Merit Is A Must!

A Clinical Clerk’s Guide to

Oral Revalida Emergencies

2020
 DISCLAIMER

Medicine is an ever-changing science. As new research and

clinical experience broaden our knowledge, changes in
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This reviewer should serve as supplement and is not

intended to replace textbooks and/or guidelines.

Should there be discrepancies or inconsistencies, please

refer to the current clinical practice guidelines, latest medical
textbooks, or locally accepted practices.

Readers are encouraged to confirm the information

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Feel free to share to others if this reviewer is deemed useful.

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-CDTB.2020-
 Honora medicum
Opera eius sunt necessaria.
Deus autem est qui vitae et mortis
Habet potestatem.

Ars longa. Vita brevis.

Occasio fugit.
Experimentum periculosum.
Judicium difficile.
 Honor the physician
His works are necessary.
However, God is the one who has power
over life and death.

Art is long. Life is short.

Opportunity fleeting.
Experiment perilous.
Judgement difficult.
 TABLE OF CONTENTS

1. BASIC LIFE SUPPORT ........................................................................................................................................................................................................ 1

2. ACUTE UPPER AIRWAY OBSTRUCTION ......................................................................................................................................................................... 3
3. ACUTE ASTHMA IN EXACERBATION................................................................................................................................................................................ 8
4. RESPIRATORY DISTRESS SYNDROME ......................................................................................................................................................................... 13
5. ANAPHYLAXIS ................................................................................................................................................................................................................... 16
6. INTESTINAL OBSTRUCTION IN CHILDREN ................................................................................................................................................................... 20
7. DIARRHEA & DEHYDRATION .......................................................................................................................................................................................... 27
8. SHOCK ............................................................................................................................................................................................................................... 33
9. ACUTE ABDOMEN ............................................................................................................................................................................................................ 37
10. ACUTE CHOLANGITIS .................................................................................................................................................................................................... 45
11. GASTROINTESTINAL BLEEDING .................................................................................................................................................................................. 48
12. PORTO-SYSTEMIC ENCEPHALOPATHY ...................................................................................................................................................................... 52
13. HYPERTENSIVE CRISIS ................................................................................................................................................................................................. 54
14. ACUTE HEART FAILURE ................................................................................................................................................................................................ 60
15. ACUTE MYOCARDIAL INFARCTION.............................................................................................................................................................................. 65
16. PULMONARY EMBOLISM ............................................................................................................................................................................................... 77
17. SEVERE ASTHMA ........................................................................................................................................................................................................... 81
18. HEMOPTYSIS .................................................................................................................................................................................................................. 90
19. PNEUMOTHORAX ........................................................................................................................................................................................................... 92
20. ACUTE RESPIRATORY FAILURE .................................................................................................................................................................................. 95
21. ADRENAL CRISIS .......................................................................................................................................................................................................... 101
22. DIABETIC KETOACIDOSIS ........................................................................................................................................................................................... 105
23. THYROID STORM .......................................................................................................................................................................................................... 110
24. UREMIA .......................................................................................................................................................................................................................... 114
25. RABIES ........................................................................................................................................................................................................................... 118
26. TETANUS ....................................................................................................................................................................................................................... 121
27. INCREASED INTRACRANIAL PRESSURE .................................................................................................................................................................. 124
28. STROKE ......................................................................................................................................................................................................................... 127
29. STATUS EPILEPTICUS ................................................................................................................................................................................................. 133
30. SPINAL CORD COMPRESSION ................................................................................................................................................................................... 135
31. VAGINAL BLEEDING IN PREGNANCY ........................................................................................................................................................................ 138
32. HYPERTENSION IN PREGNANCY ............................................................................................................................................................................... 142
33. GYNECOLOGIC EMERGENCIES ................................................................................................................................................................................. 143
34. HEAD TRAUMA .............................................................................................................................................................................................................. 147
35. MAXILLOFACIAL INJURY ............................................................................................................................................................................................. 150
36. MECHANICAL INTESTINAL OBSTRUCTION ............................................................................................................................................................... 152
37. SPINE TRAUMA ............................................................................................................................................................................................................. 154
38. THERMAL BURNS ......................................................................................................................................................................................................... 157
39. FRACTURES .................................................................................................................................................................................................................. 159
40. ACUTE URINARY RETENTION .................................................................................................................................................................................... 161
41. OCULAR TRAUMA ......................................................................................................................................................................................................... 163
42. FOREIGN BODY IN THE ESOPHAGUS/AIRWAY ........................................................................................................................................................ 165
43. APPENDICITIS ............................................................................................................................................................................................................... 168
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

1. BASIC LIFE SUPPORT • Choking Relief in an Unresponsive or Child

• The care healthcare providers and public safety professionals provide to o Shout for help. If someone else is available, send that person to activate
patients who are experiencing: the emergency response system
o Respiratory arrest o Gently lower the victim to the ground if you see that he is becoming
o Cardiac arrest unresponsive
o Airway obstruction o Begin CPR. Do not check for a pulse
• It includes: o Each time you open the airway to give breaths, open the victim’s mouth
o Performing high-quality cardiopulmonary resuscitation wide. Look for the object
o Use of automated external defibrillator (AED) ▪ If object seen & can be easily removed, remove with fingers
o Relief of airway obstruction ▪ If you object is not seen, continue CPR
• Chain of Survival o After about 5 cycles or 2 minutes of CPR, activate emergency response
o Provides a useful metaphor for the elements of the emergency system if someone has not already done so
cardiovascular care (ECC) systems-of-care concept • Removal of airway obstruction is successful if
o In-Hospital Cardiac Arrest (IHCA) o Air movements can be felt, & chest rise can be seen with breaths
▪ Surveillance, prevention, and treatment of prearrest conditions o Foreign body is seen and removed from victim’s mouth
▪ Immediate recognition of cardiac arrest and activation of the
emergency response system
▪ Early CPR with an emphasis on chest compressions
▪ Rapid defibrillation
▪ Multidisciplinary post-cardiac arrest care
o Out-of-Hospital Cardiac Arrest (OHCA)
▪ Immediate recognition of cardiac arrest and activation of the
emergency response system
▪ Early CPR with an emphasis on chest compressions
▪ Rapid defibrillation with an AED
▪ Effective advanced life support (including rapid stabilization and
transport to post-cardiac arrest care)
▪ Multidisciplinary post-cardiac arrest care
o Pediatric Chain of Survival
▪ Prevention of arrest
▪ Early high-quality bystander CPR
▪ Rapid activation of the emergency response system
▪ Effective advanced life support (including rapid stabilization and
transport to post-cardiac arrest care)
▪ Integrated post-cardiac arrest care
• Cardiac Arrest vs. Heart Attack
o Sudden cardiac arrest: when the heart develops an abnormal rhythm
and cannot pump blood
o Heart attack: when blood flow to part of heart muscle is blocked
• Cardiorespiratory Resuscitation
o Main components of CPR
▪ Chest compressions
▪ Airway
▪ Breathing (CAB)
o Elements of a high-quality CPR (SPAMGA)
▪ Start compressions within 10 seconds of recognition
▪ Push hard (depth of 5 to 6 cm or 2 to 2.4 inches), push fast (rate of
100 to 120/min)
▪ Allow complete chest recoil after each compression
▪ Minimize interruptions in compressions (<10 seconds)
▪ Give effective breaths that make the chest rise
▪ Avoid excessive ventilation
o Types of CPR
▪ Hands-Only CPR
• Single rescuer with little training and limited equipment
• Chest compressions only until help arrives
▪ 30:2 CPR
• Both chest compressions and breaths
• 30 compressions to 2 breaths
▪ Teamwork (Multirescuer coordinated CPR)
• 1st rescuer performs chest compressions
• 2nd rescuer gives breaths with a bag-mask device
• 3rd rescuer uses the defibrillator
• Choking Relief

• Choking Relief in a Responsive Adult or Child

o Stand/kneel behind & wrap your arms around victim’s waist
o Make a fist with one hand
o Place the thumb side of your fist against the victim’s abdomen, in the
midline, slightly above navel & well below breastbone
o Grasp your fist with your other hand and press your fist into the victim’s
abdomen with a quick, forceful upward thrush
o Repeat thrusts until the object is expelled from the airway or the victim
becomes unresponsive
o Give each thrust with separate, distinct movement to relieve obstruction

1. BASIC LIFE SUPPORT | 1

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

BLS Healthcare Provider Adult Cardiac Arrest Algorithms

• Is it safe?
• Is immediate danger involved?
Scene size-up: gives clues to what happened
• What happened? What is the nature of the illness or mechanism of injury?
and any potential dangers that may exist
• How many patients are involved?
Verify scene safety
• Is anyone else available to help?
• Unconsciousness
What is your initial impression? (signs that may
• Abnormal skin color
indicate a life-threatening emergency)
• Life-threatening bleeding
• Check for responsiveness. Tap the victim’s shoulder and shout, “Are you OK?”
• If the victim is not responsive, shout for nearby help.
Check for • Activate the emergency response system as appropriate in your setting.
responsiveness o Hospital: activating a specific hospital code, medical emergency team, or rapid response team
and get help o Prehospital: Activating EMS, paramedics, medic units, or advanced life support or calling for backup
o Workplace/facility: Calling 911 or activating workplace emergency response protocols
• If alone, get the AED/defibrillator & emergency equipment. If someone else is available, send that person to get it.
Assess breathing • If breathing, monitor victim until additional help arrives
Breathing: scan for victim’s chest rise and fall
and pulse • If not breathing/only gasping (agonal gasps): not normal breathing (sign of cardiac arrest)
simultaneously for Pulse: palpate a carotid pulse (groove between
<10 seconds • If no definite pulse within 10 seconds, begin high-quality CPR
trachea and neck muscles at the side of the neck)
• If victim is breathing normally and a pulse is present [(+) breaths, (+) pulse]: Monitor the victim
Determine next
• If victim is not breathing normally but a pulse is present [(-) breaths, (+) pulse]: Provide rescue breathing & check pulse every 2 minutes
actions
• If victim is not breathing normally or only gasping and has no pulse [(±) breaths, (+) pulse]: Begin high-quality CPR
• Place victim on firm surface to allow chest & heart compression to create blood flow.
• Position yourself at the victim’s side. Make sure the victim is lying faceup on a firm, flat surface.
• Remove or move the clothing covering the victim’s chest so that you can locate appropriate hand placement for
compressions. This will also allow placement of the AED pads when the AED arrives.
• Position your hands and body to perform chest compressions
o Put the heel on one hand in center of the victim’s chest, on the lower half of breastbone (sternum)
o Put the heel of the other hand on top of the first hand
Start with chest
compressions • Straighten arms and position shoulders directly over the hands
• Commence chest compressions
o Rate: 100 to 120/min; Depth: 2 to 2.4 inches (5 to 6 cm)
o Allow complete chest recoil after each compression
o Minimize interruptions in compressions
• Do not move the victim while CPR is in progress UNLESS:
o Victim is in a dangerous environment
o CPR cannot be performed effectively in victim’s present position or location
Begin high-quality • Opening the airway
CPR o Head tilt-chin lift
▪ Place one hand on the victim’s forehead and push the head back
▪ Place the fingers of the other hand under the bony part of the lower jaw near the chin
▪ Lift the jaw to bring the chin forward
o Jaw thrust (if head/neck/spinal injury is suspected)
▪ Place one hand on each side of the victim’s head.
▪ Place fingers under angles of victim’s lower jaw & lift with both hands, displacing jaw forward
Adult breaths ▪ If the lips close, push the lower lip with your thumb to open the lips
• Bag-Mask Device: used to provide positive-pressure ventilation
o Position yourself directly above the victim’s head
o Place the mask on the victim’s face, using the bridge of the nose as a guide for correct position
o Use the E-C clamp technique to hold the mask in place while you lift the jaw to hold airway open
▪ Perform a head tilt & place the mask on face with narrow portion at bridge of nose
▪ Thumb and index finger: make a “C” on the side of mask, pressing the edges of mask to face
▪ Remaining 3 fingers: form an “E” to lift the angles of jaw, open airway, and press face to mask
o Squeeze bag to give breaths (1 second each) while watching for chest rise.
• Once the AED arrives, plate it at the victim’s side, next to the rescuer who will operate it.
• Open the carrying case. Power on the AED if needed. Follow the AED prompts as a guide to next steps.
• Attach adhesive AED pads to the victim’s bare chest and attach cables.
o Anterolateral placement
▪ One AED pad: directly below right collarbone
▪ Other pad: side of the left nipple, with top edge a few inches below the armpit
o Anteroposterior placement
▪ One AED pad: between victim’s left side of the breastbone and left nipple
▪ Other pad: left side of the victim’s back next to the spine
o Special Circumstances
▪ Hairy chest: shave the area/pull off hairy areas before attaching AED pads
Attempt
▪ Water: pull the victim out of the water, quickly wipe the chest before attaching the AED pads
defibrillation with
▪ Implanted defibrillators and pacemakers: avoid placing AED pad directly over implanted device
the AED
▪ Transdermal medication patches: remove the patch and wipe area before attaching the AED pad
• “Clear” victim and allow the AED to analyze the rhythm
o Identifies presence of shockable rhythms
▪ Pulseless ventricular tachycardia: ventricles pump so quickly and inefficiently that no pulse can be detected
▪ Ventricular fibrillation: heart’s electrical activity becomes distorted; quiver in fast, unsynchronized way so heart does not pump blood
o Be sure that no one is touching the victim during analysis, not even the rescuer in charge of giving breaths
• If the AED advises a shock, it will tell you to clear the victim and then deliver a shock
o Be sure that no one is touching the victim
o Loudly state a “clear the victim” message, such as “Everybody clear” or simply “Clear”
o Look to be sure that no one is in contact with the victim (“shocking in 3, 2, 1”)
o Press the shock button (“shock delivered”). The shock will produce a sudden contraction of the victim’s muscles.
• If no shock is needed (“no shock advised”), and after any shock delivery, immediately resume CPR
Resume high-
• After about 5 cycles or 2 minutes of CPR, the AED will prompt you to repeat. Continue until advanced life support providers take over or the
quality CPR
victim begins to breathe, move, or otherwise react (return of spontaneous circulation, ROSC).

2 | 1. BASIC LIFE SUPPORT

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

2. ACUTE UPPER AIRWAY OBSTRUCTION APPROACH TO A CHILD WITH STRIDOR

STRIDOR • Immediately assess a child with stridor
• Characterized as a high-pitched, harsh, monophonic sound o Stridor indicates a difficult airway
produced by turbulent airflow through a partially obstructed airway o Advanced airway management may be necessary
• Both inspiratory and expiratory stridor are associated with airway • History
obstruction o Time and events surrounding the onset of stridor
• Bernoulli’s principle: as air is forced through a narrow tube, it o Presence of fever
undergoes an increase in speed and a decrease in pressure o Known congenital anomalies
o Decrease in lateral pressure causes the walls of airway to o Cardiac abnormalities
temporarily collapse & vibrate, generating this stridulous sound o Perinatal complications
• Hagen-Poiseuille’s law: resistance to laminar airflow increases o Prematurity
markedly with small decreases in the airway radius o NICU interventions
o A small amount of inflammation can result in significant airway o Previous endotracheal intubation or instrumentation
obstruction in children • The level of obstruction can often be identified on examination
𝟖 × 𝜼 (𝒗𝒊𝒔𝒄𝒐𝒔𝒊𝒕𝒚) × 𝒍 (𝒍𝒆𝒏𝒈𝒕𝒉) o Sonorous sounds (stertor): partial obstruction of upper airway at
𝑹 (𝒓𝒆𝒔𝒊𝒔𝒕𝒂𝒏𝒄𝒆) =
𝝅 × 𝒓𝟒 the nasopharynx and/or oropharynx
o Inspiratory stridor: obstruction above true vocal cords
o Expiratory stridor: obstruction below true vocal cords
o Biphasic stridor: obstruction at the level of true vocal cords
• Consider airway foreign body until proven otherwise if there is a
marked variation in the pattern of stridor

STRIDOR IN INFANTS <6 MONTHS OLD

• An infant <6 months old with a long duration of symptoms often has a congenital cause of stridor
• Stridor presenting in the 1st 6 months of life will often require direct airway visualization through endoscopy or advanced imaging
o The timing of this evaluation (emergent or outpatient) is dictated by the severity of symptoms and clinical suspicion
Laryngomalacia Vocal Cord Paralysis Subglottic Stenosis Hemangiomas Vascular Rings & Slings
• 60% of all neonatal
• Benign congenital tumor
laryngeal problems
of endothelial cells or
• Results from a
vascular malformations
developmentally weak
• Can occur anywhere
larynx • Rare congenital
o 80%: above clavicles
• Collapse occurs with anomalies of the aortic
o Airway hemangioma:
each inspiration at the arch and pulmonary
obstruction & stridor
epiglottis, aryepiglottic artery
• Can be congenital or • May be congenital or • Course: enlarge
Description folds, and arytenoids • Anomalous vessels can
acquired acquired throughout 1st year of life,
• Usually manifests shortly compress
may not be noticed at
after birth trachea/esophagus
birth, and tend to
o Key diagnostic feature o Examples: double- or
spontaneously regress by
o Generally resolves by right-sided aortic arch
age 5 years old
18 months of age
• Cutaneous
• Laryngotracheomalacia:
hemangiomas, in beard
tracheal support
distribution, may be clue
structures are affected
• Congenital: diagnosed in
• Unilateral cord paralysis:
1st few months of life
more common than • Symptoms present from
o Child is noted to have
• Worsens with crying & bilateral birth or early in 1st month
persistent inspiratory
agitation o Feeding problems, of life
stridor • Consider in new-onset
• Improves with neck stridor, hoarse voice, o Progressive &
Clinical o Mild cases: present stridor beginning after 1st
extension & in prone changes to child’s cry exaggerated during
Features later in childhood as month of life without
• Exacerbations: URTI or • Bilateral cord paralysis: intercurrent URTI
recurrent/persistent another explanation
increased work of normal voice + stridor & o Difficulty with feeding: if
croup
breathing from any cause dyspnea esophagus is
• Acquired: prolonged
o Symptoms: cyanosis compressed
endotracheal intubation in
and apneic episodes
premature infants
• Chest radiograph: subtle
narrowing or anterior
compression of trachea
• Diagnosed when there is on lateral view or an
• Flexible fiberoptic • Flexible • Airway visualization
Diagnosis narrowing of the laryngeal abnormal (e.g., right-
laryngoscopy nasolaryngoscopy through endoscopy
lumen sided) aortic arch
• Bronchoscopy, CTA, &
2D-echo (congenital
heart anomalies)
• Most hemangiomas
• Endotracheal intubation spontaneously regress
• Surgery is required if a
can be difficult with • Large malformations &
child suffers from failure • Treatment: based on the
Treatment bilateral cord paralysis those causing significant • Surgery
to thrive, apnea, or severity of the stenosis
• Surgical airway required respiratory symptoms
pulmonary hypertension
to secure airway may require β-blockers,
steroids, laser, surgery

2. ACUTE UPPER AIRWAY OBSTRUCTION | 3

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
STRIDOR IN CHILDREN >6 MONTHS OLD
• The child >6 months old with a relatively short duration of symptoms
(hours to days) characteristically has an acquired cause of stridor
o Inflammatory/infectious: croup or epiglottitis
o Noninflammatory: foreign body aspiration
Croup (viral laryngotracheobronchitis)
• Epidemiology: most common cause of stridor outside neonatal
period, commonly affecting 6 months to 3 years old
• Etiology: parainfluenza virus & rhinovirus
o Others: influenza, respiratory syncytial virus, metapneumovirus,
enterovirus, and coronavirus
o Measles in prevalent areas
o Coinfection by more than one virus is not uncommon, and
bacterial superinfection, although rare, is also possible
• Clinical Features
o Symptoms typically begin after 1-3 days of nasal congestion,
rhinorrhea, cough, and low-grade fever
o Classic symptoms: harsh barking cough, hoarse voice, stridor
o Often worse at night
o Severity related to amount of edema & inflammation of airway
o Assess for tachypnea, stridor at rest, nasal flaring, retractions,
lethargy or agitation, and oxygen desaturation
o Self-limited & short in duration, resolving spontaneously within 3
days (may last longer depending on etiology)
• Diagnosis: clinical
o Place children in a position of comfort, often in lap of caretaker,
and assess respiratory distress through observation
▪ Agitation and crying increase oxygen demand, creating
turbulent airflow, and resulting in greater airway resistance
o Laboratory studies, viral tests, or radiographs are needed if:
▪ In children who fail to respond to conventional therapy
▪ If considering another diagnosis such as epiglottitis,
retropharyngeal abscess, or aspirated foreign body
o Radiography: subglottic narrowing (“steeple sign”)
▪ May be present in normal children
▪ Can be absent in up to 50% of those with croup
▪ Provide close monitoring (agitation may worsen existing
airway obstruction)
• Treatment: nebulized epinephrine & corticosteroids
o Nebulized epinephrine (1:1000) 0.5 mL/kg (maximum 5 mL)
▪ For moderate to severe croup (stridor at rest)
• Mild croup generally does not require epinephrine
▪ ↓ airway edema (vasoconstrictive α-receptor effects)
▪ Clinical effects seen in as few as 10 minutes
▪ Observe for at least 3 hours for progression
o Dexamethasone 0.15-0.60 mg/kg PO/IM (maximum 10 mg)
▪ For all patients with croup
▪ Reduces severity and duration of symptoms
▪ Equally effective given parenterally or orally
▪ Onset: 4-6 hours after PO (effects seen within 1 hour)
▪ Injectable dexamethasone (4 mg/mL) for oral administration
• Provides less volume than oral (0.1 mg/mL or 1 mg/mL)
• Can improve tolerability and minimize risk of emesis
▪ Nebulized budesonide 2 mg & IM dexamethasone:
alternatives to oral dexamethasone if vomiting
o Endotracheal intubation: for severe croup with respiratory
failure despite medical therapy, may be necessary
• Disposition and Follow-up
o Most children with croup can be safely discharged to home
▪ No stridor at rest and 3 hours since last epinephrine
▪ Normal color, pulse oximetry, and mental status
▪ Able to tolerate oral fluids
▪ Caretaker can recognize worsening of symptoms
o Admission: Persistent stridor at rest, tachypnea, retractions,
and hypoxia or those who require >2 treatments of epinephrine
o ICU: respiratory failure and those requiring intubation
4 | 2. ACUTE UPPER AIRWAY OBSTRUCTION
Epiglottitis
• Acute inflammatory condition of the epiglottis
o May progress rapidly to life-threatening airway obstruction
• Epidemiology: older children (mean age 6-12 years)
o Widespread administration of H. influenzae type B vaccine has
significantly reduced number of cases of childhood epiglottitis
• Etiology
o Infectious: Haemophilus influenzae type B (prevaccine era)
▪ Postvaccine era: Streptococcus & Staphylococcus species
▪ Immunocompromised patient: Candida species
o Noninfectious: thermal injury, caustic burns, & direct trauma
• Clinical Features
o Abrupt onset of fever, stridor, drooling, and sore throat
o May progress rapidly, with inability to handle oral secretions
followed by stridor and respiratory distress
o Cough is often absent, and voice may be muffled
o Most appear toxic & anxious
o May assume tripod/sniffling position (neck hyperextended &
chin forward) to maintain the airway
• Diagnosis
o Lateral neck radiography (unnecessary if classic presentation)
▪ When diagnosis is uncertain, obtain soft tissue neck
radiography with the neck extended during inspiration
• Affected children typically hold their heads in a sniffing
position and have prolonged inspiration already, making
it quite simple to obtain radiographs
▪ Shows enlarged epiglottitis protruding from anterior wall of
hypopharynx (“thumb sign”) & thickened aryepiglottic folds
o Direct visualization of epiglottis (laryngoscopy): if suspicion
for diagnosis still exists despite normal-appearing radiographs
• Treatment
o Keep the child seated and upright in a position of comfort
o Provide oxygen only if this does not further agitate the child
o Nebulized L-epinephrine to decrease airway edema
o Observe for possibility of intubation or tracheotomy
▪ If intubation is unsuccessful: emergent surgical airway
o Antibiotic coverage should target S. pneumoniae, S. aureus,
and H. influenzae, with consideration of MRSA
▪ Ceftriaxone & vancomycin continued for 7-10 days
o Steroids: often used to decrease mucosal edema of epiglottis
o ICU admission: all suspected or confirmed epiglottitis
Bacterial Tracheitis (membranous laryngotracheobronchitis or bacterial croup)
• Uncommon; can cause life-threatening upper airway obstruction
• It can be a primary or secondary infection
• Epidemiology: age of presentation is 5-8 years of age
• Etiology: S. aureus (most commonly isolated pathogen obtained
from culture at bronchoscopy)
o Other organisms S. pneumoniae, S. pyogenes, Moraxella
catarrhalis, H. influenzae, and oral anaerobes
• Clinical Features
o Often develop secondarily after viral URTI (influenza A)
o History of URTI + sudden worsening with high fever, stridor
(biphasic), & cough (productive with thick sputum) + toxic
appearance
o Thick mucopurulent secretions of trachea: upper airway
obstruction
o Often complain of sore throat (point to trachea when asked
where it hurts)
o There is often tenderness with palpation of the trachea
• Diagnosis
o Laboratory studies other than tracheal cultures (during
bronchoscopy) are of limited use in the diagnosis
o Neck radiographs are not needed to make the diagnosis
▪ When obtained to evaluate for other potential diagnostic
entities, neck films may show subglottic narrowing of
trachea & irregular tracheal margins
o Bronchoscopy is the diagnostic method of choice
▪ No single clinical/radiographic feature can make a diagnosis

• Treatment
o Management is similar to epiglottitis, with patients ideally going
to OR for sedation, intubation, and bronchoscopy
o No clear benefit from β-agonists or glucocorticoids
o Administer empiric antibiotics to cover likely pathogens
▪ Vancomycin/clindamycin + 3rd generation cephalosporin
▪ Children with tracheostomies: prior lower respiratory
cultures may also guide initial antibiotic choices
▪ Definitive antibiotic: depend on cultures & Gram stain of
mucopurulent secretions from bronchoscopy
o Bronchoscopy: removal of purulent pseudomembranes
▪ improves tracheal toilet
▪ May lessen upper airway obstruction
o Most patients require definitive airway & ventilatory support
Airway Foreign Body
• Epidemiology: children between 1-3 years
o Increasing mobility and oral exploration
o In children <6 months old: often involves a well-meaning sibling
who places an object in the infant’s mouth
• Etiology: most common objects aspirated objects: food and toys
o Commonly aspirated foods include peanuts, sunflower seeds,
carrots, raisins, grapes, and hotdogs
• Clinical Features
o History of sudden coughing and choking (most predictive of all)
o Consider in a young child with respiratory symptoms, regardless
of duration (may present >24 hours after foreign body aspiration)
o History of witnessed choking (sudden onset of cough, shortness
of breath): highly suggestive of airway foreign body
▪ Not witnessed by a caregiver in many cases
o Location of the aspirated foreign body plays a role in
determining the symptoms and signs on presentation
▪ Great overlap between groups
▪ Some children may be asymptomatic on presentation
o “Classic dogma”
▪ Laryngotracheal foreign bodies: stridor & hoarseness
▪ Bronchial foreign bodies: unilateral wheezing & decreased
breath sounds (large majority are found in bronchi)
o Children can develop severe immediate-onset stridor or even
cardiopulmonary arrest, but there are proportions of patients
who will remain minimally symptomatic
o The most important factor in reducing mortality from an airway
foreign body is recognition of the child in acute airway disease
• Diagnosis
o Radiographs: helpful to confirm, not to exclude, diagnosis
▪ Normal in >50% of tracheal FB & 25% of bronchial FB
▪ >75% of airway FB <3 years of age are radiolucent
▪ Laryngeal and tracheal foreign bodies often constitute an
acute emergency, and radiography is omitted
• If performed, PA & lateral neck radiographs are
radiographic examinations of choice
▪ Proximal esophagus: may also cause airway compression
• Tracheal vs. esophageal FB on neck radiographs
o Trachea: in profile
o Esophagus: en face
▪ Bronchial foreign bodies: PA & lateral chest films
• May produce focal atelectasis and consolidation
▪ Indirect radiologic signs of radiolucent airway FB
• Unilateral obstructive emphysema: produced by a
check-valve obstruction on expiration
o Hyperinflation of affected side
o Potential mediastinal shift to the opposite side
• Atelectasis
• Consolidation
▪ Inspiratory and expiratory chest radiographs
• Hyperinflation (air trapping) on expiratory films
o Bronchoscopy: to rule out clinically suspected foreign body
aspiration, regardless of the chest radiograph findings
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Treatment
o Emergency basic life support: relieve airway obstruction
▪ Complete airway obstruction: unable to breathe or speak
o Direct laryngoscopy and foreign body extraction
▪ If basic life support maneuvers fail
o Orotracheal intubation with dislodgement of the foreign
body more distally (often into the right mainstem bronchus)
▪ When foreign body is not visible or able to be removed
▪ May relieve complete obstruction and be lifesaving
o Surgical airway (needle cricothyroidotomy or emergency
tracheostomy)
▪ If the foreign body cannot be removed and ventilation
cannot be provided through an endotracheal tube
o Bronchoscopic removal under general anesthesia
▪ For children with partial airway obstruction
▪ Monitor respiratory status closely
Retropharyngeal Abscess
• Retropharyngeal space
o Between posterior pharyngeal wall & prevertebral fascia
o Extends from base of skull to level of 2nd thoracic vertebrae
o Fused down the midline
o Important potential complication: mediastinitis (caudal spread)
o Contains 2 chains of lymph nodes extending down each side
• Epidemiology: decreasing frequency in older children
o Obliteration of the retropharyngeal space by age 4 years old
▪ Due to regression of 2 chains of lymph nodes extending
down each side of retropharyngeal space
• Etiology: mixed flora (S. aureus, S. pyogenes, S. viridans, and β-
lactamase-producing gram-negative rods; oral anaerobes)
• Pathophysiology
o Suppuration of retropharyngeal lymph nodes seeded from a
distant infection
o Localized penetrating trauma with subsequent invasion by
bacteria (falling with a stick or similar object in mouth)
o Traumatic esophageal instrumentation
o Ventral extension of vertebral osteomyelitis
o Retropharyngeal infection typically progresses from an
organized phlegmon to a mature abscess
• Clinical Features
o Most cases evolve insidiously over a few days after a relatively
minor upper respiratory infection or pharyngitis
o Fever is typically present but may be absent in >10% of patients
o Additional signs & symptoms: neck pain, odynophagia,
dysphagia, trismus, excessive drooling, and neck swelling
o Unusual neck positions: stiffness, torticollis, & hyperextension
o Muffled voice
o Anterior cervical lymphadenopathy is common
o Bulging of the posterior oropharynx: unique finding
o Considered if cannot fully extend neck to look up (Bolte’s sign)
o Abscess progression can lead to stridor and respiratory distress
o Pleuritic chest pain (ominous sign): extension into mediastinum
• Diagnosis
o Soft tissue lateral neck radiography
▪ Taken during inspiration with the neck extended
▪ Diagnosis suggested if retropharyngeal space at C2 is
• Twice diameter of vertebral body
• Greater than ½ the width of the C4 vertebral body
▪ Rarely, gas may be seen within the collection
o Contrast-enhanced CT scan
▪ May demonstrate necrotic nodes, inflammatory phlegmon,
or fluid collection within a ring-enhancing abscess
▪ Helpful for diagnosing and defining the extent of the
infection and surgical planning
▪ Limited in their ability to differentiate between abscess and
cellulitis/phlegmon
▪ Imaging should be correlated to clinical findings when
guiding decision of conservative versus surgical treatment
▪ Unstable patents should be intubated prior to CT scan
2. ACUTE UPPER AIRWAY OBSTRUCTION | 5
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

• Treatment • Clinical Features

o Carefully monitor and stabilize the airway
o IV or IO access: administer fluids, antibiotics, and CT contrast
o Antibiotic therapy alone
▪ Retropharyngeal cellulitis
▪ Small, localized abscesses
o Incision and drainage: all other cases
o Empiric antibiotic therapy
▪ Clindamycin 15 mg/kg/dose every 8 hours IV
▪ Ampicillin-sulbactam 50 mg/kg/dose every 6 hours IV
• Unusual complications: airway obstruction, spontaneous abscess
perforation, mediastinitis, sepsis, aspiration, and jugular venous
thrombophlebitis/thrombosis (Lemierre’s syndrome)
Peritonsillar Abscess (quinsy)
• Posterior oropharyngeal infection
• Epidemiology: adolescents and young adults
• Pathophysiology: typically begins as a superficial infection that
progresses to an accumulation of pus in a space between the
tonsillar capsule and the superior constrictor muscle
• Etiology: polymicrobial infections (anaerobes, group A β-hemolytic
streptococci, S. aureus, and H. influenzae)
• Clinical Features
o Most are unilateral, whereas <10% are bilateral
o Typically present with sore throat (often unilateral), fever, chills,
trismus, and voice change (“hot potato voice”)
o Patients will often complain of “the worse sore throat” of their life
and may drool due to difficulty swallowing their saliva
o Ipsilateral ear pain and torticollis may be present
o On examination, bulging of the affected tonsil and deviation of
the uvula away from the involved tonsil are evident
o If toxic, consider peritonsillar abscess until proven otherwise
• Diagnosis: clinical diagnosis
o Routine laboratory or imaging studies are not needed
o Gram stain and culture of purulent material if drained
o Imaging in cases without typical exam findings to distinguish
cellulitis form abscess
▪ US (intraoral or submandibular) in cooperative children
▪ CT with IV contrast: suspected deep space neck infection
▪ Lateral radiographs of neck: retropharyngeal abscess
• Treatment
o Aspiration or incision and drainage with local anesthetics
▪ Procedural sedation: in young & uncooperative children
▪ Complications: hemorrhage, puncture of the carotid artery,
airway aspiration of purulent material
o Oral antibiotics
▪ Younger children with few prior episodes of tonsillitis and
small abscesses (may not need drainage)
▪ Non-toxic-appearing adolescents with good follow-up and
findings most consistent with peritonsillar cellulitis
o Empiric coverage includes
▪ Amoxicillin-clavulanate 45 mg/kg/dose every 12 hours to a
maximum of 875 mg/dose
▪ Clindamycin 10 mg/kg/dose every 8 hours
o Adjunct therapy with single high-dose steroid administration
▪ Seems to improve symptoms after drainage
o Usually begins with mild infection
o Progresses rapidly to include fever, chills, severe mouth pain,
drooling, trismus, tongue protrusion, & brawny neck swelling
o Assumes a “sniffing position” to maximize airway diameter
o Stridor may develop with progressive airway obstruction
• Treatment
o Control the airway early, because intubation can be extremely
difficult late in the clinical course of the disease
o Empiric antibiotics & oral surgery to remove dental abscess
o IV antibiotics should cover β-lactamase-producing aerobic or
anaerobic gram-positive cocci and gram-negative bacilli
▪ Ampicillin-sulbactam
▪ Clindamycin
▪ Penicillin G
o Consider additional coverage for community-acquired MRSA in
those at risk for colonization
Diphtheria
• Acute toxin-mediated disease
• Etiology: Corynebacterium diphtheria
o Gram-positive non-spore-forming bacillus
o Transmitted from person to person through respiratory
secretions or skin lesions
• Clinical Features
o Pharyngeal diphtheria: sore throat, malaise, dysphagia, & low-
grade fever
▪ Pseudomembranes (thick gray membranes) over tonsils &
soft palate: can cause respiratory obstruction and death
o Laryngeal diphtheria: classic “barking” cough, stridor,
hoarseness, and difficulty breathing
▪ “Bull neck” appearance: marked edema of the neck
• Diagnosis: culture of a nasopharyngeal swab
• Treatment: antitoxin, antibiotics, and respiratory support as needed
• Complications: myocarditis and neuritis potentially leading to
diaphragmatic paralysis and death from respiratory failure

Ludwig’s Angina
• Potentially life-threatening, rapidly expanding infection of the
submandibular space
• Submandibular space: 2 spaces subdivided by mylohyoid into
sublingual & submylohyoid (submaxillary space)
o From floor of mouth to muscular attachments at the hyoid bone
• Pathophysiology
o Infectious expansions into this space spreads superiorly and
posteriorly and often involves the entire submandibular space
o Most cases arise from an odontogenic source, often from the
spread of periapical abscesses of mandibular molars
• Etiology: typically polymicrobial involving oral flora
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

6 | 2. ACUTE UPPER AIRWAY OBSTRUCTION

 Croup
Epidemiology 6 months to 3 years old
Parainfluenza, rhinovirus
Others: influenza, RSV,
Etiology metapneumovirus,
enterovirus, coronavirus
Measles in prevalent areas
Begin after 1-3 days of URTI
Classic symptoms: harsh
barking cough, hoarse
voice, stridor
Often worse at night
Assess for tachypnea,
Clinical
Features
stridor at rest, nasal flaring,
retractions, lethargy or
agitation, and oxygen
desaturation
Self-limited & short in
duration, resolving
spontaneously within 3
days (may last longer
depending on etiology)
Epiglottitis Bacterial Tracheitis Airway Foreign Body Retropharyngeal Abscess Peritonsillar Abscess Ludwig’s Angina Diphtheria
Decreasing frequency in Adolescents & young
Mean age 6-12 years 5-8 years of age 1-3 years of age
older children adults
H. influenzae type B
Most common: food & toys Mixed flora (S. aureus, S.
(prevaccine era), S. aureus, S. pneumoniae, Polymicrobial infections
Commonly aspirated foods pyogenes, S. viridans, & β-
Streptococcus & S. pyogenes, M. catarrhalis, (anaerobes, group A β-
include peanuts, sunflower lactamase-producing gram- Polymicrobial (oral flora) Corynebacterium diphtheria
Staphylococcus spp. H. influenzae, oral hemolytic streptococci, S.
seeds, carrots, raisins, negative rods; oral
(postvaccine era), Candida anaerobes aureus, and H. influenzae)
grapes, and hotdogs anaerobes)
sp. (immunocompromised)
Evolve over a few days after Pharyngeal diphtheria: sore
History of sudden coughing
a minor UTRI or pharyngitis throat, malaise, dysphagia,
and choking Most are unilateral
low-grade fever
Abrupt onset of fever, (<10% bilateral)
Fever, neck pain, Pseudomembranes (thick
stridor, drooling, sore throat Young child with respiratory
odynophagia, dysphagia, gray membranes) over
History of URTI + sudden symptoms, regardless of Sore throat (unilateral), Begins with mild infection
trismus, excessive drooling, tonsils & soft palate:
Progress rapidly, with worsening (high fever, duration fever, chills, trismus, voice
neck swelling respiratory obstruction &
inability to handle oral biphasic stridor, productive change (“hot potato voice”) Progresses rapidly: fever,
death
secretions, stridor, cough) + toxic appearance History of witnessed chills, severe mouth pain,
Unusual neck positions:
respiratory distress choking (sudden onset of “Worst sore throat” of their drooling, trismus, tongue
stiffness, torticollis, & Laryngeal diphtheria:
Thick mucopurulent cough, shortness of breath) life; drooling due to difficulty protrusion, brawny neck
hyperextension classic “barking” cough,
Cough is often absent, and secretions of trachea: upper swallowing their saliva swelling
stridor, hoarseness,
voice may be muffled airway obstruction Laryngotracheal FB: stridor
Muffled voice, anterior difficulty breathing
& hoarseness Ipsilateral ear pain and “Sniffing position” to
cervical lymphadenopathy, “Bull neck” appearance:
Most appear toxic & Sore throat (point to trachea torticollis may be present maximize airway diameter
bulging of the posterior marked edema of neck
anxious when asked where it hurts) Bronchial FB: unilateral
oropharynx
wheezing, ↓ breath sounds Bulging of affected tonsil Stridor: progressive airway
Tripod/sniffling position Tracheal tenderness and deviation of uvula away obstruction
Stridor & respiratory
(neck hyperextended & chin Severe immediate-onset from involved tonsil
distress (progression)
forward) to maintain airway stridor or cardiopulmonary
arrest; or minimally Toxic-looking
Pleuritic chest pain:
symptomatic
extension into mediastinum
Lateral & PA radiographs

Laryngotracheal FB: acute

emergency (radiography is
omitted)
Routine laboratory or
imaging are not needed
Tracheal vs. esophageal FB Soft tissue lateral neck
Trachea: in profile radiography (during
Bronchoscopy is the Gram stain and culture of
Clinical diagnosis Esophagus: en face inspiration, neck extended):
diagnostic method of choice purulent material if drained
Clinical diagnosis retropharyngeal space (C2)
Lateral neck radiography: Bronchial FB: focal 2x diameter of vertebral
Tracheal cultures from Ultrasound (intraoral or
Observe for respiratory enlarged epiglottitis atelectasis & consolidation body or >½ the width of C4
bronchoscopy submandibular) in Culture of nasopharyngeal
Diagnosis distress protruding from anterior wall vertebral body
cooperative children swab
of hypopharynx (“thumb Indirect radiologic signs of
Neck radiographs:
Radiography: subglottic sign”) & thickened radiolucent airway FB: Contrast-enhanced CT:
subglottic narrowing of CT with IV contrast:
narrowing (“steeple sign”) aryepiglottic folds unilateral obstructive necrotic nodes,
trachea & irregular tracheal suspected deep space neck
emphysema, atelectasis, inflammatory phlegmon, or
margins infection
consolidation fluid collection within a ring-
enhancing abscess
Lateral radiographs of neck:
Expiratory radiographs:
retropharyngeal abscess
hyperinflation (air trapping)

Bronchoscopy: rule out

clinically suspected FBA,
regardless of CXR findings
Keep child seated & upright Emergency BLS: relieve
Nebulized epinephrine in a position of comfort airway obstruction
(1:1000) 0.5 mL/kg
(maximum 5 mL): moderate Oxygen only if this does not Sedation, intubation, and Direct laryngoscopy & FB Carefully monitor & stabilize Aspiration or incision and
to severe croup further agitate the child bronchoscopy extraction: if BLS fails airway drainage with local Early airway control
anesthetics
Dexamethasone 0.15-0.60 Nebulized L-epinephrine to Empiric antibiotics: Orotracheal intubation with
IV/IO access: fluids, Empiric antibiotics + oral
mg/kg PO/IM (maximum 10 decrease airway edema vancomycin/clindamycin + dislodgement of FB more
rd antibiotics, & CT contrast Empiric antibiotic therapy: surgery to remove dental
mg): all patients with croup 3 gen. cephalosporin distally (R mainstem
amoxicillin-clavulanate 45 abscess Antitoxin, antibiotics, and
Treatment
Intubation or tracheotomy bronchus): when FB not
Incision and drainage mg/kg/dose q12h, max 875 respiratory support as
Nebulized budesonide 2 mg Bronchoscopy: removal of visible/able to be removed;
Antibiotic coverage: mg/dose; clindamycin 10 IV antibiotics: ampicillin- needed
& IM dexamethasone: purulent may relieve complete
eftriaxone & vancomycin Empiric antibiotic therapy: mg/kg/dose q8h sulbactam, clindamycin,
alternatives to oral pseudomembranes obstruction & be lifesaving
continued for 7-10 days clindamycin 15 mg/kg/dose penicillin G, vancomycin (if
dexamethasone if vomiting
Surgical airway: if FB q8h IV; High-dose steroids as at risk for MRSA
Most patients require
Steroids: decrease mucosal cannot be removed and ampicillin-sulbactam 50 adjunct: improve symptoms colonization)
Endotracheal intubation: for definitive airway &
edema of epiglottis ventilation difficult with ET mg/kg/dose q6h IV after drainage
severe croup with ventilatory support
respiratory failure despite
medical therapy ICU: all suspected or Bronchoscopy with GA:
confirmed epiglottitis partial airway obstruction
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

2. ACUTE UPPER AIRWAY OBSTRUCTION | 7

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

3. ACUTE ASTHMA IN EXACERBATION Symptoms suggestive of asthma in children 5 years and younger
• Wheeze
ASTHMA AND WHEEZING IN YOUNG CHILDREN (<5 years old) o Most common and specific symptom associated with asthma in
• Most common chronic disease of childhood children 5 years and younger
• Leading cause of childhood morbidity from chronic disease as o A wheeze that occurs recurrently, during sleep, or with triggers
measured by school absences, ER visits, and hospitalizations such as activity, laughing, or crying, is consistent with a
• Often begins in early childhood; in up to half of people with asthma, diagnosis of asthma
symptoms commence during childhood o Clinician confirmation is important, as parents may describe any
• Onset of asthma is earlier in males than females noisy breathing as ‘wheezing’
• No intervention has yet been shown to prevent the development of • Cough
asthma or modify its long-term natural course o Generally non-productive, recurrent and/or persistent
• Atopy is present in majority of children >3 years old with asthma o Usually with wheezing episodes and breathing difficulties
• Allergen-specific sensitization (and particularly multiple early-life o Nocturnal cough or a cough that occurs with exercise, laughing
sensitizations) is one of the most important risk factors for the or crying, in the absence of an apparent respiratory infection,
development of asthma supports a diagnosis of asthma
• Breathlessness
Viral-induced wheezing o “Difficult breathing”, “heavy breathing”, “shortness of breath”
• Recurrent wheezing occurs in a large proportion of children <5 yrs o Breathlessness that occurs during exercise and is recurrent
• It is typically associated with upper respiratory tract infections increases the likelihood of the diagnosis of asthma
(URTI), which occur in this age group around 6-8 times per year o In infants and toddlers, crying and laughing are equivalent to
• Some viral infections (respiratory syncytial virus and rhinovirus) are exercise in older children
associated with recurrent wheeze throughout childhood • Activity and social behavior
• Not all wheezing indicates asthma o Physical activity is an important trigger of asthma symptoms
o Young children with poorly controlled asthma often abstain from
• A large proportion of wheezing episodes in young children is virally
strenuous play or exercise to avoid symptoms, but many parents
induced whether the child has asthma or not
are unaware of such changes in their children’s lifestyle
o Careful review of the child’s daily activities, including their
Wheezing phenotypes
willingness to walk and play, is important when assessing a
• Symptom-based classification
potential asthma diagnosis in a young child
o Episodic wheeze
o Parents may report irritability, tiredness, & mood changes in
▪ during discrete time periods
their child as main problems when asthma is not well controlled
▪ often associated with URTI
Feature Characteristics suggesting asthma
▪ with symptoms absent between episodes
Cough • Recurrent or persistent non-productive cough
o Multiple-trigger wheeze that may be worse at night or accompanied by
▪ episodic wheezing with symptoms also occurring between some wheezing and breathing difficulties
these episodes (e.g. during sleep or with triggers such as • Cough occurring with exercise, laughing, crying,
activity, laughing, or crying) or exposure to tobacco smoke, particularly in the
absence of an apparent respiratory infection
• Time trend-base classification Wheezing • Recurrent wheezing, including during sleep or
o Transient wheeze with triggers such as activity, laughing, crying, or
▪ symptoms began and ended before the age of 3 years exposure to tobacco smoke or air pollution
o Persistent wheeze Difficulty or heavy • Occurring with exercise, laughing, or crying
breathing or shortness
▪ symptoms began before the age of 3 years and continued of breath
beyond the age of 6 years Reduced activity • Not running, playing, or laughing at the same
o Late-onset wheeze intensity as other children; tires earlier during
▪ symptoms began after the age of 3 years walks (wants to be carried)
Past or family history • Other allergic disease (atopic dermatitis or
allergic rhinitis, food allergy). Asthma in first-
CLINICAL DIAGNOSIS OF ASTHMA
degree relative(s)
• Limitations of making a diagnosis of asthma in children <5 years Therapeutic trial with • Clinical improvement during 2-3 months of
o Episodic respiratory symptoms (wheezing, cough) are also low dose inhaled controller treatment and worsening when
common in children without asthma (0-2 years old) corticosteroid, and as- treatment is stopped
needed SABA
o Not possible to routinely assess airflow limitation or
bronchodilator responsiveness in this age group
Questions that can be used to elicit features suggestive of asthma
• A probability-based approach may be helpful for discussion with
• Does your child have wheezing? Wheezing is a high-pitched noise
parents/caregivers
which comes from the chest and not from the throat. Use of a video
SYMPTOM PATTERN (may change over time) questionnaire, or asking a parent to record an episode on a
Few have asthma Some have asthma Most have asthma
smartphone if available can help to confirm the presence of wheeze
• Symptoms (cough, • Symptoms (cough, • Symptoms (cough,
wheeze, heavy wheeze, heavy wheeze, heavy and differentiate from upper airway abnormalities
breathing) for <10 days breathing) for >10 breathing) for >10 • Does your child wake up at night because of coughing, wheezing,
during URTI days during URTI days during URTI or ‘difficulty breathing’, ‘heavy breathing’, or ‘breathlessness’?
• 2-3 episodes/yr • >3 episodes/yr, or • >3 episodes/yr, or
• Does your child have to stop running, or play less hard, because of
• No symptoms between severe episodes severe episodes
episodes and/or night worsening and/or night coughing, wheezing, or ‘difficulty breathing’, ‘heavy breathing’, or
• Between episodes, worsening ‘shortness of breath’?
child may have • Between episodes, • Does your child cough, wheeze, or get difficult breathing, heavy
occasional cough, child has cough,
wheeze, or heave wheeze, or heavy
breathing, or shortness of breath when laughing, crying, playing with
breathing breathing during play/ animals, or when exposed to strong smells or smoke?
laughing • Has your child ever had eczema, or been diagnosed with allergy to
• Allergic sensitization, foods?
atopic dermatitis, food
allergy, or family • Has anyone in your family had asthma, hay fever, food allergy,
history of asthma eczema, or any other disease with breathing problems?

