenomenon is a fluid shift into
gluconate) are considered as optimal for perioperative
the so-called third space. Unlike the interstitial fluid
fluid replacement.
that is reabsorbed by lymphatics, losses toward this
• The deterrent to the use of normal saline came in compartment are assumed to be trapped and lost for
with the awareness that, normal saline is not “normal” extracellular exchange.
or physiologic, as it contains a mix of two electrolytes
• This pathologic fluid shift is caused by dysfunction
sodium and chloride in water. This translates to the
of the vascular barrier. In contrast to the other type,
fact that administration of 1.0 L of normal saline will
this fluid crossing the barrier contains proteins
dilute the body’s stores of bicarbonate by 1.0 L.
close to plasma concentration. The reasons for this
The dilutional hyperchloremic acidosis that results,
shift are, surgical manipulation, which increases
could affect renal function by causing constriction of
capillary protein permeability excessively. Secondly,
afferent renal arterioles and activation of the renin
angiotensin aldosterone axis. reperfusion injury and inflammatory mediators
compromise the vascular barrier and as mentioned,
• The alternate crystalloid solutions available are iatrogenic hypervolemia can lead to glycocalyx
Ringer’s lactate, Ringer’s acetate , Plasmalyte and degradation and fluid shifts.

What should be the guidelines for intraoperative fluid The end points in GDT are, achievement of supranormal
replacement? oxygen delivery measured by cardiac index, oxygen
extraction ratio and oxygen delivery indices(DO2I).
• Standard teaching in anaesthesia would be, to
replace the fluid deficits that occur during starvation In India, the Flotrac Vigileo, and its newer platform EV 1000
per operatively. In addition depending upon the extent have been used in the setting of GDT and, few studies have
of the surgery the fluids replaced are administered at established improved recovery although, the concurrent
6, 8 or 10 ml/kg body weight per hour. restrictive strategy and GDT may be difficult to achieve.
• Minor surgeries without tissue exposure may only Cardiac output monitors
need the maintenance requirements at 2-4 ml/kg/
hour. • Cardiac output monitoring using minimally invasive
cardiac output monitors, may be useful in assessing
• With this formula, it is not uncommon to infuse volume status during surgery.
6-8 litres crystalloid and 1 litre colloid for a major
• These systems are derived from arterial pulse contour
abdominal surgery.
analysis, where the cardiac output derived from the
Liberal versus restrictive fluid strategy integrity of the arterial trace and vascular compliance,
can provide the systemic vascular resistance.
• A restrictive rather than liberal fluid strategy, has
• The technology varies between different monitors,
been shown to be beneficial in colorectal surgery.
uncalibrated using patient demographics Flotrac
Excess use of fluids particularly crystalloids ,is known
Vigileo (Edward Lifesciences), using indicator dilution
to be associated with bowel edema, postoperative
for cardiac output by pulse contour analysis(LidCO).
ileus and prolonged postoperative recovery.
Flotrac Vigileo and its newer platform EV 1000, (with
• A restrictive strategy is part of the ERAS guidelines in continuous derived SVR from CVP feedback)are
abdominal surgery. most user friendly, and its simplicity allows a wider
use amongst non-cardiac anaesthetists.
• Allowing the patient to drink fluids (400ml to 2 h prior
to surgery) eliminates need for fasting replacement. • Stroke volume variation (SVV) is the technology in
the Flotrac Vigileo monitors. It is a naturally occurring
• Perioperatively, the use of an epidural analgesia phenomenon in which the arterial pulse pressure
and anaesthetic agents, contribute to vasodilatation falls during inspiration and rises during expiration,
and fall in blood pressure. The anaesthesiologist due to changes in intra-thoracic pressure secondary
commonly corrects this by fluid administration. to negative pressure ventilation (spontaneously
Studies have unequivocally shown that, a restrictive breathing). Variations over 10mmHg have been
strategy resulted in shorter ICU stay, lesser ileus and referred to as pulsus paradoxus. The normal range
improved outcomes. of variation in spontaneously breathing patients has
been reported between 5-10mmHg.Reverse pulsus
• The restrictive policy can be implemented by
paradoxus is the same phenomenon with controls
concurrent use of vasopressors and appropriate
mechanical ventilation.
colloids when possible. The concerns on the
restrictive use is, adequacy of renal perfusion and • Arterial pressure rises during inspiration and falls
lactate levels. during expiration due to changes in intra-thoracic
pressure, secondary to positive pressure ventilation.
Goal directed therapy In addition to reverse pulsus paradoxus, it has also
Goal directed therapy is aimed at improving surgical been referred to as paradoxical pulsus, respiratory
outcomes in high risk patients, the goals being improvements paradox, systolic pressure variation and pulse
in tissue oxygenation. This has been possible, by the use of pressure variation.
minimally invasive cardiac output monitors. This technique • Traditionally SVV is calculated by taking the SVmax
was originally applied in surgical patients, to achieve - SVmin / SV mean, over a respiratory cycle or other
normal or supranormal values of CO and DO2 to prevent period of time. An SVV value < 10%, is considered
the oxygen debt caused by the perioperative increase in indicative of adequate filling during surgery.
oxygen consumption.

