Fundamentals of Critical Care

Supporting pharmacists new to the

critical care setting during the
COVID19 pandemic

Updated March 2020

www.ukclinicalpharmacy.org
 Plan
Introduction
Sedation and muscle relaxants
Vasoactives
GI
Fluids
Haemofilter
General house keeping

www.ukclinicalpharmacy.org
 You already know the basics!

Care of surgical
Encompasses Interpreting Managing Respiratory
patients/
all other topics Lab results infection Disease
elderly/renal

www.ukclinicalpharmacy.org
 Critical Care
The term Level 3
Staffed with
critical care 1 nurse
covers ‘ICU ’ per patient
requiring 2 or more
(level 3) and different organ support or
‘HDU’ (level 2) respiratory failure requiring
mechanical ventilation.

Level 2
1 nurse to 2 patients, receiving single organ
support (e.g. post-surgical or on low dose
vasopressors such as noradrenaline)
Level 1
Normal ward care – no organ support (may require IV or
oxygen by face mask)

www.ukclinicalpharmacy.org
 Aims of Critical Care

• To preserve life and prevent,

reverse or minimise damage
to vital organs

• To optimise cardiovascular
and respiratory function to
maximise oxygen delivery to
tissues

www.ukclinicalpharmacy.org
 Monitoring in ICU
SIMPLE MORE COMPLEX

Respiratory rate Arterial line

Heart rate CVP line on central line

Blood pressure Oesophageal doppler

Temperature ECHO

Oxygen saturations ECG

Urine output

www.ukclinicalpharmacy.org
 Lines
Central Line
➔ Inserted into a large vein in the
patient
➔ Neck (jugular) vein
➔ subclavian vein (the vein lying
beneath the collar bone)
➔ femoral vein
(large vein in the groin)
Branches off into smaller lines (or
lumens). This provides ports where
intravenous fluids, drugs and monitoring
can be attached. Each lumen can be
treated as separate line when
considering compatibilities
www.ukclinicalpharmacy.org
Arterial line
➔ Inserted into an artery (usually in
the wrist or the groin)
It has 2 functions:
1. It is attached to a system to
measure BP etc
2. It is set up to enable easy, frequent
arterial blood sampling, with no
stress to the patient.
There is a flush bag connected to the
transducer setup is encased in a pressure
cuff that constantly squeezes the bag.
This allows the fluid from the flush bag to
flow into the artery. This is important
because without pressure from the
flush, the arterial line tubing would fill
with blood.
 Ventilation
• Lots of different modes

• The higher the % oxygen

used can estimate how sick
patient is

• More invasive modes may

require more sedation to
tolerate

www.ukclinicalpharmacy.org
 Methods of ventilation
Endotracheal tube (ETT)
• Placed in through the mouth and
into the trachea
• Can be very uncomfortable and the
patient is sedated to tolerate it
A tracheostomy
• An opening is made into the trachea
allowing for ventilator support with
minimal or no sedation.
• Useful if patient has excessive
secretions during weaning
• Mouth care is easier

Disadvantages
• Bleeding
• Communication
difficulties

Both methods can cause ventilator associated pneumonia

www.ukclinicalpharmacy.org
 Sedation
Patient sedated to
a prescribed score Example – Richmond Agitation Scale (RASS)
Score Description
• How sedated does a
+4 Combative, overtly combative or violent, immediate danger to staff.
patient need to be?
+3 Very agitated, pulls on or removes tubes or catheters or is aggressive.
– Awake?
Unrousable? +2 Agitated, frequent non-purposeful movement or ventilator dyssynchrony.

Aware? +1 Restless, anxious or apprehensive but movements not aggressive or vigorous.

0 Alert and calm.

• Beneficial practices to Drowsy, but sustains more than 10 seconds awake, with eye opening in response to verbal command.
-1
assess sedation
-2 Light sedation: Awakens briefly (less than 10 seconds) with eye contact to verbal command.
– Sedation breaks
– Sedation scoring -3 Moderate sedation: Any movement, except eye contact, in response to command.

-4 Deep sedation: No response to voice, but any movement to physical stimulation

-5 Unarousable: No response to voice or physical stimulation

www.ukclinicalpharmacy.org
 Indications for sedation
Reduce anxiety and distress

Alleviation of pain

Ventilation

Primary Therapy
(reduce intracranial pressure, refractory status epilepticus)

During neuromuscular blockade

www.ukclinicalpharmacy.org
 Sedation and analgesia
• Anaesthetic (propofol, midazolam etc)
• Analgesia (alfentanil, remifentanil,
fentanyl, morphine etc)