8 | 3. ACUTE ASTHMA IN EXACERBATION


TESTS TO ASSIST IN DIAGNOSIS
• Therapeutic trial
o A trial of treatment for at least 2-3 months with as-needed short-
acting beta2-agonist (SABA) and regular low dose inhaled
corticosteroids (ICS) may provide some guidance about the
diagnosis of asthma
o Response should be evaluated based on:
▪ Symptom control (daytime and night-time)
▪ Frequency of wheezing episodes and exacerbations
o Marked clinical improvement during treatment, and deterioration
when treatment stopped, support a diagnosis of asthma
o Due to the variable nature of asthma in young children, a
therapeutic trial may need to be repeated in order to be certain
of the diagnosis
• Tests for allergic sensitization
o Using either skin prick testing or allergen specific IgE
o Allergic sensitization is present in the majority of children with
asthma once they are over 3 years of age, however, absence of
sensitization to common aeroallergens does not rule out a
diagnosis of asthma
o Allergen sensitization is the best predictor for development of
persistent asthma
• Chest X-ray
o Radiographs are rarely indicated
o May help exclude structural abnormalities, chronic infections,
inhaled foreign body, or other diagnoses
• Lung function testing
o Lung function testing, bronchial provocation testing, and other
physiological tests do not have a major role in the diagnosis of
asthma due to the inability of most children 5 years and younger
to perform reproducible expiratory maneuvers
o By 5 years of age, many children are capable of performing
reproducible spirometry if coached by an experienced
technician and with visual incentives
DIFFERENTIAL DIAGNOSIS
Condition Typical features
Recurrent viral Mainly cough, runny congested nose for <10 days; no
respiratory tract symptoms between infections
infections
Gastroesophageal Cough when feeding; recurrent chest infections; vomits
reflux easily especially after large feeds; poor response to
asthma medications
Foreign body Episode of abrupt, severe cough and/or stridor during
aspiration eating or play; recurrent chest infections and cough;
focal lung signs
Persistent bacterial Persistent wet cough; poor response to asthma
bronchitis medications
Tracheomalacia Noisy breathing when crying or eating, or during upper
airway infections (noisy inspiration if extrathoracic or
expiration if intrathoracic); harsh cough; inspiratory or
expiratory retraction; symptoms often present since
birth; poor response to asthma medications
Tuberculosis Persistent noisy respirations and cough; fever
unresponsive to normal antibiotics; enlarged lymph
nodes; poor response to bronchodilators or inhaled
corticosteroids; contact with someone who has TB
Congenital heart Cardiac murmur; cyanosis when eating; failure to thrive;
disease tachycardia; tachypnea or hepatomegaly; poor
response to asthma medications
Cystic fibrosis Cough starting shortly after birth; recurrent chest
infections; failure to thrive (malabsorption); loose
greasy bulky stools
Primary ciliary Cough and recurrent chest infections; neonatal
dyskinesia respiratory distress, chronic ear infections and
persistent nasal discharge from birth; poor response to
asthma medications; situs inversus occurs in about
50% of children with this condition
Vascular ring Respirations often persistently noisy; poor response to
asthma medications
Bronchopulmonary Infant born prematurely; very low birth weight; needed
dysplasia prolonged mechanical ventilation or supplemental
oxygen; difficulty with breathing present from birth
Immune deficiency Recurrent fever and infections (including non-
respiratory); failure to thrive
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Key indications for referral of a child 5 years or younger for further
diagnostic investigations or therapeutic decisions
• Failure to thrive
• Neonatal or very early onset of symptoms (especially if associated
with failure to thrive)
• Vomiting associated with respiratory symptoms
• Continuous wheezing
• Failure to respond to asthma medications (ICS, OCS, SABA)
• No association of symptoms with typical triggers, such as viral URTI
• Focal lung or cardiovascular signs, or finger clubbing
• Hypoxemia outside context of viral illness
GOALS OF ASTHMA MANAGEMENT
• To achieve good control of symptoms and maintain normal activity
levels
• To minimize future risk; that is to reduce risk of flare-ups, maintain
lung function and lung development as close to normal as possible,
and minimize medication side-effects
ASSESSMENT OF ASTHMA
• Asthma control
o Extent to which the manifestations of asthma are controlled, with
or without treatment
GINA Assessment of Asthma Control in Children 5 years & younger
A. Symptom control
In the past 4 weeks, has the child had:
• Daytime asthma symptoms for more than a few minutes, more than once a
week?
• Any activity limitation due to asthma? (Runs/plays less than other children,
tires easily during walks/playing?)
• Reliever medication needed more than once a week?
• Any night waking or night coughing due to asthma?
Level of asthma symptom control
• Well controlled – None of these
• Partly controlled – 1-2 of these
• Uncontrolled – 3-4 of these
B. Future risk for poor asthma outcomes
Risk factors for asthma exacerbations within the next few months
• Uncontrolled asthma symptoms
• One or more severe exacerbations (ED attendance, hospitalization, or
course of OCS) in previous year
• The start of the child’s usual ‘flare-up’ season (autumn/fall)
• Exposures: tobacco smoke; indoor or outdoor air pollution; indoor allergens
(house dust mite, cockroach, pets, mold), especially in combination with viral
infection
• Major psychological or socio-economic problems for child/family
• Poor adherence with controller medication, or incorrect inhaler technique
• Outdoor pollution (NO2 and particles)
Risk factors for fixed airflow limitation
• Severe asthma with severe hospitalizations
• History of bronchiolitis
Risk factors for medication side-effected
• Systemic: Frequent courses of OCS, high-dose and/or potent ICS
• Local: moderate/high-dose or potent ICS; incorrect inhaler technique; failure
to protect skin or eyes when using ICS by nebulizer or spacer with face mask
MEDICATIONS FOR SYMPTOM CONTROL AND RISK REDUCTION
• Which children should be prescribed regular controller treatment?
o If the history and symptom pattern suggest a diagnosis of
asthma and respiratory symptoms are uncontrolled and/or
wheezing episodes are frequent.
o If the diagnosis of asthma is in doubt, and inhaled SABA therapy
or courses of antibiotics needed to be repeated frequently.
REVIEWING RESPONSE AND ADJUSTING TREATMENT
• Assessment at every visit should include asthma symptom control
and risk factors and side-effects
• The child’s height should be measured every year, or more often
• Need for continued controller treatment should be regularly
assessed (e.g. every 3-6 months)
• If therapy is stepped down or discontinued, schedule a follow-up visit
3-6 weeks later to check whether symptoms have recurred
3. ACUTE ASTHMA IN EXACERBATION | 9
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
STEP 1: As-needed inhaled short-acting beta2-agonist (SABA)
• Preferred option: as-needed inhaled short-acting beta2-agonist
(SABA)
o Use of SABA for relief of symptoms on average more than twice
a week over one-month period indicates the needed for a trial of
controller medication
• Other options
o Oral bronchodilator therapy is NOT recommended due to
▪ slower onset of action
▪ higher rate of side-effects compared with inhaled SABA
o Intermittent high dose ICS
▪ For children with intermittent viral-induced wheeze and no
interval symptoms (underlying atopy) in whom inhaled
SABA is not sufficient
▪ only considered if the physician is confident that the
treatment will be used appropriately
STEP 2: Initial controller treatment plus as-needed SABA
• Preferred option: regular daily low dose ICS + as-needed SABA
o Should be given for at least 3 months to establish its
effectiveness in achieving good asthma control
• Other options
o Leukotriene receptor antagonist (LTRA)
▪ in young children with persistent asthma, regular treatment
modestly reduces symptoms and need for oral
corticosteroids compared with placebo
o As needed or episodic ICS
▪ May be considered for pre-school children with frequent
viral-induced wheezing and interval asthma symptoms
▪ trial of regular ICS should be undertaken first
▪ effect on exacerbation risk seems similar for regular and
high dose episodic ICS
• If good control is not achieved with a given therapy, trials of the
alternative Step 2 therapies are recommended prior to moving to
Step 3
10 | 3. ACUTE ASTHMA IN EXACERBATION
STEP 3: Additional controller treatment, plus as-needed SABA and
consider specialist referral
• If 3 months of initial therapy with a low dose ICS fails to control
symptoms, or if exacerbations continue to occur, check the following
before any step up in the treatment is considered
o Confirm that the symptoms are due to asthma rather than a
concomitant or alternative condition
o Check & correct inhaler technique. Consider alternative delivery
systems if indicated
o Confirm good adherence with the prescribed dose
o Enquire about risk factors (allergen or tobacco smoke exposure)
• Preferred option: moderate dose ICS (double the ‘low’ daily dose)
o Assess response after 3 months
o The child should be referred for expert assessment if:
▪ Symptom control remains poor and/or flare-ups persist
▪ Side-effects of treatment are observed or suspected
• Other options: Addition of a LTRA to low dose ICS
STEP 4: Continue controller treatment and refer for expert
assessment
• If doubling the initial dose of ICS fails to achieve and maintain good
asthma control
o Carefully reassess inhaler technique and medication adherence
o Reassess & address control of environmental factors
o Reconsider the asthma diagnosis
• Preferred option: refer child for expert advice & further investigation
• Other options:
o If confirmed asthma, (preferably with specialist advice):
▪ Further increase the dose of ICS for a few weeks until
control of child’s asthma improves. Monitor for side-effects
▪ Add LTRA
▪ Add LABA in combination with ICS
▪ Add theophylline, or a low dose or oral corticosteroid (for a
few weeks only) until asthma control improves
▪ Add intermittent ICS to the regular daily ICS if exacerbations
are the main problem

DIAGNOSIS OF EXACERBATIONS
Flare-up / Exacerbation of asthma
• Acute or sub-acute deterioration in symptom control that is sufficient
to cause distress or risk to health, and necessitates a visit to a health
care provider or requires treatment with systemic corticosteroids
• Sometimes called ‘episodes’
• Early symptoms of an exacerbation may include any of the following:
o Onset of symptoms of respiratory tract infection
o An acute or sub-acute increase in wheeze & shortness of breath
o An increase in coughing, especially while the child is asleep
o Lethargy or reduced exercise tolerance
o Impairment of daily activities, including feeding
o A poor response to reliever medication
INITIAL HOME MANAGEMENT OF ASTHMA EXACERBATIONS
• Need for urgent medical attention if:
o Acutely distressed
o Symptoms are not relieved promptly by inhaled bronchodilator
o Period of relief after SABA doses becomes progressively shorter
o For <1 year, requires repeated inhaled SABA over several hours
• Initial treatment at home
o Inhaled SABA via a mask or spacer, and review response
▪ Inhaled SABA (Salbutamol 200 mcg) 2 puffs, give 1 puff at
a time via a spacer device with or without a face mask every
20 minutes for 3 doses
▪ Maintain in a restful & reassuring atmosphere for >1 hour
▪ Medical attention should be sought urgently if
• Any of the features above apply
• On the same day, >6 puffs of inhaled SABA are required
for symptom relief within the first 2 hours
• The child has not recovered after 24 hours
o Preemptive episodic high-dose episodic ICS
▪ May reduce exacerbations in children with intermittent viral
triggered wheezing
▪ Considered only where the health care provider is confident
that the medications will be used appropriately, and the child
is closely monitored for side-effects
o Leukotriene receptor antagonists
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
PRIMARY CARE OR HOSPITAL MANAGEMENT OF ACUTE
ASTHMA EXACERBATIONS
Assessment of exacerbation severity
• SaO2 <92% on presentation (before oxygen or bronchodilator) is
associated with high morbidity and likely need for hospitalization
• Agitation, drowsiness, confusion are features of cerebral hypoxemia
• A quiet chest on auscultation indicates minimal ventilation,
insufficient to produce a wheeze
Symptoms Mild Severe*
Altered consciousness No Agitated, confused, or drowsy
Oximetry on presentation (SaO2)** >95% <92%
Speech† Sentences Words
Pulse rate
<100 >200 beats/minute (0-3 years)
beats/minute >180 beats/min (4-5 years)
Central cyanosis Absent Likely to be present
Wheeze intensity Variable Chest may be quiet
*
**
Any of these features indicates a severe asthma exacerbation
Oximetry before treatment with oxygen or bronchodilator
†
The normal development capability of the child must be taken into account
Indications for immediate transfer to hospital
• Features of severe exacerbation that fail to resolve within 1-2 hours
despite repeated dosing with inhaled SABA, with or without OCS
• Respiratory arrest or impending arrest
• Lack of supervision in the home or doctor’s office
• Recurrence of signs of a severe exacerbation within 48 hours
(particularly if treatment with OCS has already been given)
• History or severe life-threatening exacerbations
• Less than 2 years of age (risk of dehydration & respiratory fatigue)
Immediate transfer to hospital is indicated if a child ≤5 years
with asthma has ANY of the following:
• At initial or subsequent assessment
o Child is unable to speak or drink
o Cyanosis
o Subcostal retraction
o Oxygen saturation <92% when breathing room air
o Silent chest on auscultation
• Lack of response to initial bronchodilator treatment
o Lack of response to 6 puffs of inhaled SABA (2 separate puffs,
repeated 3 times) over 1-2 hours
o Persistent tachypnea * despite 3 administrations of inhales SABA,
even if the child shows other clinical signs of improvement
• Social environment that limits delivery of acute treatment, or parent/carer
unable to manage acute asthma at home
During transfer to hospital, continue to give inhaled SABA, oxygen (if available)
to maintain saturation 94-98%, and give systemic corticosteroids.
*
Normal respiratory rates: <60 breaths/minute in children 0-2 months; <50 breaths/minute in children 2-12 months;
<40 breaths/minute in children 1-5 years
Emergency treatment and initial pharmacotherapy
• Oxygen
o Treat hypoxemia urgently with oxygen by face mask to achieve
and maintain percutaneous oxygen saturation 94-98%
o Children who are acutely distressed should be treated
immediately with oxygen and SABA (2.5 mg of salbutamol in 3
mL of NSS) delivered by an oxygen-driven nebulizer
o Should not be delayed, and may be given before the full
assessment is complete
o Transient hypoxemia due to ventilation/perfusion mismatch may
occur during treatment with SABAs
• Bronchodilator therapy
o pMDI with spacer & mask/mouthpiece: 2 puffs of salbutamol
(100 mcg per puff); 6 puffs if in acute severe asthma
o Nebulizer: 2.5 mg salbutamol solution (if with desaturations)
o Ipratropium bromide may be added as 2 puffs of 80 mcg (or 250
mcg by nebulizer) every 20 minutes for 1 hour for children with
moderate-severe exacerbations & poor response to initial SABA
• Magnesium sulfate
o Nebulized isotonic magnesium sulfate may be considered as
adjuvant to standard treatment with nebulized salbutamol &
ipratropium in the 1st hour of treatment for children ≥2 years old
with acute severe asthma, particularly those with symptoms
lasting <6 hours
o Intravenous magnesium sulfate in a single dose 40-50 mg/kg
(max 2 g) by slow infusion (20-60 minutes) has also been used
3. ACUTE ASTHMA IN EXACERBATION | 11
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Initial management of asthma exacerbations in children ≤5 years KEY POINTS

Therapy Dose and administration • Recurrent wheezing occurs in a large proportion of children 5 years
Supplemental Delivered by face mask (usually 1 L/minute) to maintain and younger, typically with viral upper respiratory tract infections.
oxygen oxygen saturation 94-98% Deciding when this is the initial presentation of asthma is difficulty.
Short-acting
2-6 puffs of salbutamol by spacer, or 2.5 mg of salbutamol • Previous classifications of wheezing phenotypes (episodic wheeze
by nebulizer, every 20 minutes for first hour *, then reassess and multiple-trigger wheeze; or transient wheeze, persistent wheeze,
beta2-agonist
severity. If symptoms persist or recur, give an additional 2-3 and late-onset wheeze) do not appear to identify stable phenotypes,
(SABA)
puffs/hour. Admit to hospital if >10 puffs required in 3-4 hrs and their clinical usefulness is uncertain. However, emerging
Give initial dose of oral prednisolone (1-2 mg/kg, maximum research suggest that more stable phenotypes will be described and
Systemic
of 20 mg for children <2 years; 30 mg for children 2-5 years) phenotype-directed therapy possible.
corticosteroids
OR; IV methylprednisolone 1 mg/kg 6-hourly on day 1
• A diagnosis of asthma in young children with a history of wheezing is
Additional options in the first hour of treatment
For children with moderate-severe exacerbations, 2 puffs of
more likely if they have:
Ipratropium
ipratropium bromide 80 mcg (or 250 mcg by nebulizer) every o Wheezing or coughing that occurs with exercise, laughing or
bromide crying, or in the absence of an apparent respiratory infection
20 minutes for 1 hour only
Consider nebulized isotonic magnesium sulfate (150 mg) 3 o A history of other allergic disease (eczema or allergic rhinitis),
Magnesium allergen sensitization or asthma in first-degree relatives
doses in the 1st hour of treatment for children ≥2 years with
sulfate o Clinical improvement during 2-3 months of controller treatment,
severe exacerbation
*If inhalation is not possible, an intravenous bolus of terbutaline 2 mcg/kg may be given over 5 minutes, followed by and worsening after cessation
continuous infusion of 5 mcg/kg/hour. The child should be closely monitored, and the dose should be adjuste d
according to clinical improvement and side-effects.
• The goal of asthma management in young children are similar to
those in older patients:
o To achieve good control of symptoms and maintain normal
Assessment of response and additional bronchodilator treatment
activity levels
• Children with a severe asthma exacerbation must be observed for o To minimize the risk of asthma flare-ups, impaired lung
at least 1 hour after initiation of treatment development, and medication side-effects
o If symptoms persist after initial bronchodilator • Wheezing episodes in young children should be treated initially with
▪ A further 2-6 puffs of salbutamol may be given 20 minutes inhaled short-acting beta2-agonists, regardless whether the diagnosis
after the 1st dose & repeated every 20 minutes for an hour of asthma has been made
• A trial of controller therapy should be given if the symptom pattern
▪ Failure to respond at 1 hour, or earlier deterioration, should
suggests asthma, alternative diagnoses have been excluded, and
prompt urgent admission to hospital & short course of OCS respiratory symptoms are uncontrolled and/or wheezing episodes are
o If symptoms improved by 1 hour but recur within 3-4 hours frequent or severe.
▪ The child may be given more frequent doses of • Response to treatment should be reviewed before deciding whether
bronchodilators (2-3 puffs/hour), and OCS should be given to continue it. If the response is absent or incomplete, reconsider
▪ The child may need to remain in the ER, or, if at home, alternative diagnoses.
should be observed by the family/carer and have ready • The choice of inhaler device should be based on the child’s age and
capability. The preferred device ins a pressurized meter dose inhaler
access to emergency care and spacer, with face mask for <3 years and mouthpiece for most 3-
▪ Children who fail to respond to 10 puffs of inhales SABA 5-year-olds. Children should be switched from a face mask to
within a 3-4-hour period should be referred to hospital mouthpiece as soon as they are able to demonstrate good technique
o If symptoms resolve rapidly after initial bronchodilator and • Review the need for asthma treatment frequently, as asthma-like
do not recur for 1-2 hours symptoms remit in many young children
▪ No further treatment may be required • Early symptoms of exacerbations in young children may include
increased symptoms; increased coughing, especially at night;
▪ Further SABA may be given every 3-4 hours (up to a total of
lethargy or reduced exercise tolerance; impaired daily activities
10 puffs/24 hours) including feeding; and a poor response to reliever medication
▪ If symptoms persist beyond 1-day, other treatments • Give a written asthma action plan to parents/carers of young children
including ICS or OCS are indicated with asthma so they can recognize an impending severe attack, start
treatment, and identify when urgent hospital treatment is required
Additional Treatment o Initial treatment at home is with inhaled short-acting beta2-
agonist (SABA), with review after 1 hour or earlier
• Maintain current controller treatment (if prescribed)
o Parents/carers should seek urgent medical care if the child is
o Children who have been prescribed maintenance therapy with acutely distressed, lethargic; fails to respond to initial
ICS, LTRA, or both should continue to take the prescribed dose bronchodilator therapy, or is worsening, especially in children <1
during and after an exacerbation year of age
• Inhaled corticosteroids o Medical attention should be sought on the same day if inhaled
SABA is needed more often than 3-hourly or for more than 24
o If not previously on ICS, an initial dose of ICS twice the low daily
hours
dose may be given and continued for a few weeks or months o There is no compelling evidence to support parent-initiated oral
o High dose ICS (1600 mcg/day divided into 4 doses a day & given corticosteroids
for 5-10 days) may be used as this may reduce need for OCS • In children presenting to primary care or an acute care facility with an
o If already on ICS, doubling the dose was not effective in mild- asthma exacerbation:
moderate exacerbations in older children o Assess severity of the exacerbation while initiating treatment with
SABA (2-6 puffs every 20 minutes for first hour) and oxygen (to
• Oral corticosteroids
maintain saturation 94-98%)
o For severe exacerbations, prednisolone 1-2 mg/kg/day o Recommend immediate transfer to hospital if there is no
(maximum of 20 mg/day for <2 years & 30 mg/day for 2-5 years) response to inhaled SABA within 1-2 hours; if the child is unable
o A 3-5-day course is sufficient & can be stopped abruptly to speak or drink or has subcostal retractions or cyanosis; if
o In children discharged from ER, an intramuscular corticosteroid resources are lacking in the home; or if oxygen saturation is
may be an alternative to a course of OCS for preventing relapse <92% on room air
o Consider oral prednisone/prednisolone 1-2 mg/kg/day for up to 5
days for children attending an emergency department or
Discharge and follow up after an exacerbation admitted to hospital, up to a maximum of 20 mg/kg/day for 0-2
• Before discharge, the condition of the child should be stable (e.g. years, and 30 mg/kg/day for 3-5 years; or dexamethasone 0.6
should be out of bed & able to eat and drink without problems) mg/kg/day for 2 days
• Follow up is required to • Children who have experienced an asthma exacerbation are at risk
of further exacerbations. Follow up should be arranged within 1 week
o Ensure complete recovery
of an exacerbation to plan ongoing asthma management
o Establish cause of exacerbation
o Establish appropriate maintenance treatment and adherence
• Follow-up appointment within 1-2 days & another within 1-2 months,
depending on the clinical, social, & practical context of exacerbation
Reference: Global Initiative for Asthma (GINA): Global Strategy for Asthma Management and Prevention (2019)

12 | 3. ACUTE ASTHMA IN EXACERBATION

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

4. RESPIRATORY DISTRESS SYNDROME

INCIDENCE
• Occurs primarily in premature infants
• Incidence is inversely related to gestational age and birthweight
o 60-80% of infants <28 weeks AOG
o 15-30% of those between 32-36 weeks AOG
o Rarely in those >37 weeks AOG
Risk for development increases Risk of RDS reduced
• Maternal diabetes • Pregnancies with chronic or
• Multiple births pregnancy-associated
• Cesarian delivery hypertension
• Precipitous delivery • Maternal heroin use
• Asphyxia • Prolonged rupture of
• Cold stress membranes
• Maternal history of previously • Antenatal corticosteroid
affected infants prophylaxis

ETIOLOGY AND PATHOPHYSIOLOGY

• Surfactant deficiency (decreased production and secretion)
o Primary cause of RDS
o Significantly increased alveolar surface tension leads to CLINICAL MANIFESTATIONS
▪ Atelectasis
• Usually appear within minutes of birth
▪ Impaired ability to attain an adequate FRC is impaired
o May not be recognized for several hours in larger premature
o Progressive injury to epithelial & endothelial cells: atelectasis
infants, until rapid, shallow respirations becomes more obvious
(atelectrauma), volutrauma, ischemic injury, oxygen toxicity
o A later onset of tachypnea should suggest other conditions
▪ Formation of hyaline membranes: effusion of proteinaceous
o Some require resuscitation at birth because of intrapartum
material & cellular debris into alveolar spaces that further
asphyxia or initial severe respiratory distress (BW <1,000 g)
impairs oxygenation
• Characteristically, tachypnea, prominent (often audible)
o Alveolar atelectasis, hyaline membrane formation, and
expiratory grunting, intercostal and subcostal retractions,
interstitial edema make the lungs less compliant in RDS
nasal flaring and cyanosis are noted
▪ Greater pressure required to expand alveoli & small airways
o Breath sounds may be normal or diminished with a harsh tubular
▪ Highly compliant chest wall of the preterm infant offers less
quality, and on deep inspiration, fine crackles may be heard
resistance to the natural tendency of the lungs to collapse
• Natural course of untreated RDS: progressive worsening of
▪ Thus, at end-expiration, the volume of the thorax and lungs
cyanosis and dyspnea
tends to approach residual volume
• If inadequately treated, as the condition worsens
o Surfactant is present in high concentrations by 20 weeks AOG
o Blood pressure may fall
but does not reach surface of lungs until later
o Cyanosis and pallor increase
▪ It appears in amniotic fluid between 28-32 weeks AOG
o Grunting decreases or disappears
▪ Mature levels of pulmonary surfactant: 35 weeks AOG
o Apnea and irregular respirations are ominous signs requiring
• Major constituents of surfactant
immediate intervention
o Dipalmitoyl phosphatidylcholine (lecithin)
o Mixed respiratory metabolic acidosis, edema, ileus, oliguria
o Phosphatidylglycerol
o Respiratory failure: in infants with rapid progression
o Apoproteins (surfactant proteins SP-A, SP-B, SP-C, SP-D)
• Peak within 3 days, after which improvement is gradual
o Cholesterol
o Spontaneous diuresis
• With advancing gestational age, increasing amounts of
o Improved blood gas values at lower inspired O2 levels and/or
phospholipids are synthesized and stored in type II alveolar cells
lower ventilatory support
o Released into alveoli, where they reduce surface tension and
• Death can result from
help maintain alveolar stability at end-expiration
o Severe impairment of gas exchange
• Surfactant synthesis depends on normal pH, temperature, perfusion
o Alveolar air leaks (pulmonary interstitial emphysema,
o Asphyxia, hypoxemia, & pulmonary ischemia, particularly in
pneumothorax)
association with hypovolemia, hypotension, & cold stress, may
o Pulmonary hemorrhage
suppress surfactant synthesis
o Intraventricular hemorrhage (IVH)
o The epithelial lining of the lungs may also be injured by high O2
concentrations & mechanical ventilation, thereby further
DIAGNOSIS
reducing secretion of surfactant
• Clinical course + CXR + blood gas values = clinical diagnosis
• Atelectasis: perfused but not ventilated alveoli, causing hypoxia
• Chest radiograph
o Decreased lung compliance, smaller tidal volumes, increased
o Characteristic but not pathognomonic appearance:
physiologic dead space, insufficient alveolar ventilation
▪ Low lung volumes
eventually result in hypercapnia
▪ Diffuse, fine reticular granularity of the parenchyma (ground-
o Hypercapnia + hypoxia + acidosis: pulmonary arterial
glass appearance)
vasoconstriction with increased right-to-left shunting
▪ Air bronchograms
through foramen ovale, ductus arteriosus & within the lung itself
o Initial x-ray: occasionally normal (typical pattern during 1st day)
o Progressive injury to epithelial and endothelial cells and
o Considerable variation in radiographic findings may be seen
formation of hyaline membranes further impairs oxygenation,
▪ In infants who have already received treatment with
leading to a vicious cycle of diminished surfactant production,
surfactant replacement and/or positive pressure ventilation
worsening atelectasis, lung injury, and severe hypoxia
▪ Results in poor correlation between CXR and clinical course
• Blood gas findings
o Initial: hypoxemia
o Later: progressive hypoxemia, hypercapnia, and variable
metabolic acidosis

4. RESPIRATORY DISTRESS SYNDROME | 13

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
DIFFERENTIAL DIAGNOSIS
• Early-onset sepsis
o Neonatal pneumonia: chest radiography may be identical
o Clinical factors: maternal GBS colonization with inadequate
intrapartum antibiotic prophylaxis, maternal fever (>38.6°C) or
chorioamnionitis, or prolonged rupture of membranes (>12 hrs)
o CBC: marked neutropenia
• Cyanotic congenital heart disease (TAPVR)
o Can mimic RDS clinically and radiographically
o 2D-echo with color-flow imaging should be performed
▪ In infants who shows no response to surfactant replacement
▪ To rule out cyanotic congenital heart disease
▪ Ascertain patency of ductus arteriosus & assess pulmonary
vascular resistance
• Patients with atypical course (differentiated by CXR & other tests)
o Persistent pulmonary hypertension
o Aspiration (meconium, amniotic fluid) syndrome
o Spontaneous pneumothorax
o Pleural effusions
o Congenital anomalies (pulmonary congenital airway
malformations, pulmonary lymphangiectasia, diaphragmatic
hernia, lobar emphysema)
• Transient tachypnea of newborn
o Distinguished by its shorter and milder clinical course
o Characterized by low or no need for O2 supplementation
PREVENTION
• Important preventive strategies
o Avoidance of unnecessary or poorly timed early (<39 weeks
AOG) cesarian or induction of labor
o Appropriate management of high-risk pregnancy and labor
(including administration of antenatal corticosteroids)
o Prediction of pulmonary immaturity with possible in utero
acceleration of maturation
• Antenatal and intrapartum fetal monitoring
o May decrease risk of fetal asphyxia (associated with increased
incidence and severity of RDS)
• Antenatal corticosteroids (betamethasone & dexamethasone)
o If given at <37 weeks AOG, significantly reduces:
▪ Incidence & mortality of RDS & overall neonatal mortality
▪ Reduce overall mortality
▪ NICU admission & need for/duration of ventilatory support
▪ Incidence of severe IVH, necrotizing enterocolitis (NEC),
and neurodevelopmental impairment
o Do not ↑ maternal death, chorioamnionitis, or puerperal sepsis
o Considered in all women between 24-36 weeks AOG who
present in preterm labor & likely to deliver a fetus within 1 week
TREATMENT
• Goal of treatment: minimize abnormal physiologic variations and
superimposed iatrogenic problems
o Basic supportive care (thermoregulatory, circulatory, fluid,
electrolyte, respiratory) while FRC is established & maintained
o Careful & frequent monitoring of heart & respiratory rates, SaO2,
PaO2, PaCO2, pH, electrolytes, glucose, hematocrit, BP
o Arterial catheterization is frequently necessary
o Treatment of infants with RDS is best carried out in the NICU
• Periodic monitoring of PaO2, PaCO2, and pH
o Important part of the management
o Used to provide supportive care
o Essential in assisted ventilation
o Continuous pulse oximetry: oxygenation (SO2)
o Capillary blood samples: PCO2 & pH monitoring
o Umbilical/peripheral arterial catheter: blood gas & MABP
▪ Useful in managing shock-like state during initial hours in
premature infants with asphyxia or severe RDS
▪ Removed as soon as patients no longer need monitoring,
usually when an infant is stable and FiO2 is <40%
14 | 4. RESPIRATOYR DISTRESS SYNDROME
• Nasal Continuous Positive Airway Pressure (nCPAP)
o Warm, humidified oxygen to keep PaO2 50-70 mmHg (91-95% SaO2)
▪ Maintain normal tissue oxygenation
▪ Minimizing risk of O2 toxicity
o nCPAP at 5-10 cm H2O: rapid improvement in oxygenation
▪ If there is significant respiratory distress (severe retractions
and expiratory grunting)
▪ If SaO2 cannot be kept >90% at FiO2 of ≥ 40-70%
o Advantages of nCPAP
▪ Reduces collapse of surfactant-deficient alveoli and
improved both FRC and V/Q matching
▪ Early use for stabilization of at-risk preterm infants
beginning early (in the delivery room) reduces need for MV
o Early rescue surfactant replacement methods with nCPAP
▪ INSURE method (intubate, surfactant, and extubate)
• Intubation for prophylactic or early rescue replacement
therapy, followed by extubation back to nCPAP
immediately once infant is stable (minutes to <1 hour)
▪ MIST (minimally invasive surfactant therapy) or
LISA (less invasive surfactant administration)
• A small feeding tube, rather than an endotracheal tube,
is used to deliver intratracheal surfactant to a
spontaneously breathing infant on nCPAP
▪ INSURE, MIST, LISA methods have been associated with
the reduced need for mechanical ventilation (MV)
• Avoidance of MV is associated with a reduction in death
and/or bronchopulmonary dysplasia (BPD)
o Amount of nCPAP required decreases after ~72 hours of age
▪ Most infants can be weaned from nCPAP shortly thereafter
o Assisted ventilation & surfactant: indicated for infants with
RDS who cannot keep SaO2 >90% in FiO2 40-70% & nCPAP
▪ Infants at the extremes of GA (<24 weeks) and those that
were not exposed to antenatal corticosteroids may still
benefit from intubation and surfactant prophylaxis
o Use of nCPAP as the initial respiratory support for extremely
preterm infants is preferred
▪ Minimize ventilator-associated lung injury
▪ Prevent long-term pulmonary complications
▪ Maintain lung inflation while preventing lung injury
• Mechanical Ventilation (MV)
o Infants with respiratory failure or persistent apnea require
assisted mechanical ventilation
o Reasonable measures of respiratory failure
▪ Arterial pH <7.20
▪ PaCO2 ≥ 60 mmHg
▪ SaO2 <90% at FiO2 of 40-70% and nCPAP of 5-10 cm H2O
▪ Persistent or severe apnea
o Goal: improve oxygenation & ventilation without causing
pulmonary injury or oxygen toxicity
o Acceptable ranges of ABG values
▪ PaO2: 50-70 mmHg
▪ PaCO2: 45-65 mmHg (and higher after the 1st few days when
risk of IVH is less)
▪ pH 7.20-7.35
o During MV, oxygenation is improved by increasing either FiO2
or the mean airway pressure
▪ ↑ mean airway pressure (most effective): ↑ peak inspiratory
pressure (PIP), inspiratory time, ventilator rate, or PEEP
▪ Excessive PEEP may impede venous return, thereby
reducing cardiac output and O2 delivery
▪ Assisted ventilation for infants with RDS should always
include appropriate PEEP (4-6 cm H2O)
o CO2 elimination is determined by the minute ventilation
▪ Minute ventilation = tidal volume (dependent on inspiratory
time and PIP) and ventilator rate
o Because of the homogeneous nature of the lung pathology
associated with RDS, a high rate (≥60/min), low tidal volume
(4-6 mL/kg) strategy is generally effective
▪ Sufficient expiratory time should be allowed to avoid air-
trapping and inadvertent PEEP
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

• Surfactant Replacement Therapy Related to Catheterization

o Immediate effects
▪ Improved alveolar-arterial oxygen gradients
▪ Reduced ventilatory support
▪ Increased pulmonary compliance
▪ Improved chest radiography appearance
o Endotracheal surfactant
▪ Initiated immediately to avoid lung injury who fail nCPAP
and require intubation and MV
▪ Repeated dosing is given every 6-12 hours for a total of 2-4
doses, depending on the preparation
o Complications: transient hypoxia, hypercapnia, bradycardia &
hypotension, blockage of ETT, pulmonary hemorrhage
PROGNOSIS
• Early provision of intensive observation and care of high-risk
newborn infants can significantly reduce the morbidity and mortality
associated with RDS and other acute neonatal illnesses
• Antenatal corticosteroids, postnatal surfactant use, and improved
modes of ventilation have resulted in low mortality from RDS (~10%)
• Mortality increases with decreasing gestational age
• Optimal results depend on
o Availability of experienced and skilled personnel
o Care in specially designed and organized regional hospital units
o Proper equipment
o Lack of complications such as severe asphyxia, intracranial
hemorrhage, or irremediable congenital malformation
• Risks associated with umbilical arterial catheterization
o Vascular embolization, thrombosis, spasm, vascular perforation
o Ischemic or chemical necrosis of abdominal viscera
o Infection
o Accidental hemorrhage
o Hypertension
o Impairment of circulation to a leg with subsequent gangrene
• Aortic ultrasonography can also be used to investigate for the
presence of thrombosis
• Renovascular hypertension
o May occur days to weeks after umbilical artery catheterization in
a small proportion of neonates
• Transient blanching of the leg may occur during catheterization of
the umbilical artery
o Usually caused by reflex arterial spasm
o Incidence is lessened by using the smallest available catheter
o Catheter should be removed immediately
o Catheterization of the other artery may then be attempted
• Umbilical vein catheterization is associated with many of the
same risks as umbilical artery catheterization
o Additional risks: cardiac perforation & pericardial tamponade
o Improperly placed catheters in portal vein: lead to thrombosis
• The risk of a serious clinical complication resulting from umbilical
catheterization is probably 2-5%

COMPLICATIONS
Related to Intubation
• Most serious complications of endotracheal intubation
o Pulmonary air leaks
o Asphyxia from obstruction or dislodgement of the tube
o Bradycardia during intubation or suctioning
o Subsequent development of subglottic stenosis
• Other complications
o Bleeding from trauma during intubation
o Posterior pharyngeal pseudodiverticula
o Need for tracheostomy
o Ulceration of the nares caused by pressure from the tube
o Permanent narrowing of the nostril as a result of tissue damage
and scarring from irritation or infection around the tube
o Erosion of the palate
o Avulsion of a vocal cord
o Laryngeal ulcer
o Papilloma of a vocal cord
o Persistent hoarseness, stridor, or edema of the larynx
• Measures to reduce the incidence of these complications
o Skillful intubation
o Adequate securing of the tube
o Use of polyvinyl ETTs
o Use of the smallest tube that will provide effective ventilation in
order to reduce local pressure necrosis and ischemia
o Avoidance of frequent changes and motion of the tube in situ
o Avoidance of too frequent or too vigorous suctioning
o Prevention of infection through meticulous cleanliness and
frequent sterilization of all apparatus attached to or passed
through the tube
• Extrapulmonary air leaks (pneumothorax, pneumomediastinum,
pulmonary interstitial emphysema)
o Observed in 3-9% of extremely preterm infants with RDS
o PPV with excessive inspiratory pressures (excessive tidal
volumes), either during resuscitation at delivery or in the initial
hours of MV, is a common risk factor

Reference: Nelson Textbook of Pediatrics, 21 st edition (2020)

4. RESPIRATORY DISTRESS SYNDROME | 15

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

5. ANAPHYLAXIS PATHOGENESIS
• Serious allergic reaction that is rapid in onset and may cause death • Principal pathologic features in fatal anaphylaxis
• Occurs when there is a sudden release of potent, biologically active o Acute bronchial obstruction with pulmonary hyperinflation
mediators from mast cells and basophils, leading to o Pulmonary edema
o Cutaneous symptoms: urticaria, angioedema, flushing o Intraalveolar hemorrhage
o Respiratory symptoms: bronchospasm, laryngeal edema o Visceral congestion
o Cardiovascular symptoms: hypotension dysrhythmias, o Laryngeal edema
myocardial ischemia o Urticaria & angioedema
o Gastrointestinal symptoms: nausea, colicky abdominal pain, • Acute hypotension: from vasomotor dilation & cardiac dysrhythmias
vomiting, diarrhea • Most cases are believed to be the result of activation of mast cells
and basophils via cell-bound allergen-specific IgE molecules
ETIOLOGY o Patients initially must be exposed to the responsible allergen to
• Anaphylaxis occurring in the hospital results primarily from allergic generate allergen-specific antibodies
reactions to medications and latex o In many cases, child & parent are unaware of initial exposure
o Latex is a particular problem for children undergoing multiple ▪ From passage of food proteins in maternal breast milk
operations (patients with spina bifida and urologic disorders) ▪ Exposure to inflamed skin (i.e., eczematous lesions)
o Patients with latex allergy may also experience food-allergic o When child is reexposed to sensitizing allergen, mast cells,
reactions from homologous proteins in foods: bananas, kiwi, basophils, & possible other cells (macrophages), release a
avocado, chestnut, passion fruit variety of mediatory (histamine, tryptase) & cytokines that can
• Food allergy: most common cause of anaphylaxis outside hospital produce allergic symptoms in any or all target organs
o Peanut allergy is an important cause of food-induced • Clinical anaphylaxis may also be caused by mechanisms other
anaphylaxis (majority of fatal & near-fatal reactions) than IgE-mediated reactions
Direct release of mediators from
mast cells by medications & Morphine, exercise, cold
physical factors
Disturbances of leukotriene
Aspirin and NSAIDs
metabolism
Immune aggregates and
Blood products
complement activation
Probable complement activation Radiocontrast dyes, dialysis membranes
High-molecular weight dextran, chimeric
IgG-mediated reactions
or humanized monoclonal antibodies
• Idiopathic anaphylaxis
o Diagnosis of exclusion when no inciting agent is identified, and
other disorders have been excluded
o Symptoms are similar to IgE-mediated causes of anaphylaxis
o Episodes often recur

EPIDEMIOLOGY
• Food allergens are the most common trigger in children
• Having asthma & its severity are important anaphylaxis risk factors

16 | 5. ANAPHYLAXIS
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

CLINICAL MANIFESTATIONS LABORATORY FINDINGS

• Onset of symptoms may vary depending on the cause of reaction • Minimal utility in the acute setting
o Reactions from ingested allergens (foods, medications) are • May indicate the presence of IgE antibodies to a suspected
delayed in onset (minutes to 2 hours) vs. injected allergens causative agent, but this result is not definitive
(insect sting, medications) and tend to have more GI symptoms • Plasma histamine is elevated for a brief period (5-30 minutes) but
o In most patients, signs and symptoms begin suddenly, often is unstable and difficult to measure in a clinical setting
immediately and usually within 60 minutes of exposure • Plasma tryptase is more stable and remains elevated for several
o The faster the onset of symptoms, the more severe the reaction hours but often is not elevated, especially in food-induced
o ½ of anaphylactic fatalities occur within the 1st hour anaphylactic reactions (poor sensitivity)
• Classic presentation: pruritus, cutaneous flushing, and urticaria
o Pruritus about the mouth and face DIAGNOSIS
o Flushing, urticaria and angioedema, oral or cutaneous pruritus • Diagnosis of anaphylaxis is clinical
o Sensation of warmth, weakness, apprehension (sense of doom) • Consider anaphylaxis when involvement of any ≥2 body systems is
o Tightness in the throat, dry staccato cough and hoarseness, observed, with or without hypotension or airway compromise
periocular pruritus, nasal congestion sneezing, dyspnea, deep • Diagnosis is easily made if there is a clear history of exposure, such
cough and wheezing as bee sting, shortly followed by multisystem signs & symptoms
o Nausea, abdominal cramping, vomiting (ingested allergens) • Unfortunately, diagnosis is not always easy or clear
o Uterine contractions (manifesting as lower back pain) o Symptom onset may be delayed
o Faintness and loss of consciousness in severe cases o Symptoms may mimic other presentations (e.g., syncope,
• Severe reactions: some degree of obstructive laryngeal edema gastroenteritis, anxiety)
o “Lump in the throat” & hoarseness o Anaphylaxis may be component of other diseases (e.g., asthma)
• Cutaneous symptoms may be absent in up to 10% of cases
• Acute onset of severe bronchospasm in a previously well person
with asthma should suggest the diagnosis of anaphylaxis
• Sudden collapse in the absence of cutaneous symptoms
o Vasovagal collapse
o Myocardial infarction
o Aspiration
o Pulmonary embolism
o Seizure disorder
• Laryngeal edema + abdominal pain = hereditary angioedema
• Biphasic response: late-phase allergic reaction with recurrence of
symptoms caused by a second phase of mediator release
o Anaphylactic symptoms recur after apparent resolution
o Mechanism unknown, but appears more common when therapy
is initiated late and symptoms at presentation are more severe
o Not affected by corticosteroids during the initial therapy
o >90% occur within 4 hours, so patient should be observed for at
least 4 hours before being discharged from ER
o Peaks 8-11 hours after the initial exposure
• Symptoms in infants may not be easy to identify

DIFFERENTIAL DIAGNOSIS
• Vasovagal reaction (most common anaphylaxis imitator):
hypotension, pallor, bradycardia, diaphoresis, weakness,
sometimes loss of consciousness
• Myocardial ischemia
• Dysrhythmias
• Severe acute asthma
• Seizure
• Epiglottitis
• Foreign body airway obstruction
• Mastocytosis
• Non-IgE-mediated drug reactions
• Other forms of shock (hemorrhagic, cardiogenic, septic)
• Vasopressor reactions, including flushing syndromes (e.g.,
carcinoid syndrome)
• Ingestion of monosodium glutamate
• Scombroidosis (spoiled fish poisoning)
• Hereditary angioedema
• Panic attack
• Vocal cord dysfunction
• Pheochromocytoma
• Red man syndrome (caused by vancomycin)

5. ANAPHYLAXIS | 17
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT
Initial Management
• Assessment of airway, breathing, and circulation
• Assess vital signs and pulse oximetry
• Initiate IV access, oxygen administration, and cardiac rhythm
monitoring in patients with severe symptoms
First-Line Therapy
• Airway and Oxygenation
o In severe anaphylaxis, securing the airway is the first priority
o Examine the mouth, pharynx, and neck for signs and symptoms
of angioedema: uvula edema or hydrops, audible stridor,
respiratory distress, or hypoxia
o If angioedema is producing respiratory distress, intubate early,
since any delay may result in complete airway obstruction
secondary to progression of angioedema
o Provide supplemental oxygen to maintain SaO2 >90%
• Decontamination
o If the causative agent can be identified, termination of exposure
should be attempted
o Gastric lavage is not recommended for foodborne allergens
▪ May be associated with complications (aspiration) & delays
in administration of more effective treatments (epinephrine)
o In insect stings, remove any remaining stinging remnants
because the stinger continues to inject venom even if it is
detached from the insect
• Epinephrine
o Most important medication, should be not delayed
o MOA: mixed α1 - and β-receptor agent
▪ α1-receptor: reduces mucosal edema & treats hypotension
▪ β1-receptor: increased heart rate & myocardial contractility
▪ β2-receptor: bronchodilation, limits further mediator release
o IM to lateral thigh (1:1000 dilution, 0.01 mg/kg; max 0.5 mg)
▪ Children ≥12 years: many recommend the 0.5 mg IM dose
▪ Repeat every 5-15 minutes if symptoms persist or worsen
▪ More consistent & more rapid peak blood levels than SC
▪ Check BP in patients taking β-blockers
• Epinephrine use may result in severe hypertension
secondary to unopposed α-adrenergic stimulation
o IV bolus and/or infusion: if refractory to treatment despite
repeated IM doses or cardiovascular compromise or collapse
▪ Initial bolus: dilute solution of 100 μg (0.1 mg) IV, given over
5-10 minutes (1:10,000 dilution)
▪ If refractory to bolus: IV infusion 1 μg/min & titrate to effect
▪ Higher risk of cardiovascular complications
▪ Stop immediately if dysrhythmias or chest pain occur
o If IV access not readily available: via endotracheal or
intraosseous routes
• IV Crystalloids
o Hypotension is generally the result of distributive shock and
responds well to fluid resuscitation
o A bolus of 1-2 L (10-20 mL/kg in children) of isotonic crystalloid
solution should be administered concurrently with epinephrine
• Antihistamines
o H1 antihistamine (diphenhydramine 20-50 mg IV by slow
infusion or via IM) although clinical benefit is unproven
o H2 antihistamines (ranitidine or cimetidine): in severe cases
(circulatory shock), although evidence for benefit lacking
▪ Cimetidine should not be used for patients who are
• Elderly (side effects)
• Multiple comorbidities (interferes with drug metabolism)
• Renal or hepatic impairment
• β-blocker use (cimetidine prolongs metabolism of β-
blockers and may prolong anaphylactic state)
o After the initial IV dose of corticosteroids and antihistamines, the
patient may be switched to oral administration
• Vasopressors
o IV epinephrine infusion: anaphylaxis & shock resistant to initial
treatment (repeated IM epinephrine, oxygen, IV crystalloids)
o If dangerous dysrhythmias or tachycardia result from
epinephrine: other agents (e.g., dopamine, dobutamine,
epinephrine, norepinephrine, phenylephrine, or vasopressin)
Agents for Allergic Bronchospasm
• β2 bronchodilator (intermittent/continuous nebulized salbutamol)
should be instituted if wheezing is present
o Asthmatics are often more refractory to the treatment
• Inhaled anticholinergics & IV magnesium sulfate can be added
for severe bronchospasm refractory to inhaled salbutamol,
• Elderly patients: bronchodilators given at lower dose & slower rate
Glucagon
• Concurrent β-blockers: risk factor for severe prolonged anaphylaxis
• For patients taking β-blockers with hypotension refractory to fluids
and epinephrine, glucagon IV should be used every 5 minutes until
hypotension resolves, followed by an infusion
• Side effects: nausea, vomiting, hypokalemia, dizziness,
hyperglycemia

Second-Line Therapy
• Used to treat anaphylaxis refractory to the first-line treatments or
associated with complications and also to prevent recurrences
• Corticosteroids
o To prevent protracted and biphasic reactions
o Methylprednisolone 20-125 mg IV (2 mg/kg in children, up to
125 mg) and hydrocortisone 250-500 mg IV (5-10 mg/kg in
children, up to 500 mg) are equally effective
o Methylprednisolone: lowest mineralocorticoid effect
▪ Produce less fluid retention than hydrocortisone
▪ Preferred for elderly & for those in whom fluid retention
would be problematic

18 | 5. ANAPHYLAXIS
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

PREVENTION
• For patients experiencing anaphylactic reactions
o Triggering agent should be avoided
o Education regarding early recognition of anaphylactic symptoms
and administration of emergency medications
• Patients with food allergies: educate about allergen avoidance
o Active reading of food ingredient labels
o Knowledge of potential contamination and high-risk situations
• Any child with food allergy and a history of asthma, peanut, tree nut,
fish, or shellfish allergy or a previous systemic reaction should be
given an epinephrine autoinjector
o Considered for any patient with IgE-mediated food allergy
o In addition, liquid cetirizine (or alternatively, diphenhydramine)
and a written emergency plan should also be provided in case
of accidental ingestion or allergic reaction
• Food-associated exercise-induced anaphylaxis
o Children must not exercise within 2-3 hours of ingesting the
triggering food
o Should exercise with a friend, learn to recognize the early signs
of anaphylaxis (sensation of warmth, pruritus), stop exercising,
and seek help immediately if symptoms develop
• Children experiencing a systemic anaphylactic reaction, including
respiratory symptoms, to an insect sting should be evaluated and
treated with immunotherapy, which is >90% protective
• Reactions to medications can be reduced & minimized by
o Using oral medications instead of injected forms
o Avoiding cross-reactions
• Suspected reactions to previous radiocontrast dye
o Low-osmolarity radiocontrast dyes
o Pretreatment
• Nonlatex gloves and materials should be used in children
undergoing multiple operations
• Any child at risk for anaphylaxis should receive
o Emergency medications (including epinephrine autoinjector)
o Education on identification of signs and symptoms of
anaphylaxis and proper administration of medications
o Written emergency plan in case of accidental exposure
DISPOSITION AND FOLLOW-UP o Encouraged to wear medical identification jewelry
• With appropriate initial treatment, admission is rare (1-4%)
• ICU admission
o All unstable patients with anaphylaxis refractory to treatment
o Airway interventions were required
• Discharged home: healthy patients who remain symptom free for
1-6 hours after appropriate treatment
• Consider prolonged observation in patients
o With a past history of severe reaction
o Using β-blockers
o Living alone
o Residing long distances from medical care
o Having significant comorbidities (asthma)
Reference:
o Elderly • Nelson Textbook of Pediatrics, 21st edition (2020)
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

5. ANAPHYLAXIS | 19
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
6. INTESTINAL OBSTRUCTION IN CHILDREN
• ~1 in 1,500 children is born with intestinal obstruction
• Obstruction may be partial or complete
• Simple obstruction: luminal contents fails to move in aboral direction
• Strangulating obstruction: blood flow to the intestine is also impaired
o If not promptly relieved: leads to bowel infarction & perforation
ETIOLOGY
• Intrinsic causes: inherent abnormalities of intestinal innervation,
mucus production, or tubular anatomy
o Congenital disruption of tubular structure: most common
▪ Atresia: obliteration of the intestinal lumen
▪ Stenosis: narrowing of the intestinal lumen
o >90% of intestinal stenosis & atresia: duodenum, jejunum, ileum
o Rare causes in colon: associated with more proximal atresias
• Extrinsic causes of congenital intestinal obstruction
o Compression of the bowel by
▪ Vessels: preduodenal portal vein
▪ Organs: annular pancreas
▪ Cysts: duplication, mesenteric
o Abnormalities in intestinal rotation during fetal development
▪ Malrotation: associated with inadequate mesenteric
attachment of the intestine to the posterior abdominal wall
• Leaves the bowel vulnerable to auto obstruction due to
intestinal twisting or volvulus
• Commonly accompanied by congenital adhesions that
can compress and obstruct the duodenum as they
extend from the cecum to the right upper quadrant
PATHOGENESIS
• Obstruction is typically associated with bowel distention
o Caused by an accumulation of ingested food, gas, and intestinal
secretions proximal to the point of obstruction
• As the bowel dilates, absorption of intestinal fluid is decreased, and
secretion of fluid and electrolytes is increased
o This shift results in isotonic intravascular depletion, which is
usually associated with hypokalemia
o Also results in a decrease in blood flow to obstructed bowel
• As blood flow is shifted away from the intestinal mucosa, there is
loss of mucosal integrity
o Bacteria proliferate in the stagnant bowel, with a predominance
of coliforms and anaerobes
• Rapid proliferation of bacteria + loss of mucosal integrity
o Allows bacteria to translocate across the bowel wall & potentially
lead to endotoxemia, bacteremia, and sepsis
20 | 6. INTESTINAL OBSTRUCTION IN CHILDREN
CLINICAL MANIFESTATION
• Varies with cause, level of obstruction, & time between obstructing
event and the patient’s evaluation
• Classic symptoms of obstruction in the neonate
o Vomiting
o Abdominal distension
o Obstipation
• Obstruction high in intestinal tract
o Large-volume, frequent, bilious emesis
o Little or no abdominal distention
o Pain is intermittent and is usually relived by vomiting
• Obstruction in the distal small bowel
o Moderate or marked abdominal distention
o Emesis that is progressively feculent
• Both proximal & distal obstructions are associated with obstipation
o Meconium stools can be passed initially if
▪ Obstruction is in the upper part of the intestinal tract
▪ Obstruction developed late in the intrauterine life
DIAGNOSIS
• History + physical examination + radiologic findings
• In certain cases, the diagnosis is suggested in the prenatal period
o Routine prenatal ultrasound can detect polyhydramnios,
which often accompanies high intestinal obstruction
▪ The presence of polyhydramnios should prompt aspiration
of the infant’s stomach immediately after birth
▪ Aspiration of >15-20 mL of fluid, particularly if it is bile
stained, is highly indicative of proximal intestinal obstruction
• Postnatal period:
o Plain radiograph is the initial diagnostic study
▪ Can provide valuable information about potential associated
complications
▪ Completely obstructing lesions: bowel distention
proximal to the point of obstruction
▪ Upright or crosstable lateral views: air-fluid levels in the
distended loops
▪ Caution must be exercised in using plain films to determine
the location of intestinal obstruction
o Contrast studies of the bowel or CT images
▪ In small and large bowel obstructions (may be difficult to
distinguish with plain films because colonic haustra are not
fully developed in the neonate)
▪ Oral/nasogastric contrast medium: proximal obstructions
▪ Contrast enemas: more distal entities
• Therapeutic role in relieving distal obstruction by
meconium ileus or meconium plug syndrome
TREATMENT
• Initial treatment: fluid resuscitation and stabilizing the patient
o Nasogastric decompression usually relieves pain and vomiting
• Broad-spectrum antibiotics (after appropriate cultures)
o Ill-appearing neonates with bowel obstruction
o Suspected strangulating infarction
• Immediate surgical relief
o In patients with strangulation before the bowel infarcts, resulting
in gangrene and intestinal perforation
o Extensive intestinal necrosis results in short bowel syndrome
• Nonoperative conservative management
o Children with suspected adhesions or inflammatory strictures
that might resolve with nasogastric decompression or anti-
inflammatory medications
o If clinical signs of improvement are not evident within 12-24
hours, then operative intervention is usually indicated

HYPERTROPHIC PYLORIC STENOSIS
Epidemiology
• Males (firstborns) affected ~4-6 times as often as females
• The offspring of a mother and, to a lesser extent, the father who had
pyloric stenosis are at higher risk for pyloric stenosis
• Develops in ~20% of male & 10% of female descendants of a mother
who had pyloric stenosis
• Incidence increased in infants with B and O blood groups
• Occasionally associated with other congenital defects, including
tracheoesophageal fistula and hypoplasia or agenesis of the inferior
labial frenulum
Etiology: cause is unknown
• Associated conditions
o Eosinophilic gastroenteritis
o Apert syndrome
o Zellweger syndrome
o Trisomy 18
o Smith-Lemli-Opitz syndrome
o Cornelia de Lange syndrome
• Associated with the use of erythromycin in neonates
o Highest risk if given within the 1st 2 weeks of life
• Higher incidence among mostly female infants of mothers treated
with macrolides during pregnancy & breastfeeding
• Implicated in
o Abnormal muscle innervation
o Elevated serum levels of prostaglandins
o Infant hypergastrinemia
• Reduced nitric oxide might contribute to the pathogenesis
Clinical Manifestations
• Non-bilious vomiting: initial symptom
o May or may not be projectile initially
o Usually progressive, occurring immediately after a feeding
o May follow each feeding, or it may be intermittent
o Usually starts after 3 weeks of age, but symptoms can develop
as early as 1st week of like & as late as 5th month
o ~20% have intermittent emesis from birth that then progresses
to the classic picture
o After vomiting, the infant is hungry and wants to feed again
o As vomiting continues, a progressive loss of fluid, hydrogen ion,
and chloride leads to hypochloremic metabolic alkalosis
• Hyperbilirubinemia
o Most common clinical association (icteropyloric syndrome)
o Unconjugated hyperbilirubinemia is more common than
conjugated; usually resolves with surgical correction
▪ May be associated with a decreased level of
glucuronyltransferase (~5% of affected infants)
▪ Mutations in uridine diphosphate glucuronyltransferase
gene (UGT1A1) have also been implicated
o If conjugated hyperbilirubinemia is part of the presentation, other
etiologies need to be investigated
▪ Eosinophilic gastroenteritis
▪ Hiatal hernia
▪ Peptic ulcer
▪ Congenital nephrotic syndrome
▪ Congenital heart disease
▪ Congenital hypothyroidism
Diagnosis
• Established by palpating the pyloric mass
o Firm, movable, ~2 cm in length, olive-shaped, hard, best
palpated from left side, located above & right of umbilicus in mid
epigastrium beneath liver’s edge
o The olive is easiest palpated after an episode of vomiting
o After feeding: there may be a visible gastric peristaltic wave that
progresses across the abdomen
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Imaging
• Ultrasound: confirms the diagnosis (sensitivity ~95%)
o Pyloric thickness: 3-4 mm
o Overall pyloric length: 15-19 mm
o Pyloric diameter: 10-14 mm
• Contrast studies
o String sign: elongated pyloric channel
o Shoulder sign: bulge of the pyloric muscle into the antrum
o “Double tract sign”: parallel streaks of barium seen in the
narrowed channel
Differential Diagnosis
Small, emaciated infants Gastric waves occasionally visible
Gastroesophageal reflux ±
Differentiated in radiographic studies
hiatal hernia
Adrenal insufficiency from Absence of metabolic acidosis & elevated
adrenogenital syndrome serum potassium and urinary sodium
Recurrent emesis with alkalosis (urea cycle)
Inborn errors of metabolism or acidosis (organic acidemia) & lethargy,
coma, or seizures
Gastroenteritis Vomiting + diarrhea
Pyloric membrane or pyloric Projectile vomiting, visible peristalsis, and
duplication palpable mass (duplication)
Duodenal stenosis proximal No pyloric mass on physical examination or
to ampulla of Vater ultrasonography
Treatment
• Preoperative treatment: correct fluid, acid-base, electrolyte losses
o Correction of alkalosis is essential to prevent postoperative
apnea, which may be associated with anesthesia
o Most infants can be successfully rehydrated within 24 hours
o Vomiting usually stops when the stomach is empty, and only an
occasional infant requires nasogastric suction
• Pyloromyotomy: surgical procedure of choice; curative
o Ramstedt procedure
▪ Performed through a short transverse skin incision
▪ Underlying pyloric mass is cut longitudinally to the layer of
the submucosa, and the incision is closed
o Laparoscopic technique is equally successful
o Postoperatively:
▪ Postoperative vomiting (½ of infants): secondary to edema
of the pylorus at the incision site
▪ Feedings: initiated within 12-24 hours
• Maintenance oral feedings within 36-48 hours
▪ Persistent vomiting: incomplete pyloromyotomy, gastritis,
gastroesophageal reflux disease, other cause of obstruction
• Endoscopic balloon dilation: persistent vomiting
secondary to incomplete pyloromyotomy
o Operative mortality: 0-0.5%
• Conservative management
o Nasoduodenal feedings: in poor surgical candidates
o Oral and IV atropine sulfate (pyloric muscle relaxant): when
surgical expertise is not available; 80% success rate
▪ IV dose: 0.01 mg/kg 6 times a day 5 minutes before feeding
• Continuous ECG monitoring of heart rate during infusion
• Oral feeding: 10 mL formula 6 times a day
o Increased day by day until patients tolerate 150
mL/kg/day unless vomiting occurs >2 times a day
▪ Oral: 0.02 mg/kg 6 times a day before feeding
• When patients can tolerate the full volume of formula
without vomiting >2 times a day
o Disadvantage: worsening of nutrition status (may require TPN)
▪ Takes longer
▪ Oral feedings may not be tolerated at first
6. INTESTINAL OBSTRUCTION IN CHILDREN | 21
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
DUODENAL OBSTRUCTION
Epidemiology
• Duodenal obstruction occurs in 2.5-10/100,000 live births
• Duodenal atresia complicates 1/10,000 live births
o Accounts for 25-40% of all intestinal atresias
Etiology
• Most cases: caused by atresia, intrinsic defect of bowel formation
• Can also result from extrinsic compression
o Abnormal neighboring structures (e.g., annular pancreas,
preduodenal portal vein)
o Duplication cysts
o Congenital bands associated with malrotation
• Intrinsic & extrinsic causes can coexist
o High index of suspicion for >1 underlying etiology may be critical
to avoid unnecessary reoperations in these infants
Pathogenesis
• From failed recanalization of intestinal lumen during gestation
o 4th-5th week AOG: duodenal mucosa exhibits rapid proliferation
of epithelial cells, degenerate after the 7th week AOG
o Persistence of these cells leads to
▪ Occlusion of lumen (atresia) in approximately ⅔ of cases
▪ Narrowing (stenosis) in the remaining ⅓
• Can take several forms
o Thin membrane that occludes the lumen: most common
▪ Almost invariably occurs near the ampulla of Vater
▪ Windsock web (rare cases): membrane is distensible
• Obstruction several cm distal to origin of membrane
o Short fibrous cord that connects 2 blind duodenal pouches
o Gap that spans 2 non-connecting ends of the duodenum
• Approximately 50% of infants are premature
• Concomitant congenital abnormalities are common: long-term
follow-up of these patients into adulthood is warranted
o Congenital heart disease (30%): increased mortality
o Malrotation (20-30%)
o Annular pancreas (30%): increased late complications: GERD,
PUD, pancreatitis, gastric outlet & recurrent duodenal
obstruction, gastric cancer
o Renal anomalies (5-15%)
o Esophageal atresia ± tracheoesophageal fistula (5-10%)
o Skeletal malformations (5%)
o Anorectal anomalies (5%)
• Nearly ½ of patients have chromosomal abnormalities
o Trisomy 21 is identified in up to ⅓ of patients
Clinical Manifestations
• Bilious vomiting without abdominal distention
o Hallmark of duodenal obstruction
o Usually noted on the 1st day of life
• Peristaltic waves may be visualized early in the disease process
• A history of polyhydramnios is present in half the pregnancies
o Inadequate absorption of amniotic fluid in distal intestine
o This fluid may be bile stained because of intrauterine vomiting
• Jaundice is present in ⅓ of the infants
Diagnosis
• Plain abdominal radiograph: double-bubble sign
o Caused by a distended and gas-filled stomach and proximal
duodenum, which are invariably connected
• Contrast studies: to exclude malrotation & volvulus
o Intestinal infarction within 6-12 hours if volvulus is not relieved
o Generally not necessary and may be associated with aspiration
• Prenatal diagnosis of duodenal atresia by fetal ultrasonography
o Reveals a sonographic double-bubble
o Prenatal identification is associated with decreased morbidity
and fewer hospitalization days
22 | 6. INTESTINAL OBSTRUCTION IN CHILDREN
Treatment
• Initial treatment
o Nasogastric or orogastric decompression
o Intravenous fluid replacement
• Evaluate for associated anomalies
o Echocardiography
o Renal ultrasound
o Radiology of the chest and spine
• Definitive correction of atresia
o Postponed until life-threatening anomalies evaluated & treated
o Duodenoduodenostomy: typical surgical repair
▪ Also preferred in cases of concomitant or isolated annular
pancreas (performed without dividing the pancreas)
▪ Dilated proximal bowel tapered to improve peristalsis
o Postoperatively, a gastrostomy tube can be placed to drain the
stomach and protect the airway
o IV nutritional support or a transanastomotic jejunal tube is
needed until an infant starts to feed orally
o Long-term prognosis is excellent: ~90% survival in most series
JEJUNAL AND ILEAL ATRESIA AND OBSTRUCTION
Etiology: intrinsic abnormalities
• Jejunoileal atresias: abnormalities in anatomic development
o Generally attributed to intrauterine vascular accidents, which
result in segmental infarction and resorption of the fetal intestine
o Underlying events that potentiate vascular compromise
▪ Intestinal volvulus
▪ Intussusception
▪ Meconium ileus
▪ Strangulating herniation through an abdominal wall defect
(gastroschisis or omphalocele)
o Maternal behaviors that promote vasoconstriction may have role
▪ Cigarette smoking & cocaine use
o Only a few cases of familial inheritance have been reported
▪ Multiple intestinal atresias in an autosomal recessive pattern
▪ Linked with multiple births, low birthweight, and prematurity
o Not commonly associated with extraintestinal anomalies
• Meconium Ileus: abnormalities in mucus secretion
o Seen in cystic fibrosis, producing abnormally viscous secretions
o ~80-90% of infants with meconium ileus have cystic fibrosis, but
only 10-15% with cystic fibrosis present with meconium ileus
o In simple cases: distal 20-30 cm of ileus is collapsed and filled
with pellets of pale stool
▪ Proximal bowel: dilated & filled with thick meconium that
resembles sticky syrup or glue
▪ Peristalsis fails to propel this viscid material forward, and it
becomes impacted in the ileum
o In complicated cases: volvulus of dilated proximal bowel can
occur, resulting in intestinal ischemia, atresia, and/or perforation
▪ Meconium peritonitis: perforation in utero, which can lead to
potentially obstructing adhesions and calcifications
• Long-segment Hirschsprung disease
o Congenital absence of ganglion cells in the myenteric and
submucosal plexuses of the bowel wall
o In a small subset (5%) of patients, aganglionic segment includes
the terminal ileum in addition to the entire length of the colon
o Presents with a dilated small intestine that is ganglionated, has
hypertrophied walls, funnel-shaped transitional hypoganglionic
zone, & collapsed distal aganglionic bowel
Clinical Manifestation
• Distal intestinal obstruction is less likely detected in utero
• Polyhydramnios in 20-35% of jejunoileal atresias
o May be the first sign of intestinal obstruction
• Abdominal distention is rarely present at birth
o Develops rapidly after initiation of feeding in the first 12-24 hours
o Often accompanied by vomiting, which is often bilious
• ~80% of infants fail to pass meconium in the first 24 hours of life
• Jaundice (unconjugated bilirubinemia) in 20-30% of patients