• The pulse pressure variation is derived from the dysfunction due to the binding of the HES molecule to the
same principles and is available on the monitors platelets.
of anaesthesia work stations. The maximum and
minimum pulse pressure varations during one Most of the adverse effects reported, involve the larger
respiratory cycle are used in the calculation of molecular weight starches and were not seen when the
PPV,and values < 14 % are considered to be normal molecular weight was reduced to 130 and the molar
for fluid filling. substitution to 0.4.
• The PICCO /Volume view, appears most sensitive Three large randomised multicentric trials (6S, CRYSTMAS
amongst current monitors, as it combines and CHEST) however showed that, the administration of
transpulmonary thermodilution with arterial contour starches in critically ill patients was associated with adverse
derived cardiac output. In addition it can determine renal outcomes with no differences in mortality. The change
global end diastolic volume and extravascular lung to the usage of gelatins instead of HES did not decrease
water, that can predict early volume overload. PiCCO the incidence of acute renal failure and morbidity in a
and Volume view cardiac output monitors however, retrospective cohort of surgical intensive care patients.
needs a femoral arterial access and needs to be
Anaphylaxis is a known side effect with the use of gelatins,
used with caution.
owing to the bovine protein component.
• The advantages with the use of these advanced
monitors is that, it allows an assessment of the Clinical effects of administration of gelatins or starches
systemic vascular resistance and allows titration of on coagulation has not been reported. Few studies that
vasopressors during surgery. have evaluated coagulation by point of care testing have
confounding variables. We believe at this point that, it
• Fluid administration is guided by pulse pressure may be safe to administer limited amounts of colloids not
variation and stroke volume variation, which is based exceeding 20 ml/kg over 24 h in ASA I, II patients, who have
upon the principle that, the stroke volume variation very low risks for sepsis or renal dysfunction perioperatively.
with respiration is dependent upon fluid deficit and
correction of this deficit will increase cardiac output Summary and Conclusions
within physiologic limits.
1. To minimise fasting and allow patient clear liquids
• Transoesophageal echocardiography can help with orally, both on the night before, and upto 2 h prior to
volume assessment and perioperative ischemia surgery.12% maltodextrin that contains a complex
assessment. As parameters are objective, its carbohydrate may be superior to clear juices.
reliability is very high, however, availability of the
machine,technical training towards optimal use and 2. Intraoperative fluids as a maintenance ,can be provided
costs, have limited its availability in non-cardiac theatres. at 2 ml/kg/h. Surgical losses are to be replaced as per
the judgement of the anaesthesiologist.
Current evidence for the perioperative use of colloids?
3. Early uses of small doses of vasopressors are not
Colloids were in extensive use in last 2 decades but their associated with poorer outcomes, and can help maintain
use has significantly declined with awareness of potential restrictive strategy.
side effects in predisposed individuals. 4. Infusions of epidural can be withheld during surgery,
to reduce epidural induced vasodilatation and
The main reasons for fluid shifts to occur are surgical
hypotension.
manipulation, reperfusion injury and perioperative fluid
administration. 5. Minimally invasive surgery allows implementation of
restrictive strategies
Some clinicians have described this as 2 disorders
6. Abdominal plane blocks are effective analgesic
o Type 1 which involves passage of colloid free options in minimally invasive surgery and decreases
fluid and electrolytes hypotension associated with epidurals.
o Type 2 with the passage of protein rich fluid.
7. GDT use is reserved for high risk patients and may be
Two of the reported adverse effects with the use of colloids safer with advanced hemodynamic monitoring such as
are: renal dysfunction and coagulation abnormalities. TEE or PICCO.
Coagulation abnormalities reported, involve reductions 8. Colloids can be used judiciously to enhance the
in Factor VIII, von Willebrand factor (vWF) and platelet restrictive fluid policies during surgery.

MCQ
1. 0.9% normal saline advantages are all except 4. DEXTRAN used for microsurgical reimplantation and
ECMO can precipitate
a) Diluting packed rbc before transfusion
b) Replace salt loss a) Acute renal failure
c) Diluting drugs b) Heart failure
d) Hyperchloremic metabolic acidosis c) Acidosis
d) Alkalosis
2. Administration of ringer lactate is avoided along with
blood products because 5. What is the fluid requirement to manage the third space
loss occurring during asevere surgical trauma
a) Increased preload
b) Increased afterload a) 0-2ml/kg/hr
c) Reduction in anticoagulant activity as calcium binds b) 2-4ml/kg /hr
with citrate c) 4-6ml/kg/hr
d) Can be allergic d) 6-8ml/kg/hr
3. which is indicated as a pediatric maintenance fliud
a) DNS
b) RL
c) Isolyte-P
d) NS
5.C 4.A 3.C 2.C 1.D
ANSWERS:

45 PEEP PHYSIOLOGY AND ITS APPLICATIONS
Professor and Head Arunkumar A S

Department of Critical Care Medicine
Saveetha Medical College,
Chennai
Key points
Ø PEEP management is considered a cornerstone of overall ventilator strategy in the management of patients with
hypoxia, especially those with ARDS
Ø PEEP increases the time available for gas exchange, reduces V/Q mismatch and thereby improves oxygenation
Ø Opening up a collapsed alveoli requires generation of higher pressure than inflating an already open alveoli
Ø PEEP levels that cause alveolar recruitment increases lung compliance, while very high levels of PEEP that
causes over distention, reduces lung compliance
Ø The more diseased the lung, the higher the closing pressure and therefore, higher the PEEP requirement
Ø In a patient with a normal lung, only around 25% of PEEP applied is transmitted to the venous system
Ø The effect of PEEP on pulmonary vascular resistance is dependent on the lung volume
Ø In hypoxic patients with raised ICP, application of appropriate levels of PEEP to tackle hypoxia is far more important
than to withhold PEEP for concerns of its effect on ICP
Introduction old age, or in diseased lung. When FRC falls below closing
capacity, small airway collapse during end expiration leading
Positive end expiratory pressure (PEEP) is applied during on to impaired gas exchange during end of expiration. Thus
the end of expiration to maintain the alveolar pressure with application of PEEP, FRC remains above closing
above atmospheric pressure. PEEP management is capacity, thereby ensuring alveoli remain open throughout
considered a cornerstone of overall ventilator strategy the respiratory cycle. This increases the time available for
in the management of patients with hypoxia, especially gas exchange, reduces VQ mismatch and thereby improves
those with ARDS. However, it is important to recognise oxygenation. (Fig 1).
the physiological effect of positive pressure ventilation and
PEEP on body systems especially the cardiopulmonary PEEP and lung compliance
system. This short review will attempt to cover the effects
of PEEP on cardiopulmonary physiology and briefly touch In addition to preventing closure of alveoli at end expiration,
upon its effect on cerebral physiology. appropriate levels of PEEP opens up already collapsed
alveoli. This is called alveolar recruitment. Opening up a
Effect of PEEP on pulmonary physiology collapsed alveoli requires generation of higher pressure
than, inflating an already open alveoli. (Fig 2). Think of the
PEEP and functional residual capacity(FRC) collapsed alveoli as a fully deflated small balloon.
PEEP increases functional residual capacity by keeping the It is more difficult to initiate inflation of a balloon, than to
small airways open at end expiration. In atelectatic lung, further inflate a partially inflated one. At low levels of PEEP,
FRC falls below the closing capacity. This happens with in the presence of collapsed alveoli, the volume change in

PEEP Physiology and its Applications 424 Arunkumar A S
Fig 1: Effect of PEEP on relationship between FRC and CC
Fig 2: Alveolar pressure volume curve indicating optimal PEEP levels.