• Most units have their standard and may

use different if patient has allergies or
contraindications

• May add another in if patient is difficult

to sedate e.g. propofol + alfentanil +
midazolam

www.ukclinicalpharmacy.org
 Summary of Sedation Problems
• Accumulation can be a problem (delaying weaning
and increasing complications)
• Some have detrimental effects on circulation,
increasing inotrope (e.g. noradrenaline) requirement
• Tolerance and withdrawal
• Does not provide REM sleep

www.ukclinicalpharmacy.org
 Propofol
• Intravenous anaesthetic. Mode of action unclear, potentiates
glycine and GABA

• Dose = 1-4mg/kg/hr (practically 0-20mL/hr 1%) – max dose

4mg/Kg/hr

Advantages:
– Short duration of action (starts and stops quickly)
• t1/2 is approximately 10 – 70 minutes
– Good for assessing the patient e.g. head injury
– Anti-tussive/reduces bronchospasm

www.ukclinicalpharmacy.org
 Propofol
• Disadvantages Propofol Infusion Syndrome Clinical
o Causes hypotension features:

o High lipid load o Cardiomyopathy with acute cardiac

failure.
(1kcal/mL)
o Metabolic acidosis, ↑↑K+
o No analgesic effects o Renal Failure
o Tolerance o Hepatomegaly
o Inhibition of free fatty acid entry into
o Peanut allergy mitochondria → failure of its
o Propofol infusion metabolism.
syndrome KEEP DOSE BELOW 4mg/kg/hr

www.ukclinicalpharmacy.org
 Midazolam
• Half life 1-4 hours
• Metabolism - Liver
• 1,4 hydroxy midazolam- active metabolite
cleared by kidney

Advantages Disadvantages
➢ Bolus rapid onset ➢ No specific analgesic properties
➢ Prolonged duration of action in
➢ Ease of administration both hepatic and renal
➢ Stable in sodium chloride impairment
and glucose ➢ Accumulation
➢ Dependence

www.ukclinicalpharmacy.org
 Other sedatives
Ketamine
• Blocks NMDA- receptors Clonidine/Dexmedetomidine
• Lack of respiratory and • α2-adrenoreceptor agonists
cardiovascular depression • They are particularly useful if
• Useful for anaesthesia in asthmatic agitation is a feature or after
patients withdrawal of benzodiazepines or
• Sympathetic agonist (↑ BP ↑HR opioids.
↑CO)
• Dex- shorter acting and easy to
• Limitations: hallucinations, delirium
during withdrawal titrate
• Suggested dose range 1.0- • Clonidine- enteral available
2.5mg/kg/h
• Elimination half life 2-3 hours, renal
excretion

www.ukclinicalpharmacy.org
 Alfentanil
• Synthetic opioid
• Peak effect after 2-3 mins
• Half-life 15-137 mins
• Not affected by renal
dysfunction
• Metabolised by the liver
Advantages
✔ Easy to administer
✔ Does not cause histamine release
✔ Less vasodilatation than with
morphine
Disadvantages
⮚ Potent respiratory depressant

Very potent! Depending on patient metabolism

1mg of alfentanil is equivalent to 10-20mg of morphine

www.ukclinicalpharmacy.org
 Morphine
• Half life 1-6 hours Advantages
✔ Excellent analgesic
Metabolism ✔ Inexpensive
✔ Compatible with a range of drugs
• Morphine undergoes
conjugation with
glucuronide in the liver
• Metabolite is 40 times
Disadvantages
⮚ Poor amnesic properties
more potent, this is then
⮚ Slow onset of action due to its
excreted in urine and will slow distribution and relative lipid
accumulate in renal insolubility
impairment

www.ukclinicalpharmacy.org
 Fentanyl
• Synthetic opioid
• 50-100x more potent than morphine
• Peak effect 30 mins
• Lipophilic - Short duration when given via bolus but
long when given by continuous infusion
• Lack of emetic effect
• 80% plasma bound
• Hepatically metabolised to inactive and non toxic
compounds, 8% urinary excretion
• Renal impairment - increase in half-life

www.ukclinicalpharmacy.org
 Remifentanil
• Very potent
• Rapid onset of less than 1 min
• Predictable offset of less than 10 mins
• Metabolised by non-specific blood and
tissue esterases
• Less interpatient pharmacokinetic variability
• No bolus

www.ukclinicalpharmacy.o
 Muscle Relaxants
▪ Routine paralysis is no
Atracurium
longer recommended. • Hoffman elimination, Histamine
▪ Only indications release
▪ Critical gas Rocuronium
exchange- LIKE • Active metabolite of vecuronium
COVID 19 Patient • Renally excreted, Rapid onset of
action
▪ Control of ICP • Less histamine
▪ Multiple trauma Cisatracurium
▪ Must make sure well • Cis-isomer of atracurium
sedated • Minimal histamine release
• Less laudanosine production

www.ukclinicalpharmacy.org
 Prone Position
• Patient turns onto front or semi- Pharmaceutical Implications
prone “swimming position”
Eye, lip and skin care
• Used in resp failure and severe
hypoxia despite optimisation of May need longer infusion lines
sedation, ventilation, Absorption of feed more difficult
neuromuscular blockade and fluid
balance. More at risk of transient arrythmia-
ensure electrolytes within range
• More common in COVID patients
 Vasoactive agents