Diagnosis
• Plain Radiographs (upright or lateral decubitus positions)
o Jejunoileal atresia & long-segment Hirschsprung disease:
multiple air-fluid levels proximal to the obstruction
o Meconium ileus: typical hazy/ground-glass appearance (RLQ)
▪ Caused by small bubbles of gas that become trapped in
inspissated meconium in the terminal ileal region
▪ No air-fluid levels: viscosity of secretions in the proximal
bowel prevents layering
o Meconium peritonitis: patchy calcification, particularly in flanks
o Intestinal perforation: evidence of pneumoperitoneum
▪ Upright view: air in subphrenic regions
▪ Left lateral decubitus position: air over the liver
• Contrast studies: often required to localize the obstruction
o Water-soluble enemas are particularly useful in differentiating
atresia from meconium ileus and Hirschsprung disease
o A small microcolon suggests disuse and presence of obstruction
proximal to the ileocecal valve
• Abdominal ultrasound may be an important adjunctive study
o Can distinguish meconium ileus from ileal atresia
o Identify concomitant intestinal malrotation
Treatment
• Preoperative management: stable and in adequate fluid and
electrolyte balance before operation or radiographic attempts at
disimpaction unless volvulus is suspected
• Antibiotics: in documented infections
o Prophylactic antibiotics are usually given before surgery
• Ileal or jejunal atresia: resection of dilated proximal bowel
followed by end-to-end anastomosis
o Jejunoplasty/ileoplasty with partial excision of the web:
acceptable alternative if a simple mucosal diaphragm is present
• Uncomplicated meconium ileus: Gastrografin enemas diagnose
the obstruction and wash out the inspissated material
o Gastrografin is hypertonic: care must be taken to avoid
dehydration, shock, and bowel perforation
o May have to be repeated after 8-12 hours
o Resection not needed if no ischemic complications
o Laparotomy: if inadequate respond to water-soluble enemas
(~50% of patient with simple meconium ileus)
• Operative management
o Obstruction cannot be relieved by nonoperative management
o For infants with complicated meconium ileus
• Extent of surgical intervention depends on the degree of pathology
o Simple meconium ileus: plug relieved by manipulation or direct
enteral irrigation with N-acetylcysteine following enterotomy
o Complicated cases: bowel resection, peritoneal lavage,
abdominal drainage, and stoma formation may be necessary
• Total parenteral nutrition is generally required
MALROTATION
• Incomplete rotation of the intestine during fetal development
• Involves intestinal nonrotation or incomplete rotation around SMA
Normal Embryology: gut starts as straight tube from stomach to rectum
• Intestinal rotation and attachment: 5th week of gestation
o Midbowel (distal duodenum to midtransverse colon) begins to
elongate and progressively protrudes into the umbilical cord until
it lies totally outside the confines of the abdominal cavity
o Superior mesenteric artery (SMA) acts as an axis
• Upon reentering the abdominal cavity
o Duodenum: ligament of Treitz; becomes fixed before the colon
o Colon: directed to the LUQ
o Cecum: rotates counterclockwise and comes to lie in the RLQ
• After rotation, the right & left colon & mesenteric root becomes
fixed to the posterior abdomen
o Provide a broad base of support to the mesentery and SMA
o Prevents twisting of mesenteric root & kinking of vascular supply
• Abdominal rotation and attachment completed by 12th week AOG
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Pathogenesis
• Nonrotation: bowel fails to rotate after it returns to abdominal cavity
o 1st & 2nd portions of duodenum are in normal position
o Remainder of the duodenum, jejunum, and ileum occupy the
right side of the abdomen
o Colon is located on the left
• The most common type of malrotation involves failure of the cecum
to move into the right lower quadrant
o The usual location of the cecum is in the subhepatic area
o Associated with failure to form normal broad-based adherence
to posterior abdominal wall
o Mesentery (including SMA) is tethered by a narrow stalk, which
can twist around itself and produce a midgut volvulus
o Bands of tissue (Ladd bands) can extend from cecum to RUQ,
crossing, and possibly obstructing, the duodenum
• Often associated with other anomalies of the abdominal wall
o Diaphragmatic hernia, gastroschisis, omphalocele
• Malrotation is also associated with the heterotaxy syndrome
o Congenital anomalies including congenital heart malformations,
malrotation, biliary atresia, and either asplenia or polysplenia
Epidemiology
• Reported incidence of malrotation is ~1 in 500 infants
o Majority (75-85%) of patients present in the 1st year of life
o >50% present within the 1st month of life, with symptoms of acute
or chronic obstruction
Clinical Manifestations
• 1st month of life: vomiting is the most common symptom
o Bilious emesis & acute bowel obstruction during 1st week of life
• Older infants: episodes of recurrent abdominal pain
o Can mimic colic and suggest intermittent volvulus
• Older children: recurrent vomiting and/or abdominal pain
• Patients occasionally present with malabsorption or protein-
losing enteropathy associated with bacterial overgrowth
o From intermittent volvulus or duodenal compression by Ladd
bands or other adhesive bands affecting small & large bowel
• Adolescents: ~25-50% are asymptomatic
o Symptomatic adolescents: acute intestinal obstruction or
history of recurrent episodes of abdominal pain or
postprandial bloating and occasional vomiting
• Patients of any age with a rotational anomaly can develop acute
bowel-threatening volvulus without preexisting symptoms
• An acute presentation of small bowel obstruction without previous
bowel surgery can be result of volvulus associated with malrotation
o Life-threatening complication of malrotation, which resembles
an acute abdomen or sepsis
o Symptoms of malrotation should always be investigated
o Volvulus occurs when the small bowel twists around SMA
leading to vascular compromise of the bowel
Diagnosis
• Abdominal plain film: nonspecific
o May demonstrate a gasless abdomen
o Evidence of duodenal obstruction with a double-bubble sign
• Upper gastrointestinal series: imaging test of choice; gold
standard in the evaluation and diagnosis of malrotation & volvulus
o Normal rotation: duodenal C-loop crossing the midline and a
duodenojejunal junction located to the left of the spine
o Best exam to visualize the malposition of the ligament of Treitz
and can also reveal a corkscrew appearance of the duodenum
• Barium enema: demonstrate malposition of cecum; normal in ~20%
• Ultrasonography: can demonstrate the inversion of SMA and SMV
o SMV located to the left of SMA suggests malrotation
o Malrotation with volvulus is suggested by
▪ Duodenal obstruction
▪ Thickened bowel loops to the right of the spine
▪ SMV coiling around SMA
▪ Free peritoneal fluid
6. INTESTINAL OBSTRUCTION IN CHILDREN | 23
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Treatment
• Surgical intervention: recommended for any patient with a
significant rotational abnormality, regardless of age
• Ladd procedure
o Done laparoscopically if no volvulus and no gut ischemia
o Generally done as an open procedure if volvulus is present
• If a volvulus is present, surgery is done immediately as an acute
emergency
o Volvulus is reduced counterclockwise
o Duodenum and upper jejunum are freed of any bands & remain
in the right abdominal cavity
o Colon is freed of adhesions and placed in right abdomen
o Cecum in LLQ
o Usually accompanied by incidental appendectomy
• Purpose: minimize the risk of subsequent volvulus rather than to
return the bowel to a normal anatomic configuration
• Extensive intestinal ischemia can result in short bowel syndrome
ILEUS
• Failure of intestinal peristalsis caused by loss of coordinated gut
mobility without evidence of mechanical obstruction
Etiology
• Abdominal surgery (generally resolves within 72 hours)
• Infection (gastroenteritis, pneumonia, peritonitis)
• Metabolic abnormalities (uremia, hypokalemia, hypercalcemia,
hypermagnesemia, acidosis)
• Administration of certain drugs (opiates, vincristine, antimotility
agents such as loperamide) when used during gastroenteritis
Clinical Manifestation
• Nausea, vomiting, feeding intolerance, abdominal distention with
associated pain, and delayed passage of stool and bowel gas
• Bowel sounds are minimal or absent
Diagnosis
• Abdominal x-ray: multiple air-fluid levels throughout abdomen
o Serial radiographs usually do not show progressive distention
• Contrast radiograph: slow movement of barium into patent lumen
Treatment
• Involves correcting the underlying abnormality, supportive care of
comorbidities, and mitigation of iatrogenic contributions
• Electrolyte abnormalities should be identified and corrected, and
narcotic agents, when used, should be weaned as tolerated
• Nasogastric decompression can relieve recurrent vomiting or
abdominal distention associated with pain; resultant fluid losses
should be corrected with isotonic crystalloid solution
• Prokinetic agents (erythromycin) are not routinely recommended
• Selective peripheral opioid antagonists (methylnaltrexone) hold
promise in decreasing postoperative ileus
ADHESIONS
• Fibrous tissue bands that result from peritoneal injury
• Can constrict hollow organs
Etiology
• Major cause of postoperative small bowel obstruction
Epidemiology
• 5-year readmission risk due to adhesions varied by
o Operative region: 2.1% (colon) to 9.2% (ileum)
o Procedure: 0.3% (appendectomy) to 25% (ileostomy
formation/closure)
• Overall risk
o 5.3% excluding appendectomy
o 1.1% including appendectomy
24 | 6. INTESTINAL OBSTRUCTION IN CHILDREN
Clinical Manifestations
• Most remain asymptomatic; can arise any time after the 2nd week to
1 year after surgery, regardless of surgical extent
• Suspected in patients with abdominal pain, constipation, emesis,
and a history of intraperitoneal surgery
• Nausea and vomiting quickly follow onset of pain
• Initially, bowel sounds are hyperactive, and the abdomen is flat
• Subsequently, bowel sounds disappear, & bowel dilation can cause
abdominal distention
• Fever and leukocytosis suggest bowel necrosis and peritonitis
Diagnosis
• Plain radiographs: obstructive features
• CT scan or contrast studies: may be needed to define the etiology
Treatment
• Nasogastric decompression, IV fluid resuscitation, and broad-
spectrum antibiotics in preparation for surgery
• Nonoperative intervention is contraindicated unless a patient is
stable with obvious clinical improvement
• In children with repeated obstruction, fibrin-glued plication of
adjacent small bowel loops can reduce risk of recurrent problems
• Long-term complications: female infertility, failure to thrive, and
chronic abdominal and/or pelvic pain
INTUSSUSCEPTION
• Occurs when a portion of the alimentary tract is telescoped into an
adjacent segment
Epidemiology
• Most common cause of intestinal obstruction in 5 months to 3 years
• Most common abdominal emergency in children <2 years of age
• 60% of patients are younger than 1 year of age
• 80% of the cases occur before age 24 months; rare in neonates
• Incidence varies from 1-4 per 1,000 live births
• Male:female ratio is 3:1
Etiology
• ~90% of cases in children are idiopathic
• Prior or concurrent respiratory adenovirus (type C) infection
o Can complicate otitis media, gastroenteritis, Henoch-Schӧnlein
purpura, or other URTI
• Rotavirus vaccine (especially after the 1st dose) within 3 weeks:
slight increase in intussusception (very rare side effect)
• It is postulated that GI infection or introduction of new food proteins
results in swollen Peyer patches in the terminal ileum
• Lymphoid nodular hyperplasia is another related risk factor
o Prominent mounds of lymph tissue lead to mucosal prolapse of
the ileum into the colon, thus causing an intussusception
• Lead points: more common in children >2 years of age
o The older the child, the higher the risk of a lead point
o In adults, lead points are present in 90%
o Recognizable in 2-8% of patients
▪ Meckel diverticulum
▪ Intestinal polyp
▪ Neurofibroma
▪ Intestinal duplication cysts
▪ Inverted appendix stump
▪ Leiomyomas
▪ Hamartomas
▪ Ectopic pancreatic tissue
▪ Anastomotic suture line
▪ Enterostomy tube
▪ Posttransplant lymphoproliferative disease
▪ Hemangioma
▪ Malignant conditions such as lymphoma or Kaposi sarcoma
▪ Gastrojejunal and jejunostomy tubes can also serve as lead
points for intussusception

• Postoperative intussusception is ileoileal: occurs within several days
of an abdominal operation
• Anterograde intussusception: occur rarely following bariatric surgery
with a Roux-en-Y gastric bypass (no lead point in these cases)
• Intrauterine intussusception: associated with intestinal atresia
• Intussusception in premature infants is rare
• Ileal-ileal-intussusception may be more common than previously
believed, is often idiopathic or associated with Henoch-Schӧnlein
purpura, and usually resolves spontaneously
Pathology
• Most often ileocolic, less commonly cecocolic, & occasionally ileal
o Very rarely, the appendix forms the apex of an intussusception
• Upper portion of bowel (intussusceptum) invaginates into lower
(intussuscipiens) pulling its mesentery along into enveloping loop
• Constriction of mesentery obstructs venous return
o Engorgement of the intussusceptum (edema), & bleeding from
mucosa leads to a bloody stool, sometimes containing mucus
• Apex of intussusception can extend into transverse, descending, or
sigmoid colon, even to and through anus in neglected cases
o Must be distinguished from rectal prolapse
• Most intussusceptions do not strangulate the bowel within 1st 24
hours but can eventuate in intestinal gangrene and shock
Clinical Manifestations
• In typical cases: sudden onset of severe paroxysmal colicky pain
that recurs at frequent intervals and is accompanied by straining
efforts with legs and knees flexed and loud cries
o Infant may initially be comfortable & play normally in between
o If not reduced, infant becomes progressively weaker & lethargic
o At times, lethargy is often disproportionate to abdominal signs
• With progression: shock-like state (fever & peritonitis)
o Pulse becomes weak and thready
o Respirations become shallow and grunting
o Pain may be manifested only by moaning sounds
• Vomiting in most cases; usually more frequent in early phase
o In the later phase, the vomitus becomes bile stained
• Stool of normal appearance in 1st few hours of symptoms
o Then fecal excretions are small or more often do not occur
o Little or no flatus is passed
• Blood is generally passed in 1st 12 hours
o At times not for 1-2 days & infrequently not at all
o Currant jelly stool: with red blood & mucus (60% of infants)
• Some have only irritability & alternating or progressive lethargy
• Classic triad is seen in <30% of patients
o Pain
o Palpable sausage-shaped abdominal mass
o Bloody or currant jelly stool
• Paroxysmal pain + vomiting + palpable abdominal mass
o PPV >90%; rectal bleeding increases this to ~100%
• Palpation of abdomen: slightly tender sausage mass (ill defined)
o Increase in size & firmness during a paroxysm of pain
o Most often in right upper abdomen, long axis is cephalocaudal
o If it is felt in the epigastrium, the long axis is transverse
o Approximately 30% of patients do not have a palpable mass
• Rectal examination: presence of bloody mucus supports diagnosis
• Abdominal distention & tenderness: as intestinal obstruction
becomes more acute
• On rare occasions, advancing intestine prolapses through the anus
o Distinguished from rectal prolapse by separation between
producing intestine & rectal wall (absent in rectal prolapse)
• Ileoileal intussusception in <2 years: less typical clinical picture
o Symptoms & signs chiefly those of small intestinal obstruction
o These often resolve without treatment
• Recurrent intussusception (5-8%): more common in hydrostatic
than surgical reduction
• Chronic intussusception (milder form at recurrent intervals): more
likely to occur with or after acute enteritis
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Diagnosis
• Ultrasound: when history & PE suggest intussusception
o Diagnostic findings of intussusception
▪ Tubular mass in longitudinal views
▪ Doughnut or target appearance in transverse images
o Sensitivity of ~98-100%; specificity of ~98%
• Contrast enema
o Air, hydrostatic (saline), and, less often, water-soluble contrast
enemas have replaced barium examinations
o Demonstrate a filling defect or cupping in head of contrast
media where its advance is obstructed by the intussusceptum
o Coiled-spring sign, especially after evacuation
▪ A central linear column of contrast media visible in the
compressed lumen of the intussusceptum
▪ Thin rim of contrast seen trapped around invaginating
intestine in folds of mucosa within intussuscipiens
Differential Diagnosis
Patterns of illness, character of pain, nature
Gastroenteritis
of vomiting, onset of rectal bleeding
Less severe and less regular pain, diarrhea,
Enterocolitis
ill-looking between pains
Meckel diverticulum Painless bleeding
Henoch-Schӧnlein purpura Joint symptoms, purpura, hematuria
Distal intestinal obstruction
Seen in cystic fibrosis
syndrome
Treatment
• Reduction of an acute intussusception is an emergency procedure
& should be performed immediately after diagnosis before surgery
o In patients with prolonged intussusception and signs of shock,
peritoneal irritation, intestinal perforation, or pneumatosis
intestinalis, hydrostatic reduction should not be attempted
o Success rate of hydrostatic reduction under fluoroscopic/
ultrasonic guidance: ~80-95% in ileocolic intussusception
o Spontaneous reduction: ~4-10% of patients
o Bowel perforations:
▪ Barium and hydrostatic (saline) reductions: 0.5-2.5%
▪ Air reduction: 0.1-0.2%
• Surgical reduction
o Indications
▪ Refractory shock
▪ Suspected bowel necrosis or perforation
▪ Peritonitis
▪ Multiple recurrences (suspected lead point)
• Ileoileal intussusception: demonstrated by abdominal ultrasound
o Reduction by contrast agents, saline, or air might not be possible
o Resection of intussusception with end-to-end anastomosis: If
manual operative reduction is impossible or bowel is not viable
Prognosis
• Untreated ileal-colonic intussusception in infants is usually fatal
o Most recover if reduced in 1st 24 hours
o Mortality rate rises rapidly after this time, especially after 2nd day
o Spontaneous reduction prior to operation is not uncommon
• Recurrence rate: after reduction: ~10%; surgical reduction: 2-5%;
surgical resection: none (most occur within 72 hours of reduction)
o Corticosteroids may reduce recurrence but are rarely used
• Treatment of identifiable food allergies: in repeated reducible
episodes caused by lymphonodular hyperplasia
• Single recurrence: usually reduced radiologically
• In multiple ileal-colonic recurrences: a lead point should be
suspected, and laparoscopic surgery considered
• Intussusception caused by a lesion such a lymphosarcoma, polyp,
or Meckel diverticulum: unlikely reduced by radiologic intervention
• Adequate laparoscopic reduction: carries a very low mortality
• Many small bowel–small bowel and a few small bowel–colonic
intussusceptions reduce spontaneously
o If left untreated, ileal–colonic intussusception may lead to
intestinal infarction, perforation, peritonitis, and death
Reference: Nelson Textbook of Pediatrics, 21st edition (2020
6. INTESTINAL OBSTRUCTION IN CHILDREN | 25
 Hypertrophic Pyloric
Duodenal Obstruction Jejunal & Ileal Obstruction Malrotation Ileus Adhesions Intussusception
Stenosis
Most common intestinal
obstruction in 5 months-3
years
5-year readmission risk due to
M > F (4-6 times) adhesions varied by Most common abdominal
2.5-10/100,000 live births ~1 in 500 infants • Operative region: 2.1% emergency in children <2
Offspring parent who had
(colon) to 9.2% (ileum) years
pyloric stenosis are at higher
Duodenal atresia: complicates Majority (75-85%) of patients • Procedure: 0.3%
1/10,000 live births present in the 1st year of life (appendectomy) to 25% 60% of patients are younger
Epidemiology Develops in ~20% of male &
(ileostomy than 1 year of age
10% of female descendants of
25-40% of all intestinal >50% present within the 1st formation/closure)
a mother who had pyloric
atresias month of life, with symptoms of 80% of the cases occur before
stenosis
acute or chronic obstruction Overall risk: 5.3% excluding age 24 months; rare in
appendectomy; 1.1% including neonates
B & O blood groups
appendectomy
1-4 per 1,000 live births
M > F (3:1)
Cause is unknown
Nonrotation: bowel fails to
~90% are idiopathic
Associated conditions rotate after it returns to
Abdominal surgery
• Eosinophilic gastroenteritis Jejunoileal atresia: attributed abdominal cavity
Adenovirus (type C) infection
to intrauterine vascular
• Apert syndrome Infection (gastroenteritis,
accidents resulting in Malrotation: failure of the
• Zellweger syndrome Intrinsic defect of bowel pneumonia, peritonitis) Rotavirus vaccine
segmental infarction and cecum to move into RLQ;
• Trisomy 18 formation: duodenal atresia
resorption of fetal intestine Ladd bands
• Smith-Lemli-Opitz Metabolic abnormalities GI infection or new food
syndrome Extrinsic compression: (uremia, hypokalemia, proteins
Meconium ileus: abnormal Associated with other Major cause of postoperative
Etiology • Cornelia de Lange annular pancreas,
viscous secretions creating anomalies of abdominal wall:
hypercalcemia,
small bowel obstruction
syndrome preduodenal portal vein, hypermagnesemia, acidosis) Lymphoid nodular hyperplasia
obstruction diaphragmatic hernia,
duplication cysts, congenital
gastroschisis, omphalocele
Associated with the use of bands associated with Administration of certain drugs Lead points in children >2
Long-segment Hirschsprung
erythromycin in neonates malrotation (opiates, vincristine, years; recognizable in 2-8%
disease: aganglionic Associated with heterotaxy
antimotility agents such as
segments including the syndrome: congenital heart
Higher incidence among mostly loperamide) when used during Abdominal surgery
terminal ileum & entire colon malformations, malrotation,
female infants of mothers gastroenteritis
biliary atresia, asplenia/
treated with macrolides during Henoch-Schӧnlein purpura
polysplenia
pregnancy & breastfeeding
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Most remain asymptomatic

Bilious vomiting without Can arise any time after 2
Nausea, vomiting, feeding Severe paroxysmal colicky
abdominal distention, Bilious emesia, recurrent weeks to 1 year after surgery
Non-bilious vomiting, Polyhydramnios, abdominal intolerance, abdominal pain, lightly tender sausage
Clinical peristaltic waves early in the abdominal pain,
hyperbilirubinemia distension, failure to pass distention with pain, delayed mass, currant jelly stools,
Manifestations disease, history of malabsorption or protein- Abdominal pain, constipation,
(icteropyloric syndrome) meconium, jaundice passage of stools, bowel vomiting, abdominal distention
polyhydramnios, jaundice in losing enteropathy, volvulus emesis, intraperitoneal
sounds minimal or absent
⅓ of infants surgery, nausea & vomiting,
hyperactive then absent bowel
sounds, abdominal distention
Plain radiographs (upright or
Abdominal plain films: gasless
lateral decubitus): multiple air-

26 | 6. INTESTINAL OBSTRUCTION IN CHILDREN

abdomen, double bubble sign
fluid levels (jejunoileal atresia
(duodenal obstruction)
& long-segment Hirschsprung
Palpation of pyloric mass Plain abdominal radiograph:
disease) or hazy/ground-glass Abdominal x-ray: multiple air-
double bubble sign Upper GI series: malposition Plain radiographs: obstructive Ultrasound: tubular mass,
appearance (meconium ileus) fluid levels throughout
Ultrasound: confirms the of ligament of Treitz, features doughnut or target sign
abdomen
diagnosis Contrast studies: to exclude corkscrew appearance of
Diagnosis Contrast studies: meconium
malrotation & volvulus duodenum CT scan or contrast studies: Contrast enema: filling defect
ileus vs. Hirschsprung disease Contrast radiography: slow
Contrast studies: string sign, may be needed to define or cupping in head of contrast,
(water-soluble enemas); movement of barium into
shoulder sign, “double tract Fetal ultrasonography: Barium enema: malposition of etiology coiled-spring sign
microcolon (obstruction patent lumen
sign” sonographic bubble sign cecum
proximal to ileocecal valve)
Ultrasound: inversion of SMA
Abdominal US: meconium
& SMV
ileus vs. ileal atresia
Preoperative: fluid & Reduction: hydrostatic
Initial treatment: nasogastric
electrolyte balance, antibiotics (saline), water-soluble
Preoperative treatment: correct or orogastric decompression, Correct underlying
contrast, air
fluid, acid-base, electrolyte IV fluid replacement abnormality: electrolytes, Nasogastric decompression,
Resection of dilated proximal
losses Ladd procedure: volvulus isotonic crystalloids, IV fluid resuscitation, broad-
bowel followed by end-to-end Surgical reduction: in
Evaluate for associated reduced counterclockwise, nasogastric decompression spectrum antibiotics
anastomosis: ileojejunal refractory shock, suspected
Pyloromyotomy: Ramstedt anomalies: 2D-echo, renal adhesiolysis, appendectomy
Treatment atresia bowel necrosis/perforation,
procedure, laparoscopy US, x-ray of chest & spine Supportive care of Fibrin-glued plication of
peritonitis, multiple
comorbidities adjacent small bowel loops: in
Gastrografin enema or recurrences
Conservative management: Definitive correction: children with repeated
laparotomy: uncomplicated
nasoduodenal feedings, oral duodenoduodenostomy with Mitigation of iatrogenic obstruction
meconium ileus Ileoileal intussusception:
and IV atropine sulfate postoperative gastrostomy contributions
resection with end-to-end
tube & IV nutritional support
Total parenteral nutrition anastomosis
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

7. DIARRHEA & DEHYDRATION

ACUTE GASTROENTERITIS (AGE)
• Captures the bulk of infectious cases of diarrhea
• Most common manifestations are diarrhea & vomiting, which can
also be associated with systemic features (abdominal pain & fever)
Dysentery: syndrome characterized by frequent small stools containing
visible blood, often accompanied by fever, tenesmus, & abdominal pain
Prolonged diarrhea: lasting 7-13 days
Persistent diarrhea: lasting ≥14 days

EPIDEMIOLOGY
• 4th most common cause of child mortality worldwide (2015)
o Almost 1 billion episodes occurred in 2015 worldwide
o ~86% of episodes occurred in Africa (63%) & South Asia (23%)
• Smaller decline (10%) was observed among children <5 years
o Preventive rotavirus vaccination & improved case management
of diarrhea, as well as improved nutrition of infants and children
o Intervention includes widespread home- and hospital-based
ORS therapy & improved nutritional management
• High rates of diarrhea can be associated with long-term adverse
outcomes (recurrent, prolonged, or persistent)
o Associated w/ malnutrition, stunting, micronutrient deficiencies,
& significant deficits in psychomotor & cognitive development

ETIOLOGY

7. DIARRHEA AND DEHYDRATION | 27

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

PATHOGENESIS OF INFECTIOUS DIARRHEA

• Transmission
Infectious load Examples Transmission
Enteropathogens that Shigella, STEC, norovirus, rotavirus, Person-to-person
are infectious in small G. intestinalis, Cryptosporidium contact via the fecal-oral
inocula spp., C. difficile, E. histolytica route
Pathogens with larger Cholera, nontyphoidal Salmonella Generally require food
infectious doses (NTS), ETEC, and Campylobacter or water vehicles
• Incubation Periods
Mechanism Examples Incubation period
S. aureus, B. cereus emetic
Produce preformed toxins 1-6 hours
toxin
C. perfringens & B. cereus
Elaborate enterotoxins in situ 8-16 hours
enterotoxin
Attach to epithelium &
V. cholerae, ETEC
elaborate enterotoxins
Elaborate cytotoxins S. dysenteriae type 1, STEC 1-5 days • Cryptosporidia sporozoites (from ingested cysts) penetrate
Invade & disrupt intestinal Shigella, NTS,
epithelium Campylobacter, Yersinia intestinal epithelial cells & develop into trophozoites within the
Requires a life cycle Protozoa More extended intracellular, extracytoplasmic environment
• Other properties affecting transmissibility o After asexual multiplication & sexual development, they are
Properties affecting transmissibility Examples
released in colon as infectious oocysts causing autoinfection
Bioavailability (copious and/or prolonged fecal shedding)
Extended infectivity in the environment
Norovirus, o Host factors, in particular T-cell function, play a critical role in
Cryptosporidium
Resistance to disinfection disease severity
Large environmental or animal reservoir Campylobacter
• Cyclospora cysts: not infectious in freshly passed stools
• Ability to circumvent immune surveillance (susceptible host)
Frequent antigenic changes resulting from Examples
o Sporulate in environment for 1-2 weeks to be infectious
Recombinational events Norovirus o Usually transmitted in contaminated produce and water
Large serotype diversity Shigella
• Viral AGE
o Causes a cytolytic infection of the small intestinal villus tips
▪ Decreased absorption of water
▪ Disaccharide malabsorption
▪ Inflammation
▪ Cytokine activation
o Rotavirus protein NSP4 (viral
enterotoxin): secretory diarrhea
o Rotavirus activates the enteric nervous
system causing
▪ Decreased gastric emptying
▪ Increased intestinal mobility
o Genetic susceptibility to both rotavirus and norovirus infection
▪ Mediated by histo-blood group antigens on the epithelial
surface and in mucus secretions CLINICAL MANIFESTATION OF DIARRHEA
• Secretory diarrhea: pathogens attach to surface of epithelium and General Findings
stimulate secretion of water and electrolytes • Diarrhea: passage of ≥3 abnormally loose or liquid stools per day
Activation of adenylate cyclase Examples o Frequent passage of formed stools is not diarrhea, nor is the
Raising intracellular cAMP V. cholerae, heat-LT-producing ETEC
Raising intracellular cGMP ETEC producing heat-ST passing of loose, pasty stools by breastfed babies
o Diarrheagenic phenotype of C. difficile: production of toxins
A (enterotoxin) & B (enterotoxin & cytotoxin)
o Epidemic hypervirulent NAP1 C. difficile also makes binary
toxin: enhance colonization & augment toxin production

• Individual signs that best predict dehydration

o Prolonged capillary refill time >2 seconds
• Elicitation of inflammatory cytokines ± toxin production o Abnormal skin turgor
o Invasive phenotypes of Shigella, NTS, Campylobacter, Yersinia o Hyperpnea (deep, rapid breathing suggesting acidosis)
o The pathogenesis of Shigella, the most common cause of o Dry mucous membranes
bacillary dysentery, has been characterized in greatest detail o Absent tears
o Following invasion, Shigella induces extensive destruction & o General appearance (including activity level and thirst)
inflammation of intestinal epithelium: ulcers & microabscesses • Severe dehydration
▪ Manifest with diarrheal stools containing blood and pus o Tachycardia
o Enterotoxins: secretory diarrhea o Altered level of consciousness
▪ Can be seen early in shigellosis or as the sole manifestation o Cold extremities
o Shiga toxin (from S. dysenteriae type 1): increases severity o With or without hypotension
▪ Responsible for hemolytic uremic syndrome (HUS)

28 | 7. DIARRHEA AND DEHYDRATION

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Viral Diarrhea Protozoal Diarrhea

• Rotavirus AGE: vomiting + frequent passage of watery nonbloody • More prolonged (≥2 weeks), but usually self-limited
stools, associated with fever in about half the cases • Cryptosporidium diarrhea: duration & severity strongly influenced by
o Stool lacks fecal leukocytes, but 20% of cases contain mucus the immune and nutritional status of the host
o Recovery with complete resolution: within 7 days • Suspected when there is a prolonged diarrheal illness: episodes of
o Disaccharide malabsorption (10-20%): rarely significant somewhat-explosive diarrhea with nausea, abdominal cramps,
• Other viral agents cannot be distinguished from rotavirus clinically and abdominal bloating
o Caliciviruses & preformed bacterial toxins in an outbreak setting: • Stools: usually watery but can be greasy and foul smelling due to
brief incubation (12-48 hrs), short duration, clustering of cases concomitant malabsorption of fats (more likely if high parasite load)
▪ Caliciviruses: secondary infections (contagious outbreak) • Occasionally diarrhea may alternate with constipation
o Enteric adenovirus infections: more prolonged (7-10 days) • E. histolytica causes a range of other syndromes
o Astrovirus: shorted course (~5 days) without significant vomiting o Amebic dysentery is characterized by bloody or mucoid
diarrhea, which may be profuse and lead to dehydration or
Bacterial Diarrhea electrolyte imbalances
• Fever >40°C, overt fecal blood, abdominal pain, no vomiting o Hepatic amebiasis is limited to abscess formation in the liver,
before diarrhea onset, and high stool frequency (>10 per day) which may occur with or without intestinal disease
o Bacterial enteritis: high fever & overt fecal blood are often absent
• Classic bacterial agents (NTS, Shigella, Campylobacter, Yersinia) INTESTINAL AND EXTRAINTESTINAL COMPLICATIONS
present with 1 of 5 syndromes • Major complications from diarrhea from any cause: dehydration,
Acute • May be accompanied by fever and vomiting electrolyte, or acid-base derangements (life-threatening)
diarrhea • Clinically silent bacteremia in uncomplicated NTS AGE
(most common)
• Frequent episodes of acute diarrhea or prolonged or persistent
among healthy children <2 yrs. in industrialized countries
• Classically caused by Shigella episodes (low resource settings) are at risk for
Bloody o Poor growth and nutrition and
• Mild infection: watery diarrhea then dysentery
diarrhea or
• Dysentery indicates colitis (within hours to days) o Complications such as secondary infections and
frank
dysentery • Severe infection: may pass >20 dysenteric stools in 1 day micronutrient deficiencies (iron, zinc, vitamin A)
• Campylobacter dysentery: confused with IBD o Prolonged limitation of the diet may extend diarrheal symptoms
• Febrile illness + bacteremia without localized infection
• Diarrhea may be minimal or absent
• Viral AGE: usually self-limited and resolve after several days
• Can result from systemic spread of the classical bacterial o Rarely, intussusception is triggered by lymphoid hyperplasia
enteropathogens (S. typhi or S. paratyphi A and B) • Bacterial AGE: result of local or systemic spread of the organism
• S. typhi or S. paratyphi A and B: preschool & school-age o Bacteremia: malnourished children & HIV-infected populations
Invasive, non-
children in endemic countries
focal disease o Toxic megacolon, intestinal perforation, rectal prolapse:
(enteric fever) • Other bacterial enteropathogens: infants (<3 months),
immunocompromised, & children with malnutrition Shigella (developing countries) and C. difficile
• Additional risk factors: hemolytic anemia and o HUS: most dreaded complication of pediatric diarrhea
intravascular lesions for NTS, and iron overload, ▪ Leading cause of acquired renal failure in children (5-10%)
cirrhosis, and chelation therapy for Yersinia sepsis ▪ Usually diagnosed 2-14 days after onset of diarrhea
• Shigella sepsis: rare; malnourished, immunocompromise
▪ Unlikely to occur once diarrhea has remained resolved for
• Local invasion: mesenteric adenitis, appendicitis, and
rarely cholecystitis, mesenteric venous thrombosis, 2-3 days with no evidence of hemolysis
Extraintestinal pancreatitis, hepatic, or splenic abscess ▪ Risk factors: 6 months – 4 years, bloody diarrhea, fever, ↑
invasive • Bacteremic spread: result in pneumonia, osteomyelitis, WBC, treatment with antibiotics and antimotility agents
infections meningitis (3 conditions seen most with NTS),
▪ 2/3 of patients no longer excrete organism at time of HUS
abscesses, cellulitis, septic arthritis, endocarditis
• Shigella: noninvasive contiguous infection (vaginitis, UTI) o Pseudoappendicitis secondary to mesenteric adenitis:
• Vertical transmission of Shigella, NTS, Campylobacter Yersinia, and sometimes Campylobacter
Perinatal
• Results in a spectrum of illness from isolated diarrhea ▪ Older children and adolescents are most often affected
or hematochezia to fulminant neonatal sepsis ▪ Fever + abdominal pain + RLQ tenderness ± diarrhea
infection
• Campylobacter fetus: can result in chorioamnionitis,
▪ CT scan or sonogram may be helpful
abortion, & neonatal sepsis & meningitis
• E. coli diarrhea syndromes o Immune-mediated complications more often seen in adults
▪ Reactive arthritis: classical bacterial enteropathogens
• Crampy abdominal pain + nonbloody diarrhea ± vomiting
STEC • Several days: bloody diarrhea & abdominal pain worsens ▪ Guillain-Barré syndrome: Campylobacter infection
(EHEC) • Bloody diarrhea lasts between 1 and 22 days (median 4 days) • Protozoan illnesses
• STEC hemorrhagic colitis: large volume stools; rarely high fever o Persistent: poor weight gain (young & immunocompromised),
• Secretory watery diarrhea weight loss, malnutrition, or vitamin deficiencies
ETEC • Affects infants and young children in developing countries
o Entamoeba: severe ulcerating colitis, colonic perforation
• Major causative agent of travelers’ diarrhea (half of all episodes)
EPEC • Persistent diarrhea + malnutrition (infants: developing countries)
▪ Systemic spread: liver abscesses
• Genetically, biochemically, clinically near identical to shigella
EIEC
• Causes rare foodborne outbreaks in industrialized countries
• Persistent diarrhea in immunocompromised persons
EAEC • Sporadic diarrhea in infants in countries with varying levels of
economic development
• C. difficile toxin is associated with several clinical syndromes
o Most common: mild to moderate watery diarrhea, low-grade,
fever, and mild abdominal pain
o Occasionally progress to full-blown pseudomembranous colitis
▪ Diarrhea + abdominal cramps + fever
o Colonic mucosa contains 2-5 mm raised, yellow plaques
o Fatal cases: toxic megacolon, systemic toxicity, and multisystem
organ failure, possibly related to systemic absorption of toxin
• Vomiting: associated with S. aureus & B. cereus emetic toxin
• Diarrhea: major manifestation of C. perfringens & B. cereus
enterotoxins

7. DIARRHEA AND DEHYDRATION | 29

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

DIFFERENTIAL DIAGNOSIS LABORATORY DIAGNOSIS

• Infant/young child: anal fissures, intermittent • Most cases of AGE do not require diagnostic laboratory testing
Noninfectious intussusception, juvenile polyps, Meckel • Fecalysis: mucus, blood, neutrophils, fecal lactoferrin
diseases presenting diverticulum
as hematochezia • Premature neonates: necrotizing enterocolitis o >5 WBC/hpf or (+) lactoferrin in non-breastfeeding infant:
• Older children: inflammatory bowel disease infection with a classical bacterial enteropathogens
• Congenital secretory diarrheas o STEC & E. histolytica: negative tests
• Endocrine disorders (hyperthyroidism) • Laboratory diagnosis of viral AGE
Noninfectious causes
• Neoplasms o May be helpful when
of nonbloody diarrhea
• Food intolerance
• Medications (antibiotics)
▪ An outbreak is suspected
• Cystic fibrosis ▪ Cohorting of patients considered to limit spread of infection
Noninfectious causes o Reverse transcription quantitative PCR (RT-qPCR)
• Celiac disease
of chronic/ relapsing
• Milk protein intolerance o Commercial tests for rotavirus and enteric adenoviruses
diarrhea
• Congenital/acquired disaccharidase deficiency • Stool cultures
Significant abdominal • Appendicitis
o Restricted to patients with
pain (other infections) • Pelvic inflammatory disease
• Pyloric stenosis
▪ Clinical features predictive of bacterial AGE
• Intestinal obstruction ▪ Moderate or severe disease
Prominent vomiting ±
• Pancreatitis ▪ Immunocompromised
abdominal pain
• Appendicitis ▪ Outbreaks with suspected hemolytic-uremic syndrome
• Cholecystitis ▪ Highly suggestive epidemiologic history
o Specimens for culture need to be transported & plated quickly
CLINICAL EVALUATION OF DIARRHEA to optimize recovery of pathogens
• Initial evaluation ▪ If not quickly available, use special transport media
o Hydration status and electrolyte balance ▪ Rectal swab: if no stool & antibiotics will be administered
o Evidence of sepsis or invasive bacterial infection, which could o Standard stool culture methods recover Shigella & Salmonella
complicate bacterial AGE ▪ Notify laboratory if Campylobacter, Yersinia, Vibrio species
• History are suspected (requires specialized culture media)
o Duration of diarrhea o All bloody stools should be
o Description of stools (frequency, amount, blood/mucus) ▪ Inoculated into media specific for E. coli 0157:H7
o Fever (duration, magnitude) ▪ Directly tested for the presence of Shiga-like toxin (or both)
o Vomiting (onset, amount, frequency) o C. difficile assays not indicated in nosocomial diarrhea unless
o Amount and type of solid and liquid oral intake ▪ Immunocompromised
o Clinical signs of dehydration ▪ Investigation of a hospital outbreak
▪ Urine output (wet diapers/day, time since last urination) o Stool nucleic acid amplification test (NAAT)
▪ Whether eyes appear sunken ▪ If positive: proceed to stool culture & sensitivity
▪ Whether the child is active • C. difficile evaluation
▪ Whether the child drinks vigorously o Children >2 yrs recently received antibiotics or other risk factors
▪ Date and value of the most recent weight measurement o EIA for toxins A & B, culture cytotoxicity assay, PCR
• Fluid deficit: from documented weight loss o Cell culture & PCR are superior to immunoassay (EIA)
o Past medica history: comorbidities (↑ risk/severity of AGE) • Evaluation for intestinal protozoa
• Physical examination o Indicated in patients with diarrhea who had
o General appearance (activity, response to stimulation) ▪ Recent travel to an endemic area
o Respiratory patterns ▪ Contact with untreated water
o Skin turgor: pinching a small skin fold on the lateral abdominal ▪ Manifest suggestive symptoms
wall at the level of the umbilicus o Direct microscopy of stool for cysts and trophozoites
▪ If the fold does not promptly return to normal after release, ▪ Time consuming; lacks sensitivity (intermittent shedding)
the recoil time is quantified as delayed slightly or ≥ 2 sec ▪ Analyze 3 specimens from separate days is optimal
▪ False negative: excess subcutaneous tissue, hypernatremia ▪ Fecal concentration techniques provide some benefit
▪ False positive: malnutrition (prolong the recoil time) o Immunofluorescence antibodies
o Capillary refill time: palmar surface of child’s distal fingertip is ▪ Improves sensitivity and specificity of microscopy
pressed until blanching occurs, with child’s arm at heart level ▪ Visualization of Cryptosporidium and Giardia cysts
▪ Time elapsed until restoration of normal color after release o Enzyme immunoassays (EIA)
usually exceeds 2 sec in the presence of dehydration ▪ Cryptosporidium, Giardia, and Entamoeba
o Mucous membrane moisture level ▪ More sensitive and specific than direct microscopy
o Presence of tears ▪ Provide a useful diagnostic tool
o Extremity temperature o Molecular methods (NAAT)
• Other laboratory tests
o Serum electrolytes
▪ Severe dehydration
▪ In administration of IV fluids
▪ History of frequent watery stools yet skin pinch feels doughy
without delayed recoil (suggests hypernatremia)
o Suspected HUS: CBC, peripheral smear, platelets, serum
electrolytes, renal function tests
▪ Shigellosis: bandemia or even a leukemoid reaction
o Blood culture: suspected systemic bacterial infection
▪ Fever and/or blood in stool in infants <3 months
▪ Immunocompromised
▪ Hemolytic anemia and other risk factors
• Endoscopy: if diarrhea persists with no cause identified

30 | 7. DIARRHEA AND DEHYDRATION

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT Enteral Feeding and Diet Selection

Broad principles of management of AGE in children • Continued breastfeeding & refeeding with an age-appropriate,
• Rehydration & maintenance ORS + replacement of continued losses unrestricted diet as soon as dehydration is improving or resolved
in diarrheal stool and vomitus after rehydration o Usual energy density of any diet for diarrhea: ~1 kcal/g
• Continued breastfeeding ▪ Energy intake of ≥100 kcal/kg/day
• Refeeding with an age-appropriate, unrestricted diet as soon as ▪ Protein intake of 2-3 g/kg/day
dehydration is corrected Foods reintroduced while ORS is Complex carbohydrates (rice, wheat,
given to replace ongoing losses from potatoes, bread cereals), fresh fruits,
• Zinc supplementation: for children in developing countries emesis or stools and for maintenance lean meats, yogurt, and vegetables
Fatty foods or foods high in simple
Avoid
sugars (juices, carbonates sodas)
Adequate intake of energy-dense Addition of amylase to diet through
food is problematic germination techniques
• If normal diet includes infant formula, it should not be diluted, or
changed to a lactose-free preparation unless lactose malabsorption
o Most children are able to tolerate milk & lactose-containing diets
o Withdrawal of milk and replacement with specialized lactose-
free formulations are unnecessary
o Lactose load >5 g/kg/day: ↑ purging rates & treatment failure
o Alternative strategies for reducing the lactose load while feeding
malnourished children who have prolonged diarrhea
▪ Addition of milk to cereals
▪ Replacement of milk with fermented milk products (yogurt)
• Specialized milk-free diets: when dietary intolerance precludes the
administration of cow’s mild-based formulations or whole milk
o Comminuted or blenderized chicken-based diet or an
Hydration elemental formulation: effective yet expensive
• Dehydration must be evaluated rapidly and corrected in 4-6 hours o Alternatives: addition of rice-lentil formulations or green
according to degree of dehydration & estimated daily requirements banana/pectin to diet (effective in persistent diarrhea)
• Emesis: small volumes of ORS can be given initially by a dropper, • Locally available age-appropriate foods
teaspoon, or syringe (~5 mL at a time); increased as tolerated o Among children in low- and middle-income countries
• Low-osmolality ORS 75: global standard of care and more effective ▪ Dual burden of diarrhea and malnutrition is greatest
than home fluids ▪ Proprietary formulas & specialized ingredients limited
o Sodium: 75 mEq o Nutritionally complete diets composed of locally available
o Chloride: 64 mEq ingredients as effective as commercial specialized ingredients
o Potassium: 20 mEq
o Glucose: 75 mmol/L
o Total osmolarity: 245 mOsm/L
• Oral rehydration can also be given by a nasogastric tube if needed
• A small minority of children, including those with severe dehydration
or unable to tolerate oral fluids, require initial IV rehydration
o Oral rehydration is preferred mode of rehydration and
replacement of ongoing losses
• Limitations to ORS
o Shock
o Decreased level of consciousness
o Ileus
o Intussusception
o Carbohydrate intolerance (rare)
o Severe emesis
o High stool output (>10 mL/kg/hr)

Zinc Supplementation (oral zinc 20 mg/day for 10-14 days)

• All children >6 months of age during and continued after diarrhea
• In children with diarrhea in developing countries
o Leads to reduced duration and severity of diarrhea
o Potentially prevent a large proportion of cases from recurring
o Reduce all-cause mortality by 46% & hospital admission by 23%
• Benefits of administration of zinc in community settings
o Improves diarrhea recovery rates
o Leads to increased use of ORS
o Reduction in the inappropriate use of antimicrobials
• Role of zinc in well nourished, zinc replete populations in developed
countries is less certain

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Antibiotic Therapy
• Judicious antibiotic therapy for suspected/proven bacterial infection
o Reduce duration and severity of illness & prevent complications
• Several factors justify its limited use
o Most episodes of AGE are self-limited among otherwise healthy
o Increasing prevalence of antibiotic resistance
o Antibiotics may worsen outcome
▪ Antibiotic therapy of STEC infection increases the risk of
HUS & prolongs excretion of NTS without improvements
• Goals of treatment: treat severe infections, prevent complications
in high-risk hosts, or to limit the spread of infection
o Microbiologic (culture) confirmation of etiology and susceptibility
testing should be sought prior to treatment is possible
• Treatment of C. difficile: removal of the offending antibiotics
o Antibiotic therapy directed against C. difficile if severe/persistent
▪ First-line: oral vancomycin and metronidazole for 7-14 days
▪ First relapse: another course based on severity
▪ Recurrent: tapering and/or pulsed oral vancomycin (4-6 wk)
o Testing for C. difficile is discouraged for children <2 years
o Fecal transplant: for persistent/recurrent C. difficile colitis
o Bezlotoxumab: monoclonal antibody for C. difficile toxins A & B
32 | 7. DIARRHEA AND DEHYDRATION
Additional Therapies
• Probiotic nonpathogenic bacteria
o For prevention and therapy of diarrhea
o Has been successful in some setting, although evidence does
not support a recommendation for use in all settings
o A variety of organisms (Lactobacillus, Bifidobacterium) have a
good safety record
▪ Therapy has not been standardized
▪ Most effective (and safe) organism has not been identified
Saccharomyces boulardii
• Effective in antibiotic-associated and in
C. difficile diarrhea
Lactobacillus rhamnosus GG
• Reduction is more evident in cases of
or L. rhamnosis R0011 +
childhood rotavirus diarrhea
L. helveticus R0052
• Ondansetron (oral mucosal absorption preparation)
o Reduces incidence of emesis (more effective oral rehydration)
o Well-established in emergency management of AGE in high-
resource settings (↓ IV fluid requirements & hospitalization)
o Dose: single sublingual dose of oral dissolvable tablet
▪ 4 mg for children 4-11 years old
▪ 8 mg for children >11 years [generally 0.2 mg/kg]
o Most children do not require specific antiemetic therapy
▪ Careful ORS is usually sufficient
• Antimotility agents (loperamide)
o Contraindicated in children with dysentery
o No role in acute watery diarrhea in otherwise healthy children
PREVENTION
Promotion of Exclusive Breastfeeding and Vitamin A
• Exclusive breastfeeding (no other fluids/foods for 1st 6 mos. of life)
o Protects young infants from diarrheal disease through
▪ Promotion of passive immunity
▪ Reduction in intake of potentially contaminated food & water
o In developing countries
▪ One of the most effective interventions to reduce risk of
premature childhood mortality
▪ Has potential to prevent 12% of all deaths in <5 years of age
• Vitamin A supplementation
o Reduces all-cause childhood mortality by 25%
o Reduces diarrhea-specific mortality by 30%
Immunizations
• Reductions in rotavirus-associated & all-cause hospitalizations in
o Vaccinated infants (direct protection)
o Unvaccinated individuals (indirect, or herd protection)
• Reductions in-office visits for less severe rotavirus diarrhea
Rotavirus
• Reductions in all-cause diarrhea deaths in some countries
• Vaccine (live virus) associated rotavirus infection: reported in children
with severe combined immunodeficiency disease
• Safe in HIV-infected populations
• 2 licensed, efficacious 2-dose oral inactivated cholera vaccines
o Dukoral for children ≥2 years
o ShanCol for children ≥1 year
Cholera
o No specific indication in endemic and epidemic setting (potentially
reduce burden of severe diarrhea and mortality)
• Single-dose live oral cholera vaccine (Vaxchora): for adult travelers
• Polysaccharide IM vaccine (Vivotif): children >2 years
• Oral, live attenuated vaccine (Typhim Vi): children >6 years
Typhoid
fever • Conjugated polysaccharide vaccines: children <2 years
o Infants & children ≥6 months in endemic areas
o Catch-up vaccination campaigns for children up to 15 years
Improved Water and Sanitary Facilities & Promotion of Personal
and Domestic Hygiene
• Much of reduction in diarrhea prevalence in the developed world:
improvement in standards of hygiene, sanitation, and water supply
• Strikingly, ~88% of all diarrheal deaths worldwide can be attributed
to unsafe water, inadequate sanitation, and poor hygiene
• Measures to reduce risk of diarrhea
o Handwashing with soap (48% reduction)
o Safe excreta disposal (36% reduction)
o Improvements in water quality (17% reduction)
Reference: Nelson Textbook of Pediatrics, 21st edition (2020)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