the lung per unit change in pressure is low. (Compliance basal alveoli thereby better matching ventilation and
is low – Low yield area Fig 2). With Moderate PEEP, as perfusion. However, excessive PEEP can cause over
the collapsed alveoli open up (alveolar recruitment), the distention of already ventilated alveoli and convert them into
compliance of the lung increases, as shown by a larger WEST zones.
increase in lung volume per unit change of pressure.
(Optimal range area Fig 2). With very high levels of PEEP, This is because the over distended alveoli will compress
there is alveolar over distention, and further inflation of the the capillaries in the alveolar interstitium, thereby reducing
lung becomes more difficult (decreased lung compliance.) or cutting off blood supply to these alveoli, creating an area
Hence, the effect of PEEP on lung compliance changes of lung which are well ventilated but poorly perfused. These
with the lung volume. PEEP levels that cause alveolar areas represent the dead space. Thus, moderate levels of
recruitment increases lung compliance, while very high PEEP aid in improving V/Q matching while excessive PEEP
levels of PEEP that causes over distention, reduces lung can worsen V/Q matching by increasing alveolar pressure
compliance. An important thing to mention is that the above pulmonary capillary pressure, thereby creating zone
sigmoid shape of the pressure-volume inspiratory curve 1 lung.
and the hump-shaped relationship between PEEP and Effect of PEEP on cardiovascular physiology
compliance is something which becomes more relevant in
cases of ARDS-like lung pathology, as compared to healthy PEEP and right ventricular preload
lungs. The more “normal” your lungs, the more of their
PEEP increases pleural pressure. This results in
pressure-volume curve is described by the steep middle
compression of the vena cava resulting in a decreased
gradient, i.e. the compliance remains good at a wider range
venous return to the right atrium. The increase in pleural
of pressures. In summary, the more diseased the lung, the
pressure due to PEEP also compresses the right atrium,
higher the closing pressure and therefore the higher the
increasing the intramural right atrial pressure. The right
PEEP requirement.
atrial intramural pressure being the downstream pressure
PEEP and VQ matching for venous return to the right atrium, an increase of this
pressure reduces venous return. Hence both these
Supine, mechanically ventilated patients have basal lung mechanisms reduce right atrial preload (Fig 3). A reduction
atelectasis. This is because the pressure form overlying in right atrial preload leads to a decrease flow into the left
structures squeeze out all the air from basal alveoli leading side possibly resulting in a reduced cardiac output. These
to their collapse. However, these basal areas receive the changes are more marked in a hypovolemic patient and can
maximum blood supply due to the effect of gravity. This be countered with a full intravascular space. It also need to
blood supply in poorly ventilated lung areas represent the be noted that in a patient with a normal lung only around
shunt. Application of PEEP will open up these collapsed 25% of PEEP applied is transmitted to the venous system.
Fig 3: PEEP reduces venous return to right heart. Shaded area in the box represent PEEP

Fig 4: High levels of PEEP increases RV afterload. Shaded area in the box represent PEEP
PEEP, pulmonary vascular resistance and right squeezes out the blood contained in the capillaries toward
ventricular afterload the left side of the heart.
Increase in alveolar pressure with application of PEEP PEEP, left ventricular filling and LV compliance
results in pulmonary capillary compression in West zones
I (pulmonary arterial pressure < alveolar pressure) and A decrease in right ventricular output as seen above can
II (pulmonary venous pressure < alveolar pressure) of cause a decrease in left ventricular filling. PEEP levels
the lung resulting in an increased pulmonary vascular high enough to cause a rise in PVR, will increase the RV
resistance (Fig 4). This results in an increased right pressure and RV dilatation. This will push the interventricular
ventricular afterload. However the effect on PVR is septum into the left side, there by reducing left ventricular
also dependent on the lung volume. When lung volume ejection. In addition, the raised intrathoracic pressure can
increases, intra alveolar vessels are compressed while be directly transmitted to the left ventricle there by reducing
extra alveolar vessels gets stretched due to radial interstitial its compliance and left ventricular dispensability. This can
force of the lungs. At lung volume above FRC, the effect increase the filling pressure and increase LV wall tension.
of compression on intra alveolar vessels are predominant These effects may be more prominent in patients with
causing an increase of PVR. At lung volume below FRC, diastolic dysfunction.
the effects on extra alveolar vessels are predominant with PEEP and left ventricular afterload
minimal effect on PVR. However, it must be noted that a
very low end expiratory lung volume due to inadequate Left ventricular transmural pressure, (difference between end
PEEP can result in atelectasis, hypoxia and activation of systolic left ventricular pressure and intrathoracic pressure)
hypoxic pulmonary vasoconstriction ultimately resulting in represents left ventricular afterload. Application of PEEP or
a raised PVR. Generally it has been observed that PEEP, IPPV increases intrathoracic pressure, thereby decreasing left
by reducing hypoxia, decreases PVR. Any increase in ventricular transmural pressure and left ventricular afterload. In
PVR result in a decreased right ventricular output. Hence, addition, PEEP puts a positive pressure on intrathoracic aorta
the overall effect of PEEP on PVR is an interplay between creating a pressure gradient between it and the rest of systemic
the amount of PEEP applied, instant lung volume, and the vasculature which is at atmospheric pressure. This resulting
presence or absence of hypoxia. Unlike in Zone I and II, gradient decreases the force necessary to eject blood from the
in West zones III (alveolar pressure < pulmonary venous left ventricle favouring blood flow into the systemic circulation,
pressure), the increase in alveolar pressure due to PEEP thereby decreasing left ventricular workload (Fig. 5 A, B).

Fig 5A: An example of pleural pressure, left ventricular pressure, intra and extra thoracic vascular pressures in the absence
of PEEP
Fig 5B: Note how application of PEEP creates a favourable pressure gradient aiding left ventricular ejection thereby reducing
left ventricular workload
The clinical implication of the above mechanism is, the ability left ventricular failure as you wean a patient off the ventilator.
of PEEP to reverse left ventricular failure by decreasing This is an important cause of weaning failure and must be
left ventricular preload and afterload, thereby reducing left considered in all cases of weaning failure. Unlike the positive
ventricular wall stress, which in turn decreases myocardial impact of PEEP on left sided cardiac function, excessive PEEP
oxygen demand thus moving the left ventricle into a more can have a deleterious effect on right ventricular function.
efficient position on the Frank Starling curve. A corollary to the This is especially true in conditions like ARDS, where there is
above physiological changes is, the unmasking of an occult already excessive right ventricular strain.