VASOPRESSOR – a drug
INOTROPE - a drug that CHRONOTROPE - a drug
which causes
affects myocardial that affects the
contraction of muscular
contractility positive / myocardial contraction
tissue in capillaries and
negative rate
arteries

all have short half-lives ~ stable plasma

2minutes and must be concentrations are
administered by infusion achieved within 10-15
for prolonged effect minutes

www.ukclinicalpharmacy.org
 Haemodynamic values
● Cardiac output (CO): amount of blood
• MAP= CO x SVR ejected from the heart into systemic
circulation each minute
○ *Normal = 4-8 L/min

• CO= HR x SV
● Cardiac index (CI): CO adjusted for BSA
○ *Normal = 2.5-4 L/min

• SVR=Systemic vascular
resistance ● Stroke volume (SV): amount of blood
ejected from the heart into systemic
circulation with each contraction
○ SV = CO (mls) / HR
○ *Normal = 60-130 / beat

www.ukclinicalpharmacy.org
 Summary of Actions
Receptor Drug with predominate Adrenaline receptor
Site Effect affinity (Dose
agonist effect dependant)

α1 Arterial Vasoconstriction Noradrenaline ++

Vasculature Metaraminol, Phenylephrine

V1 Vascular Vasoconstriction Vasopressin

smooth muscle Terlipressin

β1 Heart ↑myocardial Dobutamine +++

contractility
↑heart rate

β2 Lungs, blood Bronchodilation ++

vessels Vasodilation

Phosphodiesterase III Mycocardial diastolic Milrinone

inhibitors in cardiac and relaxation Enoximone
smooth muscle

www.ukclinicalpharmacy.org
 Drug delivery - Gut
• If the gut works use it!
– For both nutrition and drugs
• Post GI surgery may be nil by mouth
• Non-ventilated patients may be fine to
swallow tablets normally
• Ventilated patients will normally have an
NG tube
• Ask whether the patient is absorbing
feed

www.ukclinicalpharmacy.org
 Drugs via NG tube
• Avoid MR/EC preparation
– Can change to ‘normal release’ if possible &
amend frequency
• Consider safety for staff
– finasteride
• Liquids – watch bioavailability
• Patches
• Alternative drugs for same condition/same
class
– Often anaesthetists looking after patients
that aren’t familiar with every day drugs

www.ukclinicalpharmacy.org
 Gastric stasis
• Some patients in shock/sepsis may have
gastric stasis.
• Also called ileus
• Opiates also slow peristalsis
• Won’t absorb feed
• Drug absorption likely to be impaired
• Treat with prokinetics
– low dose erythromycin IV 125mg-
250mg BD
– Metoclopramide IV 10mg TDS

www.ukclinicalpharmacy.org
 Blood Glucose
• In critically ill patients there is impaired
Consider implications
hepatocyte response to insulin which
correlates with increased risk of death of poor SC absorption
• Hypoglycaemia associated with worse
outcomes.
Further reading
• Hyperglycaemia (due to insulin resistance) is
common in the critically ill patient (inc. non
www.saferinsulin.org
diabetics)
• All patients should have HbA1C checked on
admission
• REVIEW all oral agents- check policy &
resource section of www.saferinsulin.org

www.ukclinicalpharmacy.org
 IV Fluid Therapy
4 phases of IV Fluid Therapy
Fluid overload big
problem in COVID
patients
Only give small
boluses in
resuscitation phase
Consider all COVID
patients fluid
restricted
Hoste et al 2014

www.ukclinicalpharmacy.org
 DAILY REQUIREMENTS (GIFTASUP Guidance)

Water 25-35 ml/kg (30)

Sodium Approx. 1 mmol/kg

Potassium Approx. 1 mmol/kg

Calories Minimum 400 calories (i.e. 100g glucose)

(CALORIES HELP TO DEAL WITH ELECTROLYTES NORMALLY)

www.ukclinicalpharmacy.org
 Methods of RRT
⚫Haemofiltration (Usually continuous venous-venous
so called CVVH)
⚫MOST COMMON FORM
⚫ Dialysis
⚪ Diffusion
⚪ Rarely ever (never) used on its own
⚪ Sudden big shifts in fluids/electrolytes make haemodynamically unstable
patients difficult to manage

⚫Haemodiafiltration
⚪ A combination of the two

⚫Continuous vs intermittent

www.ukclinicalpharmacy.org
 Dialysis compared to CVVH
Dialysis Filtration
⚫Convection
⚫Diffusion

⚫Moves down a ⚫Pressure gradient

concentration drives water and
gradient across a molecules through a
semi-permeable highly permeable
membrane membrane

⚫<5,000 daltons (500- ⚫ <30-40,000 daltons

2,000) (10,000-30,000)

www.ukclinicalpharmacy.org
 Considerations
• Set amount of fluid removed and replacement fluid added before blood
returned to patient.