8. SHOCK CLASSIFICATION OF SHOCK

• Clinical condition of organ dysfunction resulting from an imbalance Distributive Shock
between cellular oxygen supply and demand • Primary physiologic disturbance: reduction in SVR
• Unique among the types of shock: compensatory increase in CO
PATHOPHYSIOLOGY OF SHOCK • Central venous pressure (CVP) and pulmonary capillary wedge
• Most commonly related to impaired oxygen delivery in the setting pressure (PCWP) are usually reduced
of circulatory failure • Sepsis: life-threatening organ dysfunction due to
o Shock can also develop during states of increased oxygen Sepsis (most dysregulated host response to infection
consumption or impaired oxygen utilization common cause) • Septic shock: sepsis + persistent hypotension
requiring vasopressor support
• In the setting of insufficient oxygen supply, the cell is no longer • Predominantly an IgE-mediated allergic reaction that
able to support aerobic metabolism Anaphylaxis can rapidly develop after an exposure to an
o Without sufficient oxygen supply, the cell is forced into (anaphylactic allergen (food, medication, insect bite)
anaerobic metabolism, in which pyruvate is metabolized to shock) • Profound distributive type of shock mediated through
histamine (both venous and arterial vasodilation)
lactate with much less ATP generation (per mole of glucose)
Severe brain or • Related to disruption of autonomic pathways that
o ATP-dependent ion pumping systems, such as the Na+/K+ spinal cord injury regulate vascular tone
ATPase, consume 20-80% of the cell’s energy (neurogenic • Pooling of blood in venous system with a resulting
• Inadequate oxygen delivery & decreased ATP disrupt cell’s ability shock) decreased venous return and decreased CO
to maintain osmotic, ionic, & intracellular pH homeostasis • Chronic steroid use, metastatic malignancy, adrenal
hemorrhage, infection (TB, HIV), autoimmune
o Influx of calcium can lead to activation of calcium-dependent Adrenal adrenalitis, amyloidosis
phospholipases & proteases (cellular swelling & death) insufficiency • During stress (infection/surgery): deficit may
o In addition to direct cell death, cellular hypoxia can cause (adrenal crisis) become apparent with an inability to increase cortisol
damage at the organ system level via leakage of the intracellular leading to vasodilation as well as aldosterone
deficiency-mediated hypovolemia
contents into the extracellular space activating inflammatory Others • Pancreatitis, severe burns, liver failure
cascades and altering microvascular circulation
Cardiogenic Shock
DETERMINANTS OF OXYGEN DELIVERY • Reduction in CO owing to a primary cardiac problem
• Disease processes affecting any of the components of oxygen
• Compensatory increase in SVR
delivery have the potential to lead to the development of shock
• When the left ventricle is affected (MI): elevation of PCWP
• Disturbances to key determinants of oxygen delivery form the basis
• When the right ventricle is affected: elevation of CVP
of the 4 major shock types
Determinants of CO Associated processes
Equation Interpretation Myocardial Myocardial infarction, ischemic cardiomyopathies,
Major components of oxygen delivery contractility primary myocarditis
DO2 = CO x CaO2 (DO2) are cardiac output (CO) and SV
Mechanical valvular diseases (acute mitral
arterial oxygen content (CaO2) Afterload/SVR
insufficiency or aortic insufficiency)
Components of cardiac output (CO) are Both bradyarrhythmias and tachyarrhythmias (from
CO = HR x SV HR
heart rate (HR) & stroke volume (SV) either an atrial or ventricular source)
Major determinants of stroke volume
(SV) are preload, afterload (systemic
vascular resistance, SVR), and cardiac Hypovolemic Shock
contractility • Reduce CO via a reduction in preload
• Preload refers to the myocardial • Characterized by an elevated SVR and low CVP and PCWP related
fiber length before contraction
SV α (Preload x contractility)/SVR (ventricular end-diastolic volume) to decreased intravascular volume
• Contractility refers to the ability of • Most commonly related to hemorrhage
the ventricle to contract independent o External: trauma
of preload and afterload o Internal: upper or lower gastrointestinal bleeding
• SVR represents the afterload, or the
force against which the ventricles • Nonhemorrhagic processes
must contract o GI illnesses causing profound emesis or diarrhea
The arterial oxygen content (CaO2) is o Renal losses: osmotic diuresis associated with diabetic
CaO2 = (Hb x 1.39 x SaO2) + composed of oxygen carried by ketoacidosis or diabetes insipidus
(PaO2 x 0.03) convection with hemoglobin and
oxygen dissolved in blood o Skin loss: severe burns, Stevens-Johnson syndrome
• A disease process that affects these variables (HR, preload,
contractility, SVR, SaO2, or Hb) has the potential to reduce oxygen Obstructive Shock
delivery and cause cellular hypoxia • Reduced CO due to an extracardiac processes impairing blood flow
• Processes that can impede return to the heart and reduce CO
o Pneumothorax
o Cardiac tamponade
o Restrictive pericarditis
• Processes that obstruct cardiac outflow
o Pulmonary embolism (right heart)
o Aortic dissection (left heart)

8. SHOCK | 33
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

STAGES OF SHOCK • Insight into hemodynamics & assist in elucidating type of shock
• Compensated shock (preshock) o JVP & peripheral edema: right-sided cardiac pressures
o Physiologic responses counteract initial insult & attempts to o Pulmonary auscultation: left-sided cardiac dysfunction
reestablish the adequate perfusion and oxygen delivery • Differentiate shock with high CO (distributive) vs. low CO (others)
o No overt signs of organ dysfunction High output shock Warm peripheral extremities, brisk capillary refill (<2 s),
o Laboratory evaluation: mild organ dysfunction (elevated (distributive) bounding pulses
Low CO Cool extremities, delayed capillary refill, weak pulses
creatinine or troponin) or a mild elevation of lactate
o Specific compensatory response is determined by the initial • Can distinguish among those with low CO between conditions with
pathophysiologic defect increased intravascular filling pressure (cardiogenic shock) and
▪ Early sepsis (↓ SVR): compensatory rise in HR (and CO) intravascular volume depletion (hypovolemic shock)
▪ Early hemorrhagic volume loss: compensatory ↑ SVR o Cardiogenic shock (right-sided failure): ↑ JVP, S3 gallop
o Hypovolemic shock: ↓ JVP (<8 cm)
• Shock (decompensated shock)
o As the host compensatory responses are overwhelmed, the • May identify the specific etiology of shock (particularly helpful in
patient transitions into true shock the patient who cannot provide a detailed history)
Distributive • Sepsis: site of an untreated infection (cellulitis, abscess,
o With evidence of organ dysfunction shock infected pressure injury, focal)
• Irreversible shock Cardiogenic
• Brady- or tachyarrhythmia
o If untreated, the patient will progress to irreversible shock shock
o Organ dysfunction is permanent • Large ecchymosis: significant bleed related to trauma or
Hypovolemic
o Patient often progresses to multisystem organ failure (MSOF) spontaneous retroperitoneal bleeding
shock
• Rectal examination: may reveal GI hemorrhage
• Cardiac tamponade: pulsus paradoxus + elevated JVP
EVALUATION OF THE PATIENT WITH SHOCK Obstructive • Tension pneumothorax: paucity of breath sounds over the
• 2 specific aims shock affected side, deviation of trachea away from affected
o Confirm the presence of shock side, or subcutaneous emphysema
o Identify specific etiology or determine type of shock present • Shock index (SI) = HR/SBP
o To identify high risk patient populations
History o Elevated SI (>0.9): more sensitive indicator of transfusion
• Details indicating new organ dysfunction requirement and of patients with critical bleeding among those
o Most easily identified: new-onset altered mental status or with hypovolemic (hemorrhagic) shock than HR or BP alone
decrease in renal function (oliguria) o May identify patients at risk for postintubation hypotension
• Apparent type of shock (and specific disease process) • Quick Sequential Organ Failure Assessment (qSOFA)
Condition History o Rapid assessment scale
Distributive shock o 1 point for SBP <100, RR >22, altered mental status (GCS <15)
Septic shock Fever + focal site of infection o A qSOFA ≥2 (with a concern of infection) is associated with a
Onset of hives, dyspnea, new facial edema + significantly greater risk of death or prolonged ICU stay
Anaphylactic shock
exposure to common allergens
Cardiogenic shock
o Identifies the most acutely ill subset of patients with sepsis
Cardiogenic shock Onset of exertional chest discomfort
Significant arrhythmia Palpitations + syncope/presyncope
Hypovolemic shock
History of trauma (blunt or penetrating) or GI bleed
Hemorrhagic shock
(hematemesis, melena, hematochezia)
Obstructive shock
Acute aortic dissection Hypertension + tearing chest or back pain
Acute onset chest pain + dyspnea in the setting of
Pulmonary embolism
immobility and/or underlying malignancy
• Can be helpful in raising the likelihood of particular type of shock
Preexisting immune dysfunction/medication-induced
Septic shock
neutropenia + hypoperfusion + new organ dysfunction
Cardiogenic shock Extensive cardiac disease

Physical Examination
• Aims of the physical examination
o Is shock present? (compensated vs. decompensated)
o What type of shock is present? (distributive, cardiogenic,
hypovolemic, obstructive)
• Compensated phase of shock
o Tend to be nonspecific; may herald development of end-organ
dysfunction if perfusion and oxygen delivery are nor restored
o Tachycardia: body’s attempt to increase CO
o Tachypnea: compensate for developing metabolic acidosis
o Hypotension (MAP <60 mmHg): circulatory failure
• Can confirm the presence of shock prior to return of labs
• Decreased oxygen delivery to the brain
• Early stage of shock: body will redirect blood
CNS: encephalopathy & flow to CBS to maintain adequate perfusion
confusion • Shock + altered mental status: usual
compensatory mechanisms have been
outstripped by magnitude of shock
• Urinary catheter can be placed for accurate
Renal: urine output hourly assessment
(oliguria) • Oliguria (<0.5 mL/kg/h) may indicate shock in
patients with normal baseline renal function
Skin: decreased capillary
• Signs of hypoperfusion
refill & cold clammy skin

34 | 8. SHOCK
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Diagnostic Testing • Optimizing the Circulation

• Aims o Fluids
o Assess extent of end-organ dysfunction ▪ Adequate intravascular access through large-bore
o Gain insight into the possible etiology of shock peripheral venous lines (16G or 18G)
• Blood Tests ▪ Fluid resuscitation should begin with isotonic crystalloid
BUN, creatinine, AST, ALT Extent of end-organ dysfunction • Amount & rate of infusion are determined by an estimate
States of hypovolemia or decreased of the hemodynamic abnormality
Urine electrolytes with FENa
effective circulating volume
• Administer fluid rapidly (over 5-20 minutes), in set
Elevated: biliary obstruction (source of
Alkaline phosphatase quantities of 500 or 1000 mL of normal saline, and
infection in distributive shock)
Elevated: primary cardiac problem with reassess the patient after each bolus
Cardiac enzymes myocyte damage related to ischemia, • Patients with a modest degree of hypovolemia usually
myocarditis, or a pulmonary embolism
require an initial 20-30 mL/kg of isotonic crystalloid
Complete blood count (CBC) Elevated WBC w/ left shift: infective process
Arterial blood gas (ABG) Acidosis and/or hypoxia Lactated Ringer’s For large fluid volumes to avoid hyperchloremic
Solution (LRS metabolic acidosis associated with NSS
o Undifferentiated shock: high index of suspicion for infection 0.9% normal saline Where hypochloremia can be predicted (GI losses
▪ Urinalysis & urine sediment: evaluate for pyuria solution (NSS) from vomiting; urinary excretion due to diuretics)
▪ Blood cultures, urine cultures, sputum cultures In hypovolemic shock due to ongoing hemorrhage, or
Packed RBCs
▪ Radiographic evaluation: seek sources of infection in hemoglobin <7 g/dL even without hemorrhage
suggested by history and PE Platelets & fresh In cases of massive transfusion to offset dilution of
frozen plasma (FFP) these components during volume replacement
o Serum Lactate: role in diagnosis, risk stratification, & treatment
▪ Assessment of volume status (adequacy of resuscitation)
▪ Hyperlactemia & lactic acidosis (hyperlactemia + pH <7.35)
• Can predict responsiveness to additional IVF by
▪ Lactate: product of anaerobic glucose metabolism Physical providing patient with an endogenous volume bolus
▪ Elevated lactate correlates with a worse outcome examination: • Semi-recumbent position at 45°, bed is placed in
▪ Serial lactate measurements in the evaluation of critically ill Passive Leg Raise trendelenburg (head horizontal & legs extend at 45°)
patients and their response to therapy (PLR) • Immediate (<1 min) assessment of changes in CO
(or pulse pressure variation as a surrogate)
• ECG • IVC diameter & IVC collapse, serial measurements
ECG Findings Condition Echocardiography
of LV function
Bradycardia/tachycardic arrhythmia Reduction in CO • Placement into central venous circulation & through
ST segment elevation Myocardial infarction right heart
S1 Q3 T3 pattern Pulmonary embolism • Direct measurement of CVP, pulmonary artery, and
Reduced voltage + electrical alternans Pericardial tamponade Pulmonary artery
pulmonary capillary wedge pressure (PCWP)
catheter (PAC)
• Echocardiography (transthoracic echocardiography/TTE) • PCWP: surrogate for LA pressure
o Help categorize shock; rapid and noninvasive • Used in mixed shock (distributive and cardiogenic)
or those with ongoing shock of unclear etiology
o 2D mode: ventricular size & wall thickness, LVEF, pericardial
o Vasopressors
tamponade, valve function (mitral valve rupture)
▪ If inadequate response to volume resuscitation or if
contraindicated to volume infusion
INITIAL TREATMENT OF SHOCK
▪ Most effective when the vascular space is “full” and least
Key Principles in the Treatment of Shock
effective when the vascular space is depleted
• Recognize shock early
▪ Improve perfusion pressure in the large vessels
• Assess for type of shock present
▪ Decrease capillary blood flow in certain tissue beds,
• Initiate therapy simultaneous with evaluation into etiology of shock especially GI tract and peripheral vasculature
• Restoration of oxygen delivery is the aim of therapy ▪ If multiple vasopressors are used, they should be simplified
• Identify shock etiologies requiring additional lifesaving interventions as soon as the best therapeutic agent is identified
▪ In addition to a vasopressor, an inotrope may be needed to
ABCDE Tenets of Shock Resuscitation directly increase CO by increasing contractility and SV
• Establishing the Airway ▪ Careful vasopressor infusion initially through a peripheral IV
o Best obtained through endotracheal intubation is unlikely to result in tissue injury and will improve the time
o Sedatives used to facilitate intubation may cause arterial to achieve hemodynamic stability
vasodilatation, venodilation, or myocardial suppression and may ▪ The use of vasopressors and inotropes must be tailored to
result in hypotension the primary physiologic disturbance
o Positive-pressure ventilation (PPV) reduces preload and CO Shock Vasopressor Description
o Sedative agents + PPV = hemodynamic collapse Norepinephrine • α1: vasoconstriction
o To avoid this unwanted situation, initiate volume resuscitation (first-choice) • β1: positive inotropy & chronotropy
and vasoactive agents before intubation and PPV • Higher doses: similar to norepinephrine
• Lower doses: β effects predominate
• Controlling the Work of Breathing Distributive
Epinephrine • Associated with tachyarrhythmia,
o Required when significant work of breathing accompanies shock shock: aim myocardial ischemia, decreased
▪ Respiratory muscles are significant consumers of oxygen is to increase splanchnic blood flow, pulmonary
during shock and contribute to lactate production SVR hypertension, acidosis
o Mechanical ventilation & sedation • Acts on vasopressin receptor to
reverse vasodilation & redistribute flow
▪ Allows adequate oxygenation (maintain SpO2 92-95%) Vasopressin
to splanchnic circulation
▪ Improvement of hypercapnia • 2nd line for hypotension in septic shock
▪ Assisted, controlled, synchronized ventilation • Synthetic catecholamine with primarily
o Consider the patient’s compensatory minute ventilation prior to β-mediated effects & minimal α
adrenergic effects
intubation to ensure appropriate initial settings are selected Cardiogenic Dobutamine
• β1: increased inotropy
o After a patient is placed on mechanical ventilation, obtain ABG shock (first line agent)
• β2: vasodilation with ↓ afterload
to evaluate acid-base status, oxygenation, and ventilation • Can be used with norepinephrine in
o Neuromuscular blocking agents mixed distributive & cardiogenic shock
▪ Further decrease respiratory muscle oxygen consumption
▪ Preserve oxygen delivery to vital organs, especially if
patients are severely hypoxemic due to ARDS

8. SHOCK | 35
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

• Ensuring Adequate Oxygen Delivery

o Hyperadrenergic state: from compensatory response to shock,
physiologic, stress, pain, cold treatment rooms, anxiety
o Pain: further suppresses myocardial function, impairing oxygen
delivery, and increasing consumption
o Providing analgesia, muscle relaxation, warm covering,
anxiolytics, and even paralytic agents, when appropriate,
decreases this inappropriate systemic oxygen consumption
o Once BP is stabilized through optimization of preload and
afterload, oxygen delivery can be assessed and further
manipulated
▪ Restore arterial oxygen saturation to ≥91%
▪ In shock states, consider a transfusion of packed RBCs to
maintain hemoglobin ≥7 g/dL
• End Points of Resuscitation
o Goal of resuscitation: use hemodynamic and physiologic
values to guide therapy in order to maximize survival and
minimize morbidity
o No therapeutic end point is universally effective
o Hypotension at presentation is associated with poor outcomes
o Noninvasive parameters (BP, HR, UO) may underestimate
degree of remaining hypoperfusion and oxygen debt
o Goal-directed approach during ER resuscitation of septic shock
▪ Mean arterial pressure (MAP) >65 mmHg
▪ CVP 8-12 mmHg
▪ Mixed venous oxygen saturation (SCVO2) >70%
▪ Urine output >0.5 mL/kg/h
o Source control (infection, hemorrhage, other state of shock) is
essential in the initial stages of management
o If shock or hypotension persists, reassessment at the patient’s
bedside is essential while considering important issues

Specific Causes of Shock Requiring Tailored Intervention

Type of Shock Cause Treatment
PROGNOSIS
Removal of inciting allergen,
administration of epinephrine, • Clinical variables associated with poor outcome
Anaphylaxis
Distributive vascular support with IV resuscitation o Severity of shock
shock and vasopressors o Temporal duration
Adrenal Replacement with IV stress dose o Underlying cause
insufficiency steroids
Advanced cardiac life support o Preexisting vital organ dysfunction
Arrhythmia (ACLS) algorithms or placement of o Reversibility
Cardiogenic artificial pacemaker • Early recognition, intervention, source control, and smooth care
shock Acute ischemic Revascularization and temporary transitions optimize outcomes
events mechanical supportive measures
Valve dysfunction Emergency surgery
Hypovolemic Trauma Surgical intervention
shock GI source of blood Endoscopic or interventional
(hemorrhage) loss radiology
Tension
Immediate decompression
pneumothorax
Proximal
Obstructive Thrombolytic therapy or surgical
pulmonary
shock removal of the clot
embolism
Dissection of References:
Surgical intervention • Harrison’s Principles of Internal Medicine, 20 th edition (2018)
ascending aorta
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harsh Mohan Textbook of Pathology, 7 th edition (2015)

36 | 8. SHOCK

9. ACUTE ABDOMEN
PATHOPHYSIOLOGY
• Visceral Pain
o Obstruction, ischemia, or inflammation can cause stretching of
unmyelinated fibers (innervate the walls or capsules of organs)
o Often described as “crampy, dull, or achy”
o Can be either steady or intermittent (colicky)
o Localized by the sensory cortex to an approximate spinal cord
level determined by the embryologic origin of the organ involved
▪ Visceral afferent nerves follow a segmental distribution
Origin Involved Organs Location of Pain
Stomach, 1st/2nd parts of duodenum,
Foregut Epigastric area
liver, gallbladder, pancreas
3rd/4th parts of duodenum, jejunum,
Midgut ileum, cecum, appendix, ascending Periumbilical area
colon, first 2/3 of transverse colon
Last 1/3 of transverse colon,
Hindgut descending colon, sigmoid, rectum, Suprapubic area
intraperitoneal GU organs
o Intraperitoneal visceral pain tends to be felt in the midline
▪ Intraperitoneal organs are bilaterally innervated
▪ Stimuli are sent to both sides of the spinal cord
• Parietal (Somatic) Pain
o Caused by irritation of myelinated fibers (innervate parietal
peritoneum, usually portion covering anterior abdominal wall)
o Localized to dermatome superficial to the site of painful stimulus
▪ Parietal afferent signals: from a specific area of peritoneum
o As underlying disease process evolves, symptoms of visceral
pain give way to signs of parietal pain (tenderness & guarding)
o As localized peritonitis develops: rigidity & rebound tenderness
▪ Patients with peritonitis generally prefer to remain immobile
• Referred Pain
o Felt at a location distant from the diseased organ
o Patterns are also based on developmental embryology
o Usually perceived on the same side as the involved organ (not
mediated by fibers that provide bilateral innervation to the cord)
o Felt in midline only if pathologic process is also located midline
CLINICAL FEATURES
Clinical Risk
• Patient Acuity: Is This Patient Critically Ill?
o Critically ill patients need immediate stabilization
o Markers of high acuity
▪ Extremes of age
▪ Severe pain of rapid onset
▪ Abnormal vital signs
▪ Dehydration
▪ Visceral involvement (e.g., pallor diaphoresis, vomiting)
o The intensity of abdominal pain may bear no relationship to the
severity of illness
o Serious illness may be present even if vital signs are normal,
particularly in high-risk groups (elderly, immunocompromised)
o Shock that develops rapidly after the onset of acute abdominal
pain is usually the consequence of intra-abdominal hemorrhage
▪ SBP does not drop until blood loss reaches 30-40%
▪ Tachycardia is a useful parameter for assessment of volume
depletion, but its absence does not exclude blood/fluid loss
o If pulse & BP are normal, but there is reason to suspect
intravascular volume depletion, obtain orthostatic vital signs
▪ Increase in pulse rate of 30 bpm after standing for 1 minute
(or near-syncope with lesser increase): 1 L blood loss or
equivalent (20% blood loss; ~3 L normal saline)
▪ The presence of orthostatic tachycardia is useful, but its
absence does not exclude severe bleeding
▪ Orthostatic hypotension is a later finding (failure of
sympathetic reflex tachycardia to maintain cardiac output)
▪ Threshold of 20 points of pulse change NOT applicable to:
• Patients on medications such as β-blockers
• Diabetic patients (may have autonomic neuropathy)
• Elderly (effects of aging on cardiac conduction system)
▪ Should NOT be performed in hypotensive patients
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
o Tachypnea may indicate a cardiopulmonary process, metabolic
acidosis, anxiety, or pain
o Temperature: neither sensitive/specific for disease process or
patient condition (fever cannot distinguish surgical from medical)
o Resuscitation of the critically ill patient with abdominal pain
▪ Cardiac monitor
▪ Oxygen (2-4 L/min via nasal cannula or mask)
▪ Large-bore IV access
▪ Isotonic fluid bolus (for age, weight, & cardiovascular status)
▪ Blood samples should be drawn at the time for IV insertion
• Electrolytes
• BUN and creatinine
• CBC with platelets
• Clotting studies
• Type and antigen screen of blood
▪ Order cross-matched blood if hemorrhage is suspected or if
urgent transfusion is anticipated
▪ Bedside US: identify emergent causes of abdominal pain in
the patient with hemodynamic collapse (abdominal aortic
aneurysm & intra-abdominal hemorrhage)
• Hemodynamic status: evaluation of heart function, IVC
size & respiratory response to guide resuscitative efforts
• Risk Factors: Are There Special Conditions or Risk Factors
That Affect Clinical Risk or Mask the Disease Process?
o Identify pertinent information
▪ Past medical illness: diabetes, heart disease, hypertension,
liver disease, renal disease, HIV status, STDs
▪ Previous abdominal surgeries, pregnancies, and menstrual
history: deliveries, abortions, ectopics
▪ Medications: steroids, immune suppressants, acetylsalicylic
acid/NSAIDs, antibiotics, laxatives, narcotics, fertility
agents, IUDs, chemotherapeutic agents
▪ Allergies
▪ Any recent trauma
o Previous episodes: abdominal pain, diagnostics, treatments
o Review previous medical records
o Obtain a social history that includes
▪ Habits: tobacco, alcohol, other drug use
▪ Occupation
▪ Possible toxic exposures
▪ Living circumstances: homeless, dwelling heated, running
water, living alone, family members ill with similar symptoms
o A number of conditions camouflage critical illness in
patients with acute abdominal pain. High-risk groups include:
▪ Patients with cognitive impairment secondary to dementia,
intoxication, psychosis, mental retardation, or autism
▪ Patients who cannot communicate effectively because of
aphasia or language barriers
▪ Patients in whom physical or laboratory findings may be
minimal (elderly) or obscured (spinal cord injury)
▪ Asplenic patients
▪ Neutropenic patients
▪ Transplant patients
▪ Patients whose immune systems are impaired by illness:
HIV, chronic renal disease, diabetes, cirrhosis,
hemoglobinopathy, malnutrition, chronic malignancy,
autoimmune disease, mycobacterial infection
▪ Patients taking immune-suppressive or immune-modulating
medications: steroids, calcineurin inhibitors, TNF inhibitors,
antimetabolic agents, monoclonal & polyclonal antibodies,
chemotherapeutic agents
o In general, patients with mild to moderate immune dysfunction
have delayed or atypical presentations of common diseases
▪ Patients with severe immune dysfunction are more likely to
present with opportunistic infections
▪ CD4 count: most important measure of immune
competency in patients with AIDS
▪ CD4 counts >200/mm3 are much less likely to have
opportunistic infections
9. ACUTE ABDOMEN | 37
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

PHYSICAL EXAMINATION APPROACH TO EVALUATION

• Obtain a clear description of the pain itself (OP2QRST2) • One common approach to the evaluation of acute abdominal pain is
o Onset to use the location of the pain (diffuse, RUQ, RLQ, LUQ, LLQ) to
o Provocative/Palliative factors guide the generation of a differential diagnosis
o Quality
o Radiation
o Associated Symptoms
o Timing
o What the patient has taken for the pain
• Note the patient’s skin (color, temperature, turgor, perfusion status)
• Perform a targeted heart and lung examination

Abdominal Examination
• Inspection
Distention ascites, ileus, obstruction, volvulus
Obvious masses hernia, tumor, aneurysm, distended bladder
Surgical scars adhesions
Ecchymoses trauma, bleeding diathesis
Stigmata of liver disease spider angiomata, caput medusa
• Auscultation of Bowel Sounds (nonspecific diagnostic signs)
Decreased ileus, mesenteric infarction, narcotic use, peritonitis
Hyperactive small bowel obstruction
• Percussion
Can be estimated by the presence of percussion dullness in
Liver size
midclavicular line, except in cases of severe bowel distension
Fluid wave May suggest ascites
Tympany May suggest dilated bowel loops
• Palpation
o Vast majority of clinical information is acquired through gentle
palpation using middle 3 fingers, saving painful area for last
o Voluntary guarding: contraction of the abdominal musculature
in anticipation of or in response to palpation
▪ Can be diminished by asking patients to flex the knees
• If still guarded, place hand over the patient’s, and patient
is asked to use own hand to palpate
• Distracting the patient with conversation may divert • Alternatively, abdominal crises may be grouped according to
attention from the examination presenting symptomatology: pain, vomiting, abdominal
o Optimally, the patient’s tenderness will be confined to 1 of the 4 distention, muscular rigidity, and/or shock
traditional abdominal quadrants (RUQ, RLQ, LUQ, LLQ), and o These symptoms and etiologic groupings are a guideline and
pain location can be used to generate a differential diagnosis are not intended to be a rule
Symptoms Associated Abdominal Diseases
▪ Often, this is not the case, and one finds more diffuse
• Acute pancreatitis
tenderness involving ≥2 of the 4 abdominal quadrants • Diabetic gastric paresis
o Peritoneal irritation is suggested by: Pain/vomiting/±rigidity
• Diabetic ketoacidosis
▪ Rigidity: involuntary guarding or reflex spasm of abdominal • Incarcerated hernia
muscles • Bowel obstruction
Pain/vomiting/distention
▪ Referred tenderness: pain referred to the point of maximum • Cecal volvulus
tenderness when palpating an adjacent quadrant • Acute diverticulitis
• Adnexal torsion
o Rebound tenderness, often regarded as the sine qua non for Pain (± vomiting) • Mesenteric ischemia
peritonitis, has several limitations: • Myocardial ischemia
▪ In peritonitis, rigidity, referred tenderness, & pain with • Testicular torsion
coughing usually provides sufficient diagnostic confirmation • Abdominal sepsis
that little additional information is gained by eliciting rebound • Aortic dissection
• Hemorrhagic pancreatitis
▪ >1/3 surgically proven appendicitis: NO rebound tenderness
Pain/shock • Leaking/ruptured abdominal aortic aneurysm
▪ False positives: perhaps due to nonspecific startle response • Mesenteric ischemia (late)
o Evaluate the abdominal aorta, particularly in patients >50 years • Myocardial ischemia
of age with acute abdominal, flank, or low back pain • Ruptured ectopic pregnancy
▪ Palpation cannot exclude abdominal aortic aneurysm • Perforated appendix
▪ Presence/absence of femoral pulses is generally not helpful • Perforated diverticulum
Pain/shock/rigidity • Perforated ulcer
in the clinical diagnosis of abdominal aortic aneurysm
• Ruptured esophagus
o Pelvic examination: lower abdominal pain in women of • Splenic rupture
reproductive age who have not had a total hysterectomy Distention (± pain) • Elderly with bowel obstruction/volvulus
▪ Peritoneal signs, cervical motion tenderness, & unilateral or • Although the location of the patient’s pain and the grouping of
bilateral abdominal and/or pelvic tenderness suggests symptoms can both help to differentiate among known diseases,
pelvic infection, or ectopic gestation in pregnant women clinical suspicion and an understanding of the individual is
o Hernia, testicular, and prostate examinations in males paramount, because the causes of acute abdominal pain vary
▪ Disorders of these can cause lower abdominal pain considerably with patient demographics
o Rectal examination does not increase diagnostic accuracy o Older adults: biliary disease, diverticulitis, and bowel obstruction
beyond what has already been obtained by other components o Younger adults: appendicitis
of the physical examination o In the words of Sir William Osler, it is important to know “what
▪ Main value: detection of grossly bloody, maroon, or sort of patient has the disease.”
melanotic stool

38 | 9. ACUTE ADBOMEN
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

SYMPTOM TREATMENT AND FURTHER CLINICAL DIAGNOSIS Diagnostic Imaging

• Provide symptomatic relief • Does not take the place of a conscientious history & physical exam
o Opioid analgesia relieves pain and will not obscure abdominal • Not all patients with abdominal pain require imaging
findings, delay diagnosis, or increase morbidity/mortality • If the clinical impression suggests that the need for surgery is
o DO NOT withhold in acute undifferentiated abdominal pain obvious, it is not necessary to wait for diagnostic imaging before
o The information on the safety of opioids cannot be extrapolated surgical consultation
to NSAIDs (parenteral ketorolac) because NSAIDs are not pure • Plain Radiographs
analgesics and can mask early peritoneal inflammation o Abdominal series: upright abdomen, upright chest, supine film
• Administer antiemetics as needed ▪ Include the inguinal region to identify incarcerated hernia
o Ondansetron & metoclopramide reduce postoperative o Radiographic evidence of small bowel obstruction may be seen
nausea and vomiting (both drugs had equivalent effects) 6-12 hours before symptoms develop
o Ondansetron 4 mg or 8 mg (0.45 mg/kg total daily) to a ▪ Signs may be absent in up to ½ of patients with developing
maximum of 32 mg daily (headache is a reported side effect) small bowel obstruction
o IV metoclopramide 10 mg given slowly to minimize o Upright chest film: better to detect free air than abdominal film
extrapyramidal side effects ▪ Sensitivity for small amounts of free air is only about 30%
▪ IV diphenhydramine 25-50 mg: dystonia prophylaxis o Plain abdominal radiographs: screening for obstruction,
▪ Patients with akathisia or dystonic reactions from sigmoid volvulus, or severe constipation
metoclopramide cannot tolerate any other agents of the • Ultrasound (LGBPS or KUBP)
same class and should be given ondansetron o Visualize the gallbladder, pancreas, kidneys and ureters, urinary
▪ Such reactions are extremely rare from ondansetron bladder volume, and aortic dimensions
• Consider placement of nasogastric and urinary catheters ▪ Not useful for diagnosis of small or large bowel disorders
o Nasogastric aspirate may confirm upper GI bleeding o Detection of free air or appendicitis is operator dependent and
o Nasogastric suction: used to decompress bowel obstruction limited by patient obesity and bowel gas
o Urinary catheter will relieve bladder obstruction, and hourly o Preferred modality for the evaluation of biliary tract disease
urine output helps to gauge renal perfusion ▪ Cholescintigraphy: if ultrasound is normal when acute
cholecystitis or biliary dyskinesia is strongly suspected
Laboratory Testing • POCUS (Point-of-Care Ultrasound)
• Does not take the place of a conscientious history & physical exam o Abdominal resuscitative POCUS involves rapid assessment for
o No evidence to support usefulness of “routine abdominal labs” free intra-abdominal fluid (FAST), abdominal aortic aneurysm,
• Information obtained by laboratory testing should help refine the and cardiac/inferior vena cava status
differential diagnosis or alter the plan of treatment o Abdominal diagnostic POCUS studies are focused urinary tract
• Suggested laboratory studies for goal-directed clinical testing and biliary evaluation
Laboratory Test Clinical Suspicion • Abdominal-Pelvic CT Scanning
Amylase (if lipase is not available) • Pancreatitis o Sensitive & specific for many causes of abdominal pain
Lipase • Pancreatitis o Disadvantages:
β-human chorionic gonadotropin • Pregnancy
▪ Delays in surgical management
(serum/urine; qualitative/quantitative) • Ectopic or molar pregnancy
• GI bleeding ▪ Increase in ER times if oral contrast is used
Coagulation studies (prothrombin ▪ Radiation dose: 10 msV (10x plain abdominal radiography)
• End-stage liver disease
time/partial thromboplastin time)
• Coagulopathy o Most studies have focused on the CT diagnosis of appendicitis
• Dehydration o Options: noncontrast studies, or PO, PR, and/or IV contrast
Electrolytes
• Endocrine or metabolic disorder o Noncontrast abdominopelvic CT
• Diabetic ketoacidosis
Glucose ▪ 97% specificity for acute appendicitis, except low BMI (<25)
• Pancreatitis
• Cervicitis/urethritis
▪ Preferred imaging modality for kidney & ureteral stones
Gonococcal/chlamydia testing o Oral contrast CT
• Pelvic inflammatory disease
Hemoglobin • GI bleeding ▪ Imaging modality of choice in many institutions for
• Mesenteric ischemia suspected GI abscess, perforation, or fistula
Lactate
• Sepsis ▪ Factors that affect the usefulness of oral contrast:
• Cholecystitis • Patient vomiting
Liver function tests • Cholelithiasis
• Hepatitis • Type and volume of oral contrast administered
Platelets • GI bleeding • Transit time to distal colon (variable, several hours)
• Dehydration • Gastric emptying time (delayed induction of anesthesia)
Renal function tests • Renal insufficiency • Inadequate bowel opacification
• Acute renal failure
• Prolonged ER times
• Urinary tract infection
Urinalysis • Pyelonephritis o Rectal contrast CT
• Nephrolithiasis ▪ Identify distal large bowel obstruction
ECG • Myocardial ischemia or infarction o IV contrast CT
• Obtain an electrocardiogram for patients with upper abdominal ▪ Superior visualization of bowel mucosa, visceral organs,
pain, especially in elderly patients and vascular structures
• Limitations of laboratory studies ▪ Can identify small and large bowel obstruction and the
o Complete blood count (CBC) transition point
▪ Does not offer sufficiently powerful likelihood ratios to revise ▪ Initial test of choice for suspected abdominal aortic
disease probability aneurysm rupture or mesenteric ischemia
▪ Take note only of high threshold abnormalities (e.g., very ▪ Risks of IV contrast: nephrotoxicity, allergic reactions
elevated WBC >20,000/mm3) • Patients should be hydrated with 1-2 L normal saline if
▪ Do not draw any reassurance from a “normal” WBC there are no contraindications to vigorous hydration
▪ A single WBC cannot exclude serious or surgical disease ▪ Contraindications:
o Serum lactate • Patients with history of allergy to IV contrast or to iodine
▪ Up to 25% of patients with acute mesenteric ischemia have • Serum creatinine >1.5 or GFR <60, EXCEPT in life-
a normal serum lactate on initial presentation threatening situations

9. ACUTE ABDOMEN | 39
 Common Diagnoses for Acute Abdominal Pain in Adults
Diagnosis Epidemiology
Early: periumbilical
Peak age:
Appendicitis adolescence and
young adulthood trimester pregnancy:
F>>M before age 60,
Biliary colic Hispanic > white >
black
Bladder outlet Benign prostatic
obstruction hypertrophy
History of previous
Bowel obstruction
abdominal surgery
Most common
surgical cause of
Cholecystitis
abdominal pain in
elderly
M > F before age 40 Sigmoid (85%): LLQ
Diverticulitis
Incidence ↑ with age Cecal/Meckel: RLQ
Epiploic appendagitis Middle age; M > F
Mesenteric arterial
Atrial fibrillation
occlusion
Mesenteric venous Hypercoagulable
thrombosis states, liver disease
Mesenteric ischemia Critically ill patients;
(nonocclusive) vasoactive drugs
Myocardial ischemia - Upper midline
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
M>F
Pancreatitis Risks: alcohol; biliary
disease; drugs; ERCP
Sexually transmitted
PID diseases; prior PID;
multiple partners
Peak age: 50s; M > F;
chronic aspirin or
Peptic ulcer disease
NSAIDs; smoking;
alcohol; H. pylori
Perforated viscus - Any
Ovarian torsion - RLQ or LLQ
Average age: 30-40;
Renal/ureteral colic white > black; family
history of stones
Previous ectopic; PID;
Ruptured ectopic infertility treatment;
pregnancy IUD <1 y; tubal
surgery
Older; male;
Ruptured/leaking
atherosclerotic CV
abdominal aortic Mid-abdomen or flank
disease; smoker; (+)
aneurysm
family history
Unilateral or bilateral
Tubo-ovarian abscess PID lower abdominal or
Typical Location Typical Radiation Typical Quality Helpful Cautions Laboratory Imaging Complications
RLQ pain; migratory
Anorexia, vomiting, No WBC count or
Late: RLQ pain from CT preferred in adults
Initially dull, becomes fever, and ↑ WBC CRP level can
If retrocecal or 3rd - periumbilical area; & nonpregnant Perforation, abscess
severe have poor individual exclude or confirm the
pain before vomiting; women
sensitivities diagnosis
may be RUQ rigidity
Initially colicky,
Bloating and
Right subscapular becomes continuous; Suspect common bile
RUQ > epigastric dyspepsia are not - US Cholecystitis
area colic typically resolves duct stone if ↑ bilirubin
related to gallstones
<6 h
Suprapubic - - - - - Bedside US -
Plain films: 77% Sn Incarceration,
Diffuse - Colicky Vomiting, distention - -
CT: 93% Sn strangulation
(+) Murphy sign
Up to 90% afebrile No single test can
increases likelihood US: 81% Sn Common bile duct
↑ WBC: 63% Sn, exclude diagnosis
Right subscapular of cholecystitis (odds Hepatobiliary obstruction;
RUQ > epigastric Continuous 57% Sp ↑ bilirubin/AST/ALP
area ratio 2.3-2.8); iminodiacetic acid ascending
Cholangitis: each 70% Sn, 42%
jaundice suggests (HIDA) scan: 96% Sn cholangitis; gangrene
↑ WBC 80% Sn Sp
obstruction
50% report previous Temperature may be
CT: 93-100% Sn, Perforation; abscess;
- - episode of similar normal WBC may be normal
100% Sp fistula; obstruction
pain 25% (+) FOBT
Fever unusual;
In general, patients
nausea & vomiting
LLQ - - are not systemically - CT -
infrequent; diarrhea
ill
25%
Pain out of proportion
Lactate 86% Sn, not Selective CT
Any - Severe to physical findings; Atrial fibrillation Metabolic acidosis
specific; ↑ WBC: 90% angiography: 94% Sn
nausea & vomiting
Most commonly:
Contrast-enhanced
generalized or - - - - - -
CT
epigastric
- - - - - - Angiography -
Troponin sensitivity &
- Steady, dull Abnormal ECG ECG may be normal specificity vary based - -
on available assay
Contrast-enhanced
Hemorrhage;
Nausea and vomiting May have low-grade Lipase: 90% Sn CT is the gold
Epigastric Back Severe, constant pseudocyst; ARDS;
common fever first 24 h standard; US may
sepsis
show edema
Tubo-ovarian
abscess;
Vaginal discharge; Elevated WBC not
Fever not necessary perihepatitis;
RLQ and/or LLQ - - dyspareunia; cervical necessary for -
for diagnosis infertility; ectopic
motion tenderness diagnosis
pregnancy; chronic
pain
Nonulcer dyspepsia
more likely if: age
Epigastric - Severe, persistent Vomiting, tachycardia <40, no weight loss, - - Perforation; bleeding
no night pain, no
vomiting
CT excellent
- Severe - - - Plain radiography has -
clinical utility
Sudden onset, Ovarian salvage
Pelvic US with
Back, flank, or groin severe, sharp; may Adnexal mass - - decreases with delay
Doppler flow
have nausea/vomiting in diagnosis
Severe; colicky; 85-90% have
Ipsilateral
Right or left flank nausea and vomiting hematuria; only 30% - Urinalysis CT, US Obstruction; infection
groin/scrotum
40 | 9. ACUTE ADBOMEN
common have gross hematuria
Sudden onset; severe Pelvic exam may be
RUQ or LLQ - Pelvic mass Pregnancy test Transvaginal US Shock
pain normal
Only 50% are
hypotensive at
Severe; sudden Pulsatile mass Bedside US: 100%
Back, groin, or thigh presentation. - Shock
onset; constant detected: 22-96% Sn Sn
Normal pulses do not
exclude diagnosis
Leukocytosis may be Rupture, peritonitis,
- - - Fever may be absent Transvaginal US
absent shock
pelvic pain

TREATMENT
• Antibiotics
o Indicated for suspected abdominal sepsis and peritonitis
o Endogenous gut flora: abdominal infections in the GI or GU tract
o Intra-abdominal nongynecologic infections: coverage
minimally target anaerobes & facultative aerobic gram negatives
▪ EXCEPT in spontaneous (primary) bacterial peritonitis:
provide additional coverage for gram-positive aerobes (e.g.,
Pneumococcus)
o High-risk community-acquired (septic, elderly, comorbid
conditions, immunosuppressed, delayed presentation, known
resistant organism) and healthcare-associated intra-abdominal
infections require broader-spectrum antibiotic coverage
o Treatment for PID requires different antibiotic combinations
DISPOSITION AND FOLLOW-UP
• Surgical consultation: required once a surgical diagnosis is made
• Otherwise, consider hospital admission or observation for:
o High-risk patients: elderly, immunocompromised, unable to
communicate, cognitively impaired
o Patients who appear ill
o Have intractable pain or vomiting
o Unable to comply with discharge or follow-up instructions
o Lack appropriate social support
• Patients with an unclear diagnosis at discharge, even if the CT scan
is “negative” (or for whom response to treatment is a concern)
should be asked to return to the ER or their primary care physician
for reevaluation within 12 hours
• Discharge instructions
o Diet: clear liquids only, push fluids, no fatty food, no acidic foods
o Medication: antacids, analgesics, avoid narcotics
• Patient and family should understand that the diagnosis is uncertain,
and they should know which symptoms warrant a return to the ER
(increased/different pain, fever, vomiting, syncope, bleeding)
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
SPECIAL POPULATIONS
• Women
o Common gynecologic causes of lower abdominal/pelvic pain
▪ Adnexal torsion (potential threat to life)
▪ Endometriosis
▪ Endometritis/salpingitis (PID) (potential threat to life)
▪ Myoma (degenerating)
▪ Ruptured ectopic pregnancy (potential threat to life)
▪ Ruptured ovarian cyst (potential threat to life)
▪ Tubo-ovarian abscess (potential threat to life)
▪ Adnexal/uterine masses
o Hemorrhage from an ectopic gestation
▪ Leading cause of pregnancy-related maternal death in the
1st trimester, despite improved diagnostic and treatment
modalities
o Obtain a qualitative/quantitative urine/serum pregnancy test
in women of childbearing age with acute abdominal pain who
have not had a hysterectomy
▪ If positive: transvaginal sonography
• Gestational sac visible if β-hCG >1,5000 mIU/L
o Suspect ectopic pregnancy in a woman of reproductive age
with hemodynamic collapse
▪ RLQ pain in a woman with an appendix is a common
diagnostic dilemma
o Guides for further imaging
▪ Results of pelvic examination
▪ Patient risk factors for gynecologic vs GI disease
▪ Clinician’s best estimate of pretest probability for
gynecologic vs Gi disease
• If pretest probability favors gynecologic disease, a
transvaginal ultrasound would be the next step
• If pretest probability favors GI disease/appendicitis,
abdominopelvic CT scanning would be the next step
• Elderly patients
o Symptoms may be mild, vague, or underreported
o Presentations may be late and atypical
o Among those >80 years old, mortality almost doubles if
diagnosis is incorrect at the time of admission
o Poor hearing, decreased vision, and impaired cognition may
affect the ability to give an adequate history
o Surgical complications are more common
▪ Perforated viscus
▪ Gangrenous gallbladder
▪ Necrotizing pancreatitis
▪ Strangulated hernia
▪ Infarcted bowel
o Fever is not a reliable marker for serious disease
▪ May be hypothermic in serious abdominal infection
o <20% of elderly patients with perforated appendicitis have a
“classic” presentation
o WBC has a low predictive value for surgical disease in elderly
o Most common surgical entity in elderly with abdominal pain
▪ Cholecystitis
▪ Small bowel obstruction
▪ Perforated viscus
▪ Appendicitis
▪ Large bowel obstruction
o Viral gastroenteritis is uncommon
o Diarrhea occurs in 31-40% of patients with mesenteric ischemia
o Any acute abdominal pain is important in an elderly patient
▪ No single test can distinguish among patients who should
be admitted and patients who can be safely discharged
o A liberal imaging/admission/observation policy is strongly
advocated when diagnosis is in doubt or follow-up is uncertain
Reference:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 20th edition (2017)
9. ACUTE ABDOMEN | 41
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9. ACUTE ABDOMEN | 43
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44 | 9. ACUTE ADBOMEN

10. ACUTE CHOLANGITIS
• The most serious and lethal complication of gallstones
• Pus under pressure in the bile ducts leads to rapid spread of bacteria
via the liver into the blood, with resulting septicemia
• Diagnosis of cholangitis is often problematic (especially in the critical
early phase of the disease) because clinical features that point to
the biliary tract as the source of sepsis are often absent
ETIOLOGY
• Bile duct obstruction is necessary but not a sufficient cause
o Stone embedded in the bile duct with resulting bile stasis (85%)
o Neoplasms (15% of bile duct obstruction)
▪ Malignant obstruction is more often complete and less
commonly permits reflux of bacteria from duodenal contents
into the bile ducts
o Biliary strictures: in post-traumatic bile duct strictures
o Parasitic infections
o Congenital abnormalities of the bile ducts
• Bacterial species most commonly cultured from the bile:
o Escherichia coli
o Klebsiella
o Pseudomonas
o Proteus
o Enterococci
o Anaerobes (Bacteroides fragilis & Clostridium perfringens) in
about 15% of appropriately cultured bile specimens; usually
accompany aerobes, especially E. coli
PATHOPHYSIOLOGY
• A stone in the bile duct causing bile stasis
• Bacterial superinfection of stagnant bile
o Most likely to be result when a bile duct that already contains
bacteria becomes obstructed
o Most patients with choledocholithiasis and stricture
o Few patients with neoplastic obstruction
• Early bacteremia
o Shaking chills & fever of cholangitis are due to bacteremia from
bile duct organisms
o The degree of regurgitation of bacteria from bile into hepatic
venous blood is directly proportional to the biliary pressure and,
hence, the degree of obstruction
o Decompression alone often effectively treats the illness
SYMPTOMS
• Charcot’s triad is present in 70% of patients (hallmark)
o Pain (RUQ): mild & transient; often accompanied by chills
o Jaundice
o Fever
• Older adult patients: may present solely with mental confusion,
lethargy, and delirium and may suggest sepsis
• Reynold’s pentad occur in severe suppurative cholangitis
o Charcot’s triad + altered mental status + hypotension
PHYSICAL FINDINGS
• Fever (95%): usually >39°C
• RUQ tenderness (90%)
• Jaundice (80%)
• Peritoneal signs (15%)
• Hypotension and mental confusion (forming the Reynolds’ pentad)
coexist in 15% and suggest Gram-negative sepsis
• In overlooked cases of severe cholangitis, intrahepatic abscess may
manifest as a late complication
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
LABORATORY FINDINGS
• Leukocytosis (80%)
o Remainder may have a normal WBC ± band forms
• Serum bilirubin level >2 mg/dL (80%)
• Serum ALP is usually elevated
• Blood cultures are usually positive for enteric organisms, especially
during chills or a fever spike
o The organism found in the blood is invariably the same as that
found in the bile
o 2 organisms are grown in cultures from half of patients
DIAGNOSTIC STUDIES
• Ultrasound for choledocholithiasis
o Dilated bile duct (75%)
o Stones in the bile duct (50%)
o Normal findings do not exclude choledocholithiasis in a patient
who presents with cholangitis
• Abdominal CT
o Excludes gallstone complications (acute pancreatitis, abscess)
o Standard abdominal CT not capable of excluding bile duct stone
• ERCP
o Definitive test for diagnosis of bile duct stones and cholangitis
o The ability of ERCP to establish drainage of infected bile under
pressure can be lifesaving
• Percutaneous transhepatic cholangiography
o If ERCP is unsuccessful
TREATMENT
• Emergency ERCP with stone removal or at least biliary
decompression
• Antibiotics to cover Gram-negative and possibly anaerobic
organisms and Enterococcus spp.
o Mild cases: initial therapy with a single drug is usually sufficient
▪ Cefoxitin 2 g IV every 6-8 hours
o Severe cases: more intensive therapy is indicated
▪ Gentamicin, ampicillin, and metronidazole
▪ Broad-spectrum agent such as piperacillin-tazobactam
3.375 g IV every 6 hours
▪ If resistant organisms suspected: meropenem 1 g IV q8h
o Patient’s condition should improve within 6-12 hours, and in
most cases, the infection comes under control within 2-3 days
▪ Defervescence
▪ Relief of discomfort
▪ Decline in WBC count
▪ Definitive therapy can be planned on an elective basis
o If after 6-12 hours of careful observation, clinical status declines
(worsening fever, pain, mental confusion, hypotension), the bile
duct must be decompressed immediately
▪ If available, ERCP with stone extraction, or at least
decompression of the bile duct with an intrabiliary stent, is
the treatment of choice
• Subsequent cholecystectomy
PROGNOSIS
• A high mortality rate if unrecognized, with death from septicemia
• Emergency decompression of the bile duct (usually by ERCP)
improves survival dramatically
Reference:
• Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 10th edition (2016)
• Tokyo Guidelines 2018 - Diagnostic Criteria and Severity Grading Acute Cholangitis
• Tokyo Guidelines 2018 - Initial Management of Acute Biliary Infection and Flowchart for
Acute Cholangitis
• Tokyo Guidelines 2018 - Antimicrobial Therapy for Acute Cholangitis and Cholecystitis
10. ACUTE CHOLANGITIS | 45
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10. ACUTE CHOLANGITIS | 47