Effect of PEEP on cerebral physiology Summary
PEEP, intracranial pressure and cerebral perfusion In summary, PEEP has varying effects on cardio respiratory
pressure physiology depending on the level of PEEP applied and the
circumstances where it is applied. Its effect varies depending
Rise in intrathoracic pressure due to PEEP is thought to on the intravascular volume status of the patient, right and
compress the superior vena cava impeding cerebral venous left ventricular function, the lung volume of the patient, the
drainage, which in turn increases intra cranial pressure. respiratory compliance and also the oxygenation status.
Hence, there always has been a concern in application of
PEEP in patients with raised intracranial pressure. However Recommended reading
clinical studies have not shown a consistent relation between
PEEP and intracranial pressure. One study showed that 1. PEEP Role in ICU and Operating Room: From
only PEEP levels above 15 cm H20 increased ICP, while Pathophysiology to Clinical Practice. Vargas. M,
another showed that PEEP levels that result in alveolar over Sutherasan. Y et al. The Scientific World Journal.
distention, raised ICP by causing CO2 retention, which in Volume 2014, doi.org/10.1155/2014/852356.
turn increased cerebral blood flow. 2. Changes in Arterial Pressure during Mechanical Ventilation.
It is to be noted that hypoxia has a far more deleterious effect Michard. F. Anesthesiology 2005; 103:419–28.
on cerebral function than any other impaired physiology. 3. Interactions between respiration and systemic
Hence, in hypoxic patients with raised ICP, application of hemodynamics. Part II: practical implications in critical
appropriate levels of PEEP to tackle hypoxia is far more care. Broccard A.F, Feihl. F. Intensive Care Med. 2009,
important than to withhold PEEP for concerns of its effect 35:198–205
on ICP.
4. Regional distribution of gas and tissue in acute
The effect of PEEP on other bodily systems are miniscule, respiratory distress syndrome III. Consequences of the
and not clinically relevant and hence not covered here. effect of positive end expiratory pressure. Puybasset.
L, Gusman. P, Muller. C.J et al. Intensive Care Med.
2000 26: 1215 – 1227.

MCQ
4. Effective methods to decrease an elevated PaCO2 may

1. All of the following can occur with high levels of PEEP include all except:
except
a) Increase tidal volume
a) Overdistension of alveoli b) Increase inspiratory pressure
b) Increased lung compliance c) Decrease circuit dead space
c) Decreased lung compliance d) Increase peep
d) Worsen v/q matching
5. All are possible adverse effects of PEEP except
2. PEEP is of major advantage in left ventricular failure
patients but is deleterious in patients with right ventricle a) Increased physiologic dead space
failure which is more common in b) Increase in right to left shunt across patent foramen
ovale(PFO)
a) ARDS c) Redirect pulmonary blood flow to atelectatic lung
b) Fluid Overload areas worsening oxygenation
c) Hypothyroidism d) Increase cardiac output
d) Dilated Cardiomyopathy
3. Intracranial pressure rises when the levels of PEEP

go above
a) 5mmhg
b) 10mmhg
c) 15mmhg
d) 20mmhg
5.D 4.D 3.C 2.A 1.B
ANSWERS:

TCI SESSIONS
46 TCI IN CHILDREN: THE STATE OF THE ART
Department of Anesthesia and Intensive Care Rossella Garra

Catholic University of Sacred Heart,
Rome, Italy
Key points
Ø Propofol anaesthesia in children is associated with quicker recovery, reduced nausea and vomiting, decreased
postoperative delirium, less environmental pollution and reduced postoperative analgesic consumption
Ø TCI system uses a continuously variable rate of drug administration to achieve and maintain predetermined
concentrations of a given drug either in plasma or at the site effect
Ø Targeting the effect site may offer advantages compared to plasma, particularly in non-steady-state concentrations
Propofol has a pharmacokinetic profile making it suitable for The “Paedfusor”, a prototype target-controlled infusion
the use by infusion. Compared with the conventional inhaled (TCI) system for children, was developed in 1998 and
agents, propofol anaesthesia in children is associated with has incorporated a real-time PK model wherein central
quicker recovery, reduced nausea and vomiting, decreased compartment volume and clearance have a non–linear
postoperative delirium, less environmental pollution, and correlation with weight. Using the Paedfusor data, it has
reduced postoperative analgesic consumption. The reduced been found that to achieve a plasma concentration of 3 mcg/
airway activity, improved postoperative ciliary function, and ml in children, the dose of propofol infusion is approximately
the preservation of cerebral vascular reactivity as well as twice than in the adults and this corresponds to the manual
the middle ear pressure represent other advantages which infusion scheme devised by McFarlan (11) using the Kataria
reflect positively in specific clinical settings. Moreover, the data set in children aged 1-6 yrs. According to this scheme,
availability of this new fast acting drug allows repeated anaesthesia is induced with a propofol bolus dose of 2.5 mg/
administrations in children undergoing brief radiologic or kg and maintained with a propofol infusion regimen of 15 mg/
painful procedures (radiation therapy, MRI, bone marrow kg/h for the first 15 minutes, 13 mg/kg/h for the next 15 min;
aspiration, gastrointestinal endoscopy), or in those at risk 11 mg/kg/h from 30 to 60 minutes, 10 mg/kg/h from 1 to 2
of malignant hyperthermia and when there is a need to use hours and 9 mg/kg/h from 2 to 4 hours. The lower age limit
evoked motor and auditory brain potentials. for the use of Paedfusor is 1 year and the lower weight limit
is 5 kg. The Kataria model is also well validated in children:
The first available infusion system for propofol (Diprifusor) the lower age for its use is 3 years, and the lower weight limit
launched in late 1996, was not recommended for patients is 15 kg. The accuracy with which Paedfusor can target the
aged less than 16 years. A comparison of how Diprifusor blood concentration of Propofol was evaluated in a cohort
would perform in 3-11 years children has been shown by of 29 children undergoing cardiac catheterization or surgery
Marsh et al. (9) who found a blood propofol concentration (12). The authors reported a median performance error
under predicted of about 50% and lasting for about 20 (MDPE) of 4.1%, that is far less than the bias values of 16%
minutes even after increasing the target of Diprifusor up to found in adult studies using the Diprifusor TCI system; and a
50% above the desired concentration. The explanation of this median absolute performance error (MDAPE) reflecting the
sub-therapeutic plasma concentration is related to the larger size of error (precision) of 9.7%, provided that acceptable
central volume and the increased clearance of propofol in values for an infusion system are a MDPE < 10-20% and a
children when compared to adults. Although many studies MDAPE < 20-40%.
regarding propofol PK in children have been published, the
target-controlled infusions devices (TCI propofol) are not TCI system uses a continuously variable rate of drug
still available to many anaesthetists all around the world administration, to achieve and maintain predetermined
and particularly in the United States where they have not concentrations of a given drug either in plasma (Cp) or at the
yet been licensed. site effect (Ce). Targeting the effect site may offer advantages