Composition of replacement fluid • All the potassium that is removed

should soon become level in
replacement fluid
• If remains high- check input or likely
cell death releasing potassium
• No phosphate in replacement fluid-
look to replace- regular phosphate
Sandoz before gets too low and
requires IV
Anticoagulation often required-
Check local policy and recommended
plan with DVT prophylaxis

www.ukclinicalpharmacy.org
 Doses during filtration
• Ask “what harm I am going to
do if give too much
Drug Clearance
• “What harm if give too little” Likely
• Check reason for filtration
– Sepsis, don’t reduce • Small water soluble
antibiotic doses molecules
• Avoid renal toxic drugs • Lower levels of protein
• Some doses may be higher binding
– Fluconazole • Smaller Volume of
• Renal Handbook only good for Distribution
pharmacokinetics

www.ukclinicalpharmacy.org
 TPN
• TPN is not an emergency drug so should not be
started out of hours.
• Check for local guidelines and advice

www.ukclinicalpharmacy.org
 Delirium
Very common in crit care. Patients are screened daily
• Types: Hyperactive -Restless, agitated, hyper vigilant, paranoid,
hallucinations, aggressive, combative
• Hypoactive: Lethargic, short attention span, withdrawn,
apathetic
• Mixed: combination

• Non-pharmacological
Multi-component interventions may be helpful
• Pharmacological
• Atypical antipsychotic (Quetiapine, Olanzapine, Risperidone)
• Typical antipsychotics (Haloperidol)

www.ukclinicalpharmacy.org
 Directly deliriogenic drugs
Analgesics Cardiovascular agents Corticosteroids
Codeine Atenolol Dexamethasone
Fentanyl Digoxin Hydrocortisone
Morphine Dopamine Prednisolone
Pethidine Lidocaine

Antidepressants Antipsychotics Hypnotic agents

Amitriptyline Chlorpromazine Chlordiazepoxide
Paroxetine Diazepam

Anticonvulsants Antimuscarinics Miscellaneous agents

Phenytoin Atropine Furosemide
Phenobarbitone Hyoscine Ranitidine

Antihistamine Antiemetics
Chlorphenamine Prochlorperazine
Promethazine

www.ukclinicalpharmacy.org
 Everyday considerations

• Stress ulcer prophylaxis if not being fed

• Infection prevention
• Bowel management
• Electrolytes
• Eye/mouth hygiene

www.ukclinicalpharmacy.org
 Step down patients

Meds rec on step down

Considering stopping crit care meds- omeprazole,

amiodarone, antipsychotics, inhalers

Consider restarting usual meds but only if needed

www.ukclinicalpharmacy.org
 Summary points
Don’t be afraid of critical care, you know lots of info already

Drugs which are unusual to you are familiar to critical care staff,
and often titrated against response

Route is important. Can be IV via either peripheral line or central

line (check out how many lumens) but also NG, PO, rectal, etc.

Just as important to stop drugs as start them

In COVID patients, avoid unneccessary fluid, low dose steroids

considered

Never be afraid to ask

www.ukclinicalpharmacy.org
 Daily checklist
Organ system Issue
General Meds rec, U&Es, coag, interactions, allergies, co- morbidities (including
alcohol and smoking)
CVS BP meds, pump failure, fluid balance
GI Feeding (ideally enteral), bowels, blood glucose, prokinetic, stress ulcer
Renal urine output, urea/creatinine, dose adjustments, CVVH
CNS Sedative or analgesic effects, previous meds, tolerance and withdrawal
Infection Micro (including route and choice), steroids
Liver LFTs (abnormal in sepsis), drug interactions
Haem Clotting, DVT prophylaxis
Administration Available stock, instructions on safe admin, compatibilities

www.ukclinicalpharmacy.org
 Useful resources
• SPC
• Other pharmacists – UKCPA Message board
• Renal drug handbook – only for pharmacokinetics
• UKCPA guidance e.g. minimum volumes, dosing in
extremes of bodyweight, compatibility
• ToxBase
• Medusa
• UpToDate

www.ukclinicalpharmacy.org
 Acknowledgements

Emma Boxall, Specialist Critical Care Pharmacist

Greg Barton, Specialist Pharmacist Critical Care and Burns

www.ukclinicalpharmacy.org