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
11. GASTROINTESTINAL BLEEDING
Overt Gastrointestinal Bleeding
• Hematemesis: vomitus of red blood or “coffee-grounds” material
• Melena: black, tarry stool
• Hematochezia: passage of red or maroon blood from the rectum
Occult Gastrointestinal Bleeding
• Symptoms of blood loss or anemia: lightheadedness, syncope,
angina, dyspnea
• Iron deficiency anemia or positive FOBT
EPIDEMIOLOGY
• Upper Gastrointestinal Bleeding
o Difference in prevalence between countries is attributable to:
▪ Variations in Helicobacter pylori rates
▪ Socioeconomic conditions
▪ Prescription of ulcer-healing & ulcer-promoting medications
o Factors associated with increased morbidity and mortality
▪ Increasing age
▪ Coexistent organ system disease
▪ Recurrent hemorrhage
• Lower Gastrointestinal Bleeding
o Occurs more often than UGIB (incidence: 109 per 100,000/year)
o UGI bleeds: most common source for all causes of blood in LGI
▪ Blood from upper GI tract down to lower GI tract
o Most common causes of lower GI bleeding
▪ Diverticular disease
▪ Colitis
▪ Hemorrhoids
▪ Adenomatous polyps/malignancies
▪ More common in females & increases significantly in elderly
▪ About 80% of episodes of LGIB resolve spontaneously
UPPER GASTROINTESTINAL BLEEDING (UGIB)
• Any GI bleeding originating proximal to the ligament of Treitz
PATHOPHYSIOLOGY
• Includes gastric, duodenal, esophageal, & stomal ulcers
Peptic Ulcer
• Most common cause of UGIB
Disease
• Causes: aspirin, NSAIDs, smoking, H. pylori infection
• Predisposing factors: alcohol, salicylates, NSAIDs
• Infection, toxic ingestion, radiation, and stress from
Erosive severe illness may also cause erosive gastritis
Gastritis and • Stress-related mucosal disease: overwhelming sepsis,
Esophagitis trauma, respiratory failure with mechanical ventilation
• Potential sources of esophageal bleeding from infection:
Candida, herpes simplex virus, cytomegalovirus, HIV
• Result from portal hypertension
• Most often a result of alcoholic liver disease
• Can rebleed and carry a high mortality rate
Esophageal • Many patients with history of varices presenting with
and Gastric UGIB will actually bleed from nonvariceal sites
Varices • Variceal bleeding is the cause of UGIB in cirrhotics 59%
of the time, followed by PUD in 16% of cases
• In-hospital mortality rates for any type of GI bleed in
cirrhotics are essentially double those of noncirrhotics
• Bleeding secondary to a longitudinal mucosal tear at the
gastroesophageal junction
Mallory-
• History: repeated vomiting + bright red hematemesis
Weiss
Syndrome • Associated with: alcohol binge drinking, diabetic
ketoacidosis, chemotherapy administration, Valsalva
maneuver (from coughing or seizures)
• Arteries of GI tract that protrude through the submucosa
• Most commonly found in lesser curvature of stomach but
may be found anywhere in the GI tract
Dieulafoy o 80-95% are within 6 cm of gastroesophageal junction
Lesions • Intermittent massive GI bleeding, without standard
predisposing factors of liver disease or NSAID use
• Difficult to diagnose endoscopically (patients had multiple
previous diagnostic maneuvers with negative results)
• AV malformation & malignancy
• Significant bleeding from ear, nose, and throat sources
can also masquerade as GI hemorrhage
Other Causes • An aortoenteric fistula secondary to a preexisting aortic
graft is an unusual but important cause of bleeding
o “Herald” bleed (hematemesis or hematochezia), which
precedes massive hemorrhage and exsanguination
48 | 11. GASTROINTESTINAL BLEEDING
LOWER GASTROINTESTINAL BLEEDING
• Loss of blood from the GI tract distal to the ligament of Treitz
• Considered potentially life threatening until proven otherwise
PATHOPHYSIOLOGY
• Hematochezia: bright red or maroon-colored rectal bleeding
o If originated from UGI: indicates brisk UGIB
▪ Accompanied by hematemesis and hemodynamic instability
▪ Approximately 10% may be associated with UGI bleeding
• Melena: dark or black-colored stools
o Bleeding from a UGI source (proximal to the ligament of Treitz)
o May also represent slow bleeding from an LGI source
• Usually painless; may be massive
• From erosion into penetrating artery of diverticulum
• 90% will resolve spontaneously; can recur in up to half
Diverticulosis • Most common location of diverticula: left colon
(diverticular • Most common location of div. bleeding: right colon
bleeding) • Increased morbidity and mortality in:
o Elderly patients with underlying medical illnesses
o Those with increased needs for transfusion
o Those taking anticoagulants or NSAIDs
• Includes AV malformation & angiodysplasias of colon
• Common cause of LGI bleeding
Vascular o Can also be present in small bowel; difficult to diagnose
Ectasia • Large bowel: chronic process; increases with aging
• Inherited conditions can give rise to AV malformations
• Valvular HD: risk factor for bleeding vascular ectasias
• Most common cause of intestinal ischemia; transient
• Colon is susceptible to ischemia because of poor
vascular circulation and high bacterial content
• Risk factors
o Aneurysmal rupture
o Vasculitis
Ischemic
o Hypercoagulable states
Colitis
o Prolonged strenuous exercise
o Cardiovascular insult
o Irritable bowel syndrome
o Medications that cause vasoconstriction/slow motility
• Diagnosis: endoscopy
• Most cases resolve on its own; 20% will require surgery
• Can lead to bowel necrosis; caused by:
o Thrombosis or embolism of superior mesenteric artery
o Mesenteric venous thrombosis
o Nonocclusive mesenteric ischemia associated with low
arterial flow (vasoconstriction)
• Diagnosis is difficult, & presentation can mimic other
Mesenteric intra-abdominal pathologies
ischemia o Requires high index of suspicion, especially in patients
>60 years old & in AF, CHF, recent MI, postprandial
abdominal pain, or unexplained weight loss
o CT: specificity of 92%, sensitivity of 64%
o Angiography: diagnostic study of choice
• Despite aggressive treatment, prognosis is poor, with a
survival of 50% if diagnosed within 24 hours
• From embryonic tissue, most commonly in terminal ileum
Meckel’s • >1/2 of lesions contain ectopic gastric tissues: secrete
Diverticulum gastric enzymes, erode mucosal wall & cause bleeding
• Rare but important condition, especially in children
• Most common source of anorectal bleeding
• Massive hemorrhage is unusual
Hemorrhoids • Bleeding is usually associated with bowel movements
• Usually painless
• Diagnosis: made at bedside as a cause for LGIB
• Infectious colitis, radiation colitis, rectal ulcers, trauma,
inflammatory bowel disease
• Polyps & carcinomas: usual source of chronic anemia
o Delayed hemorrhage can occur up to 3 weeks after
Other causes polypectomy
of LGIB • Patients with left ventricular assist device are prone
to GI bleeding due to
o Anticoagulation
o Risk of AV malformations
o Acquired von Willebrand’s disease
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

DIAGNOSIS
History
Hematemesis, • Hematemesis & coffee-ground emesis: UGI source
coffee-ground • Melena + <50 years old: more likely UGIB vs LGIB
emesis, melena • Vomiting/retching + hematemesis: Mallory-Weiss tear
• Signs & symptoms of hypotension, tachycardia,
Associated angina, syncope, weakness, or altered mental status
symptoms • Pain, trauma, ingestion/insertion of foreign bodies,
• Weight loss & changes in bowel habits: malignancy
Prior episodes • Recurrent bleeding may originate from other sources
of GI bleeding & • History of aortic graft: bleeding from aortoenteric fistula
interventions • Recent colonoscopies
• Antiplatelets, glucocorticoids, NSAIDs,
Medications
anticoagulants all place patient at high risk for GI bleed
• Alcohol abuse: strongly associated with PUD, erosive
gastritis, and esophageal varices
Diet • Ingestion of iron or bismuth can simulate melena
• Liquid medications with red dye, as well as certain
foods (beets) can simulate hematochezia
• History can also be misleading
o What initially appears to be LGIB may be a UGIB in disguise
o Bright red/maroon rectal bleeding from UGIB: 14% of the time
▪ Factors that suggest a UGI source for hematochezia:
anemia, previous history of UGIB
Physical Examination
Visual
• Bloody, maroon, or coffee-ground appearance
inspection of
the vomitus • Most reliable way to diagnose UGIB in ER
• May reveal obvious hypotension and tachycardia
• More subtle findings: ↓ pulse pressure or tachypnea
• Minimal/no changes in VS (can tolerate volume loss):
o Younger patients & those without comorbidities
Vital signs • Paradoxical bradycardia may occur even in the face of
profound hypovolemia
• Changes in vital signs may be masked by:
o β-blockers: prevent tachycardia
o Hypertension: relatively normal BP in hypovolemia
• Spider angiomas, palmar erythema, jaundice, and
gynecomastia suggest liver disease
• Petechiae & purpura: underlying coagulopathy
Skin
• Facial lesions, cutaneous macules, telangiectasias may
be suggestive of the Peutz-Jeghers, Rendu-Osler-Weber,
or Gardner’s syndromes
ENT • Can reveal occult bleeding source resulting in swallowed
examination blood & coffee-ground emesis
• Tenderness, masses, ascites, organomegaly
Abdominal • Lack of abdominal tenderness: bleeding from disorders
examination involving vasculature (diverticulosis or angiodysplasia)
• Abdominal tenderness: inflammatory bowel disorders
• Presence of blood and its appearance (bright red,
maroon, or melanotic)
• May reveal an obvious source of bleeding (laceration,
masses, trauma, anal fissures, external hemorrhoids)
• A vaginal or urinary source of bleeding mistaken for a GI
Rectal
source will be identified by examination and testing
examination
• Digital rectal examination: to detect gross blood (bright
red or maroon) and for guaiac testing
• Bedside anoscopy: source of bleeding (hemorrhoids)
o Blood originating beyond the level of visualization
should raise the suspicion for other causes
Extremities • Cool, pale skin & ↑ capillary refill can be signs of shock
Imaging
• Can sometimes detect site of bleeding & help guide
surgical management
• Permits therapeutic options (transcatheter arterial
Angiography
embolization or infusion of vasoconstrictive agents
• Require a relatively brisk bleeding rate (≥0.5 mL/min)
• Serious complications in up to 10% of cases
• If traditional endoscopy is unavailable or endoscopic
visualization is unable to find source
Technetium-
• Can localize site of bleeding in obscure hemorrhage
labeled red cell
scintigraphy • More sensitive than angiography (0.1 mL/min)
• Potential value over angiography if bleeding occurs
intermittently (requires ≥3 mL of blood to pool)
&
• Sn: 100%; Sp: 99% for active/recent GI bleeding
Multidetector CT
• About 93% accurate in determining site of bleeding
angiography
• Useful tool prior to conventional angiography
• Routine abdominal and chest radiographs are of limited value and
are not needed in the absence of specific clinical indications
• Barium contrast studies are contraindicated because barium may
hinder subsequent endoscopy or angiography
Nasogastric Lavage
• NG intubation and aspiration are diagnostic and therapeutic
o Visual inspection of aspirate: bloody, maroon, coffee-ground
o If bright red blood or clots: perform gentle gastric lavage
o Early NG lavage: associated with decreased time to endoscopy
o Room temperature water is the preferred irrigant
o Maintain the NG tube on mild, intermittent suction
o Vigorous suction: may produce gastric erosions that can
confuse findings on subsequent endoscopy
o No evidence that NG tube passage may provoke variceal bleeds
• Positive aspirate: strong evidence for a UGI source of bleeding
o Bloody aspirates: high-risk lesions are more likely
• Negative NG aspirate does not conclusively exclude a UGI source
o False-negative results: intermittent bleeding, pyloric spasm, or
edema preventing reflex of duodenal blood
o Positive in only 23% of occult UGIB without hematemesis
Risk Stratification
• Glasgow-Blatchford Score (for UGIB)
o Score of 0-1 or 0-2: discharge from ER (outpatient treatment)

Laboratory Testing
Blood typing &
• In case transfusion is needed in significant bleeding
crossmatching
• Acute brisk bleeding: initial hematocrit may not
CBC
reflect actual amount of blood loss
BUN, creatinine, • BUN: elevated (bleeding from a source higher in GI
electrolyte, tract; digestion & absorption of hemoglobin) • Factors associated with a high morbidity rate:
glucose, • BUN:creatinine ratio ≥ 30: UGI source of bleeding o Hemodynamic instability
coagulation, liver • Coagulation studies (INR, aPTT, platelet count): o Repeated hematochezia
function studies anticoagulant use & with underlying hepatic disease o Gross blood on initial rectal examination
• Patients with underlying coronary artery disease o Initial hematocrit <35%
ECG • Silent cardiac or mesenteric ischemia can develop if
bleeding decreases cardiac or mesenteric perfusion o Syncope
• Single ↑ lactate: sentinel sign of severe illness o Nontender abdomen (predictive of severe bleeding)
Lactate • Dynamic lactate levels: can assess success or o History of diverticulosis or angioectasia
failure of resuscitation efforts (↑ lactate = ↑ mortality) o Elevated creatinine
o Aspirin or NSAID use (predictive of diverticular hemorrhage)
o >2 comorbid conditions

11. GASTROINTESTINAL BLEEDING | 49

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT
• Emergent resuscitation in hemorrhagic shock
o Administer oxygen and institute cardiac monitoring
o Place 2 large-bore IV lines & replace volume with crystalloids
o Typed and crossmatched blood
o Early airway management
▪ Intubating hemodynamically unstable UGIB can be perilous
▪ Aggressive resuscitation prior to intubation
▪ Consider smaller doses of induction agent to minimize peri-
intubation hypotension or arrest
• Nasogastric tube placement if LGIB is significant
o Hematochezia unexpectedly originates from UGI sources
approximately 10-14% of the time
o Nasogastric aspiration: low sensitivity & NPV for UGIB
o Nasogastric tube is likely beneficial only for significant ongoing
UGIB in whom immediate intervention will occur
• Refer to Surgery and Gastroenterology for uncontrollable bleeding
• Lifesaving in severe UGIB
Blood • Restrictive transfusion threshold: <7 g/dL in most
Transfusion patients & <9 g/dL in older patients with comorbidities
who are not tolerating acute anemia
• In life-threatening bleeding: reverse coagulopathy
regardless of INR unless contraindicated (stents)
• In less severe bleeding: consider risks of reversal
Coagulopathy o INR ≥1.5: significant predictor of mortality in UGIB
o Reversal: ↑ INR or platelet counts <50,000/μL
• Reversal should not delay time to endoscopy
• Tranexamic acid: no benefit in management of UGIB
Proton Pump • For nonvariceal bleeding from PUD: reduce need for
Inhibitors surgery, length of hospital stay, and signs of bleeding
(Omeprazole 80 mg
IV bolus followed by
• In high doses, gastric pH remains neutral
8 mg/h infusion) • Clot formation from platelet aggregation: pH >6.0
• Long-acting somatostatin analog
• Elicits several actions in UGIB
Octreotide o Inhibits secretion of gastric acid
50 μg bolus
o Reduces blood flow to gastroduodenal mucosa
BALLOON TAMPONADE
followed by 25-50
μg/h infusion o Causes splanchnic vasoconstriction • Effective short-term solution for life-threatening variceal bleeding
• Does not appear to provide a clear benefit on mortality • High rate of complication
o With early endoscopy: may reduce bleeding • Reserved for temporary stabilization of patients for transfer to an
Antibiotics • Cirrhotics: impaired immune system; ↑ risk of gut
(Ciprofloxacin 400 bacterial translocation during acute bleeding episode appropriate institution or until endoscopy can be done
mg IV or • Reduce infectious complications, may decrease • Adverse reactions: mucosal ulceration, esophageal or gastric
ceftriaxone 1g IV) mortality, and should be started as soon as possible rupture, asphyxiation from tracheal compression, aspiration
Promotility • Used to enhance endoscopic visualization o Strongly consider intubation prior to balloon tamponade
Agents • Not recommended for routine use
(erythromycin & • Considered if patient undergoes endoscopy in ER &
metoclopramide) suspected to have large amounts of blood in UGI tract SURGERY
• Emergent surgery/surgical consultation
ENDOSCOPY o Uncontrolled bleeding
• Both diagnostic and therapeutic o Unresponsive to both pharmacologic & endoscopic treatments
o Diagnostic: visualization of source of bleeding (in most cases) • In variceal bleeding, 2 types of operations
o Therapeutic: administration of hemostatic therapy o Shunt: transjugular intrahepatic portosystemic shunt procedure
• Treatment options commonly used for variceal bleeding o Nonshunt: esophageal transection, GEJ devascularization
o Variceal ligation • In nonvariceal bleeding
o Injection sclerotherapy o Percutaneous embolization
o Electrocoagulation o Subtotal or total gastrectomy
o Clips, thermocoagulation, and sclerosant injections alone or in
combination with epinephrine injections (in ulcerative lesions) DISPOSITION AND FOLLOW-UP
• Timing of endoscopy can vary • Very-low-risk patients: ER observation or discharged home
o Emergent endoscopy (immediately): in unstable patients • Significant UGIB: ICU admission and early endoscopy
o Early endoscopy (6-24 h: stable; 12-36 h: unstable): most px • LGIB: require hospital admission & early referral to an endoscopist
o Delayed endoscopy: appropriate in stable patients o ICU admission: unstable or with active bleeding
• Sedation • Variables associated with morbidity:
o Pretreat with antiemetic (ondansetron) o Hemodynamic instability
o Short-acting titratable drugs with both analgesic (fentanyl) and o Repeated hematochezia within 4 hours of evaluation
sedative properties (midazolam or propofol) o Nontender abdomen
o Ideal agents can be reversed if the condition changes o Aspirin use
o Unstable: cardiovascular stable agents (etomidate or ketamine) o >2 comorbid conditions
o While providing sedation, consider that the most noxious part of • Candidates for outpatient treatment
the procedure is when the scope is passed around the tongue o Obvious case of mild bleeding (from hemorrhoids/anal fissures)
• Diagnostic study of choice in UGIB o Rectal examination: no bright red blood/maroon/melanotic stool
UGI Endoscopy
• If colonoscopy fails to see source of bleeding in LGIB o Hemodynamically stable and without major comorbidities
Colonoscopy • Diagnose LGIB (diverticulosis, angiodysplasia)
Flexible • Evaluate possible distal colonic & rectal sources References:
sigmoidoscopy • Cannot identify more proximal sources of bleeding • Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
• Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 20 th edition (2017)

50 | 11. GASTROINTESTINAL BLEEDING

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11. GASTROINTESTINAL BLEEDING | 51

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

12. PORTO-SYSTEMIC ENCEPHALOPATHY

HEPATIC ENCEPHALOPATHY (HE)
• Encompasses a wide array of transient and subtle reversible
neuropsychiatric manifestations found in patients with chronic liver
disease & portal hypertension, but also seen acute liver failure
• Develops in 50-70% of patients with cirrhosis

ETIOLOGY
• Often triggered by an inciting event → rise in serum ammonia level
o GI bleeding
o Electrolyte abnormalities
o Infections
o Medications
o Dehydration
• Common after transjugular intrahepatic portosystemic shunt
o Portal blood is shunted to inferior vena cava, bypassing the liver
o Done to reduce portal hypertension and variceal bleeding CLINICAL FEATURES AND CLASSIFICATION
o Slows metabolism of nitrogenous wastes by ↓ hepatic flow • May present as a spectrum of reversible neurocognitive
• 3 major types of HE symptoms and signs that range from mild changes in cognition to
Type A Acute liver failure profound coma in patients with acute or chronic liver disease
Type B Portosystemic shunts in absence of liver disease • Occasionally, HE may be initial presentation of chronic liver disease
Type C Chronic & end-stage liver disease & portal hypertension Subtle findings in overt HE As HE worsens, findings include
• Forgetfulness • Asterixis
PATHOPHYSIOLOGY • Alterations in handwriting • Agitation
• A number of factors have been implicated in the development of HE • Difficulty with driving • Disinhibited behavior
o Production of neurotoxins • Reversal of the sleep-wake cycle • Seizures
• Coma
o Altered permeability of the blood-brain barrier
• To appreciate presence or worsening of encephalopathy, determine
o Abnormal neurotransmission
if there are changes in personality, worsening dementia, a decrease
• Ammonia: best-described neurotoxin involved in HE
in levels of consciousness, or declining neuromuscular function
o Produced primarily in the colon, where bacteria metabolize
• Stages of Clinical Hepatic Encephalopathy
proteins and other nitrogen-based products into ammonia
Stage Features
o Enterocytes synthesize ammonia from glutamine I General apathy
o Once produced, ammonia enters portal circulation and, under II Lethargy, drowsiness, variable orientation, asterixis
normal conditions, is metabolized and cleared by hepatocytes III Stupor with hyperreflexia, extensor plantar reflexes
o Cirrhosis & portal hypertension: reduced hepatocyte function & IV Coma
portosystemic shunting → increased circulating ammonia levels • Asterixis (Stage II): elicited by
o Arterial hyperammonemia is observed in up to 90%, although Maneuver Positive result
levels are neither sensitive nor specific indicators of its presence Hold arms straight up & extend wrists Hands flap repetitively (liver flap)
Extend the tongue Back-and-forth tongue movement
o Increased permeability of the blood-brain barrier increases
• SONIC (Spectrum of Neurocognitive Impairment in Cirrhosis)
uptake & extraction of ammonia by cerebellum & basal ganglia
o Nomenclature to reflect the wide spectrum of clinical findings
o Acute hyperammonemia appears to have a direct effect on
and improve the clinical classification of HE for research studies
▪ Brain edema
o Eliminates need to distinguish minimal HE from grade 1 HE
▪ Astrocyte swelling
o Disorientation to time is a distinct clinical feature that
▪ Transport of neutrally active compounds (myoinositol)
▪ Distinguishes grade 1 from grade 2 HE
• Other alterations in HE affect neuronal membrane fluidity, CNS
▪ Distinguishes covert from overt HE
neurotransmitter expression, & neurotransmitter receptor
expression and activation
o γ-aminobutyric acid (GABA)-benzodiazepine system
▪ Enhanced activation by increased sensitivity of the astrocyte
(peripheral-type) benzodiazepine receptor
▪ Occurs in part through a feed-forward system in which
production of neurosteroids (allopregnanolone and
tetrahydrodeoxycorticosterone) by astrocytes further
activates the GABAA-benzodiazepine receptor system
o Other factors that influence CNS neurotransmission
▪ Serotonin (5-hydroxytryptamine [5-HT])
▪ Nitric oxide (NO)
▪ Circulating opioid peptides
▪ Manganese
▪ Increased oxygen free radical production
• Distinct allelic mutations in glutaminase gene increases risk for overt
HE, independent of synthetic function or presence of minimal HE
o May be mediated by enhanced glutaminase transcriptional
activity that results in increased levels of ammonia & glutamate
• Differences in colonic mucosal microbiota in cirrhotic patients ± HE
could influence production of substances that lead to of HE
• Hyperammonemia, particularly in acute liver failure, also increases
astrocyte glutamine production via glutamine synthetase
o The rise in astrocyte glutamine & glutamate concentrations
contributes to factors associated with CNS dysfunction

52 | 12. PORTO-SYSYEMIC ENCEPHALOPATHY


DIAGNOSIS
• Diagnosis of excluision
• No specific laboratory findings indicate presence of HE definitively
• Blood ammonia levels are commonly measured in patients with
cirrhosis & portal hypertension but not sensitive or specific for HE
o Other factors that may raise the blood ammonia level
irrespective of the presence of HE
▪ GI bleeding
▪ Ingestion of certain medications (e.g., diuretics, alcohol,
narcotics, valproic acid)
▪ Use of tourniquet when blood is drawn
▪ Delayed processing and cooling of a blood sample
o Arterial ammonia measurement offers no advantage over
venous ammonia levels in patients with chronic liver disease
o May be a useful indicator of HE in the absence of cirrhosis and
portal hypertension
▪ Metabolic disorders that influence ammonia generation or
metabolism, such as urea cycle disorders
▪ Disorders of proline metabolism
• Standardized neuropsychometric and neurocognitive tests
o Has led to the recognition that routine evaluation is insensitive
for the diagnosis of clinically relevant HE
o Portosystemic encephalopathy syndrome test (PSET) and
Stroop test
▪ Attention, concentration, fine motor, skills, orientation
▪ Have been shown to be highly specific for diagnosis of HE
o With the use of these tests, covert HE
▪ Has been found to be common
▪ Negatively influence a patient’s quality of life & driving ability
▪ Increase the risk of overt HE
o Moreover, treatment of minimal HE improves quality of life,
cognitive test results, and a patient’s driving ability
• A number of novel imaging and functional tests for the diagnosis
of HE have also been studied
o Magnetic resonance spectroscopy (MRS) and MR T1 mapping
with partial inversion recovery (TAPIR) have been used to
measure clinically relevant parameters quantitatively
o The critical flicker frequency test, a simple light-based test that
assesses cerebral cortex function, has been shown to be a
reliable marker of minimal HE
DIFFERENTIAL DIAGNOSIS for altered mental status: considered
and rapidly excluded in patients suspected of having HE
Differential diagnosis Mechanism of altered mental status
Hypoglycemia and
nutritional • ↓ hepatic gluconeogenesis & glycogen stores
encephalopathies • Poor nutritional status
(Wernicke-Korsakoff syndrome)
• Cirrhotic patients often are treated with diuretics
and can develop hyper- or hyponatremia
• Altered mental status can result from decreased
Medication ingestion
hepatic clearance of drugs such as
benzodiazepines & opiates, prolonging effect &
resulting in accidental overdose
Structural intracranial • Patients with end-stage liver disease are
abnormalities from typically coagulopathic and may develop a
coagulopathy/trauma spontaneous or traumatic subdural hematoma
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
TREATMENT
• Goals of Treatment
o Eliminate or correct precipitating factors (bleeding, infection,
hypokalemia, medications, dehydration)
o Reduce blood ammonia levels
o Avoid toxic effects of ammonia on the CNS
• Limiting protein-calorie intake is not beneficial in HE
• Vegetable & dairy proteins may be preferable to animal
proteins for a more favorable calorie-to-nitrogen ratio
Diet
• Although branched-chain amino acid supplementation
may improve symptoms modestly, the benefits are not
sufficient to justify its routine use
• MOA: metabolized by colonic bacteria primarily into
lactic acid causing catharsis & reducing intestinal pH
o Ammonia is trapped and excreted in stool
o Blood ammonia levels can decrease up to 50%
o Also inhibits glutamine-dependent ammonia
production in the gut wall
Lactulose • Oral: 20 g diluted in a glass of water, fruit juice, or
(nonabsorbable carbonated drink
synthetic • Rectal: 300 mL of syrup + 700 mL water/normal saline
disaccharide): (enema retained for 30 minutes)
cornerstone of o For patients with increased risk of aspiration,
treatment of HE although efficacy has not been evaluated
• Improve symptoms in patients with acute & chronic HE
• Does not improve psychometric tests or mortality
• Side effects: abdominal cramping, flatulence, diarrhea,
electrolyte imbalance
• Goal: promote 2-3 soft stools per day
o Titrate amount of lactulose to achieve desired effect
• Aim: modify intestinal flora & lower stool pH to enhance
excretion for ammonia
• Second-line agents after lactulose or in patients who
Oral antibiotics are intolerant of nonabsorbable disaccharides
• Rifaximin 550 mg orally twice daily for treatment of
chronic HE & reduction in risk of recurrent of overt HE
in patients with advanced liver disease
Potential • Acarbose (intestinal α-glucosidase inhibitor)
treatments for o Inhibits intestinal absorption of carbohydrates
HE o Results in their enhanced delivery to colon
(may modify o Ratio of saccharolytic to proteolytic bacterial flora is
intestinal floral & increased, and blood ammonia levels are decreased
modulate
o Improves mild HE in cirrhosis & adult-onset DM
generation of
intestinal • Probiotic regimens
absorption of o Modify intestinal flora & ↓ ammonia generation
ammonia) o May be beneficial in humans with mild HE
• Na benzoate, Na phenylbutyrate, Na phenylacetate
o IV sodium phenylacetate + sodium benzoate
o Increase ammonia excretion in urine
o For hyperammonemia in urea cycle enzyme defects
o May improve HE in patients with cirrhosis
o Sodium benzoate: results in high sodium load;
efficacy not clearly established
• Zinc supplementation
o Zinc deficiency is common in patients with cirrhosis
Strategies to o Sometimes helpful in HE; relatively harmless
enhance o Increases activity of ornithine transcarbamylase
ammonia (enzyme in urea cycle), may also improve HE;
clearance however, clear efficacy has not been established
• Extracorporeal albumin dialysis using molecular
adsorbent recirculating system (MARS)
o Reduction in blood ammonia levels & improvement
in severe HE in acute-on-chronic liver failure
o Further studies are needed to clarify role in HE
• L-ornithine-L-aspartate (LOLA)
o Salt of ornithine & aspartic acid
o Activates urea cycle & enhance ammonia clearance
o Shown to improve HE compared with lactulose
PROGNOSIS
• Occurrence of HE in cirrhosis is a poor prognostic indicator
o Projected 1-year survival rate (no liver transplantation): 42%
o Projected 3-year survival rate (no liver transplantation): 23%
o Liver transplantation generally reverses HE
• Stage I or II who is otherwise well & has no other acute
comorbidities may be managed as an outpatient after consultation
References:
• Sleisenger and Fordtran’s Gastrointestinal and Liver Disease, 10 th edition (2016)
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
12. PORTO-SYSTEMIC ENCEPHALOPATHY | 53
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
13. HYPERTENSIVE CRISIS
HYPERTENSIVE EMERGENCIES
• Severe elevations in BP (>180/120 mmHg) associated with
evidence of new or worsening target organ damage
• 1-year death rate: >79%; Median survival: 10.4 months if left
untreated
• The actual BP level may not be as important as the rate of BP rise;
patients with chronic hypertension can often tolerate higher BP
levels
• Demand immediate reduction of BP (not necessarily to normal) to
prevent or limit further target organ damage
• Use of oral therapy is discouraged
o Oral loading doses of antihypertensive agents can engender
cumulative effects, causing hypotension after discharge from
the emergency department or clinic
54 | 13. HYPERTENSIVE CRISIS
HYPERTENSIVE URGENCIES
• Situations associated with severe BP elevation in otherwise stable
patients without acute or impending change in target organ damage
or dysfunction
• Many of these patients have withdrawn from or are noncompliant
with antihypertensive therapy and do not have clinical or laboratory
evidence of acute target organ damage
• Treated by reinstitution or intensification of antihypertensive therapy
and treatment of anxiety as applicable
• No indication for referral to the emergency department, immediate
reduction in BP in the emergency department, or hospitalization for
such patients
PATHOPHYSIOLOGY
• Determinants of arterial pressure
o Sodium is a primary determinant of the extracellular fluid volume
▪ ↑ vascular volume (↑ preload) → ↑ cardiac output
▪ Pressure natriuresis: ↑ arterial pressure due to ↑ NaCl intake; ↑
urinary Na excretion & maintenance of Na balance at the expense of
↑ arterial pressure
o Adrenergic reflexes (short-term BP regulation)
▪ Long-term: adrenergic + hormonal & volume-related factors
o Renin-angiotensin-aldosterone system (RAAS)
▪ Vasoconstrictor properties of angiotensin II
▪ Sodium-retaining properties of aldosterone
o Vascular radius and compliance of resistance arteries (Poiseuille’s law)
• Chronic hypertensive patients have biochemical & structural changes in the
arterial walls that shift the vascular autoregulatory curve, requiring higher
arterial pressures to maintain end-organ blood flow, notably in the brain.
• Eventually, the ability to adapt is passed, resulting to mechanical wall stress
and endothelial injury
o Increased permeability
o Excessive perfusion of cerebral, cardiac, & renal vascular beds
o Activation of the coagulation cascade and platelets (deposition of fibrin
results in fibrinoid necrosis of the arterioles)
• Further contributing to the damage are prostaglandins, free radicals,
cytokines, and mitogenic, chemoattractant, and proliferation factors
o Endothelial damage, smooth muscle proliferation, thrombosis
• RAAS may also be activated, leading to vasoconstriction
o Pressure natriuresis occurs, leading to volume depletion, prompting
additional release of vasoconstrictors from the kidney
o Hypoperfusion, ischemia, and dysfunction of end organs
• Endothelial dysfunction can persist for years after the acute event
APPROACH TO DIAGNOSIS & MANAGEMENT
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT
• Therapeutic goal: minimize target organ damage safely by
o Rapid recognition of the problem
o Early initiation of appropriate antihypertensive treatment
• In hypertensive emergency, admission to ICU is recommended for:
o Continuous monitoring of BP and target organ damage
o Parenteral administration of an appropriate agent.
• Selection of an antihypertensive agent should be based on:
o Drug’s pharmacology
o Pathophysiological factors underlying the patient’s hypertension
(as well as they can be rapidly determined)
o Degree of progression of target organ damage
o Desirable rate of BP decline
o Presence of comorbidities
• Compelling conditions requiring rapid lowering of SBP (<140 mmHg)
in the first hour of treatment include:
o Aortic dissection (to <120 mmHg)
o Severe preeclampsia or eclampsia
o Pheochromocytoma with hypertensive crisis
• For adults without a compelling condition:
o SBP should be reduced by <25% within the first hour
o If stable, to 160/100 mmHg within the next 2 to 6 hours
o Cautiously to normal during the following 24 to 48 hours

13. HYPERTENSIVE CRISIS | 55

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

HYPERTENSION

CAUSES
• Genetic Predisposition
o Hypertension is a complex polygenic disorder in which many
genes or gene combinations influence BP
• Environmental Risk Factors
o Environmental exposures: components of diet, physical activity,
and alcohol consumption
o Diet-related factors: overweight and obesity, excess intake of
sodium, & insufficient intake of potassium, calcium, magnesium,
protein (especially from vegetable), fiber, and fish fats
o Underlying causes: poor diet, physical inactivity, excess intake
of alcohol
o Overweight and Obesity
▪ Direct relationship with hypertension
▪ Direct relationship between BMI & BP
▪ Relationship between obesity at a young age & change in
obesity status over time is strongly related to future risk of
hypertension
▪ Becoming normal weight reduced risk of developing
hypertension to level similar to those never been obese
o Sodium Intake
▪ Accounts for much of the age-related increase in BP
o Potassium
▪ Potassium intake is inversely related to BP and stroke
▪ Higher levels seem to blunt the effect of sodium on BP
o Physical Fitness
▪ Inverse relationship between physical activity and physical
fitness and level of BP and hypertension
▪ Even modest levels of physical activity have been
associated with a decrease in risk of incident hypertension
▪ Attenuates the rise of BP with age and prevents the
development of hypertension
o Alcohol
▪ Direct relationship between alcohol consumption and BP
• Secondary Forms of Hypertension

56 | 13. HYPERTENSIVE CRISIS

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

PATIENT EVALUATION
Goals:
• Identify target organ damage & possible secondary causes
• Asist in planning effective treatment regimen

History

Physical examination
• Accurate measurement of BP

o Out-of-office BP measurements: recommended to confirm the

diagnosis of hypertension & for titration of BP-lowering
medication, in conjunction with clinical interventions
▪ Ambulatory BP monitoring (ABPM): accepted as the best
out-of-office measurement method, over a period of 24
hours; conducted while going about normal daily activities
▪ Home BP monitoring (HBPM): more practical approach in
clinical practice; taken by the patient

• Drugs and other substances with potential to impair BP control

13. HYPERTENSIVE CRISIS | 57

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT OF HIGH BP
Approach to Management

Non-Pharmacologic Interventions

• Orthostatic hypotension: change in BP from seated to standing

position (SBP >20 mmHg or DBP >10 mmHg after 1 minute)
• For adults ≤30 years old with ↑ brachial BP, a thigh BP measurement
is indicated (If thigh < arm pressures: consider coarctation)
• Assessment of hypertension-related target organ damage
• Physical features that suggest secondary hypertension

Laboratory Tests and Other Diagnostic Procedures

• Obtained for all patients with a new diagnosis of hypertension to:
o Facilitate CVD risk factor profiling
o Establish a baseline for medication use
o Screen for secondary causes of hypertension
• Serum Na & K monitoring (diuretic/RAS blocker titration)
Pharmacologic Treatment
• Serum creatinine & urinary albumin (markers of CKD progression)
• First-line agents: thiazide diuretics, CCBs, & ACEI or ARBs
• TSH (detects hypothyroidism & hyperthyroidism)
o Monotherapy: Adults with stage 1 HTN & BP goal <130/80
• Additional laboratory testing appropriate in the context of:
mmHg with dosage titration & sequential addition of other
o Increased hypertension severity
agents to achieve the BP target
o Poor response to standard treatment approaches
o Combination drug therapy with 2 first-line agents of different
o A disproportionate severity of target organ damage for BP
classes (separate agents or fixed-dose combination): Adults
o Historical or clinical clues that support a secondary cause
with stage 2 HTN & average BP >20/10 mmHg above BP target
• Avoid drug combinations that have similar MOA/clinical effects
o 2 drugs from the same class
o 2 drugs from classes that target the same BP control system
(less effective & potentially harmful), EXCEPT:
▪ Thiazide diuretic, K-sparing diuretic, and/or loop diuretic
▪ Dihydropyridine and non-dihydropyridine CCBs
o Simultaneous administration of RAS blockers (ACEI + ARB,
ACEI/ARB + aliskiren) increases cardiovascular and renal risk
• BP Goal for Patients with Hypertension: <130/80 mmHg
o For adults with confirmed hypertension and known CVD or 10-
year ASCVD event risk of ≥10%
o For adults with confirmed hypertension, without additional
markers of increased CVD risk

58 | 13. HYPERTENSIVE CRISIS

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Follow-Up After Initiating Antihypertensive Drug Therapy

• Adults initiating a new or adjusted drug regimen for hypertension
should have a follow-up evaluation of adherence and response to
treatment at monthly intervals until control is achieved
• Components of the follow-up evaluation should include:
o Assessment of BP control
o Orthostatic hypotension
o Adverse effects from medication therapy
o Adherence to medication and lifestyle therapy
o Need for adjustment of medication dosage
o Laboratory testing (including electrolyte & renal function status)
o Other assessments of target organ damage

RESISTANT HYPERTENSION
• The diagnosis is made when:
o A patient takes 3 antihypertensive medications with
complementary MOAs but does not achieve control, OR
o BP control is achieved but requires ≥4 medications
• Common risk factors: older age, obesity, CKD, black race, DM
• Risk of MI, stroke, ESRD, and death with resistant hypertension and
CHD may be 2-6-fold higher than in hypertensive adults without
resistant hypertension
• Evaluation involves consideration of:
o Patient’s characteristics
o Pseudoresistance (BP technique, white coat hypertension,
medication compliance)
o Screening for secondary causes of hypertension
• “Refractory Hypertension”
o Extreme phenotype of antihypertensive treatment failure
o Failure to control BP despite use of at least 5 antihypertensive
agents of different classes, including a long-acting thiazide-type
diuretic (chlorthalidone) and a mineralocorticoid receptor
antagonist (spironolactone)
o High rates of CVD complications (LVH, HF, stroke)
• Treatment
o Goals:
▪ Improving medication adherence
▪ Improving detection & correction of secondary hypertension
▪ Addressing other patient characteristics
o Pharmacological therapy with combinations of medications with
complementary mechanisms of action provides an empirical
approach that enhances BP control while mitigating untoward
effects of potent vasodilators (fluid retention, reflex tachycardia)
o Common 3-drug regimen: CCBs, RAS inhibitors, chlorthalidone
o Addition of spironolactone to multidrug regimens provides
substantial BP reduction when compared to placebo

Follow-Up After Initial BP evaluation

Disposition Management
Elevated BP or Stage 1
• Nonpharmacological therapy
HTN with 10-year ASCVD
risk <10% • Repeat BP evaluation within 3-6 months
• Nonpharmacological + antihypertensive drug
Stage 1 HTN with 10-year
therapy
ASCVD risk ≥10%
• Repeat BP evaluation in 1 month
• Evaluated by or referred to a primary care
provider within 1 month of initial diagnosis
Stage 2 HTN • Nonpharmacological + antihypertensive drug
therapy (2 different-class agents)
• Repeat BP evaluation in 1 month References:
• 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention,
Very high average BP
• Evaluation followed by prompt Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College
(e.g., SBP ≥180 mmHg or of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines
antihypertensive drug treatment • Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
DBP ≥110 mmHg) • Harrison’s Principles of Internal Medicine, 20 th edition (2018)
Adults with normal BP • Repeat evaluation every year • Robbins and Cotran Pathologic Basis of Disease, 9 th edition (2015)

13. HYPERTENSIVE CRISIS | 59

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

14. ACUTE HEART FAILURE Important Risk Factors for HF

• A complex clinical syndrome that results from any structural or functional
impairment of ventricular filling or ejection of blood
• “Acute heart failure”: acute exacerbation of chronic HF or a new-onset HF
• Heart failure with reduced ejection fraction (HFrEF)
o Clinical diagnosis of HF and EF ≤40%
o CAD with antecedent MI is a major cause of HFrEF
o Mechanistically, the ventricle has difficulty ejecting blood, leading to
increased intracardiac volume & afterload sensitivity
o With circulatory stress (e.g., walking), failure to improve contractility
despite increasing venous return results in increased cardiac pressures,
PATHOPHYSIOLOGY
pulmonary congestion, and edema
• Heart failure with preserved ejection fraction (HFpEF)
o Clinical signs/symptoms of HF with evidence of preserved or normal
LVEF & evidence of abnormal LV diastolic dysfunction (by Doppler
echocardiography or cardiac catheterization)
o Diagnosis of exclusion of other potential noncardiac HF causes
o Patients are usually older women with a history of hypertension
o Characterized by impaired ventricular relaxation, causing an abnormal
relation between diastolic pressure and volume
o This results in a LV that has difficulty receiving blood
o Decreased LV compliance necessitates higher atrial pressures to endure
adequate left ventricular diastolic filling, creating a preload sensitivity
• Hypertension (single most important modifiable risk factor for HF)
o Greater with, older age & longer duration of hypertension
• Diabetes Mellitus (obesity & insulin resistance)
o Markedly increases likelihood of HF if without structural heart disease &
adversely affects outcomes with established HF
• Metabolic Syndrome (any 3): abdominal adiposity, hypertriglyceridemia, low
HDL, hypertension, fasting hyperglycemia
• Atherosclerotic Disease (coronary, cerebral, or peripheral vessels)
• HF is a progressive disorder that is initiated after an index event:
o Result of the index event:
▪ Myocardial damage (loss of functioning cardiac myocytes)
▪ Disruption of the ability of the myocardium to generate force
(prevents normal contraction of the heart)
o Nature of the index event:
▪ Abrupt onset (myocardial infarction)
▪ Gradual/insidious onset (hemodynamic pressure or volume
overloading)
▪ Hereditary (many of the genetic cardiomyopathies)
o Produce a decline in the pumping capacity of the heart
• Compensatory mechanisms (activated in presence of cardiac injury and/or
LV dysfunction): modulate LV function within a physiologic/homeostatic range
to preserve functional capacity:
o RAAS & adrenergic nervous system (↑ salt & water retention)
o Increased myocardial contractility
o Vasodilatory molecules to offset ↑ peripheral vasoconstriction
▪ ANP & BNP (degraded by a neprilysin)
▪ Bradykinin (degraded by a neprilysin)
▪ Prostaglandins (PGE2 and PGI2)
▪ Nitric oxide (NO)

EPIDEMIOLOGY
• Most ER visits for acute heart failure result in hospital admission
o Hospitalization marks an inflection point in HF trajectory, with higher
mortality than a matched non-hospitalized cohort
• Prevalence is expected to increase over the next decade due to:
o Aging population
o Increased survival from acute myocardial infarction
o Evidence-based outpatient treatment options

PROGNOSIS
• 30-40% of patients die within 1 year of diagnosis
• 60-70% die within 5 years, mainly from worsening HR or as a sudden event
(probably because of a ventricular arrhythmia)
• Functional status is an important predictor of patient outcome
o NYHA class IV patients have a 30-70% annual mortality rate
o NYHA class II patients have a 5-10% annual mortality rate

ETIOLOGY
• Any condition that leads to an alteration in LV structure/function can
predispose a patient to developing heart failure
• At some point, patients become overtly symptomatic HF, with a resultant
striking increase in morbidity and mortality rates
o Accompanied by ↑ activation of neurohormonal, adrenergic, & cytokine
systems that lead to LV remodeling

60 | 14. ACUTE HEART FAILURE


Acute Heart Failure Classification
• Hypertensive acute heart failure
o Often have a precipitous presentation
o May have significant pulmonary edema and hypoxia
o Symptoms may be due to fluid redistribution more than overload
o Treatment initially focuses on antihypertensive therapy
• Pulmonary edema
o May benefit from noninvasive ventilation to decrease the work of
breathing and avoid intubation
• Cardiogenic shock
Physical Examination
o Considered in heart failure accompanied by hypotension or poor
perfusion without another cause
o Think of an ischemic or structural heart trigger
o Patients often benefit form inotropic agents and invasive hemodynamic
monitoring to guide other therapies
• Acute-on-chronic heart failure
o Gradual symptoms and weight gain over days to weeks
• High-output heart failure
o Distinguished by a relatively normal ejection fraction
o Often caused by anemia or thyrotoxicosis
• Isolated right heart failure
o Characterized by lower extremity edema and jugular venous distension
but little or no pulmonary congestion
o Cause is usually from pulmonary disease, valvular disease such as
tricuspid regurgitation, or obstructive sleep apnea
o Treatment approaches center on identifying & treating underlying cause,
often without volume removal because low-output states may coexist
CLINICAL MANIFESTATIONS
Symptoms
• Cardinal symptoms: fatigue and shortness of breath
• Fatigue: due to low cardiac output in HF; can also be due to skeletal-muscle
abnormalities and other noncardiac comorbidities (anemia)
• Dyspnea: exertional at first, progressing ultimately with dyspnea at rest
o Mechanisms of cardiac dyspnea
▪ Pulmonary congestion: accumulation of interstitial/intra-alveolar fluid
→ activates juxtacapillary J receptors → rapid, shallow breathing
▪ Others: reductions in pulmonary compliance; increased airway
resistance; respiratory muscle and/or diaphragm fatigue; anemia
o May become less frequent with onset of RV failure tricuspid regurgitation
• Orthopnea: dyspnea in recumbent position (later manifestation of HF)
o Fluid redistribution from splanchnic circulation & lower extremities into
central circulation during recumbency → ↑ pulmonary capillary pressure
o Nocturnal cough: common manifestation; frequently overlooked symptom
o Relieved by sitting upright or sleeping with additional pillows
o May also occur in abdominal obesity or ascites, pulmonary disease
whose lung mechanics favor upright posture
• Paroxysmal Nocturnal Dyspnea (PND)
o Acute episodes of severe shortness of breath & coughing that occurs at
night & awakens patient from sleep (usually 1-3 hours after patient retires)
o Manifest as cough or wheezing, due to ↑ pressure in bronchial arteries →
airway compression & interstitial pulmonary edema → airway resistance
o Persistent coughing and wheezing even after assuming upright position
o Cardiac asthma (closely related to PND): wheezing secondary to
bronchospasm (vs. primary asthma & pulmonary causes of wheezing)
• Cheyne-Stokes Respiration (“periodic respiration” or “cyclic respiration”)
o Present in 40% of patients with advanced HF
o Usually associated with low cardiac output; caused by an increased
sensitivity of respiratory center to PaCO2 and a lengthy circulatory time
o Apneic phase: ↓ PaO2 &↑ PaCO2 → stimulate respiratory center →
hyperventilation & hypocapnia → recurrence of apnea
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Acute Pulmonary Edema
• Other Symptoms
o GI symptoms (anorexia, nausea, early satiety associated with abdominal
pain & fullness): related to edema of bowel wall and/or a congested liver
o RUQ pain: liver congestion & stretching of Glisson capsule
o Cerebral symptoms (confusion, disorientation, sleep & mood
disturbances): in severe HF, particularly elderly patients with cerebral
arteriosclerosis & reduced cerebral perfusion
o Nocturia: common in HF; may contribute to insomnia
• General Appearance and Vital Signs
o Mild/moderately severe HF: not in distress at rest; feeling uncomfortable
when lying flat for more than a few minutes
o More severe HF: must sit upright, labored breathing, not able to finish a
sentence because of shortness of breath
o SBP: N/↑ in early HF; ↓ in advanced HF (severe LV dysfunction)
o Pulse pressure: diminished (↓ stroke volume)
o Sinus tachycardia: nonspecific sign (↑ adrenergic activity)
o Cool peripheral extremities & cyanosis of the lips and nail beds
(peripheral vasoconstriction caused by excessive adrenergic activity)
• Jugular Venous Pressure (JVP) [normal: ≤8 cm H2O]
o Provides an estimation of right atrial pressure
o Best appreciated with patient lying recumbent, with head tilted at 45°
o Height of venous column of blood above sternal angle then add 5 cm
o Early stages of HF: normal at rest; may become abnormally elevated with
sustained (~15s) pressure on abdomen (positive abdominojugular reflux)
o Giant v waves: tricuspid regurgitation
• Pulmonary Examination
o Pulmonary crackles (rales or crepitations)
▪ Transudation of fluid from the intravascular space into the alveoli
▪ Rales in pulmonary edema may be heard widely over both lung fields
and may be accompanied by expiratory wheezing (cardiac asthma)
▪ Specific for HF in patients without concomitant lung disease
▪ Absent in patients with chronic HF, even in ↑ LV filling pressures,
because of increased lymphatic drainage of alveolar fluid
o Pleural effusions
▪ Result from the elevation of pulmonary capillary pressure and the
resulting transudation of fluid into the pleural cavities
▪ Occur most commonly in biventricular failure since pleural veins
drain into both the systemic and the pulmonary veins
▪ Often bilateral; if unilateral, more frequently in the right pleural space
• Cardiac Examination
o Frequently does not provide useful information about the severity of HF
o Point of maximal impulse (PMI)
▪ Cardiomegaly: PMI displaced below 5 th ICS and/or lateral to MCL,
palpable over 2 interspaces
▪ Severe LV hypertrophy: sustained PMI
o Third heart sound (S3 or protodiastolic gallop)
▪ Audible and palpable at the apex in some patients
▪ Present in volume overload who have tachycardia & tachypnea
▪ Often signifies severe hemodynamic compromise
o Fourth heart sound (S4)
▪ Nonspecific indicator of HF; usually present in diastolic dysfunction
o Sustained & prolonged left parasternal impulse throughout systole
▪ Enlarged or hypertrophied right ventricles
o Mitral and tricuspid regurgitation murmurs
▪ Frequently present in patients with advanced HF
• Abdomen and Extremities
o Hepatomegaly
▪ Important sign in patient with HF
▪ Frequently tender and may pulsate during systole if TR is present
o Ascites
▪ A late sign; occurs as a consequence of increased pressure in the
hepatic veins and the veins draining from the peritoneum
o Jaundice
▪ Secondary to hepatic congestion and hepatocellular hypoxemia
▪ Associated with elevations of both direct and indirect bilirubin
o Peripheral edema
▪ Cardinal manifestation of HF
▪ Nonspecific; absent in patients adequately treated with diuretics
▪ Usually symmetric and dependent in HF
▪ Ambulatory patients: predominantly in ankles & pretibial region
▪ Bedridden patients: sacral area (presacral edema) & scrotum
▪ Long-standing edema: associated with indurated & pigmented skin
• Cardiac Cachexia
o With severe chronic HF, there may be marked weight loss and cachexia
o Mechanism not entirely understood, probably multifactorial
o Augurs a poor overall prognosis
14. ACUTE HEART FAILURE | 61
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
DIAGNOSIS
Potential clues suggesting
etiology of HF
Duration of illness
Severity and triggers of
dyspnea and fatigue,
presence of chest pain,
exercise capacity, physical
activity, sexual activity
Anorexia and early satiety,
weight loss
Weight gain
Palpitations, (pre)syncope,
ICD shocks
Symptoms suggesting TIA
or thromboembolism
Peripheral edema or ascites
Disordered breathing at
night, sleep problems
Recent or frequent prior
hospitalizations for HF
History of discontinuation of
medications for HF
Medications that may
exacerbate HF
Diet
Adherence to medical
regimen
PHYSICAL EXAMINATION
BMI and evidence of weight
loss
Blood pressure (supping and
upright)
Pulse
Examination for orthostatic
changes in blood pressure and
heart rate
Jugular venous pressure at
rest and following abdominal
compression
Presence of extra heart
sounds and murmurs
Size and location of point of
maximal impulse
Presence of right ventricular
heave
Pulmonary status: respiratory
rate, rales, pleural effusion
Hepatomegaly and/or ascites
Peripheral edema
Temperature of lower
extremities
Laboratory Evaluation
• Initial: CBC, urinalysis, electrolytes (including Ca 2+ & Mg2+), BUN, creatinine,
FBS, lipid profile, liver function tests, TSH, 12-lead ECG
• Serial monitoring: serum electrolytes, renal function tests
Biomarkers
62 | 14. ACUTE HEART FAILURE
HISTORY
A careful family history may identify an underlying familial
cardiomyopathy in patients with idiopathic DCM
Patient with recent-onset systolic HF may recover over time
To determine NYHA class; identify potential symptoms of
coronary ischemia
GI symptoms are common in patients with HF. Cardiac
cachexia is associated with adverse prognosis
Rapid weight gain suggests volume overload
Palpitations may be indications of paroxysmal AF or VT.
ICD shocks are associated with adverse prognosis
Affects consideration of the need for anticoagulation
Suggests volume overload
Treatment for sleep apnea may improve cardiac function
and decrease pulmonary hypertension
Associated with adverse prognosis
Determine whether lack of medications in patients with
HFrEF reflects intolerance, an adverse event, or perceived
contraindication to use. Withdrawal of these medications
has been associated with adverse prognosis
Removal of such medications may represent a therapeutic
opportunity
Assess awareness and restriction of sodium and fluid intake
Access to medications; family support; access to follow-up;
cultural sensitivity
Obesity may be a contributing cause of HF; cachexia
may correspond with poor prognosis
Assess for hypertension/hypotension. Width of pulse
pressure may reflect adequacy of cardiac output.
Response of blood pressure to Valsalva maneuver may
reflect LV filling pressures
Manual palpation will reveal strength and regularity of
pulse rate
Consistent with volume depletion or excess vasodilation
from medications
Most useful finding on physical examination to identify
congestion
S3 is associated with adverse prognosis in HFrEF.
Murmurs may be suggestive of valvular heart disease
Enlarged and displaced point of maximal impulse
suggests ventricular enlargement
Suggests significant right ventricular dysfunction and/or
pulmonary hypertension
In advanced chronic HF, rales are often absent despite
major pulmonary congestion
Usually markers of volume overload
Many patients, particularly those who are young, may be
not edematous despite intravascular volume overload. In
obese patients and elderly patients, edema may reflect
peripheral rather than cardiac causes
Cool lower extremities may reflect inadequate cardiac
output
Noninvasive Cardiac Imaging
• Patients with suspected or new-onset HF, or those presenting
with acute decompensated HF
Chest X-Ray • Assess heart size and pulmonary congestion
• Detect alternative cardiac, pulmonary, and other diseases
that may contribute to the symptoms
• Performed during initial evaluation of HF
• Assess ventricular function, size, wall thickness, wall motion,
and valve function
• Repeat measurement of EF & measurement of severity of
2D-Echo with structural remodeling is useful in patients with HF:
Doppler o With significant change in clinical status
o Experienced or recovered form a clinical event
o Received treatment that might have had a significant effect
on cardiac function
o May be candidates for device therapy
Stress nuclear • Noninvasive imaging to detect myocardial ischemia & viability
imaging or • Reasonable in HF with CAD and no angina when planning for
echocardiography revascularization
Magnetic Resonance • Assesses myocardial infiltrative processes or scar burden
Imaging • Assesses LV volume & EF at least as accurately as 2D echo
• Useful to assess LVEF & volume when 2D echo is inadequate
• Cannot directly assess valvular structure, function, or
Radionuclide
ventricular wall thickness
ventriculography
• Useful for assessing LV volumes in patients with significant
baseline wall motion abnormalities or distorted geometry
Invasive Evaluation
• Indications:
o Persistent symptoms despite empiric adjustment of standard therapies
o Uncertain fluid status, perfusion, systemic/pulmonary vascular resistance
o ↓ SBP (<90 mmHg), or associated with symptoms, despite initial therapy
o Worsening renal function with therapy
o Patients requiring parenteral vasoactive agents
o Consideration for mechanical circulatory support or transplantation
• Monitoring with a pulmonary artery catheter
• Performed in patients who have respiratory distress
Right-Heart Catheterization
or clinical evidence of impaired systemic perfusion
when clinical assessment is inadequate
Left-Heart Catheterization/ • Reasonable when ischemia may be contributing to
Coronary arteriography HF for patients eligible for revascularization
• Useful when a specific diagnosis is suspected that
Endomyocardial biopsy would influence therapy
• Should not be performed in routine evaluation
Point-Of-Care Cardiopulmonary Ultrasound
• Advantages:
o Can help to determine the cause of dyspnea
o Can determine left ventricular function and volume status
• Not a substitute for comprehensive echocardiography
• Can address three questions:
o Are there signs of pulmonary congestion?
o Are there signs of volume overload by IVC size & collapsibility?
o Is the left ventricular ejection fraction low or normal?
• Pulmonary US: used first to determine if pulmonary congestion is present
o Sonographic B lines
▪ Ring-down artifacts that arise from interface of visceral & parietal
pleura when there is swelling of the lung’s interlobular septa due to
lymphatic congestion (pulmonary edema)
▪ Sonographic equivalent of Kerley B lines seen on chest radiography
▪ >2 B lines in any sonographic window along anterior & anterolateral
chest are pathologic & highly specific for alveolar & interstitial edema
▪ Can be present in other conditions: pulmonary fibrosis, pulmonary
contusion, bilateral pneumonia
o Rapid assessment for elevated central venous pressure
▪ Marker of right heart congestion
▪ IVC >2 cm or collapsibility index of <50%: indicative of elevated CVP
▪ In the absence of significant pulmonary disease, highly correlated
with pulmonary capillary wedge pressure & specific for acute HF
▪ Other causes of elevated right heart pressure: pulmonary embolism,
clinically significant tricuspid regurgitation
• Left ventricular ejection fraction
o Visual estimation of left ventricular ejection fraction into broad categories
of normal, moderately reduced, or severely reduced