TCI in Children: The State of the Art 434 Rossella Garra
compared to plasma, particularly in non-steady-state emergence was not significantly affected by the choice of
concentrations (when concentration needs to be changed) Keo, hence for expert users of TIVA in children during short
and delayed effect could otherwise occur as the real effect procedures, predicted emergence times should not provide
site of drug is not the plasma but the central nervous system. clinical advantages. Inter-individual variability has been well
The publication of the PK dataset for the Paedfusor (10) documented in neonates and infants in relation to progressive
allows the construction of a paediatric TCI system targeting changes in body composition, with subsequent effects on the
Ce. The Keo value, that is the time course of plasma effect distribution volume of lipophilic compounds (17) the ontogeny
site equilibration needed for targeting effect site, has been of glucuronidation activity and, the major metabolic pathway
evaluated for Paedfusor model (Keo 0.91 min-1 ) and for the of propofol (18, 19). In neonates undergoing cardiac surgery,
Kataria (Keo 0.41 min-1) in a study on children aged 3-11 it has been found that increased distribution of propofol into
years (13). As it is not possible to directly measure the slowly equilibrating tissues was seen compared to older
concentration of the drug at the effect site, the Keo can be children (20). This is evidenced by the large slow peripheral
estimated measuring clinical effect (PD) such as EEG, BIS compartment (V3) and the slow redistribution rate (K3-1)
and auditory evoked potentials in relation to the drug blood constant from this compartment as body weight decreases
concentration. Jelearzcov et al (14) using BIS index during leading to relevant clinical effects: a rapid emergence but
propofol anaesthesia found that the Keo is age dependent a delayed full recovery after the discontinuation of propofol
varying from 0.91 min-1 at 1 year of age to 0.15 min-1 at 16 infusion. Preterm neonates and neonates in the first week of
years: this reflects the need of higher target plasma and postnatal life are even prone to display propofol accumulation
effect site concentration to induce anaesthesia in children during either continuous or repeated bolus administration
than in adults and also the longer time to reach the peak as a consequence of the overall reduced clearance and its
effect, probably because of a larger volume of distribution inter-individual variability (322%) (21, 22), when compared
(13, 14). In fact the t peak that is the time of maximal to toddlers and children.
effect site concentration of a drug after bolus depends on
What does all this mean in clinical practice?
two simultaneously processes: the decreasing plasma
concentration and the increasing effect site concentration. Propofol is highly suitable for sedation in children: either
Faster the decrease of plasma concentration is, sooner t peak alone, when only immobility is required, or associated with
occurs. Both Kataria and Paedfusor models in children predict ketamine or opioids during painful procedures. Using TIVA,
a slower decrease of plasma concentration compared with we usually start with an initial bolus of 1-2 mg/kg according
Schneider model in adults, and this could be an explanation to preoperative conditions (premedication, drug therapy,
for a slower t peak in this age (132 sec) (13). Children also etc) followed by a starting infusion of 10 mg/kg/hr and
present an increase in the context sensitive half-time of waiting the recovery from apnoea. When the bolus is not
propofol compared to adults (from 10 min at 1h to 19.6 min used, sometimes 20-30 mg/kg/hr are required at induction
at 4h vs 6.7 min and 9.5 min respectively). This implies drug to achieve a clinical effect. Usually we prefer the second
accumulation in the body and a slower recovery time which the option because the induction is smoother and apnoea
anaesthetist has to consider in clinical practice. Theorically, doesn’t occur. As during anaesthesia, during sedation also
TCI models predict the time required for a calculated effect a progressive decrease of drug dosing is required in the end
site concentration to decline to a predetermined Ce-awake of the procedure to allow a faster recovery. Using Paedfusor
value, provided that Ce awake is known. Ce awake values of or Kataria PK models, at least 3 mcg/ml are required to
around 1.8 mcg/ml have been described in adults (15) but maintain an adequate sedation level but it is recommendable
not yet in children, because of the marked inter-individual PK to achieve this target gradually starting from 1-2 mcg/ml to
variability of propofol distribution and metabolism. Recently avoid apnoea. During painful procedures, analgesic drugs
Mc Cormack et al (16) assessed the effect of different Keo should be used, such as small doses of ketamine (0.5-2 mg/
values on emergence time, indentified a Ce-awake of 2.0 kg) or alfentanil (2 mcg/kg repeated bolus).
mcg/ml in children aged 3 months to 9 years during brief
day case surgical procedures. This value corresponded to References
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1) Glaisyer HR, Sury MR. Recovery after anesthesia
of propofol TCI using Paedfusor. The authors also observed
for short pediatric oncology procedures: propofol and
a trend to higher Ce targets, increased propofol consumption
remifentanil compared with propofol, nitrous oxide,
in younger patients and a trend to a more rapid emergence
and sevoflurane. Anesth Analg. 2005 Apr;100(4):959-
from propofol in older children. In this study, the time to
63.

TCI in Children: The State of the Art 435 Rossella Garra
2) Rüsch D, Happe W, Wulf H. Postoperative nausea 13) Muñoz HR, Cortínez LI, Ibacache ME et al. Estima� -
and vomiting following stabismus surgery in children. tion of the plasma effect site equilibration rate constant
Inhalation anesthesia with sevoflurane-nitrous oxide in (ke0) of propofol in children using the time to peak ef-
comparison with intravenous anesthesia with propo- fect: comparison with adults. Anesthesiology. 2004
fol-remifentanil. Anaesthesist. 1999 Feb;48(2):80-8. Dec;101(6):1269-74.
3) Grundmann U, Uth M, Eichner A et al. Total intrave- 14) Jeleazcov C, Ihmsen H, Schmidt J et al. Pharmaco-
nous anaesthesia with propofol and remifentanil in dynamic modelling of the bispectral index response to
paediatric patients: a comparison with a desflurane-ni- propofol-based anaesthesia during general surgery in
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Scand. 1998 Aug;42(7):845-50.
15) Iwakiri H, Nishihara N, Nagata O et al. Individual ef�-
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2005 Jan;100(1):107-10.
5) Cheng SS, Yeh J, Flood P. Anesthesia matters: pa-
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Anesth Analg. 2008 Jan;106(1):264-9. of recovery from anesthesia in children. Pediatr An-
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8) Ozturk O, Demiraran Y, Ilce Z et al. Effects of sevoflu�

- 19) Guitton J, Buronfosse T, Desage M et al. Possible in�
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rane and TIVA with propofol on middle ear pressure. volvement of multiple human cytochrome P450 isofor-
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1998 Jun;80(6):788-95.
9) Marsh B, White M, Morton N et al. Pharmacokinet-
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Anaesth. 1991 Jul;67(1):41-8. cokinetics of propofol infusions in critically ill neonates,
infants, and children in an intensive care unit. Anes� -
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21) Allegaert K, Peeters MY, Verbesselt R et al. In-
11) McFarlan CS, Anderson BJ, Short TG. The use of ter-individual variability in propofol pharmacokinetics
propofol infusions in paediatric anaesthesia: a practi- in preterm and term neonates. Br J Anaesth. 2007
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catheterization. Br J Anaesth. 2003 Oct;91(4):507-13. bility? Paediatr Anaesth. 2004 Jun;14(6):435-8.