TREATMENT
Initial Approach
• Supplemental oxygen (guided by pulse oximetry to maintain SaO2 >95%)
o Do not withhold oxygen even when there is concern about CO 2 retention
o Capnometry and arterial blood gas measurements can later help titrate
therapy in the crucially ill or if CO2 retention is likely
• Noninvasive positive-pressure ventilation
o Oftenimprove symptoms in patients with HF or pulmonary edema
o Requires close monitoring, hemodynamic stability, facial anatomy that
allows an adequate facemask seal, and patient cooperation
Normotensive Heart Failure
o Reduce the need for intubation and improves respiratory distress and
metabolic disturbance versus standard therapy alone
• Other standard initial measures: cardiac monitoring, pulse oximetry, IV
access, frequent vital sign assessment
o Urinary catheter: may aid in monitoring fluid status in severely ill or
incontinent; reserved for those with extreme illness or an inability to void
Hypertensive Acute Heart Failure
• Prompt recognition & afterload reduction can avoid need for intubation
• Nitroglycerin
o Short-acting, rapid-onset, systemic venous and arterial dilator
o Decreases MAP by reducing preload and, at high doses initially, afterload
o May have coronary vasodilatory effects, decreasing myocardial ischemia
and improving cardiac function
o Route is based on severity of symptoms
▪ Sublingual nitroglycerin (0.4 mg every 1-5 minutes)
• Easily administered, rapidly bioavailable, given as often as
needed to reach desired clinical end point given adequate BP
• Repeated until relief or replacement with IV nitroglycerin
▪ IV nitroglycerin (0.5-0.7 mcg/kg/min starting dose, max 200 mcg/min)
• High doses may be beneficial in the acute setting
• Adverse events are uncommon
▪ Transdermal nitroglycerin (0.5-2 inches to chest wall based on BP)
• Only after initial therapy has improved conditions
• If symptoms are minor (slow onset of action)
o Most important complication: hypotension, often only lasting transiently
and at times even seen with overall clinical improvement
▪ Usually resolves after cessation of NTG
▪ If persistent, think of a concomitant volume depletion or RV infarct,
and deliver a normal saline fluid bolus (250-1000 mL)
▪ Headache is frequent, but paracetamol usually is adequate
▪ Methemoglobinemia is a theoretic possibility but not a concern
unless high doses are used for extended intervals
• Nitroprusside (0.3 mcg/kg/min, titrated every 5-10 mins, max 10 mcg/kg/min)
o If further afterload reduction is required, use IV nitroprusside
▪ Continued high SVR usually manifested by persistent elevated BP
and continued symptoms despite NTG doses >200 mcg/min
o Potent arterial vasodilator
o Hemodynamic effects: ↓ BP, ↓ LV filling pressure, ↑ cardiac output
o Complications: hypotension, thiocyanate toxicity (especially with high
doses, prolonged [>3 days] use), and hepatic or renal impairment
o Critical endpoint: rapid ↓ filling pressure to prevent intubation
o Give IV vasodilators as soon as with vascular access if BP remains high
• Loop Diuretics (furosemide)
o May be needed in some patients after vasodilator therapy after BP control
o May increase mortality & worsen renal dysfunction if given alone
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Contraindications and Alternatives to Vasodilation in Select Settings
o Signs of hypoperfusion or existing hypotension: flow-limiting, preload-
dependent states (RV infarction, aortic stenosis, HOCM, volume
depletion) increases risk of vasodilator-associated hypotension
▪ IV β-blockers: ↓ outflow gradient by ↓ heart rate & cardiac contractility
▪ Treatment is best done in ICU with invasive hemodynamic guidance
o Coexistent shock in the setting of HOCM
▪ Phenylephrine 40-100 mcg/min IV creates peripheral
vasoconstriction without increased cardiac contractility
• Loop Diuretics (starting dose: furosemide 40 mg IV)
o Provide rapid symptomatic relief of congestive symptoms and improve
the effects of ACEI by decreasing intravascular volume
o Promote water & Na excretion, effective except severe renal dysfunction
o IV route: bowel wall edema may prevent proper GI absorption
▪ Rapid diuresis after an IV dose, often within 10-15 minutes
o Dosing is guided by symptoms & prior usage:
▪ Lowest possible dose that relieves congestion
▪ If already taking oral dose, give a total daily IV bolus dose 1-2.5 times
previous total daily oral dose, divided in half, & given every 12 hours
▪ Once congestion is resolved, continue fixed maintenance dose to
prevent recurrence
▪ With greater symptoms or less response to initial IV diuretics, double
the dose & repeat in 30-60 minutes or as needed based on UO
o Adverse effects
▪ May worsen renal function and create hypokalemia
▪ ↑ QT interval (hypocalcemia, hypokalemia, hypomagnesemia)
▪ Ototoxicity (rare) if used in conjunction with aminoglycosides
▪ K+-sparing diuretics (spironolactone 25-50 mg PO): reserved for
advanced chronic HF; more for mortality benefit than diuretic effect
o Ongoing congestion or dyspnea after a loop diuretic may signal the need
for another therapy, such as a vasodilator
• Other treatments
o Ultrafiltration
▪ Extracorporeal removal of plasma water from whole blood across a
semipermeable membrane with a transmembrane pressure gradient
▪ Advantages over diuresis
• more precise regulation of fluid removal
• avoidance of diuretic-associated electrolyte abnormalities
• higher level of sodium removal for a given amount of volume
• attenuation of significant fluctuations in intravascular volume
▪ If all diuretic and medical strategies are unsuccessful, consider
ultrafiltration for patients with obvious volume overload to alleviate
congestive symptoms and excessive weight
o Morphine (dose: 2-5 mg IV, small titrated doses with close monitoring)
▪ Relieves congestion and anxiety; for venodilation or pain control
▪ Associated with adverse events: need for mechanical ventilation,
prolonged hospitalization, ICU admission, mortality
o Nesiritide (recombinant human B-type natriuretic peptide)
▪ Second-line agent when nitroglycerin is ineffective or contraindicated
o ACEIs and ARBs
▪ Oral ACEI decrease mortality & hospitalizations in HFrEF
▪ Oral ARBs: alternatives to or can be added to ACEI in select HFrEF
o β-blockers (control rate-related heart failure)
▪ Not usually initiated in the acute setting; reserved for stable patients
▪ Rationale: norepinephrine is ↑ in HF, ↑ myocardial hypertrophy, ↑
afterload & coronary vasoconstriction, & associated with mortality
▪ Reduce SNS activity & used for mortality reduction & symptom relief
• Drugs to Avoid in Acute Heart Failure
o Oral CCBs: have myocardial depressant activity
▪ Amlodipine may be used for compelling clinical reason (antianginal
agent despite maximal therapy with nitrates & β-blockers)
o NSAIDs: can cause sodium & water retention; blunt effects of diuretics;
may increase morbidity & mortality
14. ACUTE HEART FAILURE | 63
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

ACUTE DECOMPENSATED HEART FAILURE

• Heterogeneous clinical syndrome most often resulting in need for
hospitalization due to confluence of interrelated abnormalities of decreased
cardiac performance, renal dysfunction, & alterations in vascular compliance
• Admission with a diagnosis of ADHF is associated with ↑ morbidity & mortality:
o Nearly half of these patients readmitted for management within 6 months
o High short-term (5% in-hospital) & long-term CV mortality (20% at 1 year)
• Long-term aggregate outcomes remain poor
o Combined incidence of CV deaths, HF hospitalization, MI, strokes, or
sudden death reaching 50% at 12 months after hospitalization
• Management principally revolves around volume control & decrease of
vascular impedance while maintaining end-organ perfusion (coronary & renal)
o Identify precipitants of decompensation: medication nonadherence,
prescribed medicines (NSAIDs, cold & flu preparations) with cardiac
stimulants, herbals (licorice, ginseng, herbal forms of ephedrine)
o Treat active infection & pulmonary thromboembolism if present
o When possible, arrhythmias should be corrected
▪ Control HR or restore sinus rhythm in poorly tolerated rapid AF
▪ Correct ongoing ischemia with coronary revascularization or by
correcting offenders (ongoing bleeding in demand-related ischemia)
o A parallel step is to stabilize hemodynamics in those with instability
o Pulmonary artery catheter is should be restricted to
▪ Those who respond poorly to diuresis
▪ ↓ BP or signs/symptoms of ↓ CO with unclear therapeutic targets
• Parameters associated with worse outcomes: BUN <43 mg/dL; SBP <115
mmHg; serum creatinine >2.75 mg/dL; elevated troponin I
Volume Management
• Intravenous Diuretic Agents
o Rapidly and effectively relieve symptoms of congestion
o Essential when oral drug absorption is impaired
o Continuous infusion may be needed when high doses are required, or
when effect is suboptimal to reduce toxicity & maintain stable drug levels
o Change in weight is often used as a surrogate for adequate diuresis Heart Failure with Reduced Ejection Fraction (HFrEF)
o Continue diuresis until euvolemia has been achieved
o JVP + biomarker trends are useful in timing discharge planning
o Cardiorenal syndrome: complication of ADHF; interplay between
abnormalities of heart & kidney function, with deteriorating function of one
organ while therapy is administered to preserve the other
▪ Complex interplay of neurohormonal factors and “backward failure”
(↑ intraabdominal pressure & impaired renal venous blood return)
▪ Abnormal renal function at baseline (30% of ADHF patients) is
associated with longer hospitalizations and increased mortality
▪ Most patients demonstrate a preserved cardiac output
▪ Continued use of diuretic therapy may be associated with ↓ GFR &
worsening of CRS when right-sided filling pressures remain elevated
▪ In patients in the late stages of disease (profound low cardiac output
state), inotropic therapy or mechanical circulatory support has
been shown to preserve or improve renal function in selected
individuals in the short term until more definitive therapy such as
assisted circulation or cardiac transplantation is implemented
o Ultrafiltration (UF): “aquapheresis”: electrolyte depletion-sparing effects
▪ Invasive fluid removal technique; may supplement diuretic therapy
▪ Proposed benefits: controlled rates of fluid removal, neutral effects
on serum electrolytes, decreased neurohormonal activity
Vascular Therapy
• Vasodilators (IV nitrates, nitroprusside, nesiritide) have been advocated for
upstream therapy in an effort to stabilize ADHF
• Serelaxin (recombinant human relaxin-2): peptide upregulated in pregnancy;
examined in ADHF patients with a normal or elevated blood pressure Heart Failure with Preserved Ejection Fraction (HFpEF)

Inotropic Therapy
• Positive inotropic agents: ↑ intracellular cAMP → ↑ cytoplasmic calcium
o Direct pathways (sympathomimetic amines [dobutamine])
o Indirect pathways (phosphodiesterase-3 inhibitors [milrinone])
▪ Slower acting, renally excreted, requires renal dose adjustments
▪ May provide advantage in patients with β-blockers during admission
• Novel inotropic agents: based on myofilament calcium sensitization concept
o Levosimendan: also possesses PDE-3 inhibition properties (unsuitable in
states of low output in the setting of hypotension)
o Omecamtiv mecarbil: prolongs ejection period & ↑ fractional shortening;
force of contraction not increased = myocardial O2 demand not increased
• Advantages: in low output states: augments cardiac output, improves
perfusion, and relieves congestion acutely
o Currently indicated as bridge therapy (to either LV assist device support
or to transplant) or as selectively applied palliation in end-stage HF
• Disadvantages: long-term: ↑ mortality; short-term: ↑ arrhythmia, ↓ BP

References:
• 2013 ACCF/AHA Guideline for the Management of Heart Failure
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)

64 | 14. ACUTE HEART FAILURE


15. ACUTE MYOCARDIAL INFARCTION
Acute coronary syndrome (ACS)
• ST-segment elevation acute myocardial infarction (STEMI)
o Myocardial necrosis with elevation of cardiac biomarkers
• Non-ST-segment elevation acute coronary syndrome (NSTE-ACS)
o Non-ST-segment elevation myocardial infarction (NSTEMI)
o Unstable angina (UA)
▪ Clinical diagnosis defined by chest pain or an equivalent (neck or
upper extremity pain) from inadequate myocardial perfusion that is
new, occurring with greater frequency, less activity, or at rest
▪ No pathologic ST-segment elevation or cardiac biomarker elevation
▪ At risk of eventual myocardial damage if no recognition & treatment
EPIDEMIOLOGY
• Coronary artery disease (CAD): epicardial coronary artery atherosclerosis
o Accounts for the vast majority of patients with ischemic heart disease
o Predominant symptom: chest pain
• 15% of patients presenting with acute chest pain will have ACS
o Approximately 1/3 have AMI, and the remainder have UA
• Factors associated with the emergence of ischemic heart disease:
o Genetic factors
o High-fat & energy-rich diet
o Smoking
o Sedentary lifestyle
• Powerful risk factors for IHD:
o Obesity
o Insulin resistance
o Type 2 diabetes mellitus
• Males: ~70% with angina pectoris; greater proportion of those aged <50 years
• Women: angina pectoris is often atypical in presentation
• Relative incidence of NSTEMI is rising due to the increasing burden of
diabetes and chronic kidney disease in an aging population, while STEMI is
declining due to greater use of aspirin, statins, and less smoking
• Among patients with NSTE-ACS, the proportion with NSTEMI is rising while
that with UA is falling because of the wider use of troponin assays with higher
sensitivity to detect myocyte necrosis, thereby reclassifying UA as NSTEMI
• Acute myocardial infarction (AMI) is the most common diagnosis in
hospitalized patients in industrialized countries
o About half of AMI-related deaths occur before reaching the hospital
o In-hospital mortality rate after admission for AMI has declined from 10 to
about 5% over the past decade
o 1-year mortality rate after AMI is about 15%
o Mortality is approximately fourfold higher in elderly patients (aged >75)
as compared with younger patients
o Epidemiologic studies indicate there is a shift in the pattern of AMI over
the last 15 years with more patients with NSTEMI than STEMI
ANATOMY
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
PATHOPHYSIOLOGY
Myocardial ischemia: imbalance between oxygen (O2) demand & O2 supply
O2 supply O2 demand
• O2-carrying capacity of blood: Hb + SaO2 • Heart rate
• Coronary artery blood flow: diastolic relaxation • Myocardial contractility
+ vascular resistance • Myocardial wall tension (stress)
o Coronary vascular resistance: humoral,
neural, metabolic, & extravascular
compressive forces + local autoregulation
• Exercise-induced myocardial ischemia and its sequelae usually occur as a
result of fixed atherosclerotic lesions
o Atherosclerosis limits appropriate ↑ perfusion when demand for flow is
augmented (exertion or excitement) by ↓ lumen of coronary arteries
• ACS may be caused by secondary reduction in myocardial blood flow due to:
o Coronary arterial spasm (Prinzmetal’s angina)
o Disruption/erosion of atherosclerotic plaques (coronary emboli)
o Platelet aggregation or thrombus formation at atherosclerotic lesion
o Factors extrinsic to the coronary arteries:
▪ Increased myocardial O2 demand (fever, tachycardia, thyrotoxicosis)
▪ Reduced blood flow (hypotension)
▪ Reduced O2 delivery (anemia, hypoxemia, carboxyhemoglobin)
• Rarely cause myocardial ischemia by itself
• May ↓ threshold for ischemia in moderate coronary obstruction
Coronary Atherosclerosis
• Major risk factors for atherosclerosis:
o High levels of plasma LDL
o Low plasma HDL
o Cigarette smoking
o Hypertension
o Diabetes mellitus
Normal function of vascular endothelium Abnormal consequence
• Local control of vascular tone • Inappropriate constriction
• Maintenance of antithrombotic surface • Luminal thrombus formation
• Control of inflammatory cell adhesion and • Abnormal interactions between
diapedesis blood cells (monocytes & platelets)
and activated vascular endothelium
• Epicardial coronary arteries: major site of atherosclerotic disease
o Develops at irregular rates in different segments
o Predilection to sites of ↑ turbulence in coronary flow (branch points)
o Leads to segmental reduction in cross-sectional area (narrowing)
o 50% reduction of diameter: limited ability to ↑ flow to meet ↑ demand
o 80% reduction of diameter: ↓ blood flow at rest
▪ Further minor ↓ in stenotic orifice area → dramatic ↓ coronary flow
→ myocardial ischemia at rest or with minimal stress
• Atherosclerotic plaque forms through repetitive injury to the vessel wall
o Main cellular elements: macrophages and smooth muscle cells
o Predominant extracellular milieu: lipids
o Functional changes in the vascular milieu ultimately result in subintimal
collections of fat, smooth muscle cells, fibroblasts, & intercellular matrix
• “Vulnerable plaques” responsible for ischemia may show eccentric stenosis
with scalloped or overhanging edges & narrow neck on coronary angiography
o Composed of a lipid-rich core with a thin fibrous cap
15. ACUTE MYOCARDIAL INFARCTION | 65
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Plaque Rupture EFFECTS OF ISCHEMIA

• Plaque fissuring and rupture are affected by: Transient Mechanical Disturbances of the Myocardium
o Features inherent to the plaque (composition and shape) • Regional disturbances of ventricular contractility cause segmental
o Shear stress, coronary arterial tone, coronary arterial perfusion pressure hypokinesia, akinesia, or, in severe cases, bulging (dyskinesia), which
o Movements of the artery in response to myocardial contractions can reduce myocardial pump function
• Upon exposure of plaque contents to blood:
o Platelets are activated and aggregate
• Through weak platelet interactions with subendothelial adhesion
Platelet molecules (collagen, fibronectin, laminin)
adhesion • Binding of GP Ib-V-IX receptor to subendothelial von Willebrand factor
• Adherent platelets are strongly thrombogenic
• Conformational change: ↑ platelet surface area + GPIIb/IIIa activation
• Secretion of granules: collagen, ADP, TXA2, epinephrine, serotonin
Platelet (autostimulatory agonists of platelet activation)
activation • Recruitment by ADP & TXA2: further platelet activation & potential
resistance to fibrinolysis
• Thrombin & local shear forces are also potent platelet activators
• Activated platelet glycoprotein IIb/IIIa receptors become cross-linked by
Platelet fibrinogen or von Willebrand factor
aggregation • Since fibrinogen is a multivalent molecule, it can bind to 2 different
platelets simultaneously, resulting in platelet cross-linking & aggregation • Abrupt development of severe ischemia (total/subtotal coronary occlusion):
o Coagulation cascade is activated almost instantaneous failure of normal muscle relaxation & contraction
▪ Exposure of tissue factor from damaged endothelial cells & lipid- o Relatively poor perfusion of subendocardium causes more intense
laden macrophages (plaque core & adventitia of vessel wall) ischemia of this portion of wall (compared with the subepicardial region)
▪ Factors VII & X are activated, ultimately leading to conversion of o Ischemia of large portions of ventricle causes transient left ventricular
prothrombin to thrombin, which then converts fibrinogen to fibrin failure; if papillary muscle apparatus is involved, mitral regurgitation
▪ Fluid-phase & clot-bound thrombin participates in autoamplification ▪ ↑ LV end diastolic pressure & end systolic volume (↓ CO, ↓ SV, ↓ BP)
reaction leading to further activation of coagulation cascade ▪ ↑ LA & pulmonary capillary pressure → HF & pulmonary edema
• Combination of a “vulnerable vessel” in a patient with “vulnerable blood” ▪ Poor perfusion to brain (altered mental status) & kidneys (AKI)
promotes a state of hypercoagulability and hypofibrinolysis o Transient ischemia: associated with angina pectoris
o Prolonged ischemia: can lead to myocardial necrosis & scarring ± AMI
Coronary Narrowing/Stenosis and Obstruction/Occlusion
• The culprit coronary artery eventually becomes occluded by a thrombus Transient Biochemical Disturbances of the Myocardium
o Composed of platelet aggregates and fibrin strands that traps RBCs • Normal myocardium: fatty acids & glucose → CO2 & water
o Can reduce coronary blood flow, leading to myocardial ischemia • Severe oxygen deprivation
• Location of obstruction influences quantity of myocardium rendered o Fatty acids cannot be oxidized, and glucose is converted to lactate
ischemic and determines severity of clinical manifestations o ↓ intracellular pH & myocardial stores of ATP & creatine phosphate
o Critical obstructions in vessels (left main coronary artery and proximal left • Impaired myocyte cell membrane function leads to:
anterior descending coronary artery) are particularly hazardous o Leakage of potassium
o Collateral vessels develop in chronic severe coronary narrowing & o Uptake of sodium by myocytes
myocardial ischemia, especially when narrowing develops gradually o Increase in cytosolic calcium
• With progressive worsening of a stenosis in a proximal epicardial artery, the • Severity & duration of O2 supply-demand imbalance determine reversibility:
distal resistance vessels (when they function normally) dilate to reduce o Reversible: ≤20 minutes for total occlusion in the absence of collaterals
vascular resistance and maintain coronary blood flow o Permanent, with subsequent myocardial necrosis (>20 minutes)
o When resistance vessels are maximally dilated, myocardial blood flow
becomes dependent on pressure in coronary artery distal to obstruction
o In these circumstances, ischemia can be precipitated by:
▪ Increased myocardial oxygen demand: physical activity, emotional
stress, tachycardia
▪ Changes in the caliber of the stenosed coronary artery
• Physiologic vasomotion
• Loss of endothelial control of dilation (atherosclerosis)
• Pathologic spasm (Prinzmetal’s angina)
• Small platelet-rich plug
• Amount of myocardial damage caused by coronary occlusion depends on:
o Territory supplied by the affected vessel
o Partial/total occlusion of the vessel
o Duration of coronary occlusion
o Collateral vessels to the affected tissue
o Oxygen demand of myocardium with occluded vessel
o Factors that can produce early spontaneous lysis of occlusive thrombus
o Adequacy of myocardial perfusion in infarct zone when flow is restored

Transient Electrical Disturbances of the Myocardium

• Causes characteristic changes in the ECG (repolarization abnormalities):
o Transient T-wave inversion: nontransmural, intramyocardial ischemia
o Transient ST-segment depression: patchy subendocardial ischemia
o ST-segment elevation: more severe transmural ischemia
• Electrical instability → isolated ventricular premature beats, VTach, or VFib
o Sudden death: from ischemia-induced ventricular tachyarrhythmias

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

CLINICAL CORRELATES
• The extent of O2 deprivation and the clinical presentation of ACS depend on
the limitation of O2 delivery imposed by thrombus adhering to a plaque
Stable angina
• Episodic clinical syndrome due to transient myocardial ischemia
• Ischemia occurs only when activity induces O2 demands beyond the supply
restrictions imposed by a partially occluded coronary vessel
• Ischemia occurs at a relatively fixed point & changes slowly over time
• Atherosclerotic plaque has not ruptured with little/no superimposed thrombus
Unstable Angina
• Rest angina
o Angina occurring at rest and that is prolonged, usually >20 minutes
o Patients with NSTEMI usually present with angina at rest
• New-onset angina
o New-onset angina that markedly limits ordinary physical activity (walking
1-2 blocks, climbing 1 flight of stairs, performing lighter activity)
• Increasing angina
o Previously diagnosed angina that has become distinctly more frequently,
has a longer duration, or is lower in threshold, limiting ability to walk 1-2
blocks or climb 1 flight of stairs or perform lighter activity

NSTE-ACS
• Caused by an imbalance between myocardial oxygen supply and demand
resulting from thrombus formation
o Disruption of an unstable coronary plaque due to plaque rupture, erosion,
or a calcified protruding nodule that leads to intracoronary thrombus
formation and an inflammatory response
o Coronary arterial vasoconstriction
o Gradual intraluminal narrowing
o Increased myocardial oxygen demand (fever, tachycardia, thyrotoxicosis)
in the presence of fixed epicardial coronary obstruction
• Among patients with NSTE-ACS studied at angiography
o ~10% have stenosis of the left main coronary artery
o 35% have three-vessel CAD
o 20% have two-vessel disease
o 20% have single vessel disease
o 15% have no apparent critical epicardial coronary artery stenosis
▪ Coronary microcirculation obstruction &/or epicardial vessel spasm
STEMI: Role of Acute Plaque Rupture
• Occurs when coronary blood flow decreases abruptly after a thrombotic
occlusion of a coronary artery previously affected by atherosclerosis
o Slowly developing, high-grade coronary artery stenoses do not typically
precipitate STEMI because of development of rich collateral network
o Risk factors: cigarette smoking, hypertension, and lipid accumulation
• In most cases, STEMI occurs when the surface of an atherosclerotic plaque
becomes disrupted (exposing its contents to the blood) and conditions (local
or systemic) favor thrombogenesis
• In rare cases, STEMI may be due to coronary artery occlusion caused by
o Coronary emboli
o Congenital abnormalities
o Coronary spasm
o Variety of systemic (particularly inflammatory) diseases
• Patients at increased risk for developing STEMI include:
o Multiple coronary risk factors
o Unstable angina (UA)
o Hypercoagulability
o Collagen vascular disease
o Cocaine abuse
o Intracardiac thrombi or masses that can produce coronary emboli

15. ACUTE MYOCARDIAL INFARCTION | 67

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

CLINICAL MANIFESTATION Physical Examination

History and Associated Symptoms • NSTEMI: may appear well with no signs of distress, or may
be uncomfortable, pale, cyanotic, or in respiratory distress
• Investigate cardiac (ACS) vs. noncardiac chest pain causes General Survey
• STEMI: anxious & restless, attempting unsuccessfully to
o Seek features of life-threatening causes of chest pain (ACS, aortic relieve pain by moving in bed, altering position, & stretching
dissection, PE, severe pneumonia, esophageal rupture) • Variable (transmural infarction: ↓ SBP by ~10-15 mmHg)
o STEMI: simulate pain from acute pericarditis, pulmonary embolism, acute Blood
• Elevated: baseline HTN, sympathetic stimulation, anxiety
aortic dissection, costochondritis, GI disorders pressure
• Decreased: pump failure, inadequate preload
• Typical patient with angina: man >50 years of a woman >60 years Vital • Tachycardia: ↑ sympathetic tone; ↓ LV stroke volume
• Main symptom of IHD: chest discomfort or pain Signs
Pulse Rate • Bradycardia: ischemia/infarction involving conduction
o Levine’s sign: hand over the sternum with a clenched fist, indicating a system, or alterations in SNS & PNS activation of SA & AV
squeezing, central, substernal discomfort node (more common with inferior wall myocardial ischemia)
Temperature • Elevations (38°C) possible during 1st week after STEMI
• Additional questions:
Neck • Carotid pulse: often ↓ in volume (↓ stroke volume)
o Prior evaluations for similar symptoms
Inspection • Precordium is usually quiet
o Frequency of anginal episodes & any changes in frequency of episode
• Apical impulse may be difficult to palpate
o Any increase in severity or duration of symptoms Palpation • Anterior wall infarction: abnormal systolic pulsation
o Whether less effort is required to precipitate symptoms (dyskinetic bulging of infarcted myocardium) in periapical
• Acute myocardial ischemia: area within first 5 days of the illness, & then may resolve
o More prolonged and severe chest discomfort • Abnormal heart sounds:
o More prominent associated symptoms o S3 or S4 gallop (S3 present in 15-20% [failing myocardium])
o Little response to initial sublingual nitroglycerin o Diminished S1
Any time of the day or night (circadian variations: clusters seen in morning o Paradoxical splitting of S2
within a few hours of awakening)
Chest • Murmurs
Onset Occurs at rest (or with minimal exertion) o New murmurs: chordae tendinae rupture or aortic root
Relatively recent onset (i.e., within the prior 2 weeks) Auscultation dissection, papillary muscle dysfunction, flail leaflet of
Retrosternal/substernal left anterior chest the mitral valve with resultant MR, VSD
Location o Transient midsystolic or late systolic apical murmur:
Central portion of chest and/or epigastrium
dysfunction of the mitral valve apparatus
Anginal pain: 2-10 minutes (crescendo-decrescendo nature)
o Pericardial friction rub: transmural STEMI at some time
Duration Unstable angina: 10-30 minutes (crescendo pattern)
in the course of the illness if examined frequently
AMI: >30 minutes
▪ Crackles: ischemia-induced congestive heart failure
Common: heavy, crushing, squeezing, smothering, choking, tightness, ▪ Rales ± S3 gallop: LV dysfunction and left-sided HF
Character pressure, fullness (deep and visceral)
Extremities • Pallor with perspiration & coolness of extremities
Less common: knife-like, sharp, stabbing, burning
Aggravating: exertion, vigorous exercise, emotional stress, cold PE findings most PE findings suggesting Large area of myocardial
Aggravating/ environment, medical or surgical illness strongly associated with right-sided heart failure ischemia or
Alleviating Alleviating: improves within 2 to 5 minutes after rest or NTG; during AMI in acute chest pain large NSTEMI
exertion, does not subside with cessation of activity
• Hypotension • Jugular venous • Diaphoresis
Either arms (ulnar sides of forearm & hand), shoulder, back, interscapular • S3 gallop distention • Pale, cool skin
Radiation region, root of neck, jaw, teeth, epigastrium
• Diaphoresis • Hepatojugular reflex • Sinus tachycardia
May radiate as high as occipital area but not below umbilicus
• Peripheral edema • S3 or S4
Timing Continuous
• Basilar rales
Severity Distinctly more severe, prolonged, or frequent than previous
• Hypotension (sometimes)
Associated Diaphoresis, dyspnea, nausea, vomiting, light-headedness, syncope,
symptoms palpitations, weakness, anxiety, sense of impending doom
DIAGNOSIS
• Anginal Equivalents (women, diabetics, elderly, patients with psychiatric Clinical Myocardial ischemia/necrosis
disease or altered mental status) Hx & PE Cardiac markers ECG: ST-elevation
o Dyspnea at rest/exertion
NSTE- UA + - -
o Nausea
o Light-headedness
ACS NSTEMI + + -*
o Generalized weakness STEMI + +** +
*Evidence of myocardial ischemia: ST-segment depression or T-wave inversion; **Optional; clinical & ECG would suffice for diagnosis
o Acute changes in mental status
o Diaphoresis
o Shoulder, arm, or jaw discomfort
o Epigastric or upper abdominal discomfort
o Sudden-onset breathlessness (may progress to pulmonary edema)
o Painless STEMI: greater in DM, increases with age
o Other less common presentations, with or without pain, include:
▪ Sudden loss of consciousness
▪ A confusional state
▪ A sensation of profound weakness
▪ The appearance of an arrhythmia
▪ Evidence of peripheral embolism
▪ Merely an unexplained drop in arterial pressure

Laboratory Findings
• When evaluating the results of diagnostic tests for STEMI, temporal phase of
the infarction must be considered
o Acute (first few hours-7 days)
o Healing (7-28 days)
o Healed (≥29 days)
• Laboratory tests of value in confirming the diagnosis:
o ECG
o Serum cardiac biomarkers
o Cardiac imaging
o Nonspecific indices of tissue necrosis and inflammation

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Electrocardiography (ECG) o Other causes of myocardial necrosis unrelated to ACS

• Single best test to identify patients with AMI upon ER presentation
• Obtain initial 12-lead ECG & interpret tracing quickly, ideally within 10 minutes
• NSTE-ACS
o New ST-segment depression: about 1/3 of patients with NSTE-ACS
▪ May be transient but may persist for several days following NSTEMI
o T-wave changes: more common but less specific sign of ischemia
▪ Unless they are new and deep T-wave inversions (≥0.3 mV)
• <5% of ER patients with chest pain have evidence of STEMI on ECG
o Candidate for reperfusion therapy: ST-segment elevation of ≥2 mm in 2
contiguous precordial leads and ≥1 mm in 2 adjacent limb leads
• ST-segment elevations also occur in pericarditis, myocarditis, early
repolarization, LVH, ventricular aneurysms

• CK-MB
o Elevate within 4-8 hours after AMI
o Peak between 12-24 hours
o Return to normal between 36-72 hours
o Useful when timing of infarction is unclear
▪ Both elevated: acute infarct
▪ Elevated cTn only: remote/subacute infarction
o Disadvantages:
▪ Less sensitive alternative for NSTEMI
▪ Cardiac surgery, myocarditis, electric cardioversion often results in
elevated CK-MB
• Myoglobin
o STEMI in the listed distributions suggests acute transmural injury
o Small heme-containing protein found in skeletal and cardiac muscle
o ST-segment depressions in these distributions suggest ischemia o Rise within 3 hours of symptoms
• Inferior wall AMIs should have a right-sided lead V4 (V4R) obtained o Peak at 4-9 hours
o ST-segment elevation in V4R is highly suggesting of RV infarction o Return to baseline within 24 hours
• For patients with a nondiagnostic tracing and persistent symptoms who have o False-positive common; false-negative in delayed presentation
a high risk of ACS, repeat ECG to detect developing changes o No added value in the early detection of AMI
• New left bundle-branch block: “STEMI equivalent” (<10% of patients) • BNP
• The more elevated the ST segments and the more ST segments that are o Not specific for myocardial ischemia or infarction
elevated, the more extensive is the injury o Will rise with any ventricular dysfunction
• ECG changes correlate often with the infarct-related vessel • Nonspecific reaction to myocardial injury
o Inferior wall AMIs: occlusion of the LCX or RCA o Polymorphonuclear leukocytosis
▪ LCX lesion: ST-segment elevation in ≥1 lateral lead (V5, V6, or aVL) ▪ Within a few hours after the onset of pain
with an isoelectric or elevated ST segment in lead I ▪ Persists for 3-7 days
▪ RCA occlusion: ST-segment elevation in lead III > lead II ▪ 12,000-15,000/uL
• When accompanied by ST-segment elevation in V1 or a V4R: o ESR rises more slowly than WBC
proximal RCA lesion + right ventricular infarction ▪ Peaking during the first week
▪ Reciprocal anterior ST-segment depressions in V1 through V4 ▪ Sometimes remaining elevated for 1-2 weeks
o Anterior wall AMIs: distal or proximal LAD

Serum Markers of Myocardial Injury

• Certain proteins are released form necrotic heart muscle after STEMI
• Total quantity of protein released correlates with infarct size, peak protein
concentration correlates only weakly with infarct size
• Criteria for AMI: rise and/or fall in cardiac biomarker values with at least one
above the 99th percentile of the upper reference limit for normal individuals
• Patients with diagnostic ST-segment elevation on initial ECG do not require
serum marker measurement to make treatment and disposition decision
• Serum markers are useful in patients with nondiagnostic ECGs for diagnosis
of NSTEMI and risk stratification of patients with STEMI, NSTEMI, & UA
• Cardiac Troponins (cTns)
o Proteins essential to cardiac muscle contraction
o Complexed with actin & myosin filaments within cardiac myofibrils
o Present within cardiac myocyte cytoplasm
o Myocardial injury → disruption of myocyte cell membrane integrity or
myofibril destruction → extracellular cTn leak → detected in the patient’s
peripheral blood (used to identify and quantify myocardial damage)
o Specific, sensitive, & preferred markers of myocardial necrosis
o AMI vs. nonischemic elevations: pattern of elevation & clinical context
o Diagnostic criteria for AMI: gradual rise and fall of cTn with a maximum
value above the 99 th percentile of a reference population (upper limit),
combined with any of the following:
▪ Symptoms consistent with ischemia
▪ Characteristic acute ECG changes (ST- and T-wave changes, new
LBBB, new Q waves)
▪ Imaging evidence of a new regional wall motion abnormality or a new
loss of viable myocardium
o Detected as early as 2 hours after AMI; reliably present at 6 hours
o Peak: 12-24 hours post onset of symptoms
o Remain elevated for 7-10 days after STEMI
▪ Good tool in diagnosing AMI in patients with delayed presentations
o Intermittent symptoms for days + elevated cTn: remote or new infarct
▪ CK-MB: returns to normal sooner
o Obtain cTn levels in all patients with suspected ACS
▪ Identifies 80% with AMI within 2-3 hrs of ER arrival
o Serial troponin testing is recommended to identify acute disease
▪ Early presentations (<6 hours onset) or with intermittent symptoms
▪ Constant symptoms for >8-12 hrs: a single cTn at short time intervals
(2-4 hours) to evaluate for serial change
▪ A serial high-sensitivity troponin interval as short as 2 hours coupled
with a low TIMI risk score (<2) virtually excludes AMI

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Cardiac imaging
• Two-dimensional echocardiography (2D-echo)
o When ECG is not diagnostic of STEMI, early detection of wall motion
abnormalities can aid in management decisions such as whether patient
should receive reperfusion therapy (fibrinolysis vs PCI)
o Estimation of LV ventricular function is useful prognostically
▪ Reduced function: indication for therapy with RAAS inhibitors
o May also identify the presence of RV infarction, ventricular aneurysm,
pericardial effusion, LV thrombus
o Doppler echocardiography: detection & quantitation of VSD & MR
o Acute STEMI cannot be distinguished from an old myocardial scar or from
acute severe ischemia
• Radionuclide Imaging Techniques
o Evaluates patients with suspected STEMI
o Used less often than echocardiography: more cumbersome, lack
sensitivity and specificity in many clinical circumstances
o Myocardial perfusion imaging with [ 201Tl] or [99mTc]-sestamibi
▪ Distributed in proportion to myocardial blood flow
▪ Concentrated by viable myocardium
▪ Reveals defect (“cold spot”) in most patients during the first few
hours after development of a transmural infarct
▪ Extremely sensitive; not specific for diagnosis of acute MI (cannot
distinguish acute infarcts from chronic scars)
o Radionuclide ventriculography with [ 99mTc]-labeled RBC
▪ Demonstrates wall motion disorders & ventricular EF reduction
▪ Of value in assessing hemodynamic consequences of infarction and
in aiding in the diagnosis of RV infarction when RVEF is depressed
▪ Nonspecific (many cardiac abnormalities other than MI alter results)
• High-resolution Cardiac MRI (“late enhancement”)
o Standard imaging agent (gadolinium) is administered
o Images are obtained after a 10-minute delay
o Little gadolinium enters normal myocardium (tightly packed myocytes)
o percolate into the expanded intercellular region of the infarct zone (bright
signal in areas of infarction that appears in stark contrast to the dark areas
of normal myocardium)
CLINICAL RISK SCORES AND DECISION AIDS
• Thrombosis in Myocardial Infarction (TIMI) score
o Help stratify patients with potential ACSs in the ER
o Score of 0-2: 2-9% 30-day risk of death, MI, or revascularization
• Global Registry of Acute Coronary Events
o Can aid ACS risk stratification
o Low-, intermediate, or high-risk groups for ACS
o Low risk: note sensitive enough to exclude ACS or identify patients for
early discharge without further evaluation
70 | 15. ACUTE MYOCARDIAL INFARCTION
INITIAL MANAGEMENT
• Upon arrival of patient presenting with chest pain at the ER:
o Initiate cardiac monitoring
o Obtain IV access
o Obtain ECG, ideally within 10 minutes
o Identify and treat immediate life needs (ABCs)
o Measure VS promptly and at regular intervals
o Administer oxygen if ambient saturation is <95%
• Goals for the management of patients with suspected STEMI
o Control of cardiac discomfort
o Rapid identification of candidates for urgent reperfusion therapy
o Triage of lower-risk patients to the appropriate location in the hospital
o Avoidance of inappropriate discharge of patients with STEMI
Management in the Emergency Department
• Aspirin (loading dose: buccal absorption of a chewed 160-325 mg tablet)
o Maintenance dose: 75-162 mg daily oral aspirin
o Essential in the management of patients with suspected STEMI
o Effective across the entire spectrum of ACS
o Rapid inhibition of COX-1 in platelets followed by ↓ TXA2 levels
• Supplemental Oxygen (2-4 L/min for first 6-12 hours postinfarction)
o Limited clinical benefit & not cost-effective if SaO2 is normal
o Hypoxemia: administer via nasal prongs or face mask
o Reassess patient to determine continued need for oxygen
Control of Discomfort
• Sublingual nitroglycerin (0.4 mg every 5 minutes up to 3 doses)
o Can be given safely to most patients with STEMI
o Benefits:
▪ Diminishes/abolishes chest discomfort
▪ ↓ myocardial O2 demand (by lowering preload)
▪ ↑ myocardial O2 supply (dilating infarct-related coronary/collaterals)
o IV nitroglycerin: if chest discomfort persists after 3 doses, with other
evidence of ongoing ischemia (further ST-segment or T-wave shifts)
o Contraindications:
▪ Low systolic arterial pressure (<90 mmHg)
▪ RV infarction (inferior wall AMI, ↑ JVP, clear lungs, & hypotension)
▪ PDE-5 inhibitor within last 24 hours (may potentiate hypotension)
o Idiosyncratic reaction to nitrates: sudden marked hypotension
▪ Can be reversed promptly by the rapid administration of IV atropine
• Morphine (2-4 mg IV every 5 minutes)
o Very effective analgesic for the pain associated with STEMI
o May reduce sympathetically mediated arteriolar and venous constriction
▪ Resulting venous pooling may ↓ cardiac output & arterial pressure
▪ Reversal: elevation of legs, volume expansion with IV saline
o Patient may experience diaphoresis & nausea, but usually pass & are
replaced by a feeling of well-being associated with the relief of pain
o Vagotonic effect; bradycardia or advanced degrees of heart block in
patients with inferior infarction (respond to atropine 0.5 mg IV)
• IV β-blockers (Metoprolol 5 mg every 2-5 minutes for a total of 3 doses)
o Also useful in the control of the pain of STEMI
o Control pain effectively in some patients (↓ myocardial O2 demand)
o Reduce the risk of reinfarction and ventricular fibrillation
o Patient selection is important when considering β blockers for STEMI
▪ HR >60 bpm; SBP >100 mmHg; PR interval <0.24 s; rales no higher
than 10 cm up from the diaphragm
o Oral regimen (initiated 15 minutes after the last IV dose)
▪ 50 mg every 6 hours for 48 hours
▪ 100 mg every 12 hours
o Oral β-blocker therapy: initiated in first 24 hours for patients with no:
▪ Signs of heart failure
▪ Evidence of a low-output state
▪ Increased risk for cardiogenic shock
▪ Other relative contraindications to β-blockade (PR interval >0.24 s,
2nd or 3rd degree heart block, active asthma, reactive airway disease)

Limitation of Infarct Size
• Primary Percutaneous Coronary Intervention (PCI)
o ACC/AHA/ESC: PCI as preferred method of reperfusion therapy if the
first medical contact to first balloon inflation time is <90-120 minutes
o Coronary angioplasty ± stent placement is the most common PCI
▪ Coronary stents: fenestrated stainless-steel tubes expanded by a
balloon to provide scaffolding within coronary arteries
▪ Adding antiplatelet therapy (thienopyridines & GPIIb/IIIa inhibitors)
results in lower adverse events at 6 months
▪ Drug-eluting stents are associated with decreased early (within
months) vessel closure but a higher delayed closure, particularly
once antiplatelet agents (clopidogrel) are stopped
o Balloon angioplasty increases the size of the arterial lumen through:
▪ Endothelial denudation
▪ Cracking, splitting, and disruption of atherosclerotic plaque
▪ Dehiscence of intima and plaque from underlying media
▪ Stretching or tearing of underlying media and adventitia
o With successful dilatation, small amounts of arterial wall dissection and
aneurysmal expansion may be seen
o The greater the increase in luminal size, the lower is the risk of restenosis
▪ More aggressive balloon inflation can augment dissection, platelet
deposition, thrombus formation, plaque hemorrhage
o Effective in restoring perfusion in STEMI when done first few hours of MI
o Alternative PCI procedures attempt to limit complications
▪ Directional & rotational coronary atherectomy extract atherosclerotic
tissue from the coronary artery
▪ Excimer laser atherectomy vaporizes atheromatous tissue
• Results in larger luminal diameter
o Advantages over fibrinolysis
▪ More effective in establishing flow & reducing reocclusion
▪ Decreased incidence of short- & long-term death, nonfatal
reinfarction, and intracranial hemorrhage
▪ Applicable to patients who have contraindications to fibrinolytic
therapy but otherwise appropriate candidates for reperfusion
▪ Longer duration of symptoms, greater benefit
o Generally preferred when
▪ Diagnosis is in doubt
▪ Cardiogenic shock is present
▪ Bleeding risk is increased
▪ Symptoms for ≥2-3 hours (clot is more mature & less easily lysed)
o Disadvantages
▪ Expensive in terms of personnel and facilities
▪ Limited by availability, around the clock, in only minority of hospitals
• Fibrinolysis
o AHA/ACC target treatment goal
▪ ≤90 minutes: patient who arrives at a hospital with PCI capability
▪ ≤120 minutes: patients arriving at a hospital without PCI capability to
account for transfer time
o Ideally initiated within 30 minutes (door-to-needle time ≤30 minutes)
o Principal goal: prompt restoration of full coronary arterial patency
o Improves LV function and short-term and long-term mortality
o MOA: promotes conversion of plasminogen to plasmin, which
subsequently lyses fibrin thrombi (plasminogen activators)
o Indications:
▪ Patients with STEMI (as a reperfusion option) if time to treatment is
<6 to 12 hours from symptom onset and the ECG has at least 1 mm
of ST-segment elevation in 2 or more contiguous leads
▪ More beneficial if given early and for larger infarctions and anterior
infarctions than for smaller or inferior infarctions
o When assessed angiographically, flow in the culprit coronary artery is
described by TIMI grading system
▪ Grade 0: complete occlusion of the infarct-related artery
▪ Grade 1: some penetration of the contrast material beyond the point
of obstruction, but without perfusion of the distal coronary bed
▪ Grade 2: perfusion of the entire infarct vessel into the distal bed, but
with flow that is delayed compared with that of a normal artery
▪ Grade 3: full perfusion of the infarct vessel with normal flow
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
o Goal of reperfusion therapy: Grade 3 TIMI (yields far better results in
terms of limiting infarct size, maintenance of LV function, and reduction
of both short- and long-term mortality rates
o Additional method of angiographic assessment of efficacy of fibrinolysis
▪ TIMI frame count: number of frames required for dye to flow from
origin of infarct-related artery to a landmark in distal vascular bed
▪ TIMI myocardial perfusion grade: rate of entry and exit of contrast
dye from the microvasculature in the myocardial infarct zone
o Hemorrhage (most frequent & potentially most serious complication)
▪ Unnecessary venous or arterial interventions should be avoided
▪ Hemorrhagic stroke: most serious complication; rate increases with
advancing age (>70 years: twice rate of ICH vs <65 years)
o Rescue PCI (after failed fibrinolytic administration):
▪ In cardiogenic shock who are <75 years old
▪ With severe heart failure or pulmonary edema
▪ With hemodynamically compromising ventricular arrhythmias
▪ Moderate or large area of myocardium is still at risk
o Limitations of fibrinolytic therapy in STEMI
▪ Even the most potent fibrinolytic agents do not achieve early and
complete restoration of coronary blood flow in 40-50% of patients
• Optimal antithrombin therapy (enoxaparin > UFH) and DAPT
(aspirin + clopidogrel) lead to improved outcomes
▪ Approximately 0.5-1.0% of patients have intracranial hemorrhage,
which usually results in death or disabling stroke
o STEMI: should receive full-dose anticoagulants for ≥48 hours
• Integrated Reperfusion Strategy
o Cardiac catheterization and coronary angiography should be carried
out after fibrinolytic therapy if there is evidence of either:
▪ Failure of reperfusion (persistent chest pain & ST-segment elevation
>90 minutes) – rescue PCI should be considered
▪ Coronary artery reocclusion (re-elevation of ST segments and/or
recurrent chest pain) or development of recurrent ischemia
(recurrent angina in early hospital course or positive exercise stress
test before discharge) – urgent PCI should be considered
o Coronary artery bypass graft (CABG)
▪ Reserved for patients whose coronary anatomy is unsuited to PCI
but in whom revascularization appears to be advisable because of
extensive jeopardized myocardium or recurrent ischemia
HOSPITAL MANAGEMENT
• ↑ work of heart during initial hours of infarction = ↑ size of infarct
• First 6-12 hours: Complete bed rest
• Within first 24 hours: Resume an upright posture (with supervision)
o In the absence of complications
Activity o Dangle feet over the side of the bed or sit in a chair
• 2nd or 3rd day: Progressive ambulation (↑ duration & frequency)
o In the absence of hypotension and other complications
o May shower or stand at the sink to bathe
o Goal: 185 m (600 ft) at least 3 times a day
• First 4-12 hours: NPO or clear liquids only (risk of emesis, aspiration)
• Contents:
o Fat: ≤30% of total calories (cholesterol content: ≤300 mg/day)
Diet o Complex carbohydrates: 50-55% of total calories
o Portions should not be unusually large
o Foods enriched with ↑ potassium, magnesium, & fiber, ↓ sodium
o DM & hypertriglyceridemia: restriction of concentrated sweets
• Bed rest & effect of narcotics often lead to constipation
• A bedside commode rather than a bedpan
Bowel • Diet rich in bulk
management • Stool softener (dioctyl sodium sulfosuccinate 200 mg/day)
• If patient still constipated, a laxative can be prescribed
• Gentle rectal examination on patients with STEMI is safe
• To withstand the period of enforced inactivity with tranquility
• Diazepam 5 mg, oxazepam 15-30 mg, lorazepam 0.5-2 mg 3-4x/day
Sedation
• Additional dose may be given at night to ensure adequate sleep
• No substitute for reassuring, quiet surroundings
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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
ANTITHROMBOTIC AGENTS
• Maintain patency of infarct-related artery, in conjunction with reperfusion
• Reduce tendency to thrombosis and, thus, likelihood of mural thrombus
formation or DVT (either could result in pulmonary embolization)
Antiplatelet agents
• Aspirin: standard antiplatelet agent for patients with STEMI
o Loading dose: 162-325 mg; Maintenance dose: 80 mg daily
o Prevents formation of TXA2, an agonist of platelet aggregation
o Inhibition persists for the 8- to 12-day life of the platelet
o Side effects are mainly GI, accumulative, and dose related
▪ Reduced by using diluted or buffered aspirin solutions, lowest
possible doses, or concurrent antacid or H2 antagonist administration
▪ Do not withhold from patients with minor contraindications (vague
allergy, history of remote peptic ulcer, GI bleeding)
▪ Other antiplatelet agents (clopidogrel) are alternatives if true aspirin
allergy or active peptic ulcer disease exists
• P2Y12 adenosine diphosphate (ADP) receptor antagonists
o Prevent activation and aggregation of platelets
▪ In addition to aspirin reduces the risk of clinical events
▪ In fibrinolytic therapy: prevent reocclusion of a successfully
reperfused infarct artery
o Prasugrel: irreversible, potent platelet receptor antagonist
▪ Contraindications: prior CVA or TIA; pathologic bleeding
• Risk factors for bleeding: age ≥75 years, propensity for bleeding,
concomitant use of medications that increase risk of bleeding
o Ticagrelor: reversible nonthienopyridine P2Y12 receptor antagonist
▪ Effect gone within 3 days of stopping the agent
o Clopidogrel (dose: 300-600 mg loading dose, and 75 mg daily dose)
▪ Addition to aspirin & antithrombin therapy improves cardiovascular
outcomes in patients receiving fibrinolysis for STEMI
▪ Give clopidogrel to patients with true aspirin allergy
▪ Early administration is recommended in patients with ACS
regardless of whether noninvasive management of PCI is planned
▪ Warnings on efficacy
• Omeprazole: 50% reduction in antiplatelet aggregation effects
• CYP2C19 variant gene: impaired metabolism
▪ Withhold clopidogrel for 5 days before CABG when possible
▪ Do not withhold unless CABG is imminent
• Glycoprotein IIb/IIIa inhibitors
o Useful in preventing thrombotic complications in STEMI undergoing PCI
o Abciximab: chimeric antibody; irreversible; duration of action is longer
o Eptifibatide: synthetic heptapeptide; reversible
o Tirofiban: synthetic small molecule; reversible
Antithrombins/Anticoagulants
• Unfractionated heparin: standard anticoagulant used in clinical practice
o Dose (AHA/ACC):
▪ Initial bolus of 60 units/kg (max 4000 U)
▪ Infusion of 12 units/kg/h (max 1000 U/h)
o Dose (ESC):
▪ 70-100 units/kg IV bolus (no GPIIb/IIIa inhibitor)
▪ 50-60 units/kg IV bolus (with GPIIb/IIIa)
o Monitoring: aPTT should be 1.5-2 times the control value
o Aspirin + heparin
▪ Reduces short-term risk of death or AMI by 56% vs aspirin alone
▪ Recurrence of ischemia is diminished after cessation of the infusion
o IV UFH + aspirin + non-fibrin-specific thrombolytic agent (streptokinase),
additional mortality benefit occurs
o IV UFH + aspirin + relatively fibrin-specific fibrinolytic agents (tPA, rPA,
TNK) helps maintain patency of infarct-related artery
o Disadvantages
▪ Unpredictable anticoagulant response (bioavailability is variable)
▪ Requires careful laboratory monitoring and dose adjustment
▪ Heparin-induced thrombocytopenia (cease after 48 hours of therapy)
• Low-molecular-weight heparins (enoxaparin)
o Advantages:
▪ High bioavailability permitting administration SC once/twice a day
▪ Reliable anticoagulation without monitoring
▪ Greater antiXa:IIa activity
▪ Lower protein binding &longer half-life
o LMWH + aspirin + fibrinolysis: improved outcome in STEMI patient
o Not considered a first line antithrombin for primary PCI for STEMI
▪ If previously started & goes for PCI, enoxaparin should be continued
▪ If CABG is planned, hold LMWH for 12-24 hours, bridging with UFH
• Fondaparinux: synthetic pentasaccharide; binds to antithrombin-III to form
an antithrombin complex; very specific for factor Xa inhibition
o Not a monotherapy for PCI; if used, add UFH or bivalirudin before PCI
o Should not be used alone at the time of coronary angiography and PCI;
should be combined with another anticoagulant (UFH or bivalirudin)
• Bivalirudin (direct thrombin inhibitor)
o Bind to the catalytic site of thrombin, bind to thrombin in clot, and are
resistant to agents that degrade heparin
o Reduces short-term risk of postischemic complications vs. high-dose
UFH in patients undergoing PCI for unstable or postinfarction angina
72 | 15. ACUTE MYOCARDIAL INFARCTION
ANTI-ANGINAL/ANTI-ISCHEMIC AGENTS
• Nitrates (Nitroglycerin)
o MOA: metabolic conversion of organic nitrates to nitric oxide
▪ Vasodilator effects in arteries, arterioles, & veins with obstructing
atherosclerotic lesions with intact vascular smooth muscle
▪ Increases global and regional myocardial blood flows
▪ Decrease: PCWP, systemic arterial pressure, LV end-systolic & end-
diastolic volumes, RV & LV filling pressures (from peripheral
dilatation) with afterload reduction (from arterial dilatation) decrease
cardiac work & myocardial O2 requirements
▪ Platelet aggregation is also inhibited
o ACC/AHA: IV NTG for the first 24-48 hours
▪ For patient with STEMI and recurrent ischemia, CHF, or HTN
▪ Titrate to BP reduction rather than to symptom (chest pain) resolution
▪ UA/NSTEMI: in patients unresponsive to sublingual NTG tablets
▪ Benefits greatest if not receiving concurrent fibrinolytic therapy
o Most serios side effect: hypotension
▪ May result in reflex tachycardia and worsening ischemia
▪ Paradoxical bradycardia can also result following nitrate use
▪ If with hypotension, stop the drug and administer fluid for BP
o Use NTG cautiously for patients with inferior wall ischemia
▪ 1/3 might have RV involvement (volume dependent)
▪ Nitrates ↓ preload & commonly trigger hypotension, worsening infarct
o Contraindication: received PDE-5 inhibitor for erectile dysfunction
(within 24 hours of sildenafil use or within 48 hours of tadalafil use)
• β-blockers
o MOA: antidysrhythmic, anti-ischemic, antihypertensive properties
▪ ↓ myocardial O2 demand: ↓ HR, BP, & myocardial contractility
▪ Prolongation of diastole: augment perfusion to ischemic myocardium
o No benefit from early β-blocker therapy
o ACC/AHA: oral β-blockers in STEMI/NSTEMI within 24 hours with no:
▪ Signs of heart failure
▪ Evidence of a low cardiac output state
▪ Increased risk of cardiogenic shock
▪ Standard relative contraindications of β-blockade
o IV therapy is reserved for patients with significant hypertension
o Benefits of β-blockers in patients with STEMI
▪ Improves myocardial O2 supply-demand relationship
▪ Decreases pain
▪ Reduces infarct size
▪ Decreases incidence of serious ventricular arrhythmias
o Contraindications
▪ Heart failure or severely compromised LV function
▪ Heart block
▪ Orthostatic hypotension
▪ History of asthma
• ACE inhibitors
o MOA: reduces ventricular remodeling (↓ LV dysfunction & LV dilatation)
after infarction with subsequent reduction in risk of CHF
o ACC/AHA: oral ACE inhibitors within the first 24 hours for STEMI/HF
▪ UA/NSTEMI: administered within 24 hours in pulmonary congestion
or LVEF <40% in absence of contraindications
o Contraindications:
▪ Hypotension
▪ Bilateral renal artery stenosis
▪ Renal failure
▪ History of cough or angioedema due to prior ACE inhibitor use
o Maximum benefit is seen in high-risk patients
▪ Elderly
▪ Anterior infarction
▪ Prior infarction
▪ Globally depressed LV function
o Should be continued indefinitely in patients with:
▪ Clinically evident CHF
▪ Reduction in global LV function
▪ Large regional wall motion abnormality
▪ Hypertension
• Angiotensin Receptor Blockers (ARBs)
o For ACEI intolerance with clinical/radiologic signs of heart failure
• Aldosterone Blockers
o Long-term aldosterone blockade should be prescribed to STEMI patients:
▪ No significant renal dysfunction (creatinine ≥2.5 mg/dL in men and
≥2.0 mg/dL in women) or hyperkalemia (≥5.0 mEq/L) who are
already receiving therapeutic doses of ACEI
▪ LVEF ≤40%
▪ Either symptomatic heart failure or DM
• Magnesium
o MOA: systemic & coronary vasodilation; antiplatelet activity; suppresses
automaticity; protects myocytes from calcium influx during reperfusion
o Correct documented hypomagnesemia during AMI and give magnesium
for torsades-type VT with a prolonged QT interval
• Calcium Channel Blockers (CCBs)
o MOA: Antianginal, vasodilatory, antihypertensive properties
o No ↓ mortality rate after AMI; may be harmful to some with CV disease
o Verapamil & diltiazem: potentially beneficial in patients with
▪ Ongoing ischemia/AF with RVR (no CHF, LV dysfunction, AV block)
▪ When β-blockers are contraindicated
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