47 TCI: DIFFERENT SCENARIOS IN CLINICAL SETTINGS
Professor, Anesthesia, Maria Sammartino

Catholic University of the Sacred Heart,
Rome, Italy.
Key points
Ø Advantages of TIVA include: the possibility to act on different components of anesthesia (consciousness,
analgesia, myorelaxation), reduction of environmental pollution, use in Non Operating Room Anesthesia, means
to start painless infusions, reduction of PONV, reduced Emergence Delirium and Malignant Hyperthermia risk
Ø The termination of therapeutic effect of remifentanil is primarily a result of clearance rather than redistribution
Ø Remifentanil dosage should be based on ideal rather than actual body weight because compared with lean
patients, obese patients present a lesser central clearance
Ø Remifentanil is probably the only opioid that can provide REM phases like sleep
Ø Remifentanil, like other opioids, can cause chest wall rigidity. For this reason, we strongly suggest to start with a
lower dosage, and gradually increase the dose over few minutes
In the last two decades, we started to appreciate the use of onset of action (t1/2 Keo) for equilibration between plasma and
total intravenous anesthesia and nowadays this technique effect compartment of 1.3 minutes (1). Terminal elimination
is used more in adults. The reason is that pediatric half-life (t1/2 β) is 9.5 min and the rapid central clearance
anesthesiologists are few, compared with big numbers is 41.2 L/kg/min. The termination of therapeutic effect is
of general anesthesiologists and these non-pediatric primarily a result of clearance rather than redistribution.
anesthesiologists do not want to face such a risk. Anyway,
the number of pediatric anesthesiologists are increasing Body weight, age, gender, hepatic or renal failure do not
and so also children who can benefit of this technique. influence total clearance of Remifentanil, However, Kim et
Al. suggested that Remifentanil dosage should be based
The reasons of these advantages include: the possibility to on ideal rather than actual body weight because compared
act on different components of anesthesia (consciousness, with lean patients, obese patients present a lesser central
analgesia, myorelaxation), reduction of environmental clearance (42.3 vs 27.9 ml/kg/min), and higher Vss (217.2
pollution, use in Non Operating Room Anesthesia (NORA), vs 146.8 ml/kg/min) and Vc (101.9 vs 68.3 ml/kg). (2)
new generation infusion devices, means to start painless
infusions, reduction of PONV, reduced Emergence Delirium, The first available information on Remifentanil in Children is
and Malignant Hyperthermia risk reduced to zero. Besides a study from Davis (3).
all this, TCI can also count on many other drugs, among Remifentanil can be considered, actually, the best answer
which, the more recent opioid “Remifentanil” has a place of to the search of ideal opioid because of the ester linkage
honour thanks to its unique characteristics. that makes the compound susceptible to metabolism by
Remifentanil exhibits a linear and dose-independent non-specific plasma and tissues esterases and independent
pharmacokinetics profile. Its distribution can be described from hepatic and renal metabolism. In fact, it can be safely
by a two compartmental model. The distribution into the utilized even in anhepatic period of liver transplantation or
third compartment is limited, accounting for 25% of total when facing with failure or immaturity of most parenchyma.
exposure. Remifentanil has a small volume of distribution: the possible
Pharmacokinetic investigations in adult revealed a Vd of 0.39 explanation for a highly lipid soluble compound is that most
l/kg, a distribution half-life (t1/2 α) of 0.94 minutes and a rapid of the drug is metabolized within the central compartment (1).

TCI: Different Scenarios in Clinical Settings 438 Maria Sammartino
The unique feature of Remifentanil however, is the context- Moreover Remifentanil has age-related changes in kinetics
sensitive half-time of 3-5 min independent from the duration that differ from other opioids and only the VDss is similar
of infusion. That is why Anne Lynn in her editorial in 1996 to other opioids (largest values in youngest patients). This
was asking: “Is Remifentanil the answer to the search of was demonstrated by Ross (14). She chose the coefficient
the ideal opioid? The answer for infants and children was of variation (CV) as a means of quantifying clearance
not ready yet in 1996, but A. Lynn was hypothesizing that variability in paediatric population. She found that values for
“Remifentanil will hold great interest if its initial promise is sufentanil, alfentanil, and fentanil were three fold larger than
confirmed in our small patients” (4). the value of Remifentanil. She concluded that if variability
in Remifentanil effects is similar to its PK variability, then it
Now we have the answer: even if not too many should be very predictable even in smaller children.
pharmacokinetic studies were carried out on smaller
patients, some studies started to give an answer. Davis and So, encouraged by these results, many authors carried out
Lerman reported adequate analgesia and rapid recovery studies on infants and children in Anesthesia, Sedation and
utilizing Remifentanil/N2O 1 mcg/kg bolus and 1-3 mcg/kg/ Intensive Care. Remifentanil was found to be effective for
min after midazolam premedication (0.3-0.75 mcg/kg) for OroTracheal Intubation (OTI) without muscle relaxants:
strabismus correction. (5) Remifentanil 3 mcg/kg along with propofol provided excellent
conditions in 90% of children without increasing HR and
Davis reported the same anaesthesia technique efficacy in MAP (15) nor inducing bradycardia or hypotension. These
infants born at term and aged at least 8 weeks, undergoing findings were confirmed by Crawford (16) who showed a
pyloromyotomy.(6) We also used this anesthesia technique shorter recovery from apnea compared to succinylcholine
(Remifentanil/N2O) in children premedicated with oral 2 mg/kg. He showed also that the answer was similar in
midazolam undergoing strabismus correction. We monitored infants 1-12 months and children 1-6 years (propofol 4mg/
BIS index and we found values ranging from 60 to 72 with kg + Remifentanil 3mcg/kg).
no child showing recall or other kind of problems, as sleep
disturbances, until 1 month after the operation. Probably it Verghese et al. published the results shown in a previous
was true, as some authors reported, that Remifentanil is the poster of ASA Congress, on the nasal administration of
only opioid that can provide REM phases like sleep. Remifentanil 4mcg/kg: she found excellent intubating
conditions after 3 minutes in 91.7% of children.(17) These
Eck confirmed the safety of Remifentanil in three infants findings look very promising but authors suggest that this
with complex medical issues (hepatic failure, cyanotic technique could be useful to reach good OTI conditions
heart disease and renal compromise), undergoing surgical without an intravenous access. In our opinion this is very
ligation of a patent ductus arteriosus and correction of a dangerous: if something happens, such as a muscle
duodenal web) (7).Wee (8) confirmed the safety in infants rigidity, without an IV access, the situation could be highly
7 days –3 months, in blended anaesthesia (iso/peridural life threatening (18).
ropivacaine) undergoing major abdominal surgery.
TIVA-TCI can be used safely in adults and children and
TIVA propofol/Remifentanil was shown to be safe and almost in all kind of surgeries. It is very advantageous in
effective with reduced PONV and emergence agitation Neurosurgery and in Thoraco-Abdominal surgery. Use of
in children 1-12 years even with delayed spontaneous remifentanil allows deep anesthesia and rapid recovery but
ventilation, compared to desflurane/N2O. (9). adequate postoperative analgesia should be considered. It
Many studies show a clinical behaviour related to is also useful in Ear-Nose- Throat, Ophthalmology, Maxillo-
Remifentanil pharmacokinetics that is really different from Facial and Plastic Surgery.
other opioids. Greeley (10) and Davis (11) demonstrated How do we behave in practice?
that sufentanil and alfentanil have reduced clearance and
prolonged t½β (terminal half-life), normalizing with age due Unfortunately, the only disadvantage of TIVA in children
to reduced hepatic blood flow, reduced proteins content and is the intravenous cannulation before the induction of
limited hepatic enzyme function. Koehntop (12) showed anesthesia. One possible option would be to start by
that fentanyl kinetics are highly variable and influenced inhalation anesthesia, position the IV cannula and shift to
by the patient’s underlying pathophysiology and surgical intravenous anesthesia. Application of EMLA cream for
conditions (even if Singleton demonstrated that infants 40 minutes and premedication with midazolam (0.5- 0.75
tolerate larger doses of fentanyl compared to adults) (13). mg/kg) by mouth or nasal administration can facilitate
intravenous cannulation. Later, on the operating table