15. ACUTE MYOCARDIAL INFARCTION | 73

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

NSTE-ACS: MEDICAL TREATMENT • Anticoagulants

• Bed rest with continuous ECG monitoring (for ST-segment deviation and o UFH: long the mainstay of therapy
cardiac arrhythmias), preferably on a specialized cardiac unit o LMWH (enoxaparin)
• Ambulation is permitted if the patient ▪ Superior to UFH in reducing recurrent cardiac events, especially in
o Shows no recurrence of ischemia (symptoms or ECG changes) patients managed by a conservative strategy
o Does not develop an elevation of a biomarker of necrosis for 12-24 hours ▪ Accompanied by a slight increase in bleeding vs UFH
• Medical therapy o Bivalirudin (direct thrombin inhibitor)
o Acute phase: focused on clinical symptoms & stabilization of lesion(s) ▪ Similar efficacy to either UFH or LMWH
o Longer-term phase: involves therapies directed at the prevention of ▪ Causes less bleeding
disease progression and future plaque rupture/erosion ▪ Used just prior to and/or during PCI
• To provide relief and prevention of recurrence of ischemic discomfort, initial o Fondaparinux (indirect factor Xa inhibitor)
treatment should include ▪ Equivalent in efficacy to enoxaparin
o Bed rest ▪ Widely studied in patients managed either with an early conservative
o Nitrates or invasive strategy
o β-blockers ▪ Requires supplemental UFH or bivalirudin during PCI to prevent
o Inhaled oxygen (SaO2 <90% or with HF and rales) procedure-related thrombosis)
• Most important adverse effect of all antithrombotic agents (antiplatelet
agents and anticoagulants): excessive bleeding
Anti-Ischemic Treatment o Attention must be directed to the doses of the antithrombotic agents,
• Nitrates (0.3-0.6 mg sublingual or by buccal spray for 3 doses mins apart) accounting for body weight, creatinine clearance, previous history of
o IV NTG 5-10 ug/min using nonabsorbable tubing if symptoms persist excessive bleeding, as a means of reducing risk of bleeding
▪ May be increased by 10 ug/min every 3-5 minutes until either:
• Symptoms are relieved Invasive vs Conservative Strategy
• Systolic arterial pressure falls to <90 mmHg • Invasive strategy
• Dose reaches 200 ug/min o Anti-ischemic & antithrombotic agents → coronary arteriography within
o Topical or oral nitrates can be used when pain has resolved ~48 hours of presentation → coronary revascularization (PCI or CABG),
▪ May replace IV NTG if symptom-free for 12-24 hours depending on the coronary anatomy
o Absolute contraindications: hypotension, recent use of a PDE-5 inhibitor o Benefit in high-risk patients
(sildenafil, vardenafil, tadalafil) ▪ Multiple clinical risk factors
• β-blockers: other mainstay of anti-ischemic treatment ▪ ST-segment deviation
o IV route: in patients with severe ischemia ▪ Positive biomarkers
Avoided in acute/severe HF, low cardiac output, hypotension, o In patients at low risk, outcomes are similar to conservative strategy
contraindications to β-blocker therapy • Conservative strategy
o Oral: target HR 50-60 bpm is recommended o Anti-ischemic & antithrombotic therapy → “selective invasive approach”
o HR-slowing CCBs (verapamil, diltiazem) ▪ Patient is closely observed
▪ Recommended for persistent symptoms or ECG signs of ischemia ▪ Coronary arteriography is carried out if
after treatment with full-dose nitrates and β-blockers • Rest pain or ST-segment changes recur
▪ In patients with contraindications to either class of these agents • Biomarker of necrosis becomes positive
o Additional medical therapy: ACEI/ARBs • Evidence of severe ischemia on a stress test
o Intensive HMG-CoA reductase inhibitors (Atorvastatin 80 mg/day)
▪ Early administration prior to PCI and continued thereafter has been
shown to reduce periprocedural MI and recurrences of ACS
▪ Ezetimibe 10 mg daily may be added to reduce further LDL-C
• Inadequate response to maximally tolerated statin
o <50% decrease in LDL-C from untreated baseline
o LDL-C on treatment >70 mg/dL

Antithrombotic Therapy
• Antiplatelet Drugs
o Aspirin (COX inhibitor)
▪ Loading dose: at least 162 mg (oral non-enteric coated or IV)
▪ Maintenance dose: 75-100 mg/day (maintain efficacy; less bleeding)
▪ Contraindications: severe active bleeding or aspirin allergy
o Platelet P2Y12 receptor blocker
▪ Clopidogrel (thienopyridine): inactive prodrug, converted into an
active metabolite that causes irreversible blockade
• Loading dose: 600 or 300 mg; Maintenance dose: 75 mg daily
• Clopidogrel + aspirin = dual antiplatelet therapy (DAPT): 20%
relative reduction in CV death, MI, stroke vs. aspirin alone;
moderate (absolute 1%) increase in major bleeding
▪ Prasugrel (thienopyridine): more rapid onset, higher level of platelet
inhibition than clopidogrel
• For ACS patients following angiography when PCI is planned
• Loading dose: 60 mg; Maintenance dose: 10 mg/day
• Shown to significantly reduce combined risk of CV death, MI,
stroke by 19%; reduced stent thrombosis by 50%
• Contraindications: prior stroke or TIA, high risk for bleeding
▪ Ticagrelor: novel, potent, reversible
• Reduce risk of CV death, total mortality, or MI vs. clopidogrel
• Loading dose: 180 mg; Maintenance dose: 90 mg BID
• Benefit whether conservative or invasive
• Some may develop dyspnea early after administration
(transient, infrequently serious, not associated with clinical
exacerbations of COPD or CHF)
▪ Alternate P2Y12 blockers should be considered in patients
• Developed coronary event with clopidogrel + aspirin
• Hyporesponsive to clopidogrel
• High risk for ischemic complications
o IV GPIIb/IIIa inhibitors
▪ Addition to aspirin + clopidogrel (triple antiplatelet therapy) should be
reserved for unstable patients undergoing PCI
• Recurrent rest pain
• Elevated cTn
• ECG changes
• Coronary thrombus evident on angiography

74 | 15. ACUTE MYOCARDIAL INFARCTION

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

LONG-TERM MANAGEMENT PRINZMETAL’s VARIANT ANGINA

• Review and optimize the medical regimen
• Risk-factor modification with discussion of the importance of:
o Smoking cessation
o Achieving optimal weight
o Daily exercise
o BP control
o Following an appropriate diet
o Control of hyperglycemia (in diabetic patients)
o Lipid management as recommended for chronic stable angina
• Long-term therapy with 5 classes of drugs that are directed at different
components of the atherothrombotic process
o β-blockers
o Lipid lowering therapy (statins at high dose, e.g., atorvastatin 80 mg/d,
with ezetimibe if needed to achieve an LDL-C <70 mg/dL)
o ACE inhibitors/ARBs
o Antiplatelet regimen
▪ Low-dose aspirin (75-100 mg/d) + P2Y12 inhibitor (clopidogrel,
prasugrel, ticagrelor) for 1 year
▪ Continue aspirin thereafter
▪ Continue DAPT out to 3 years in selected patients at high ischemic
risk (prior MI, DM, vein graft stent, CHF) who are low risk of bleeding
POSTINFARCTION RISK STRATIFICATION AND MANAGEMENT
• Increased cardiovascular risk after initial recovery from STEMI
o Persistent ischemia (spontaneous or provoked)
o Depressed LVEF (<40%)
o Rales above the lung bases on PE or congestion on chest radiography
o Symptomatic ventricular arrhythmias
• Other features associated with increased risk
o History of previous MI
o Age >75
o Diabetes mellitus
o Prolonged sinus tachycardia
o Hypotension
o ST-segment changes at rest without angina (“silent ischemia”)
o Abnormal signal-averaged ECG
o Nonpatency of infarct-related coronary artery (angiography)
o Persistent advanced heart block or new intraventricular conduction
abnormality on the ECG
• Strategies to evaluate risk after infarction
o Submaximal exercise stress testing (before hospital discharge)
▪ Detect residual ischemia and ventricular ectopy
▪ Provide guideline for exercise in the early recovery period
o Maximal (symptom-limited) exercise stress test (4-6 wks after infarction)
o Evaluation of LV function: depressed LVEF (give RAAS inhibitors)
• High risk for recurrent MI or death from arrhythmia (cardiac
catheterization with coronary angiography and/or invasive electrophysiologic
evaluation is advised)
o Angina is induced at relatively low workload
o Large reversible defect on perfusion imaging or a depressed EF
o Demonstrable ischemia
o Exercise provokes symptomatic ventricular arrhythmias
• Timeline of recovery
o 3-5 days: usual duration of hospitalization for an uncomplicated STEMI
▪ Remainder of convalescent phase may be accomplished at home
o First 1-2 weeks: encourage increased activity (walking about the house
& outdoors in good weather; normal sexual activity may be resumed)
o After 2 weeks: regulate patient’s activity based on exercise tolerance
o 2-4 weeks: Most patients will be able to return to work
• Severe ischemic pain; occurs at rest; with transient ST-segment elevation
• Focal spasm of an epicardial coronary artery resulting in transmural ischemia
& abnormalities in LV function; may lead to acute MI, VT, VF, and SCD
• Cause of the spasm is not well defined
o May be related to hypercontractility of vascular smooth muscle due to
adrenergic vasoconstrictors, leukotrienes, or serotonin
• Clinical and Angiographic Manifestations
o Generally younger and, with the exception of cigarette smoking, have
fewer coronary risk factors than NSTE-ACS
o Cardiac examination is usually unremarkable in the absence of ischemia
o A minority of patients have a generalized vasospastic disorder associated
with migraine and/or Raynaud’s phenomenon
o Clinical diagnosis: detection of transient ST-segment elevation with rest
pain, although many patients also exhibit episodes of silent ischemia
o Coronary angiography: transient coronary spasm (diagnostic hallmark)
o Hyperventilation or intracoronary acetylcholine has been used to
provoke focal coronary stenosis on angiography or to provoke rest angina
with ST-segment elevation to establish the diagnosis
• Treatment
o Nitrates and CCBs are the main therapeutic agents
o Aspirin may actually increase the severity of ischemic episodes
▪ Possibly as a result of the sensitivity of coronary tone to modest
changes in the synthesis of prostacyclin
o Statin therapy has been shown to reduce the risk of major adverse
events, although the precise mechanism is not established
o The response to β-blockers is variable
o Coronary revascularization may be helpful in patients who also have
discrete, flow-limiting, proximal fixed obstructive lesions
o Implantable cardioverter-defibrillator: for patients who had ischemia-
associated VF despite maximal medical therapy
• Prognosis
o Many patients pass through an acute, active phase
▪ Frequent episodes of angina & cardiac events during 1st 6 months
o Survival at 5 years is excellent (~90-95%), but as many as 20% of
patients experience an MI
o Patients with no or mild fixed coronary obstruction experience a low rate
of cardiac death or MI compared to patients with associated severe
obstructive lesions, although about half of the patients without obstructive
CAD still experience frequent angina at rest
o Patients with PVA who develop serious arrhythmias during spontaneous
episodes of pain are at a higher risk for SCD
o In most patients who survive an infarction or the initial 3- to 6-month
period of frequent episodes, there is a tendency for symptoms and
cardiac events to diminish over time

SECONDARY PREVENTION
• Long-term treatment with an antiplatelet agent (usually aspirin) after STEMI:
25% reduction in the risk of recurrent infarction, stroke, or CV mortality
o Clopidogrel (75 mg/day PO): alternative in patients intolerant to aspirin
• ACEI or ARBs, and, in appropriate patients, aldosterone antagonists:
indefinitely to prevent late ventricular remodeling & recurrent ischemic events
o Clinically evident heart failure
o Moderate decrease in global EF
o Large regional wall motion abnormality
• Chronic routine use of oral β-blocker for at least 2 years after STEMI
• Warfarin
o Lowers risk of late mortality & incidence of reinfarction after STEMI
o Added to aspirin for patients at increased risk of embolism
o <75 years old: low-dose aspirin (75-81 mg/d) + warfarin (INR >2.0) is
more effective vs. aspirin alone to prevent recurrent MI & embolic CVA
▪ Increased risk of bleeding when warfarin is added to DAPT
o Patients with implanted stent and have an indication for anticoagulation
should receive DAPT + warfarin
▪ Also receive PPIs to minimize risk of GI bleeding
▪ Should have regular monitoring of hemoglobin levels and stool
hematest while on combination antithrombotic therapy
• Risk factors for atherosclerosis should be discussed & favorably modified

15. ACUTE MYOCARDIAL INFARCTION | 75

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
COMPICATIONS OF ACS
Dysrhythmias and Conduction Disturbances
• 72-100% of AMI patients treated in the coronary care unit
• Main consequences
o Impaired hemodynamic performance
▪ Dependent on ventricular function
▪ LV dysfunction: relatively fixed volume; depend on HR to alter CO
▪ Ranges of optimal HR becomes narrowed with ↑ dysfunction
▪ Slower or faster HR may further depress cardiac output
o Compromised myocardial viability (↑ myocardial O2 requirements)
o Predisposition to even more serious rhythm disturbances (↓ VF threshold)
• Sinus tachycardia
o Quite prominent with anterior wall AMI
o Persistent sinus tachycardia is associated with poor prognosis in AMI
o Causes: anxiety, pain, LV failure, fever, pericarditis, hypovolemia, atrial
infarction, pulmonary emboli, medications
• Atrial fibrillation
o Occurs in the first 24 hours and is usually transient
o In excess catecholamine release, hypokalemia, hypomagnesemia,
hypoxia, chronic lung disease, sinus node/LCX ischemia
o VT/AF with hemodynamic compromise: treated with DC cardioversion
o Partially/fully compensated or who do not respond to cardioversion:
amiodarone or β-blockers to slow the ventricular rate
o Patient with ongoing ischemia but without hemodynamic compromise,
clinical LV dysfunction, reactive airway disease, or heart block should
have rate control with β-blockers
▪ Atenolol 2.5-5 mg over 2 minutes, total of 10 mg
▪ Metoprolol 2.5-5 mg every 2-5 minutes, total of 15 mg
o Patients with contraindications to β-blockers:
▪ Digoxin 0.3-0.5 mg initial bolus, repeat dose in 4 hours
▪ Calcium channel antagonist
o Anticoagulate patients with AF & AMI to limit systemic embolization
• Sinus bradycardia
o Without hypotension does not appear to increase mortality during AMI
o Prognosis: site of infarction, site of block (intranodal vs infranodal) type
of escape rhythm, hemodynamic response to the rhythm
o Atropine
▪ For sinus bradycardia when it results in hypotension, ischemia, or
ventricular escape rhythms & for treatment of symptomatic AV block
occurring at the AV nodal level (2nd degree type I)
▪ Can improve HR, SVR, BP
▪ Caution in AMI since the parasympathetic tone is protective against
infarction extension, VF, and excessive myocardial O2 demand
• Complete heart block
o Anterior and inferior AMI (AV conduction system receives blood supply
from AV branch of RCA and septal perforating branch of LAD)
o CHB + anterior MI portends a grave prognosis
o Increased mortality is related to more extensive myocardial damage and
not to the heart block itself
Heart Failure
• 15-20% of patients with AMI (1/3 have circulatory shock)
• From diastolic dysfunction alone or systolic + diastolic dysfunction
• LV diastolic dysfunction leads to pulmonary congestion
• Systolic dysfunction: decreased forward flow, reduced CO, reduced EF
• More severe degree of LV dysfunction: higher mortality
• Degree of LV dysfunction depends on the net effect of
o Prior myocardial dysfunction
o Baseline myocardial hypertrophy
o Acute myocardial necrosis
o Acute reversible myocardial dysfunction (“stunned myocardium”)
• Mortality increases as CO decreases or pulmonary congestion increases
o No HF: 10%
o Mild HF: 15-20%
o Frank pulmonary edema: 40%
o Cardiogenic shock: 50-80%
• ↑ BNP or proBNP early in the hospital course portend a worse 30-day outcome
• Shock in AMI results in a complex spiral relationship
o Coronary obstruction → myocardial ischemia → impairs myocardial
contractility and ventricular outflow → reduced arterial BP → further
decrease in coronary artery perfusion → worsening myocardial ischemia
→ more severe myocardial necrosis
o Interruption of this downward spiral requires careful attention to fluid
management and the use of inotropic agents
Mechanical Complications
• Sudden decompensation of previously stable patients should raise concerns
for the mechanical complications of AMI
• Usually involve the tearing or rupture of infarcted tissue, not seen in UA
• Clinical presentation depends on the site of rupture
• Ventricular free wall rupture (1-5 days after infarction; 10% of AMI fatalities)
o Rupture of LV free wall: cardiac tamponade & death (in >90% of cases)
o Patients may complain of tearing pain or sudden onset of severe pain
o Hypotensive and tachycardia; onset of confusion and agitation
o ↑ neck veins, ↓ heart sounds, pulsus paradoxus may be present
o 2D-echo is the diagnostic test of choice
o Treatment is surgical
76 | 15. ACUTE MYOCARDIAL INFARCTION
• Rupture of the interventricular septum
o More often detected clinically than rupture of the ventricular free wall
o Size of defect: degree of left-to-right shunt & ultimate prognosis
o Clinical: chest pain, dyspnea, sudden new holosystolic murmur
(accompanied by a palpable thrill, heard best at lower left sternal border)
o Doppler 2D-echo is the diagnostic procedure of choice
o Pulmonary catheter blood sampling: demonstration of left-to-right shunt
▪ O2 step-up of >10% from RA to RV samples is diagnostic
o More common in anterior wall MI & with extensive (three-vessel) CAD
o Treatment is surgical
• Papillary muscle rupture (3-5 days after AMI; 1% of patients with AMI)
o More common with inferior MI
o Often occurs with a small- to modest-sized AMI
o Acute onset of dyspnea, increasing HF & pulmonary edema, and a new
holosystolic murmur consistent with MR
o Posteromedial papillary muscle is most commonly ruptured (receives
blood supply from one coronary artery, usually RCA)
o Echocardiography often can distinguish rupture of a portion of papillary
muscle from other etiologies of MR
o Treatment is surgical
Pericarditis (2-4 days after AMI)
• Early post-AMI pericarditis occurs in <5% of patients
• More common in transmural AMI and delayed initial presentations
o Inflammation adjacent on the epicardial surface of a transmural infarction
• Pericardial friction rubs are detected more often with inferior wall & RV
infarction (RV lies immediately beneath the chest wall)
• Pain can be confused with that of infarct extension or post-AMI angina
• Discomfort becomes worse with a deep inspiration, relieved by sitting forward
• Echocardiography: pericardial effusion (much more common than pericarditis,
often are present in the absence of pericarditis)
• Can be present in the absence of a pericardial effusion
• Resorption rate of post-AMI pericardial effusions is slow (several months)
• Treatment:
o Aspirin 650 mg PO every 4-6 hours
o Colchicine 0.6 mg BID
• Ibuprofen is NOT recommended (interferes with antiplatelet effect of aspirin;
can cause myocardial scar thinning and infarct expansion)
• Dressler’s syndrome (late post-AMI syndrome): 2-10 weeks after AMI; chest
pain, fever, pleuropericarditis; treatment is aspirine and colchicine
Right Ventricular Infarction
• Isolated infarction extremely rare; seen as complication of inferior infarction
• Approximately 30% of inferior wall MI involves the RV
• Associated with a significant increase in mortality and CV complications
• ECG: ST-segment elevation in precordial V4R lead in an inferior wall MI
• Elevated neck veins or hypotension in response to NTG is also suggestive
• 2D-echo or nuclear imaging can be diagnostic (less readily available in ER)
• Most serious complication is shock
o Severity of hemodynamic derangement is related to:
▪ Extent of RV dysfunction
▪ Interaction between the ventricles (RV & LV share the IVS)
▪ Interaction between pericardium and RV
o RV infarction: ↓ RV end-systolic pressure, LV end-diastolic size, CO, &
aortic pressure (RV becomes more of a passive conduit of blood flow)
o LV contraction causes bulging of interventricular septum into the RV, with
resultant ejection of blood into the pulmonary circulation
o RV infarction with concurrent LV infarction as a particularly devastating
effect on hemodynamic function
o Treatment: Fluid balance and maintenance of adequate preload
▪ Factors that reduce preload (volume depletion, diuretics, nitrates) or
decrease right atrial contraction (atrial infarction, loss of AV
synchrony) and factors that increase RV afterload (LV failure) can
lead to significant hemodynamic derangements
• Treatment:
o Maintenance of preload
▪ Volume loading (normal saline): ↑ preload improves RV CO
o Reduction of RV afterload
o Inotropic support of the ischemic RV (dobutamine)
▪ If cardiac output is not improved after 1-2 L of normal saline
o Early reperfusion
• When RV infarction is accompanied by LV dysfunction, use of NTG to reduce
afterload or intraaortic balloon counterpulsation may be of benefit
o ↓ LV afterload may help passive movement of blood through RV
Other complications (not usually seen in ER, for patients who return to ER shortly
after hospital discharge)
• LV thrombus formation
• Arterial embolization
• Venous thrombosis
• Pulmonary embolism
• Postinfarction angina
• Infarct extension
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
• Robbins and Cotran Pathologic Basis of Disease, 9 th edition (2015)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

16. PULMONARY EMBOLISM • Cancer

Pulmonary Embolism (PE) o Thrombogenic potential varies with host factors, tumor stages, tumor type
• Occurs when clotted blood enters the pulmonary arterial circulation o More undifferentiated the cell type and the larger the tumor burden
• Most PEs result from deep vein thrombosis (DVT) in the legs, arms, or pelvis (especially distant metastasis), the higher is the risk
and occasionally from the jugular vein or inferior vena cava o Thrombogenic cancers: adenocarcinoma, glioblastoma, metastatic
melanoma, lymphoma, multiple myeloma
Venous Thromboembolism (VTE)
o Notoriously high risk: pancreatic, stomach, ovarian, & renal cell cancers
• Includes pulmonary embolism (PE) & deep venous thrombosis (DVT)
o Cancers with minimal risk: localized breast, cervical, prostate, &
EPIDEMIOLOGY nonmelanomatous localized skin cancers (squamous cell carcinoma,
• Incidence of VTE increases with age, peaking at 1 in 100 per year at age 80 basal cell carcinoma) not treated with chemotherapy
• Case fatality rate from PE depends on the hemodynamic severity of the PE, o Increased risk of VTE associated with chemotherapy
age, and comorbid conditions ▪ Advanced-stage breast cancer or with breast cancer undergoing
o 45% for PE with circulatory shock chemotherapy (about 10% of patients develop symptomatic VTE)
o 4-5% with PE have shock ▪ Induction phase (L-asparaginase & bolus fluorouracil or tamoxifen)
o 1% for hemodynamically stable PE <50 years without other comorbidities ▪ Concomitant treatment with RBC growth factors (erythropoietin)
▪ Multiple myeloma treated with lenalidomide or thalidomide
PATHOPHYSIOLOGY • Family history – increases longitudinal risk of VTE, no impact on outcomes
• Blood clots occurs when coagulation exceeds fibrinolysis • Sex – no role in first-time VTE; men have more recurrent VTE
• Thrombophilias are conditions that tip the balance of coagulation-fibrinolysis • Smoking
toward excessive clotting o Causes conditions that increase risk (e.g., cancer)
• Provoked VTEs (secondary) o Acts synergistically with obesity and possible OCP use
o Acquired; often time-limited conditions o Not an independent risk factor for VTE
o Often following recent surgery, trauma, or any condition associated with
limb or body immobility
o Active cancer is a VTE provoker that often persists
o Other provoking factors:
▪ Diseases/conditions that impede venous blood flow
▪ Infection
▪ Chronic disease
▪ Estrogen use
▪ Pregnancy or initial postpartum interval
▪ Age >50 years (each year after 50 increases the risk)
o Higher 1-year death rate, likely from comorbid conditions (notably cancer)
• Unprovoked VTE (idiopathic)
o No known risk factors, suggesting an increased tendency to clot
o Most VTEs diagnosed in the ER are unprovoked
o 15% chance of recurrence the next year (vs. 5% with provoked episode)
o Usually receive longer treatment than provoked VTE
• Sites of venous thrombi large enough to cause clinically important PE:
popliteal, common & superficial femoral, pelvic, axillary, jugular, great veins
• DVT vs. PE
o At least 1/3 of patients with DVT have concomitant PE
o Only 40% of ambulatory ER patients with PE have concomitant DVT
o 75-80% of hospitalized patients with PE have image demonstrated DVT
• Blood clots that form in large veins of legs (femoral & iliofemoral veins) usually
begin on the valves, leading to scarring & poor function of venous valves.
o Causes pooling of venous blood in legs, leading to varicose veins, pain,
swelling, skin hyperpigmentation, & ulcers (postthrombotic syndrome)
• With PE, patients without prior heart/lung disease begin to experience
symptoms when approximately 20% of lung vasculature becomes occluded
o With larger clot burden, ↑ pulmonary arterial pressure → right ventricular
dilation & myocardial damage (seen on CT/2D-Echo or ↑ troponin/BNP)
→ right heart failure → increased risk of circulatory shock & death
o Persistent right heart dysfunction & severe symptoms in approximately
1/3 of survivors of large PEs
o Chronic thromboembolic pulmonary hypertension
▪ Chronic pulmonary vascular obstruction (approx. 5% of PE patients)
leading to progressive damage to lung vessels & right heart with
disabling dyspnea & pulmonary hypertension
• 2 principle mechanisms of death from PE
o Abrupt near-total pulmonary artery occlusion that leads to pulseless
electrical activity (PEA)
o Asystole from ischemic effect on the His-Purkinje conduction system
• Inherited thrombophilias increase risk of first-time VTE
• Limb immobility (increased risk):
o Acute immobilization of hip & knee in one leg with non-weight bearing
o Joint: elbow (least), shoulder, ankle, knee, hip (most)
o Whole-body immobility or neurologic immobility
• Surgery
o Average time from surgery to PE diagnosis is >10 days
o Risk increases with age, longer surgery, open surgery, and surgery
without thromboprophylaxis
o Highest-risk surgeries
▪ Abdominal surgery to remove cancer
▪ Joint replacement surgery
▪ Surgery on the brain or spinal cord in the setting of neurologic deficits
o Risk of recurrence after surgery provoked VTE is generally lower than for
unprovoked VTE

16. PULMONARY EMBOLISM | 77

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

CLINICAL FEATURES OF PULMOANRY EMBOLISM DIAGNOSIS

• PE symptoms range from none to sudden death • The presence of hypoxemia or dyspnea with clear lungs on physical
• Dyspnea unexplained by auscultatory findings, ECG changes, or clear exam and imaging suggests PE
alternative diagnosis on chest radiograph (hallmark of PE) • Routine cardiopulmonary testing in ER demonstrates nonspecific findings
• Chest pain with pleuritic features (2nd most common symptom) o Pulse oximetry readings is lower in PE than without PE
o ½ of patients with PE in the ER have no complaint of chest pain o PaO2 is lower in PE
o Classic PE pain: in thorax between clavicles & costal margin; increases o P(A-a)O2 (alveolar-arterial gradient) is increased in PE
with cough or breathing; not purely substernal & not from skin/muscle o PaCO2 is usually low, reflecting 20-50% increase in minute ventilation to
• Pulmonary infarction can inflict severe focal pain compensate for loss of lung efficiency due to increased dead space
o Pulmonary infarction in basilar lung segments: referred pain to either o ETCO2 (end-tidal CO2) is lower in spontaneously breathing PE patients
shoulder or mimic biliary or ureteral colic • Chest radiography
o Proximal PE without infarction: pleuritic chest pain without focal pain o ≥1 nonspecific abnormalities: cardiomegaly, basilar atelectasis, infiltrate,
pleural effusion
Factors that can affect the clinical presentation of patients with PE
o In <5% of patients:
Cofactor Clinical Impact Comment
Previously healthy Less severe signs & ½ of previously healthy patients with 1 st- ▪ Westermark sign – wedge-shaped area of lung oligemia, usually
& young age symptoms time PE have normal VS at diagnosis from complete lobar artery obstruction
Prior Can either amplify
Most patients with PE complicating ▪ Hampton hump – peripheral dome-shaped dense opacification,
baseline cardiopulmonary disease
cardiopulmonary or obscure history & always indicative of pulmonary infarction
describe dyspnea with PE as “worse than
disease findings
usual” • 12-lead ECG
Patient cognitive Causes the history Approx. 20% of patients with PE missed by o Nonspecific (sinus tachycardia & nonspecific ST- and T-wave changes)
dysfunction to be less reliable ER clinicians had baseline dementia o More specific when PE causes RV systolic pressure to exceed 40 mmHg:
Affects severity of Proximal clots cause V/Q mismatch &
▪ T-wave inversion in leads V1 to V4
Clot size & location dyspnea, pain, & dyspnea; distal clots cause infarction with
signs pain ▪ Incomplete or complete right bundle-branch block
Gradual loading of
Gradual onset of Has symptoms overlap with left ventricular ▪ S1-Q3-T3 pattern (classic but uncommon)
PE over time
dyspnea on dysfunction. Fewer than ½ of patients with • S wave in lead 1
exertion & fatigue PE describe symptom onset as sudden
• Q wave in lead 3
• History • Inverted T wave in lead 3
o Syncope (approximately 3-4% of ER patients)
o New-onset seizure/convulsion-like activity or confusion (1-2%)
o Paradoxical embolism syndrome
▪ Stroke-like syndromes produced by PE that increases right-sided
pressures, leading to right-to-left transit of thrombotic material in the
atria that showers into the brain circulation
▪ Seen in patent foramen ovale (worsens prognosis in PE)
o Neurologic symptoms can vary widely
▪ From classic localized findings to staring spells, transient altered
mental status, and atypical myelopathy symptoms (numbness below
the waist), all of which can fluctuate
• Physical Examination
o Vital Signs (VS)
▪ Abnormal VS suggest acute cardiopulmonary stress:
• Tachycardia (approximately ½ have HR <100 bpm at diagnosis)
• Tachypnea
• Low pulse oximetry reading
• Mild fever (>38°C in approx. 10%; >39.2°C in <2%)
▪ Approximately 1/3 have abnormal early VS that normalize in ER
▪ Results in blood flow obstruction & clot-derived autacoids
• Adrenergic efferent stimulation to heart & cause V/Q mismatch
• Clot burden does not predict vital sign changes reliably
o Lung examination
▪ Most patients have clear lungs on auscultation
▪ Wheezes or bilateral rales make an alternative diagnosis of
bronchospasm or pneumonia possible but do not exclude PE
▪ Pulmonary infarction may produce rales over affected lung segment
o Heart examination
▪ Right ventricular S3 or a split S2 with a loud second sound
o Extremities
▪ Presence of a percutaneous indwelling catheters in the arm
increases the probability of axillary vein thrombosis
▪ Less clear whether these lines, dialysis catheters, or pacemaker
wires also increase risk of symptomatic PE

CLINICAL FEATURES OF DEEP VEIN THROMBOSIS

• Extremity pain, swelling, or cramping
• A difference of ≥2 cm between right and left leg diameter at 10 cm below the
tibial tubercle doubles the likelihood of DVT
• Hand swelling or tightness around finger rings (UE catheter-related DVT)
• ¼ have tenderness & redness in swollen extremity (similar to cellulitis)
• Calf/saphenous vein clots are more likely to cause thrombophlebitis
(inflammation over vein secondary to presence of thrombotic material in vein)
o Signs & symptoms can persist after vein recannulation & clot dissolution
• Homan’s sign (calf pain elicited by passive foot dorsiflexion)
o (+) in calf vein thrombosis; low sensitivity & specificity; no predictive value
• Proximal DVT that causes complete venous obstruction leads to increased
compartmental pressures, manifested as extremely painful, swollen extremity
o Phlegmasia alba dolens – a swollen, painful, and pale or white limb
o Phlegmasia cerulea dolens – a limb with a dusky or blue color
o Either condition poses the threat of limb loss, demanding aggressive
treatment (thrombolysis or catheter-directed thombectomy)

78 | 16. PULMONARY EMBOLISM

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

DIAGNOSTIC TESTING FOR VENOUS THROMBOEMBOLISM Imaging

• Chest CT Angiography (most common imaging modality for PE)
o Clot – filling defect in contrast-enhanced pulmonary arteries
o Patient in supine & holding breath for a few seconds, approximately 120
mL of contrast is given through peripheral IV catheter
o Can detect alternative diagnoses, often pneumonia (8-22%)
o Disadvantage: inadequacy of scans (10%) from secondary motion artifact
or poor pulmonary artery opacification (obese, very tachypneic patients)
o Complications:
▪ Acute life-threatening contrast-triggered anaphylaxis or pulmonary
edema (rare, 1 in 1000 patients)
▪ Contrast nephropathy (15% of patients)
▪ Contrast extravasation (pain/compartment syndrome)
▪ Creation of a secondary thrombophlebitis
• Ventilation-Perfusion (V/Q) Lung Scanning
o Can identify a perfusion defect when ventilation is normal
o Measures scintillation produced from gamma ray-emitting atom & yields
image that plots density of scintillations from chest using 2 phases
o Perfusion images are usually obtained first and require peripheral IV
catheter for injection & patient to sit up & lie down during procedure
o Ventilation component requires the patient to breathe into a nebulizer to
inhale an aerosol that contains the isotope
o Homogeneous scintillation throughout the lung (perfusion portion): nearly
100% sensitivity in excluding PE, regardless of ventilation portion
o ≥2 apex central wedge-shaped defects (perfusion phase) with normal
ventilation: >80% probability of PE
• MRI
o Zero-radiation option for imaging the pulmonary vasculature
o May have utility in pregnant patients
o Sensitivity 75%; Specificity 80%
• Lung Ultrasound
o Adjunctive modality to help diagnose and exclude PE at bedside
o Sensitivity 85%; Specificity 83%
• Venous Ultrasound (Compression Ultrasonography)
o Imaging test of choice in DVT; can be done quickly; no ionizing radiation
o Principle: normal veins compress but thrombosed veins do not
o Sites: common femoral, superficial femoral, and popliteal veins for
comparison with the adjacent femoral and popliteal arteries
o Sonographer manually compresses the probe and compares the
flattening of the vein with that of the artery
▪ Normal compressibility: vein compresses completely whereas the
artery remains patent (absence of thrombus is inferred)
▪ (+) for thrombus: vein does not compress
o Disadvantages:
▪ Needs specialized equipment & qualified sonographer & radiologist
▪ Difficult to perform in obese patients
▪ Probability of an indeterminate result increases with higher BMI
▪ Compression causes pain in some & could promote clot embolization
▪ Difficult to determine venous noncompressibility if with history of DVT

VENOUS THROMBOEMBOLISM TREATMENT

Treatment of PE and Deep and Superficial Extremity Thromboses
• Treatment of VTE requires systemic anticoagulation to prevent clot formation
and allow endogenous fibrinolysis to proceed
• Initial treatment for VTE is heparin or heparin-like drug
o Unfractionated heparin (UFH)
o Low-molecular-weight heparin (LMWH)
o Other initial anticoagulation treatment options include oral apixaban or
rivaroxaban (requires anticoagulation with heparin)
• UFH vs LMWH
o LMWH > UFH for treatment of PE & DVT in terms of composite outcomes
(bleeding & death) & cost (though benefit is not large)
o Delay in giving heparin in PE is associated with increased mortality
D-Dimer Testing
o UFH > LMWH in severe renal insufficiency & acute DVT or PE
• Best blood test to exclude VTE (conventional cutoff: <500 ng/mL)
• Treat upper extremity DVT the same as lower extremity DVT
• Principle: fibrin in clots are degraded by plasmin, liberating D-dimer into blood
o Remove any indwelling catheters associated with clot
o Half-life: approximately 8 hours, ↑ for ≥3 days after symptomatic VTE
• Do not delay UFH for added thrombophilia testing when VTE is clearly present
• Qualitative tests: lower diagnostic sensitivity; higher specificity
o No evidence demonstrates any clinical benefit to a thrombophilia
• Quantitative tests: sensitivity: 94-98%; specificity: 50-80%)
evaluation in guiding the intensity or duration of anticoagulation
o Done in central hospital laboratory; turnaround time of at least 1 hour
• DVT that causes phlegmasia cerulea dolens requires rapid action to reduce
the venous pressure
o In addition to initiating anticoagulation, place the affected limb at a neutral
level; remove constricting clothing, cast, or dressing; and arrange for
consultant-delivered catheter-directed thrombolysis
o If no such service is available and emergency transfer cannot be
arranged within 6 hours, consider systemic fibrinolytics if there are no
absolute contraindications (alteplase 50-100 mg/IV over 4 hours)

16. PULMONARY EMBOLISM | 79

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Treatment for Superficial Thrombophlebitis
• Oral NSAIDs or topical diclofenac gel until symptoms resolve
• No need for systemic anticoagulation
• Full-dose anticoagulation for extensive superficial vein involvement
• Compression stockings do not aid this condition
Treatment for Isolated Calf Vein Thrombosis
• No universally accepted treatment guidelines
o Many use 3 months of oral anticoagulation
o Alternatives include no acute treatment with repeat US in 1 week to
identify progression of clot, or outpatient treatment with LMWH
• Patients with history of VTE or risk factors for VTE should receive 3 months of
full-dose anticoagulation unless contraindications are present
Outpatient Treatment of Pulmonary Embolism
• DVT diagnosed in the ER are typically discharged after receiving the 1st dose
of LMWH & with anticoagulation continued as outpatient
• Patients with PE and a low risk of death plus adequate home support can
qualify for outpatient anticoagulation
o Incidence of short-term mortality & bleeding risk are very low
o Overall cost of care is less, & experience is preferred by patients
• If no high-risk features exist (↑ troponin, BNP >100 pg/mL, pulmonary arterial
hypertension on ECG, bleeding risks), outpatient care after an ER stay (up to
23 hours) is an option; otherwise, short-term hospitalization is a good choice
• Biggest barrier to ER discharge is ensuring access to anticoagulation
o If warfarin is the long-term anticoagulant, the patient must receive LMWH
until prothrombin time is adequately prolonged and for at least 5 days
o For LMWH, patients/families must learn how to administer subcutaneous
injections, have access to drug, have a follow-up appointment where
prothrombin time can be monitored, and have dosing advice given
• Only rivaroxaban is approved for both DVT and PE
o Does not require blood monitoring or dosing adjustment for body size
o Primary limitation is cost
Fibrinolysis for Pulmonary Embolism
• PE is classified in to 3 categories based on severity
o Massive PE
▪ SBP <90 mmHg for >15 minutes or decrease of 40 mmHg
▪ SBP <100 mmHg with a history of hypertension
▪ >40% reduction in baseline SBP
▪ Benefit from fibrinolysis
o Submassive PE
▪ Normal or near-normal blood pressure, but with other evidence of
cardiopulmonary stress (RV dilation/hypokinesis, ↑ troponin/BNP,
persistent hypoxemia with distress)
▪ May also benefit from fibrinolysis, including higher survival and better
quality of life although at a higher bleeding risk
o Less severe PE
▪ All other PE cases are classified as less severe
▪ Should not receive fibrinolysis
80 | 16. PULMONARY EMBOLISM
• Systemic Fibrinolysis
o Consider systemic fibrinolysis if no contraindications and any of following:
▪ Cardiac arrest
▪ Hypotension
▪ Respiratory failure, evidenced by severe hypoxemia (<90%) despite
oxygen administration plus evidence of increased work of breathing
▪ Evidence of right-sided heart strain (2D-echo, ↑ troponin T/I, or both)
o Major contraindications to thrombolytic therapy
▪ Intracranial disease
▪ Uncontrolled hypertension at presentation
▪ Recent major surgery or trauma (past 3 weeks)
▪ Metastatic cancer
▪ Head trauma from syncope (CT scan prior to therapy)
o Alteplase (tissue plasminogen activator) 100 mg/IV over 2 hours
▪ Only currently approved agent for PE
o Anticoagulant (typically started after the thrombolytic infusion):
▪ Enoxaparin 1 mg/kg SC
▪ UFH 80 units/kg IV bolus followed by 18 units/kg/hour with aPTT kept
at <120 seconds
• Catheter-Directed Intrapulmonary Thrombolysis
o Option for patients >65 years old (intracranial bleeding risk is highest)
o Better outcomes vs heparin alone; not used in most massive PE patients
o Lower dose of alteplase (10 mg total), may confer lower bleeding risk
▪ Alternatively, 50 mg/IV is an option with safety advantages
o Tiered-dose tenecteplase appears to offer similar effectiveness as
alteplase, although it is not yet approved by the FDA for PE
• Surgical Embolectomy
o Option in young patients with large, proximal PE with hypotension
o Reported mortality rate is approximately 30% (often delayed)
o The amount of clot is often extensive, and removal may help limit later
cardiopulmonary complications
DISCHARGE AND FOLLOW-UP
• Severe PE or receiving any thrombolysis/extraction are placed in ICU
• Outpatient DVT & PE favored in low-risk patients who can adhere to therapy
• Indications for hospital admission in patients with DVT
o Extensive iliofemoral DVT with circulatory compromise
o Increased risk of bleeding (coagulopathy, active PUD, liver disease) that
requires close monitoring of therapy
o Limited cardiorespiratory reserve that suggests need for additional care
such as monitoring for hypoxemia
o Risk of poor compliance with home therapy regimen or inadequate
support (i.e., community, social, or medical, or concern with ability to
arrange follow-up
o Contraindication to use of LMWH, and inability to use oral target-specific
anticoagulant, which would necessitate IV heparin therapy
o Known/suspected coexistent PE with a Simplified Pulmonary Embolism
Severity Index score >0 or Hestia criteria positive
o High suspicion of heparin-induced thrombocytopenia ± thrombosis
o Renal insufficiency requiring monitoring of anti-factor Xa level, or use of
UFH
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

17. SEVERE ASTHMA
ASTHMA
• Asthma is a heterogeneous disease, usually characterized by
chronic airway inflammation.
• It is defined by the history of respiratory symptoms such as wheeze,
shortness of breath, chest tightness, and cough that vary over time
and in intensity, together with variable expiratory airflow limitation.
• Asthma is usually associated with airway hyperresponsiveness to
direct or indirect stimuli, and with chronic airway inflammation.
Asthma phenotypes
• Recognizable clusters of demographic, clinical, and/or
pathophysiological characteristics
• No strong relationship has been found between specific pathological
features and particular clinical patterns of treatment responses
Phenotype Characteristics
• the most easily recognized asthma phenotype
• often commences in childhood
• associated with a past and/or family history of
Allergic asthma allergic disease such as eczema, allergic
rhinitis, or food or drug inflammation
• usually respond well to inhaled corticosteroids
(ICS) treatment
• asthma that is not associated with allergy
Non-allergic
• cellular profile of the sputum may be
asthma
neutrophilic, eosinophilic, or contains few
inflammatory cells (paucigranulogytic)
• some adults, particularly women, present with
asthma for the first time in adult life
Adult-onset • tend to be non-allergic
(late-onset) • often require higher doses of ICS or are
asthma relatively refractory to corticosteroid treatment
• occupational asthma should be ruled out in
patients presenting with adult-onset asthma
Asthma with • some patients with long-standing asthma
persistent develop airflow limitation that is persistent or
airflow incompletely reversible
limitation • thought to be due to airway remodeling
• some obese patients with asthma have
Asthma with
prominent respiratory symptoms and little
obesity
eosinophilic airway inflammation
MAKING THE INITIAL DIAGNOSIS
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Patterns of respiratory symptoms that are characteristic of asthma
• The following features increase the probability of asthma:
o More than one symptom (wheeze, shortness of breath, cough,
chest tightness), especially in adults
▪ Symptoms often worse at night or in the early morning
▪ Symptoms vary over time and in intensity
▪ Symptoms are triggered by viral infections (colds), exercise,
allergen exposure, changes in weather, laughter, or irritants
(car exhaust fumes, smoke, strong smells)
• The following features decrease the probability of asthma:
o Isolated cough with no other respiratory symptoms
o Chronic production of sputum
o Shortness of breath associated with dizziness, light-
headedness, or peripheral tingling (paresthesia)
o Chest pain
o Exercise-induced dyspnea with noisy inspiration
Diagnostic criteria for asthma in adults, adolescents, and children 6-11 years
Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation.
It is defined by the history of respiratory symptoms such as wheeze, shortness of breath,
chest tightness, and cough that vary over time and in intensity, together with variable
expiratory airflow limitation.
DIAGNOSTIC FEATURE CRITERIA FOR DIAGNOSIS OF ASTHMA
1. History of variable respiratory symptoms
Wheeze, shortness of • Generally, more than one type of respiratory symptom
breath, chest tightness, and (in adults, isolated cough is seldom due to asthma)
cough. Descriptors may • Symptoms occur variably over time and vary in intensity
vary between cultures and • Symptoms are often worse at night or on waking
by age, e.g. children may be
• Symptoms are often triggered by exercise, laughter,
described as having heavy allergens, cold air
breathing
• Symptoms often appear or worsen with viral infections
2. Confirmed variable expiratory airflow limitation
Documented excessive The greater the variations, or the more occasions excess
variability in lung function* variation is seen, the more confident is the diagnosis
(one or more of tests below)
AND documented At a time when FEV1 is reduced, confirm that FEV1/FVC is
expiratory airflow limitation* reduced (it is usually >0.75-0.80 in adults, >0.90 in children)
• Positive bronchodilator Adults: increase in FEV1 of >12% and >200 mL from
(BD) reversibility test* baseline, 10-15 minutes after 200-400 mcg salbutamol
(more likely to be (greater confidence if >15% and >400 mL)
positive if BD medication Children: increase in FEV1 of >12% predicted
is withheld before test:
SABA ≥4 hours, LABA
≥15 hours)
• Excessive variability in Adults: average daily diurnal PEF variability >10%**
twice-daily PEF over 2 Children: average daily diurnal PEF variability 13%**
weeks*
• Significant increase in Adults: increase in FEV1 by >12% and >200 mL (or PEF†
lung function after 4 by >20%) from baseline after 4 weeks of treatment, outside
weeks of anti- respiratory infections
inflammatory treatment
• Positive exercise Adults: fall in FEV1 of >10% and >200 mL from baseline
challenge test* Children: fall in FEV1 of >12% predicted, or PEF >15%
• Positive bronchial Fall in FEV1 from baseline of ≥20% with standard doses of
challenge test (usually methacholine or histamine, or ≥15% with standardized
only performed in adults) hyperventilation, hypertonic saline, or mannitol challenge
• Excessive variation in Adults: variation in FEV1 of >12% and >200 mL between
lung function between visits, outside of respiratory infections
visits* (less reliable) Children: variation FEV1 of >12% in FEV1 or >15% in PEF†
between visits (may include respiratory infections)
BD: bronchodilator (short-acting SABA or rapid-acting LABA); FEV1: forced expiratory volume in 1 second; LABA: long-acting beta2-agonist;
PEF: peak expiratory flow (highest of three readings); SABA: short-acting beta2-agonist.
*These tests can be repeated during symptoms or in the early morning.
**Daily diurnal PEF variability is calculated from twice daily PEF as ([day’s highest minus day’s lowest]/mean of day’s highest and lowest) and
averaged over one week.
†
For PEF, use the same meter each time, as may become persistent over time. If bronchodilator reversibility is not present at initial presentation,
the next step depends on the availability of other tests and the urgency of the need for treatment.
In a situation of clinical urgency, asthma treatment may be commenced, and diagnostic testing arranged within the next few weeks, but other
conditions that can mimic asthma should be considered, and the diagnosis of asthma confirmed as soon as possible.
History and family history
• Features that increases the probability that the respiratory
symptoms are due to asthma
o Commencement of respiratory symptoms in childhood
o History of allergic rhinitis or eczema
o Family history of asthma or allergy
Physical Examination
• Often normal
• Most frequent abnormality: expiratory wheezing (rhonchi)
o May be absent during severe asthma exacerbations due to
severely reduced airflow (“silent chest”). At such times, other
physical signs of respiratory failure are usually present.
o May also be heard with inducible laryngeal obstruction, COPD,
respiratory infections, tracheomalacia, or inhaled foreign body
• Crackles (crepitations) & inspiratory wheezing are NOT features of
asthma
• Nose exam: may reveal signs of allergic rhinitis/nasal polyposis
17. SEVERE ASTHMA | 81
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Lung function testing to document variable expiratory airflow How to step down controller treatment to help confirm asthma
limitation 1. ASSESS
• Airflow limitation: reduced FEV1/FVC ratio • Document the patient’s current status including asthma control and lung
function. If the patient has risk factors for asthma exacerbations, do not step
o Adults: FEV1/FVC ratio <0.75 to 0.80 down treatment without close supervision.
o Children: FEV1/FVC ratio <0.90 • Choose a suitable time (e.g. no respiratory infection, not going away on
• Variation in airflow limitation is generally assessed from variation in vacation, not pregnant).
FEV1 or PEF • Provide a written asthma action plan so the patient knows how to recognize
and respond if symptoms worsen. Ensure they have enough medication to
o Variability – improvement and/or deterioration in symptoms and resume their previous dose if their asthma worsens.
lung function 2. ADJUST
o FEV1: increase or decrease of >12% and >200 mL from baseline • Show patient how to reduce ICS dose by 25-50%, or stop extra controller
o PEF: >10% in adults; >13% in children (e.g. LABA, LTRA) if being used. Schedule a review visit for 2-4 weeks.
• Excessive variability may be identified over the course of one day 3. REVIEW RESPONSE
• Repeat assessment of asthma control & lung function tests in 2-4 weeks.
(diurnal variability), from day to day, from visit to visit, or seasonally,
• If symptoms increase and variable airflow limitation is confirmed after
or from a reversibility test stepping down treatment, the diagnosis of asthma is confirmed. The
o Reversibility – rapid improvements in FEV1 (or PEF), measured controller dose should be returned to the lowest previous effective dose.
within minutes after inhalation of a rapid-acting bronchodilator • If, after stepping down to a low dose controller treatment, symptoms do not
(salbutamol 200-400 mcg), or more sustained improvement over worsen and there is still no evidence of variable airflow limitation, consider
ceasing controller treatment and repeating asthma control assessment and
days or weeks after the introduction of effective controller lung function tests in 2-3 weeks, but follow the patient for at least 12 months.
treatment such as ICS
• Evidences of excessive variability in expiratory lung function DIFFERENTIAL DIAGNOSIS
o An increase in lung function after administration of a Age Symptoms Condition
bronchodilator, or after a trial of controller treatment Sneezing, itching, blocked nose, Chronic upper airway
o A decrease in lung function after exercise or during a bronchial throat-clearing cough syndrome
provocation test Sudden onset of symptoms,
Inhaled foreign body
o Variation in lung function beyond the normal range when it is unilateral wheeze
Recurrent infections, productive
repeated over time, either on separate visits, or on home Bronchiectasis
cough
monitoring over at least 1-2 weeks Recurrent infections, productive Primary ciliary
6-11
cough, sinusitis dyskinesia
Other tests years
Congenital heart
Cardiac murmurs
• Bronchial provocation tests disease
o To assess airway hyperresponsiveness Preterm delivery, symptoms since Bronchopulmonary
o Challenge tests: inhaled methacholine, histamine, exercise, birth dysplasia
Excessive cough and mucus
eucapnic voluntary hyperventilation, or inhaled mannitol
production, gastrointestinal Cystic fibrosis
o Moderately sensitive for a diagnosis of asthma but have limited symptoms
specificity Sneezing, itching, blocked nose, Chronic upper airway
• Allergy tests throat-clearing cough syndrome
o Presence of atopy increases the probability that a patient with Dyspnea, inspiratory wheezing Inducible laryngeal
respiratory symptoms has allergic asthma, but not specific for (stridor) obstruction
asthma nor it is present in all asthma phenotypes Hyperventilation,
Dizziness, paresthesia, sighing dysfunctional
o Skin prick testing or by specific serum IgE measurements breathing
12-39 Productive cough, recurrent
CONFIRMING THE DIAGNOSIS OF ASTHMA IN PATIENTS Bronchiectasis
years infections
ALREADY TAKING CONTROLLER TREATMENT Excessive cough and mucus
Cystic fibrosis
Current status Steps to confirm the diagnosis of asthma production
Variable respiratory Congenital heart
Diagnosis of asthma is confirmed. Assess the level of Cardiac murmurs
symptoms & variable
asthma control and review controller treatment
disease
airflow limitation Shortness of breath, family history of Alpha1-antitrypsin
Repeat BD reversibility test again after withdrawing early emphysema deficiency
BD (SABA: 4 hours; LABA: 12 or 24 hours*) or during Sudden onset of symptoms Inhaled foreign body
symptoms. If normal, consider alternative diagnoses
Dyspnea, inspiratory wheezing Inducible laryngeal
• If FEV1 is >70% predicted: consider a bronchial
(stridor) obstruction
Variable respiratory provocation test. If negative, consider stepping
symptoms but no down controller treatment & reassess in 2-4 Hyperventilation,
variable airflow weeks Dizziness, paresthesia, sighing dysfunctional
limitation • If FEV1 is <70% predicted: consider stepping up breathing
controller treatment for 3 months, then reassess Cough, sputum, dyspnea on
symptoms and lung function. If no response, exertion, smoking or noxious COPD
resume previous treatment and refer patient for exposure
diagnosis and investigation Productive cough, recurrent
Repeat BD reversibility test again after withholding 40+ Bronchiectasis
infections
BD (SABA: 4 hours; LABA: 12 or 24 hours*) or during years
Dyspnea with exertion, nocturnal
symptoms. If normal, consider alternative diagnoses Cardiac failure
Few respiratory symptoms
Consider stepping down controller treatment
symptoms, normal Medication-related
• If symptoms emerge and lung function falls: Treatment with ACE inhibitors
lung function, and no cough
asthma is confirmed. Step up controller
variable airflow Dyspnea with exertion, non- Parenchymal lung
treatment to previous lowest effective dose
limitation productive cough, finger clubbing disease
• If no change in symptoms/lung function at lowest
controller step: consider ceasing controller, & Sudden onset of dyspnea, chest pain Pulmonary embolism
monitor patient closely for ≥12 months Dyspnea, unresponsive to Central airway
Consider stepping up controller treatment for 3 bronchodilators obstruction
Persistent shortness
months, then reassess symptoms & lung function. If Chronic cough, hemoptysis,
of breath and All
no response, resume previous treatment & refer dyspnea; and/or fatigue, fever, night Tuberculosis
persistent airflow ages
patient for diagnosis & investigation. Consider sweats, anorexia, weight loss
limitation
asthma-COPD overlap.
BD: bronchodilator; LABA: long-acting beta2-agonist; SABA: short-acting beta2-agonist.
*Depending on duration of action of the LABA