during inhalation of N20/O2 mixture, we should be able to A New Pharmacokinetic Model Incorporating the
easily position the needle cannula and start intravenous Influence of Body Mass. Anesthesiology. 2017
drugs. Jun;126(6):1019-1032.
Usually we do not have these problems with adults and we 3. Davis PJ, Lerman J, Suresh S et al A randomized
can start directly with TIVA-TCI. multicenter study of Remifentanil compared with
alfentanil, isoflurane, or propofol in anesthetized
According to literature, for TIVA in children we suggest pediatric patients undergoing elective strabismus
starting with propofol bolus 2.5mg/kg followed by propofol surgery. Anesth Analg. 1997 May;84(5):982-9
infusion of 15mg/kg/hr, reduced to 8mg/kg/hr in two hrs.
4. Lynn AM. Remifentanil: the paediatric anaesthetist’s
TIVA in adults: Bolus 2mg/kg followed by propofol 10mg/kg/ opiate? Paediatr Anaesth. 1996;6(6):433-5
hr , tapered to 4mg/kg/hr.
5. Davis PJ, Lerman J, Suresh S et al A randomized
TCI in children: Propofol induction 6-8 mcg/ml until OTI and multicenter study of Remifentanil compared with
scaled to 3-2.5 mcg/ml. alfentanil, isoflurane, or propofol in anesthetized
TCI in adults: Propofol induction 6mcg/ml until OTI and pediatric patients undergoing elective strabismus
scaled to 4-3 mcg/ml. surgery. Anesth Analg. 1997 May;84(5):982-9.
TIVA Remifentanil in children: 0.25-0.5mcg/kg/min, titrated 6. Davis PJ, Galinkin J, McGowan FX A randomized
to need multicenter study of Remifentanil compared with
halothane in neonates and infants undergoing
TIVA Remifentanil in adults: 0.2-0.5mcg/kg/min, titrated to pyloromyotomy. I. Emergence and recovery profiles.
need Anesth Analg. 2001 Dec;93(6):1380-6,
TCI Remifentanil in children (12y): 1-2ng/ml, titrated to need 7. Eck JB, Lynn AM. Use of Remifentanil in infants.
Paediatr Anaesth. 1998;8(5):437-9.
TCI Remifentanil in adults: 2-4ng/ml, titrated to need
8. Wee LH, Moriarty A, Cranston A Remifentanil infusion
Remifentanil, like other opioids, can cause chest wall
for major abdominal surgery in small infants. Paediatr
rigidity. For this reason, we strongly suggest to start with
Anaesth. 8-415:)5(9;1999.
a lower dosage, and gradually increase the dose over few
minutes. 9. Grundmann U, Uth M, Eichner et al A Total intravenous
anaesthesia with propofol and Remifentanil in paediatric
Thanks to the properties of this revolutionary opioid, that
patients: a comparison with a desflurane-nitrous oxide
moreover is the best designed to be coupled with propofol,
inhalation anaesthesia. Acta Anaesthesiol Scand.
we learned to face many clinical scenarios not only in the
1998 Aug;42(7):845-50.
Operating Theatre but much more out of the OR, allowing
to perform rapid and safe sedation in adults and children. 10. Greeley WJ, de Bruijn NP, Davis DP. Sufentanil
Nowadays, the comfort of the patient is mandatory and it is pharmacokinetics in pediatric cardiovascular patients.
part of the safety and quality of our work. It is unacceptable Anesth Analg. 1987 Nov;66(11):1067-72
to see patients that have to suffer unnecessarily. This
anesthesia technique can help to improve the performances, 11. Davis PJ, Killian A, Stiller RL et al Pharmacokinetics
reducing risks and increasing safety. of alfentanil in newborn premature infants and older
children. Dev Pharmacol Ther. 1989;13(1):21-7.
References
12. Koehntop DE, Rodman JH, Brundage DM, et al
1. Glass PS, Gan TJ, Howell S. A review of the Pharmacokinetics of fentanyl in neonates. Anesth
pharmacokinetics and pharmacodynamics Analg. 1986 Mar;65(3):227-32.
of Remifentanil. Anesth Analg. 1999 Oct;89(4
Suppl):S7-14 13. Singleton MA, Rosen JI, Fisher DM. Plasma
concentrations of fentanyl in infants, children and
2. Kim TK, Obara S, Egan TD et al adults. Can J Anaesth. 1987 Mar;34(2):152-5
the Remifentanil Pharmacokinetics in Obesity
Investigators. Disposition of Remifentanil in Obesity: 14. Ross AK, Davis PJ, Dear G et al. Pharmacokinetics

of Remifentanil in anesthetized pediatric patients 17. Verghese ST, Hannallah RS, Brennan M et al The
undergoing elective surgery or diagnostic procedures. effect of intranasal administration of Remifentanil
Anesth Analg. 2001 Dec;93(6):1393-40 on intubating conditions and airway response after
sevoflurane induction of anesthesia in children. Anesth
15. Batra YK, Al Qattan AR, Ali SS, Assessment of tracheal Analg. 2008 Oct;107(4):1176-81.
intubating conditions in children using Remifentanil and
propofol without muscle relaxant. Paediatr Anaesth. 18. Sammartino M, Sbaraglia F.Minerva Anestesiol. 2017
2004 Jun;14(6):452-6. Jul;83(7):669-671 No needle...no party!
16. Crawford MW, Hayes J, Tan JM. Dose-response of

Remifentanil for tracheal intubation in infants. Anesth
Analg. 2005 Jun;100(6):1599-604

RSACPCON 2020
30th ANNUAL CONFERENCE RESEARCH SOCIETY OF
ANAESTHESI0L0GY CLINICAL PHARMACOLOGY
Excellence through evidence and experience

20th -22nd March 2020
Venue : University Auditorium
Sri Ramachandra Institute of Higher Education
& Research (SRIHER), Porur, Chennai
Award t ion
and Free Pa es ent a
per/ Poster Pr
Best paper awards in various categories inclusive of Pain, Critical Care,

Obstetric Anesthesia, Cardiac Anesthesia, Neuro Anesthesia, Pediatric
Anesthesia, Trauma, Regional Anesthesia and many more awards to win
12 A
w
Register and upload your abstracts now at and ards
priz
www.rsacp2020.com to w es
in
Organised by :
Department of Anesthesiology & Pain Medicine,
Sri Ramachandra Medical college
& Research Institute, Chennai
RSACPCON 2020
30th ANNUAL CONFERENCE OF RESEARCH SOCIETY OF
ANAESTHESI0L0GY CLINICAL PHARMACOLOGY
Venue:
University Auditorium,
Sri Ramachandra Institute of
March Higher Education & Research, Porur, Chennai.
20th -22nd Register now on www.rsacp2020.com

2020
Theme based sessions Workshops
• Basic Sciences, Technology, Monitoring • Mechanical Ventilation
• Complications & crisis management • Interventional Chronic Pain Management
• Basic and Advanced Airway
• Practice patterns - Past, Present & Future • Research Publications & Presentation
• Challenging scenarios • USG in the hands of Anesthesiologists
• Specialty anesthesia • Integrated Monitoring
Award paper and poster
Organised by
Department of Anesthesiology & Pain Medicine,
Sri Ramachandra Medical College & Research Institute,
Chennai
Contact Details
RSACPCON Secretariat, A6 OR Complex,
Department of Anesthesiology and Pain Medicine, Contact
Sri Ramachandra Institute of Higher Education & Research, 9042606596/9176481005
Porur, Chennai - 600116 rsacp2020chennai@gmail.com

Race 2020

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RACE2020

January 24th to 26th, 2020

Department of Anesthesiology and Pain Medicine

If I have seen further, it is by standing on the shoulders of giants …Isaac Newton

Wishing you all a wonderful New Year….

Dr. Aruna Parameswari

BASIC SCIENCE LECTURES

2. Preload, Afterload and Contractility Dr. Harishbabu Ravulapalli 17

3. Pharmacokinetics of Inhalational Anesthetics Dr. Aruna Parameswari 25

4. Pharmacokinetics of Intravenous anesthetics Dr. Pankaj Kundra 47

5. Physiology of gas exchange during anesthesia Dr. Naheed Azar 55

6. Heart Lung Coordination Dr. Jigi Divatia 63

7. Management of obstetric hemorrhage Dr. Sunanda Gupta 75

9. Anesthesia for scoliosis correction Dr. Anju Grewal 97

11. Anesthesia for neonatal emergencies Dr. Anila Malde 115

12. Damage control resuscitation in trauma Dr. Sudarsan Kasthuri 137

14. History of development of anesthesia practice Dr. David B. Waisel 151

15. Dexmedetomidine in NORA Dr. Keira Mason 153

16. Sepsis - Current update Dr. Chinyere Egbuta 155

18. Starlings equation - Understanding the physiology Dr. HM Krishna 177

19. Interpreting chest X rays Dr. Anupama Chandrasekaran 183

23. Preeclampsia- Current concepts Dr. Sunil Pandya 229

25. Anesthesia for Paediatric VATS Dr. Neerja Bhardwaj 251

29. Neuraxial Ultrasound Dr. Sivashanmugam T 285

32. Neuromuscular monitoring Dr. Venkatesh S 307

33. Vaporizers Dr. Pankaj Kundra 315

34. ABG Interpretation Dr. Jigi Divatia 335

35. Aspiration under anesthesia Dr.Balabhaskar S 343

36. Anaphylaxis - Recognition and management Dr. Bhimeswar MV 351

37. HIPEC Dr. Jyotsna Agarwal 355

41. Extrajunctional receptors and their implications Dr. Selvakumar R 389

42. Principles of temperature monitoring Dr. Ramkumar D 393

43. Coeliac plexus block Dr. Arul Murugan R 409

45. PEEP physiology and its applications Dr. Arunkumar AS 423

Dr.Anju Grewal Dr.Arul Murugan R

Dr. Anila Malde

Professor and Head

Dr. Anupama Chandrasekaran Coimbatore

Dr.Aruna Parameswari Karnataka

Professor & Head,

Dr.Akilandeswari M Dr.Chinyere Egbuta

JSS Medical College Boston.

Dr.Naheed Azhar Dr. Rajeshwari Subramaniam

Dr. Neerja Bhardwaj Dr. Ravi Shankar M

Dr.Nibedita Pani Dr.Rakesh Kumar

Dr. Padmaja Durga Dr.Ranjith Karthekeyan B

Dr. Pankaj Kundra Dr.Ramkumar D

Dr.Sree kumar E J Dr.Aishwarya Ramesh

Dr.Isaac Sam Clement

Dr.Jois Shravan Datta

Professor & Head

Professor and Head, Gurudatt C L

Ø Hegan- Poissuilles’ law is applied for laminar flow.

RACE 2020 Ramachandra Anesthesia Continuing Education

Figure 2 – Laminar flow

RACE 2020 Ramachandra Anesthesia Continuing Education

2. When we administer intravenous fluids to a patient,

RACE 2020 Ramachandra Anesthesia Continuing Education

Figure 4 – Turbulent flow

RACE 2020 Ramachandra Anesthesia Continuing Education

Figure 6– Onset of turbulent flow

RACE 2020 Ramachandra Anesthesia Continuing Education

RACE 2020 Ramachandra Anesthesia Continuing Education