82 | 17. SEVERE ASTHMA

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

ASSESSMENT OF ASTHMA SYMPTOM CONTROL ROLE OF LUNG FUNCTION IN ASSESSING ASTHMA CONTROL
GINA assessment of asthma control in adults, adolescents, and children 6-11 years • A low FEV1 percent predicted
A. Asthma symptom control
In the past 4 weeks, has the patient had: Level of asthma symptom control
o Identifies patients at risk of asthma exacerbations, independent
• Daytime asthma symptoms >2x/week? • Well controlled – None of these of symptom levels, especially if FEV1 is <60% predicted
• Any night waking due to asthma? • Partly controlled – 1-2 of these o Risk factor for lung function decline, independent of symptoms
• Reliever needed for symptoms* >2x/week? • Uncontrolled – 3-4 of these
• Any activity limitation due to asthma? o If symptoms are few, suggests limitation of lifestyle, or poor
B. Risk factors for poor asthma outcomes perception of airflow limitation, which may be due to untreated
Assess risk factors at diagnosis and periodically, particularly for patients experiencing airway inflammation
exacerbations.
Measure FEV1 at start of treatment, after 3-6 months of controller treatment to record the • A ‘normal’ or high FEV1 in a patient with frequent respiratory
patient’s personal best lung function, then periodically for ongoing risk assessment. symptoms (especially when symptomatic):
Having uncontrolled asthma symptoms is an important risk factor
exacerbations. o Prompts consideration of alternative causes for the symptoms;
Additional potentially modifiable risk factors for flare-ups e.g. cardiac disease, or cough due to post-nasal drip or
(exacerbations), even in patients with few symptoms†, include:
• Medications: High SABA use (with increased mortality if >1 x 200- Havin any of gastroesophageal reflux disease
dose canister/month); inadequate ICS: not prescribed ICS; poor these risk • Persistent bronchodilator reversibility
adherence; incorrect inhaler technique factors
• Comorbidities: obesity; chronic rhinosinusitis; GERD; confirmed increases the o Finding significant bronchodilator reversibility (increase in FEV 1
food allergy; pregnancy patient’s risk >12% and >200 mL from baseline) in patient taking controller
• Exposures: smoking; allergen exposure if sensitized; air pollution of
exacerbations treatment, or who has taken a SABA within 4 hours, or a LABA
• Context: Major psychological/socioeconomic problems
• Lung function: low FEV1, especially <60% predicted; high even if they within 12 hours, suggests uncontrolled asthma
have few
bronchodilator reversibility
asthma • Short-term PEF monitoring
• Other tests in patients with Type 2 inflammation: blood eosinophils; symptoms o May be used to assess response to treatment, to evaluate
elevated FENO (in adults with allergic asthma taking ICS)
Other major independent risk factors for flare-ups (exacerbations) triggers (including at work) for worsening symptoms, or to
• Ever intubated or in intensive care unit for asthma establish a baseline for action plans
• ≥1 severe exacerbation in last 12 months
Risk factors for developing persistent airflow limitation
o Excessive variation in PEF suggests sub-optimal asthma
• History: preterm birth, low birth weight and greater infant weight gain; chronic mucus control, and increases the risk of exacerbations
hypersecretion • Long-term PEF monitoring
• Medications: lack of ICS treatment
• Exposures: tobacco smoke; noxious chemicals; occupational exposures o Now generally only recommended for patients with severe
• Investigations: low initial FEV1; sputum or blood eosinophilia asthma, or those with impaired perception of airflow limitation
Risk factors for medication side-effects
• Systemic: frequent OCS; long term, high dose and/or potent ICS; also taking P450
inhibitors ASSESSING ASTHMA SEVERITY
• Local: high-dose or potent ICS; poor inhaler technique
FEV1: forced expiratory volume in 1 second; ICS: inhaled corticosteroid; OCS: oral corticosteroid: P450 inhibitors: cytochrome P450 inhibitors
• Can be assessed when the patient has been on regular controller
such as ritonavir, ketoconazole, itraconazole; SABA: short-acting beta2-agonist.
*Based on SABA reliever. Excludes reliever taken before exercise.
treatment for several months:
†
’Independent’ risk factors are those that are significant after adjustment for the level of symptom control. Poor symptom control and exacerbation
risk should not be simply combined numerically, as they may have different causes and may need different treatment strategies.
o Mild asthma
▪ Well-controlled with Step 1 or Step 2 treatment
Specific questions for assessment of asthma in children 6-11 years
Asthma symptom control
o Moderate asthma
How often does the child have cough, wheeze, dyspnea, or heavy ▪ Well-controlled with Step 3 treatment
Day symptoms breathing (number of times per week or day)? What triggers the o Severe asthma
symptoms? How are they handled?
Cough, awakenings, tiredness during the day? (If the only symptom ▪ Requires Step 4 or 5 treatment to prevent it from becoming
Night symptoms
is cough, consider rhinitis or gastroesophageal reflux disease) ‘uncontrolled’, or remains ‘uncontrolled’ despite treatment
How often is reliever medication used? (check date on inhaler or
Reliever use last prescription). Distinguish between pre-exercise use (sports) ▪ Patients with refractory asthma and those in whom
and use for relief of symptoms. response to treatment of comorbidities is incomplete
What sports/hobbies/interests does the child have, at school and in
their spare time? How does the child’s level of activity compare with
• Most common problems that need to be excluded before a diagnosis
Level of activity their peers or siblings? How many days is the child absent from of severe asthma can be made are:
school? Try to get an accurate picture of the child’s day from the
child without interruption from the parent/carer.
o Poor inhaler technique (up to 80% of community patients)
Risk factors for adverse outcomes o Poor medication adherence
How do viral infections affect the child’s asthma? Do symptoms o Incorrect diagnosis, with symptoms due to alternative conditions
interfere with school or sports? How long do the symptoms last?
How many episodes have occurred since their last medical review? (inducible laryngeal obstruction, cardiac failure, lack of fitness)
Exacerbations
Any urgent doctor/emergency department visits? Is there a written o Comorbidities and complicating conditions such as
action plan? Persistent bronchodilator reversibility is a risk factor for
exacerbations, even if the child has few symptoms. rhinosinusitis, GERD, obesity, and obstructive sleep apnea
Lung function
Check curves and technique. Main focus is on FEV1 and FEV1/FVC o Ongoing sensitizing/irritant exposure in home/work environment
ratio. Plot these values as percent predicted to see trends over time.
Check the child’s height at least yearly, as poorly controlled asthma
Side-effects can affect growth, and growth velocity may be lower in the first 1-2
years of ICS treatment. Ask about frequency & dose of ICS & OCS.
Treatment factors
Ask the child to show how they use their inhaler. Compare with a
Inhaler technique
device-specific checklist
On how many days does the child use their controller in a week (e.g.
0, 2, 4, 7, days)? Is it easier to remember to use it in the morning or
Adherence
evening? Where is inhaler kept – is it in plain view to reduce
forgetting? Check date on inhaler
Does the child or their parent/carer have any concerns about their
Goals/concerns asthma (e.g. fear of medication, side-effects, interference with
activity)? What are the child’s/parent’s/carer’s goals for treatment?
Comorbidities
Itching, sneezing, nasal obstruction? Can the child breathe through
Allergic rhinitis
their nose? What medications are being taken for nasal symptoms?
Eczema Sleep disturbance, topical corticosteroids?
Is the child allergic to any foods? (confirmed food allergy is a risk
Food allergy
factor for asthma-related death)
Obesity Check age-adjusted BMI. Ask about diet and physical activity
Other investigations (if needed0029
If no clear assessment can be made based on the above questions,
2-week diary ask child or parent/carer to keep a daily diary of asthma symptoms,
reliever use & peak expiratory flow (best of 3) for 2 weeks
Provides information about airway hyperresponsiveness and
Exercise challenge
fitness. Only undertake a challenge if it is otherwise difficult to
(laboratory)
assess asthma control
FEV1: forced expiratory volume in 1 second; FVC: forced vital capacity; ICS: inhaled corticosteroids; OCS: oral corticosteroids

17. SEVERE ASTHMA | 83

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

LONG-TERM GOALS OF ASTHMA MANAGEMENT Treatment options that may be considered after optimization of
• Achieve good control of symptoms & maintain normal activity levels existing therapy:
• Minimize the risk of asthma-related death, exacerbations, persistent • Combination high dose ICS-LABA
airflow limitation, and side-effects o May be considered in adults and adolescents
o Increase in ICS dose provides little additional benefit
ASTHMA MEDICATIONS o Increased risk of side-effects, including adrenal suppression
Categories of asthma medications o Only on a trial basis for 3-6 months when good asthma control
• Controller medications cannot be achieved with medium dose ICS-LABA and/or a 3rd
o Used to reduce airway inflammation, control symptoms, and controller (e.g. LTRA, sustained-release theophylline)
reduce future risks (exacerbations, decline in lung function) • Add-on tiotropium (long-acting muscarinic antagonist)
o In patients with mild asthma, controller treatment may be o In patients aged ≥6 years whose asthma is not well-controlled
delivered through as-needed low dose ICS-formoterol, taken with ICS-LABA
when symptoms occur and before exercise o Dose: 5 μg once daily by mist inhaler
• Reliever (rescue) medications o Modestly improves lung function and modestly increases the
o Provided to all patients for as-needed relief of breakthrough time to severe exacerbation requiring OCS
symptoms, including worsening asthma or exacerbations o No evidence with other LAMA preparations
o Also recommended for short-term prevention of exercise- • Add-on azithromycin (three times a week, off-label)
induced bronchoconstriction o For adult patients with persistent symptomatic asthma despite
o Reducing and, ideally, eliminating the need for reliever moderate-high dose ICS and LABA
treatment is both an important goal in asthma management and o Reduced asthma exacerbations in eosinophilic & non-
a measure of the success of asthma management eosinophilic asthma & improved asthma-related QOL
• Add-on therapies for patients with severe asthma o Diarrhea was more common
o May be considered when patients have persistent symptoms o Contraindications: hearing impairment, abnormal prolongation
and/or exacerbations despite optimized treatment with high- of corrected QT interval
dose controller medications (high-dose ICS + LABA) and a o Adverse effects: ototoxicity, cardiac arrhythmia
treatment of modifiable risk factors o Before considering add-on off-label therapy with azithromycin in
uncontrolled or severe asthma, sputum should be checked for
Initial asthma treatment for adults & adolescents atypical mycobacteria
Presenting symptoms Preferred INITIAL treatment o Risk of increasing antimicrobial resistance at the patient and the
All patients SABA-only treatment (without ICS) is NOT population level should be taken into account
recommended • Add-on anti-immunoglobulin E (anti-IgE) (omalizumab)
Infrequent asthma • As needed low dose ICS-formoterol
symptoms, e.g. less than Other options include ICS whenever SABA is o For patients aged ≥6 years with moderate or severe allergic
twice a month taken, in combination or separate inhalers asthma that is uncontrolled on Step 4-5 treatment
Asthma symptoms or need • Low dose ICS** with as-needed SABA, or • Add-on anti-interleukin 5 treatment
for reliever twice a month or • As-needed low dose ICS-formoterol o Subcutaneous mepolizumab: patients ≥12 years old
more Other options include LTRA (less effective
o Intravenous reslizumab: patients ≥18 years old
than ICS), or taking ICS whenever SABA is
taken either in combination or separate o For severe eosinophilic asthma uncontrolled by Step 4-5
inhalers. Consider likely adherence with • Add-on anti-interleukin 5 receptor treatment
controller if reliever is SABA o Subcutaneous benralizumab: patients ≥12 years old
Troublesome asthma • Low dose ICS-LABA† as maintenance
o For severe eosinophilic asthma uncontrolled by Step 4-5
symptoms most days; or and reliever therapy with ICS-formoterol#
waking due to asthma once or as conventional maintenance • Add-on anti-interleukin-4Rα
a week or more, especially if treatment with as-needed SABA, OR o Subcutaneous dupilumab: patients ≥12 years
any risk factors exist • Medium dose ICS with as-needed SABA
†
o For severe Type 2 asthma, or requiring treatment with
Initial asthma presentation is • Short course of oral corticosteroids AND maintenance OCS
with severely uncontrolled start regular controller treatment with
asthma, or with an acute high-dose ICS, or medium-dose ICS- • Sputum-guided treatment
exacerbation LABA# o For persisting symptoms and/or exacerbations despite high-
Before starting initial controller treatment dose ICS or ICS-LABA
• Record evidence for the diagnosis of asthma, if possible o Treatment may be adjusted based on eosinophilia (>3%) in
• Record level of symptom control and risk factors, including lung function
induced sputum
• Consider factors influencing choice between available treatment options
• Ensure that the patient can use the inhaler correctly o In severe asthma, this strategy leads to reduced exacerbations
• Schedule an appointment for a follow-up visit and/or lower doses of ICS
After starting initial controller treatment • Add-on treatment with bronchial thermoplasty
• Review patient’s response after 2-3 months, or earlier depending on o May be considered for some patients with severe asthma
clinical urgency
o Evidence is limited and in selected patients
• Step down treatment once good control has been maintained for 3 months
ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist; LTRA: leukotriene receptor antagonist; OCS: oral o The long-term effects compared with control patients, including
corticosteroids; SABA: short-acting beta2-agonist.
**Corresponds to starting at Step 2
for lung function, are not known
†

#
Corresponds to starting at Step 3 • Add-on low dose oral corticosteroids (≤7.5 mg/day prednisone)
Not recommended for initial treatment in children 6-11 years
o May be effective for some adults with severe asthma, but are
often associated with substantial side effects
o Should only be considered for adults with poor symptom control
and/or frequent exacerbations despite good inhaler technique &
adherence with Step 4, and after exclusion of other contributory
factors and other add-on treatments
o Patients should be counseled about potential side-effects, and
should be assessed and monitored for risk of corticosteroid-
induced osteoporosis
o Those expected to be treated for ≥3 months should be provided
with relevant lifestyle counselling & prescription of therapy for
prevention of osteoporosis (where appropriate)

84 | 17. SEVERE ASTHMA


STEP 1: Preferred controller: as-needed low dose combination ICS-
formoterol
• Preferred controller option:
o As-needed low dose combination ICS-formoterol
▪ For symptoms <2x/month, and no exacerbation risk factors
• Other controller options:
o Low dose ICS taken whenever SABA is taken
▪ Option when ICS-formoterol is not available or affordable
STEP 2: Preferred controller options: Daily low dose ICS plus as-needed
SABA, OR as-needed low dose ICS-formoterol
• Preferred controller options:
o Regular daily low dose ICS plus as-needed SABA
▪ To reduce the risk of severe exacerbations
o As-needed low dose combination ICS-formoterol
▪ To prevent severe exacerbations & avoid daily ICS in mild asthma
• Other controller options:
o Leukotriene receptor antagonists (LTRA)
▪ Less effective than ICS for exacerbation reduction
▪ Initial controller treatment for those unable/unwilling to use ICS; who
experience intolerable side-effects from ICS; or with concomitant AR
o Regular daily combination of low dose ICS-LABA as initial maintenance
▪ Reduces symptoms & improves lung function vs. low dose ICS alone
▪ More expensive; doesn’t further reduce risk of exacerbations vs. ICS
o Regular daily ICS or as-needed ICS-formoterol
▪ Purely seasonal allergic asthma with no interval asthma symptoms
▪ Started immediately as symptoms commence
STEP 3: Preferred controller options: Low dose ICS-LABA maintenance plus
as-needed SABA, OR low dose ICS-formoterol maintenance & reliever
• Before step-up, check for common problems (incorrect inhaler technique, poor
adherence, environmental exposures) & confirm symptoms are due to asthma
• Preferred controller options:
o Low dose ICS-LABA as maintenance with as-needed SABA
▪ LABA: additional improvements in symptoms & lung function with
reduced risk of exacerbations compared with the same dose of ICS,
but there is only a small reduction in reliever use
o Low dose ICS-formoterol as both maintenance & reliever
▪ Significantly reduces exacerbation & provides similar control at lower
doses of ICS, vs. fixed dose ICS-LABA or higher dose of ICS, both
with as-needed SABA in patients with ≥1 exacerbation in previous yr
▪ Should NOT be used as reliever with ICS-LABA with different LABA
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Other controller options:
o Sublingual allergen immunotherapy (SLIT)
▪ For AR & sensitized to house dust mite, with suboptimally controlled
asthma despite low-high dose ICS, provided FEV1 is >70% predicted
o Increase ICS to medium dose
▪ Less effective than adding a LABA
• Other less efficacious options
o Low dose ICS + LTRA
o Low dose ICS + low dose, sustained-release theophylline
STEP 4: Preferred controller: Low dose ICS-formoterol as maintenance and
reliever, OR medium dose ICS-LABA maintenance plus as-needed SABA
• Some uncontrolled asthma on low dose ICS-LABA despite good adherence &
correct technique may benefit from increasing maintenance dose to medium
• Before step-up, check for common problems (incorrect inhaler technique, poor
adherence, environmental exposures) & confirm symptoms are due to asthma
• Preferred controller options:
o Low dose ICS-formoterol as maintenance and reliever treatment
▪ For ≥1 exacerbations in previous yr, more effective in reducing
exacerbations vs. same dose of maintenance ICS-LABA or higher
doses of ICS; may be increased to medium if necessary
o Medium dose ICS-LABA with as-needed SABA
▪ For inadequately controlled asthma
• Other controller options:
o Tiotropium (long-acting muscarinic antagonist) by mist inhaler
▪ May be used as add-on therapy in patients aged ≥6 years
▪ Modestly improves lung function and reduces exacerbations
▪ Insufficient evidence for ICS+tiotropium over ICS-LABA
o Sublingual allergen immunotherapy (SLIT)
▪ For AR & sensitized to house dust mite, with suboptimally controlled
asthma despite low-high dose ICS, provided FEV1 is >70% predicted
o Theophylline
▪ Medium/high dose budesonide: efficacy improved with 4 times daily
▪ For other ICS: twice-daily dosing is appropriate
STEP 5: Preferred option: Refer for phenotypic assessment and
consideration of add-on treatment
• Indications for referral to a specialist with expertise in investigation and
management of severe asthma:
o Persistent symptoms or exacerbations despite correct inhaler technique
and good adherence with Step 4 treatment
o Other controller options have been considered
17. SEVERE ASTHMA | 85
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
STEP 1: Preferred controller: as-needed low dose combination ICS-
formoterol
• Preferred controller option:
o Taking ICS whenever SABA is taken
▪ Showed substantially fewer exacerbations compared with
SABA-only treatment
o Regular ICS with as-needed SABA
▪ Likelihood of poor adherence in children with infrequent
symptoms should be taken into account
STEP 2: Preferred controller options: Daily low dose ICS plus as-
needed SABA
• Preferred controller options:
o Regular daily low dose ICS plus as-needed SABA
▪ To reduce the risk of severe exacerbations
• Other controller options:
o Daily leukotriene receptor antagonists (LTRA)
o Low dose ICS whenever SABA is taken
STEP 3: Preferred controller options: Medium dose ICS plus as-
needed SABA OR low-dose ICS-LABA plus as-needed SABA
• Before considering a step up, check for common problems (incorrect
inhaler technique, poor adherence, environmental exposures) &
confirm that symptoms are due to asthma
• Preferred controller options:
o Medium dose ICS plus as-needed SABA
o Low dose ICS-LABA plus as-needed SABA
▪ non-inferior to the same dose of ICS alone for severe
exacerbations, with no difference in symptom control or
reliever use
• Other controller options:
o Low dose ICS + LTRA
86 | 17. SEVERE ASTHMA
STEP 4: Preferred controller: Medium dose ICS-LABA maintenance
plus as-needed SABA
• Some patients with uncontrolled asthma on low dose ICS-LABA
despite good adherence & correct technique may benefit from
increasing maintenance dose to medium
• Before stepping up, check for common problems (incorrect inhaler
technique, poor adherence, environmental exposures) & confirm
that the symptoms are due to asthma
• Preferred controller options:
o Medium dose ICS-LABA with as-needed SABA
▪ For patients whose asthma is not adequately controlled,
treatment may be increased to medium dose ICS-LABA
o Refer child for expert assessment and advice
• Other controller options:
o Tiotropium (long-acting muscarinic antagonist) by mist inhaler
▪ May be used as add-on therapy in patients aged ≥6 years
▪ Modestly improves lung function and reduces exacerbations
STEP 5: Preferred option: Refer for phenotypic assessment and
consideration of add-on treatment
• Indications for referral to a specialist with expertise in
investigation and management of severe asthma:
o Persistent symptoms or exacerbations despite correct inhaler
technique and good adherence with Step 4 treatment
o Other controller options have been considered
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

REVIEWING RESPONSE AND ADJUSTING TREATMENT Treating modifiable risk factors to reduce exacerbations
How often should asthma be reviewed? Risk factor Treatment strategy
• Regularly to monitor symptom control, risk factors and occurrence • Ensure patient is prescribed an ICS-containing
Any patient with ≥1 controller
of exacerbations, and document response to any treatment chances risk factor for • Ensure patient has a written action plan appropriate
• Improvement within days of treatment, full benefit after 3-4 months exacerbations for their health literacy
• Patients seen 1-3 months after & every 3-12 months thereafter (including poor • Review patient more frequently than low-risk patients
symptom control) • Check inhaler technique and adherence frequently
• After exacerbation, a review visit within 1 week should be scheduled
• Identify any modifiable risk factors
• Consider alternative controller regimens to reduce
Stepping up asthma treatment ≥1 severe exacerbation risk
• Sustained step up (for at least 2-3 months) exacerbation in • Consider stepping up treatment if no modifiable risk
o Some uncontrolled asthma on low dose ICS-LABA despite good last year factors
• Identify any avoidable triggers for exacerbations
adherence & correct technique may benefit to medium dose
• Encourage smoking cessation by patient/family;
o May be recommended if: Exposure to provide advice and resources
▪ Symptoms are confirmed to be due to asthma tobacco smoke • Consider higher dose of ICS if asthma poorly
▪ Inhaler technique and adherence are satisfactory controlled
▪ Modifiable risk factors (smoking) have been addressed • Consider trial of 3 months’ treatment with high-dose
Low FEV1,
ICS and/or 2 weeks’ OCS
o Any step-up should be regarded as a therapeutic trial, and the especially if <60%
• Exclude other lung disease
response reviewed after 2-3 months predicted
• Refer for expert advice if no improvement
o If no response, treatment should be reduced to previous level, • Strategies for weight reduction
and alternative treatment options or referral considered • Distinguish asthma symptoms from symptoms due to
Obesity
• Short-term step up (for 1-2 weeks) deconditioning, mechanical restriction, and/or sleep
apnea
o During viral infections or seasonal allergen exposure
• Arrange mental health assessment
o May be initiated by the patient according to their written asthma Major
• Help patient to distinguish between symptoms of
psychological
action plan, or by the health care provider anxiety and asthma; provide advice about
problems
• Day-to-day adjustment management of panic attacks
o For patients prescribed combination budesonide-formoterol or Major
socioeconomic • Identify most cost-effective ICS-based regimen
beclomethasone- formoterol as maintenance and reliever problems
o The patient adjusts the number of as-needed doses from day to Confirmed food
• Appropriate food avoidance; injectable epinephrine
day according to symptoms, while continuing maintenance allergy
• Consider trial of simple avoidance strategies;
Stepping down treatment when asthma is well controlled consider cost
Allergen exposure • Consider step up of controller treatment
• Once good asthma control has been achieved and maintained for 3 if sensitized • Consider adding SLIT in symptomatic adult HDM-
months and lung function has reached a plateau sensitive patients with allergic rhinitis despite ICS,
• Aims of stepping down: provided FEV1 is >70% predicted
o To find minimum effective treatment (maintain good control, Sputum
• Increase ICs dose independent of level of symptom
eosinophilia
minimize costs & potential for side-effects) (limited centers)
control
o To encourage the patient to continue controller treatment
• Any step-down of treatment should be considered a therapeutic trial Indications for considering referral for expert advice
Difficulty confirming the diagnosis of asthma
Options for stepping down treatment once asthma is well controlled • Patient has symptoms of chronic infection, or features suggesting a
General principles of stepping down asthma treatment cardiac or other non-pulmonary cause (immediate referral recommended)
• Consider stepping down when asthma symptoms have been well controlled and lung
function has been stable for 3 or more months. If the patient has risk factors for
• Diagnosis is unclear even after a trial of therapy with ICS or systemic
exacerbations, or persistent airflow limitation, do not step down without close supervision corticosteroids
• Choose an appropriate time (no respiratory infection, not travelling, not pregnant) • Patients with features of both asthma and COPD, if there is doubt about
• Approach each step as a therapeutic trial. Engage patient in the process; document priorities for treatment
asthma status (symptom control, lung function, risk factors); provide clear instructions; Suspected occupational asthma
provide written asthma action plan; ensure patient has sufficient medication to resume
previous dose if necessary; monitor symptoms and/or PEF; schedule for a follow-up visit
• Refer for confirmatory testing and identification of sensitizing or irritant
• Stepping down ICS doses by 25-50% at 3-month intervals is feasible & safe for most agent, specific advice about eliminating exposure and pharmacological
Current Current medication & treatment
Options for stepping down
step dose Persistent uncontrolled asthma or frequent exacerbations
• Continue ICS-LABA and reduce OCS • Patient’s symptoms remain uncontrolled, or patient has ongoing
High dose ICS-LABA plus • Sputum-guided approach to reduce OCS exacerbations or low lung function despite correct inhaler technique and
OCS • Alternate-day OCS good adherence with Step 4 treatment (moderate dose ICS-LABA). Before
Step 5
• Replace OCS with high dose ICS referral, depending on the clinical context, identify and treat modifiable risk
High dose ICS-LABA +
• Refer for expert advise factors and comorbidities
other add-on agents
Moderate-high dose ICS- • Continue ICS-LABA with 50% reduction ICS • Patient has frequent asthma-related health care utilization
LABA maintenance • Discontinue LABA may lead to deterioration Any risk factors for asthma-related death
Medium dose ICS- • Reduce maintenance ICS-formoterol* to low • Near-fatal asthma attack (ICU admission, or mechanical ventilation for
Step 4 formoterol* as maintenance dose, and continue as-nedeed low dose ICS asthma) at any time in the past
& reliever ICS-formoterol reliever • Anaphylaxis or confirmed food allergy in a patient with asthma
High dose ICS plus 2 nd
• Reduce ICS dose by 50% and continue
controller second controller
Evidence of, or risk of, significant treatment side-effects
Low dose ICS-LABA • Reduce ICS-LABA to once daily • Patients with significant side-effects from treatment
maintenance • Discontinue LABA may lead to deterioration • Need for long-term oral corticosteroid use
Step 3 Low dose ICS-formoterol*
• Reduce maintenance ICS-formoterol* dose • Frequent courses of oral corticosteroids (e.g. two or more courses a year)
to once daily & continue as-needed low Symptoms suggesting complications or sub-types of asthma
as maintenance & reliever
dose ICS-formoterol* reliever
• e.g. aspirin-exacerbated respiratory disease; allergic bronchopulmonary
Mod/high-dose ICS • Reduce ICS dose by 50%
aspergillosis
• Once-daily (budesonide, mometasone)
• Switch to as-needed low ICS-formoterol Additional reasons for referral in children 6-11 years
Low dose ICS • Adding LTRA may allow ICS step down • Doubts about diagnosis of asthma (e.g. respiratory symptoms are not
• Insufficient evidence to support step-down responding well to treatment in a child who was born prematurely)
Step 2 to as-needed ICS with SABA • Symptoms or exacerbations remain uncontrolled despite moderate dose
• Switch to as-needed low ICS-formoterol ICS with correct inhaler technique and good adherence
• Complete cessation of ICS in adults &
Low dose ICS or LTRA • Suspected side-effects of treatment (e.g. growth delay)
adolescents is not advised as risk of
exacerbations is increased with SABA-only • Asthma and confirmed food allergy
*ICS-formoterol maintenance and reliever treatment can be prescribed with low dose budesonide-formoterol or
BDP-formoterol

17. SEVERE ASTHMA | 87

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

ASTHMA EXACERBATIONS
• Episodes characterized by a progressive increase in symptoms of
shortness of breath, cough, wheezing, or chest tightness, and
progressive decrease in lung function, i.e. represent a change from
patient’s usual status that is sufficient to require change in treatment
• May occur in patients with a preexisting diagnosis of asthma or,
occasionally, as the first presentation of asthma
• “Acute severe asthma”, “flare-up”, “attack”
Common exacerbation triggers
• Viral respiratory infections
• Allergen exposure (e.g. grass pollen, soybean dust, fungal spores)
• Food allergy
• Outdoor air pollution
• Seasonal changes and/or returning to school in fall (autumn)
• Poor adherence with ICS
• Epidemics of severe asthma exacerbations may occur suddenly,
putting high pressure on local health system responses
Factors that increase the risk of asthma-related death
• A history of near-fatal asthma requiring intubation & mechanical
ventilation
• Hospitalization or emergency care visit for asthma in the past year
• Currently using or having recently stopped using OCS (a marker of
event severity)
• Not currently using ICS
• Overuse of SABAs, especially use of more than one canister of
salbutamol (or equivalent) monthly
• A history of psychiatric disease or psychosocial problems
• Poor adherence with asthma medications and/or poor adherence
with (or lack or) a written asthma action plan
• Food allergy in a patient with asthma
DIAGNOSIS OF EXACERBATIONS
• The decrease in the expiratory airflow, quantified by lung function
measurements (PEF, FEV1), are more reliable indicators of the
severity of the exacerbations than symptoms
• Frequency of symptoms may be a more sensitive measure of the
onset of an exacerbation than PEF
MANAGEMENT OF ASTHMA EXACERBATIONS IN PRIMARY CARE
Reviewing response
Assessing exacerbation severity
• During treatment, patients should be closely monitored, and
• History
treatment titrated according to their response
o Timing of onset and cause of the present exacerbation
• Indications for immediate transfer to an acute care facility
o Severity of symptoms (limiting exercise, disturbing sleep)
o Signs of a severe or life-threatening exacerbation
o Any symptoms of anaphylaxis
o Failure of response to treatment
o Any risk factors for asthma-related death
o Continuing deterioration
o All current reliever and controller medications (doses & devices
• Patients with little or slow response to SABA treatment should be
prescribed, adherence, recent dose changes, & response)
closely monitored
• Physical examination
• Lung function can be monitored after SABA therapy is initiated
o Signs of exacerbation severity & vital signs (level of
o Additional treatment should continue until PEF or FEV1 reaches
consciousness, temperature, PR, RR, BP, ability to complete
a plateau or (ideally) returns to patient’s previous best
sentences, use of accessory muscles, wheeze)
o Complicating factors (anaphylaxis, pneumonia, pneumothorax)
Follow up
o Signs of alternative conditions that could explain acute
• Discharge medications
breathlessness (cardiac failure, inducible laryngeal obstruction,
inhaled foreign body or pulmonary embolism) o As-needed reliever medication
o Short course OCS
• Objective measurements
o Regular controller treatment
o Pulse oximetry: Saturation levels <90% in children or adults
• Inhaler technique and adherence should be reviewed before
signal the need for aggressive therapy
o PEF in patients older than 5 years discharged
• Follow-up appointment should be arranged for about 2-7 days later
Treating exacerbations in primary care • At the review visit, health care provider should assess:
• Main initial therapies o Whether the flare-up has resolved
o Repetitive administration of SABAs o Whether OCS can be ceased
o Early introduction of systemic corticosteroids o Patient’s level of symptom control and risk factors
o Controlled flow oxygen supplementation o Potential cause of the exacerbation
• Goals of treatment o Written asthma action plan (or provide one)
o Rapidly relieve airflow obstruction and hypoxemia • Maintenance controller treatment can generally be stepped back to
o Address the underlying inflammatory pathophysiology pre-exacerbation levels 2-4 weeks after the exacerbation
o Prevent relapse

88 | 17. SEVERE ASTHMA


MANAGEMENT OF ASTHMA EXACERBATIONS IN EMERGENCY ROOM
Assessment
• History (conducted concurrently with initiation of therapy)
o Time of onset and cause of the present exacerbation
o Severity of symptoms (limiting exercise, disturbing sleep)
o Any symptoms of anaphylaxis
o Any risk factors for asthma-related death
o All current reliever and controller medications (doses & devices
prescribed, adherence, recent dose changes, & response)
• Physical examination
o Signs of exacerbation severity & vital signs (LOC, Temp, PR, RR, BP,
completes sentences, accessory muscles, wheeze)
o Complicating factors (anaphylaxis, pneumonia, atelectasis,
pneumothorax, pneumomediastinum)
o Alternative conditions with acute breathlessness (cardiac failure,
inducible laryngeal obstruction, inhaled foreign body, PE)
• Objective assessment
o Measurement of lung function (PEF, FEV1)
▪ Should be recorded before treatment is initiated
▪ Monitored at 1 hour and at intervals until a clear response to
treatment has occurred or a plateau is reached
o Oxygen saturation (closely monitored by pulse oximetry)
▪ Especially useful in children if unable to perform PEF
▪ Saturation <92%: predictor of the need for hospitalization
▪ Saturation <90%: need for aggressive therapy
▪ Assessed before oxygen is commenced, or 5 minutes after oxygen
is removed or when saturation stabilizes
o Arterial blood gas measurements are NOT routinely required
▪ PEF or FEV1 <50% predicted, no response, or deteriorating
▪ PaCO2 is often below normal (<40 mmHg)
▪ Fatigue & somnolence: ↑pCO2 (airway intervention needed)
▪ PaO2 <60 mmHg & normal/↑PaCO2 = respiratory failure
o Chest X-ray (CXR) is NOT routinely recommended
▪ Adults: suspected complicating/alternative cardiopulmonary
process, or unresponsive to treatment (pneumothorax)
▪ Children: pneumothorax, parenchymal disease, inhaled foreign body
Treatment in acute care settings such as emergency department
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Oxygen (via nasal cannula or mask)
o Goal: SaO2 of 93-95% (94-98% for children 6-11 years)
• Inhaled short-acting beta2-agonists (via pMDI + spacer)
o Administered frequently for acute asthma
o Initially use continuous therapy followed by intermittent on-demand
therapy for hospitalized patients
• Epinephrine (intramuscular)
o Indicated for acute asthma associated with anaphylaxis & angioedema,
not routine for other asthma exacerbations
• Systemic corticosteroids
o Speed resolution of exacerbations and prevent relapse, and should be
utilized in all but the mildest exacerbations
o Administered within 1 hour of presentation
o Particularly important in the emergency department if:
▪ Initial SABA treatment fails to achieve lasting improvement
▪ Exacerbation developed while patient was taking OCS
▪ History of previous exacerbations requiring OCS
o Route of delivery:
▪ Oral: quicker, less invasive, less expensive; require at least 4 hours
to produce a clinical improvement
▪ IV: too dyspneic; vomiting; non-invasive ventilation or intubation
▪ IM: alternative to OCS for discharged patients (adherence issues)
o Dosage:
▪ Prednisolone 50 mg as a single morning dose
▪ Hydrocortisone 200 mg in divided doses
▪ Children: 1-2 mg/kg up to a maximum of 40 mg/day
o Duration:
▪ 3-5-day course is usually considered sufficient
▪ Oral dexamethasone: 1-2 days (side-effects beyond 2 days)
• Inhaled corticosteroids
o Within the ER: High-dose ICS given within the 1st hour
o On discharge home: regular ongoing ICS-containing treatment
Reviewing response
• Clinical status and oxygen saturation should be re-assessed frequently, with
further treatment titrated according to the patient’s response
• Lung function should be measured after 1 hour, i.e. after the first 3
bronchodilator treatments
• Patients who deteriorate despite intensive bronchodilator and corticosteroid
treatment should be re-evaluated for transfer to ICU
Criteria for hospitalization vs discharge from the ER
• Clinical status (including ability to lie flat) & lung function 1 hour after treatment
are more reliable predictors of need for hospitalization than status on arrival
• Factors associated with increased likelihood of need of admission
o Pretreatment FEV1 or PEF is <25% predicted or personal best
o Post-treatment FEV1 or PEF is <40% predicted or personal best
o Female sex, older age, non-white race
o Use of >8 beta2-agonist puffs in the previous 24 hours
o Severity of the exacerbation (e.g. need for resuscitation or rapid medical
intervention on arrival, RR >22, SpO2 <95%, final PEF <50% predicted)
o Past history of severe exacerbations (intubations, asthma admissions)
o Previous unscheduled office & ER visits requiring use of OCS
• Discharge may be possible if post-treatment lung function is 40-60% predicted
• Discharge is recommended if post-treatment lung function is >60% predicted
Discharge management after hospital/ER care for asthma
Medications
Inhaled corticosteroids (ICS)
• Initiate prior to discharge if not previously prescribed
• If currently prescribed, step up for 2-4 weeks
Oral corticosteroids (OCS)
• 5-7-day course for adults (prednisolone 40-50 mg/day)
• 3-5-day course for children (1-2 mg/kg/day, max 40 mg/day)
• Review progress before ceasing
• IM corticosteroids for patients at risk of poor adherence
Reliever medication
• Transfer to as-needed rather than regular reliever medication use, based on
symptomatic and objective improvement
• If ipratropium bromide was used, may be quickly discontinued
Risk factors that contributed to the exacerbation
Identify factors that may have contributed to exacerbation and implement strategies to
reduce modifiable risk factors (irritant/allergen exposure, inadequate long-term treatment,
adherence problems, lack of written asthma action plan, viral respiratory infections
Self-management skills and written asthma action plan
• Review inhaler technique
• Review technique with PEF meter if used
• Provide a written asthma action plan or review existing plan
• Evaluate response to exacerbation
• Review patient’s use of controller treatment before & during exacerbation
Follow up appointment
A follow-up appointment within 2 days of discharge should be made with the patient’s usual
health care provider, to ensure that treatment is continued, that asthma symptoms are well
controlled, and that the patient’s lung function reaches their personal best (if known).
Reference: Global Initiative for Asthma (GINA): Global Strategy for Asthma Management and Prevention (2019)
17. SEVERE ASTHMA | 89
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

18. HEMOPTYSIS CLINICAL FEATURES

• Expectoration of blood from the lungs or tracheobronchial tree • Identify true hemoptysis & exclude hematemesis and epistaxis
• “Massive” hemoptysis o Upper GI bleeding (UGIB): history of dark stools nausea,
o From 100 mL/24 hours to >1000 mL/24 hours abdominal pain, (+) FOBT
o Midpoint value of 600 mL/24 hours o Epistaxis: identified on physical examination
• Morbidity and mortality depend on: o Hemoptysis: expectorated blood is bright colored (source is the
o Rate of bleeding upper airway or lungs)
o Ability of the patient to clear the blood
o Presence of underlying lung disease (potentiates the effects of History
blood in the airways) • Source of bleeding (accurate from the patient 50% of the time)
• “Minor” hemoptysis Clinical Clues Description
o Self-limited, small-volume expectoration of blood • Predisposes to chronic lung
Smoking inflammation & vascular disruption
o No comorbid lung disease • ↑ risk of bronchogenic carcinoma
o Normal/stable oxygenation and ventilation History of tuberculosis or • Leading cause of hemoptysis worldwide
o Normal vital signs emigration/travel from an • High-prevalence areas: Africa, inner-city
o No risk factors for continued bleeding endemic area New York, Middle East, Southeast Asia
Previous thromboembolic • May have pulmonary embolism as a
PATHOPHYSIOLOGY disease cause
Hematuria or known renal • Goodpasture’s syndrome
• Results from disruption of blood vessels with walls of airways, from insufficiency • Granulomatosis with polyangiitis (GPA)
trachea to bronchi, bronchioles, and the lung parenchyma Saddle nose deformity • Septal perforation in GPA
• Pulmonary arteries: 99% of the arterial blood flow to the lungs History of connective tissue
o Low-pressure system; rarely the source of hemoptysis disease/suggestive symptoms
• May develop vasculitis and hemoptysis
such as arthralgias, myalgias,
• Bronchial circulation: ~1% of the arterial blood flow to the lungs recurrent fevers, rash)
o High-pressure system; 90% of the cases of hemoptysis History of crab & crayfish • Paragonimus spp. can cause
o Bronchial arteries: branch off the thoracic aorta at TV5-TV6 ingestion hemoptysis in chronic infection
▪ Supplies oxygenated blood to the bronchi, pulmonary Hydatid cysts within the lungs • Ecchinococcus spp.
arteries and veins, and lung parenchyma Cyclical hemoptysis
• Catamenial source from pulmonary
coordinating with a woman’s
▪ Follow the course of the bronchi along their tortuous paths endometriosis
menstrual cycle
▪ Anastomoses occur at the level of capillaries: produce a Cocaine and heroin inhalation • Can trigger diffuse alveolar hemorrhage
physiological right-to-left shunt (5% of total cardiac output) Nitrogen dioxide exposure in
• Hemoptysis in ice hockey players
Airway Processes indoor ice arenas
Coughing in transient Use of anticoagulants or
• Minor bleeding even in otherwise healthy
airway inflammation recent procedures (Swan- • Iatrogenic causes
lungs Ganz catheter, bronchoscopy)
(acute bronchitis)
• Neoangiogenesis of bronchial arteries to
Chronic inflammatory
enhance delivery of blood to alveoli; thin- Physical Examination
states (COPD)
walled, fragile vessels prone to rupture
Visual inspection
Chronic disease states • Blood streaked or contains blood clots
of the sputum
leading to bronchiectasis • Destruction of the cartilaginous support
• Signs suggestive of massive hemoptysis or
(chronic bronchial wall predisposes blood vessels to rupture
Vital signs underlying lung disease: tachypnea, tachycardia,
inflammation)
hypotension, labored respirations, hypoxemia
• Necrotic destruction of tissue resulting in
Infections Inspect nares &
cavitary lesions with neoangiogenesis in • Evidence of epistaxis
(Aspergillus, TB) posterior pharynx
cavity walls
Airway patency • Assess for potential difficulty of intubation
• False aneurysm of dilated, tortuous branches
Rasmussen’s aneurysm of pulmonary arteries crossing wall of TB • Wheezing: airway inflammation
cavity Lung auscultation • Focally reduced breath sounds: location of blooding
• Affects airways and lung parenchyma while • Crackles: diffuse alveolar hemorrhage or HF
Heart
Neoplasms
promoting neoangiogenesis • Murmurs of valvular disease
• Squamous cell carcinoma: accounts for a auscultation
large number of cases of massive hemoptysis Skin inspection • Telangiectasia and petechiae
Cardiopulmonary Processes
Pulmonary embolism & • Compensatory ↑ bronchial artery blood flow DIAGNOSIS
pulmonary via dilation & hypertrophy at anastomotic • Minor hemoptysis: no need for tests unless on anticoagulants
hypertension level; results in hemoptysis within alveoli
• Massive hemoptysis/recurring hemoptysis
Parenchymal Processes
• Indolent or massive; affects foci or diffuse • Baseline hemoglobin: falsely elevated in acute, rapid
Bleeding from small CBC &
bleeding (equilibration may not occur for 6 hours)
• Osler-Weber-Rendu disease: friable coagulation
vessels at anastomotic
telangiectasias (pulmonary AV malformations • Thrombocytopenia & coagulopathy increase risk and
level studies
in lungs, skin, mucous membranes) morbidity from hemoptysis
• Goodpasture’s syndrome, GPA • Help narrow differential diagnosis that includes
Renal function Goodpasture’s syndrome & GPA
• Damage lung parenchyma predisposing to
Vasculitis and collagen
alveolar hemorrhage
tests & urinalysis • Can identify those at risk for contrast nephropathy if
vascular diseases imaging is contemplated
• Anemia can result from chronic diffuse
alveolar hemorrhage Metabolic profile • Electrolytes
Traumatic causes of • Deceleration injuries & penetrating trauma to
hemoptysis chest: disruption of tracheobronchial tree Imaging
• Direct arterial injury: pulmonary artery • Initial imaging modality; yields a diagnosis up to 50% of
catheterization or biopsy of lung tissue during the time; rarely normal in massive hemoptysis
Chest
Iatrogenic causes bronchoscopy • Diffuse alveolar hemorrhage: scattered alveolar infiltrates
• Biopsy of carcinoid tumor: associated with radiography
• Focal alveolar hemorrhage, infiltrates, masses,
massive hemoptysis cavitation: potential sources of hemoptysis
• Aortic fistula to airways can precipitate • Delineates abnormal bronchial & non-bronchial arteries
Fistulae
catastrophic hemoptysis • Identify bleeding from pulmonary artery (Rasmussen’s
• Tracheo-innominate fistulae: from erosion of Multidetector
aneurysm) vs. anomalous vessel (Dieulafoy’s disease)
a tracheostomy into the innominate artery Row CT
• Bronchial arterial bleeding is almost always detected
Undetermined cause (cryptogenic): ~30% of cases • Preferred over CT angiography in massive hemoptysis

90 | 18. HEMOPTYSIS
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT: MILD HEMOPTYSIS

• Identify the cause
• Reassure those with minor features and no threat of imminent harm
• Provide an appropriate ER disposition based on:
o Amount of blood expectorated
o Respiratory status
o Risk factors for continued bleeding

TREATMENT: SEVERE HEMOPTYSIS

Airway Control
• Assess & ensure airway patency & ongoing oxygenation
• Look for a trachea-innominate fistula
If with • Control by direct digital pressure on anterior
tracheostomy portion of trachea against posterior aspect of
sternum using tracheostomy as point of access
• Rapid sequence intubation using a larger-
If no
diameter ET tube to allow for bronchoscopy
tracheostomy
• Once intubated, position patient with affected
& requires
lung in dependent portion to prevent spilling of
airway control
blood into unaffected site
• Preferentially intubate main bronchus of
unaffected lung
If bleeding is
uncontrollable • Alternative: Fogarty catheter (14F/100 cm) to
tamponade bronchus of affected lung: pass
catheter adjacent to ET tube once intubated
If attempts at
• Cricothyrotomy is an option
intubation fail
• Once airway is secured, restore volume with crystalloid &
transfusion of blood products as indicated

Emergency Bronchoscopy
• Urgent bronchoscopy: can identify origin of bleeding & provide
stabilizing treatment
Awake flexible, • Visualization of more peripheral and upper lobes
fiberoptic • Does not provide optimal suctioning
bronchoscopy • Does not allow for local treatment
• Usually requires general anesthesia, but can be
performed with deep sedation
• Allows for improved airway control
• Cannot fully view upper lobes & peripheral lesions
Rigid
bronchoscopy • Offers greater suctioning ability
• Can provide treatment
o Fogarty balloon catheter (tamponade of bleeding)
o Epinephrine instillation
o Ice water lavage
• After rigid bronchoscopy, flexible bronchoscope through the lumen
of rigid bronchoscope allows for more detailed inspection
o Massive bleeding impairs visualization during bronchoscopy

Definitive Bleeding Control

• Consultation with cardiothoracic surgery & interventional radiology
• Reserved for massive hemoptysis from
o Iatrogenic pulmonary artery injury
Emergency
o Thoracic trauma
surgery
o Bleeding from trachea-innominate artery fistula at
tracheostomy site
• Initial & most effective treatment of massive & recurrent
hemoptysis
Bronchial • Can temporize bleeding & stabilize patients for elective
artery surgery
embolization • Risks: transverse myelitis (spinal cord ischemia),
pulmonary artery infarction (spread of embolic material
beyond its intended site)

DISPOSITION AND FOLLOW-UP

• Most cases of hemoptysis are mild and self-limited
• Mild hemoptysis: arrange follow-up with a primary care physician,
otolaryngologist, or pulmonologist (if lung cancer or structural
disease is suspected)
• Treat acute bronchitis with appropriate antibiotics
• Severe hemoptysis: ICU admission or transfer to tertiary care center

Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)

18. HEMOPTYSIS | 91
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

19. PNEUMOTHORAX CLINICAL FEATURES

• Arises when free air enters the potential space between the visceral • Classic symptoms of primary spontaneous pneumothorax
and parietal pleura o Sudden onset dyspnea
• Primary pneumothoraces: without clinically apparent lung disease o Ipsilateral, pleuritic chest pain (may resolve within first 24 hours)
(spontaneously or from penetration of intrapleural space by trauma) • Sinus tachycardia: most common physical finding
o Primary spontaneous pneumothorax: 10 to 18 cases for men; 2 • Other classic findings: (uncommon)
to 5 cases for women per 100,000 population o Ipsilateral decreased breath sounds
o Associated factors: cigarette smoking, male gender, mitral valve o Hyperresonance to percussion
prolapse, Marfan’s syndrome, and changes in ambient pressure o Decreased/absent tactile fremitus
o Familial patterns also suggest an inherited association • Clinical hallmarks of tension
o Physical activity or exercise can precipitate but is not a common pneumothorax
pneumothorax-triggering factor o Tracheal deviation away from the
o Traumatic pneumothoraces: iatrogenic or non-iatrogenic involved side
• Secondary pneumothoraces: with underlying lung disease o Hyperresonance of the affected side
o COPD: most common cause o Diminished or absent breath sounds
o AIDS: 5% of patients; from subpleural necrosis by Pneumocystis on the affected side
infection; carries a high mortality o Hypotension of evidence of
▪ Simple aspiration fails in this group of patients due to hypoperfusion
necrosis of lung tissue and continued air leak o Significant dyspnea
o Hemopneumothorax: 2-7% of patients with secondary o Distended neck veins
pneumothorax; life threatening if associated with large amount
of blood in the pleural cavity DIAGNOSIS
• Differential diagnosis: pleurisy, pleural effusions, infiltrates, shingles
• Imaging
• Usual initial test
• Loss of lung markings in the periphery
Chest X-ray • Thin white pleural line that runs parallel to the chest
(upright PA) wall (does not extend outside of the chest cavity)
• Deep sulcus sign: a deep lateral costophrenic angle
on the affected side
• Normal findings
o Seashore sign (M-mode): movement of the lung
PATHOPHYSIOLOGY (ocean) against the stationary chest wall (shore)
• Under normal conditions o Comet tail sign (B-mode): sonographic
reverberation distal to the pleural
o Parietal and visceral pleura are in close apposition o Lung sliding sign (B-mode): movement of visceral
o Pleural space: negatively pressured (-5 mmHg, fluctuations of Ultrasound pleura along parietal pleura during respiration
6-8 mmHg between inspiration and expiration) (POCUS) • Loculated small pneumothoraces
o Chest wall: inherent tendency to expand o Presence of intrapleural air, pleural adhesions,
effusions, and parenchymal disease
o Lungs: inherent tendency to collapse from elastic recoil o Sliding sign and comet tail sign are altered & limit
• Pneumothorax: affected lung collapses due to loss of normal specificity for pneumothorax
negative pressure in pleural space that “adheres” the visceral pleura o Bleb point may lose a sliding sign and inaccurately
(lungs) to parietal pleura (ribs) suggest a pneumothorax
• Detects 25-40% not seen on plain CXR
• Primary spontaneous pneumothorax: subpleural bleb rupture, • Can detect other pathology such as pulmonary blebs
disrupting pleural integrity; usually involves lung apex Chest CT • Indicated if there is clinical suspicion (symptomatic
• Secondary spontaneous pneumothorax: disruption of visceral high-risk patients, underlying lung disease, positive-
pleura secondary to underlying pulmonary disease processes pressure ventilation, lung biopsy) in a negative CXR
o Air travels down a pressure gradient into pleural space until
pressure equilibrium occurs with partial or total lung collapse
o Dyspnea & hypoxemia: altered V/Q & decreased vital capacity
o Positive intrapleural pressure as air enters pleural space
• Tension pneumothorax: develops as inhaled air accumulates in
the pleural space but cannot exit due to a one-way valve system
o As intrathoracic pressure (>15-20 mmHg) increases, venous
return, cardiac & lung function are severely restricted, resulting
in hypoxemia and shock
• Open pneumothorax (“sucking chest wound”): communication
between the pleural space and surrounding atmospheric pressure
o May also be due to small rents in the parietal pleura or small air
passages without an obvious penetrating injury
o Respiratory distress is due to lung collapse and subsequent
inability to ventilate the affected lung
o Air entry and breath sounds are often diminished on the affected
side, and chest wall motion can be impaired
o Initial therapeutic maneuver is to cover the wound with a three-
sided dressing such that air can exit but not enter the chest
▪ Avoid complete occlusion, as this may convert the injury into
a tension pneumothorax.
▪ Do not insert a chest tube through the trauma wound, as it
is likely to follow the missile or knife tract into the lung or
diaphragm

92 | 19. PNEUMOTHORAX
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT Needle or Catheter Aspiration

• Goals of treatment at the ER level • As effective as thoracostomy for treating the first episode of small
o Elimination of intrapleural air primary or secondary spontaneous pneumothorax
• Tension pneumothorax is a clinical diagnosis (before radiograph) • Techniques:
o Immediately needle decompression and/or tube thoracostomy o Simple one-time aspiration with a large-gauge needle or a small-
• Treatment options bore catheter
• Increases pleural air resorption 3-4-fold over the o Repeated aspirations through a small-size catheter (advantage
base 1.25% reabsorbed per day of both aspiration and chest tube placement)
Oxygen • Creates nitrogen gas pressure gradient between o Chest tube attached to one-way valve/water seal drainage
administration alveolus and trapped air
(>28%) • Recommended dosing: 3 L/min nasal cannula to
10 L/min by mask (guided by patient’s status)
• Monitor for hypercapnia in patient with COPD
• Appropriate for small, stable pneumothoraces
• Observe for at least 4 hours on supplemental
oxygen and repeat chest radiograph
Observation • If symptoms and chest radiograph improve, patient
should return in 24 hours for repeat examination
• First-time spontaneous pneumothorax of <20%
lung volume in a stable, healthy adult may be
treated initially with oxygen therapy & observation
Needle or catheter
• Single/sequential aspirations
aspiration
• Based on likelihood of recurrence and likelihood of
Tube thoracostomy spontaneous resolution
(small-size or • Likely to recur: underlying pulmonary disease,
standard chest tube) large pneumothoraces (>2 cm), air leak, inability to
return for care TREATMENT COMPLICATIONS
• Due to hypoxia, hypercapnia, and hypotension
Factors to consider when deciding to Criteria for stable patient with • Re-expansion lung injury
intervene procedurally pneumothorax o Uncommon; seen more often when there is:
• Stability of patient • RR <24 breaths/min ▪ Collapse of the lung for >72 hours
• Degree of symptoms • No dyspnea at rest, speaks in ▪ Large pneumothorax
• Size & relative change in size over time full sentences ▪ Rapid re-expansion
• Cause of pneumothorax • PR >60 & <120 beats/min ▪ Negative pleural pressure suction >20 cm
• Degree of underlying lung disease • Normal BP for patient o Observation or oxygen, with virtually no adverse outcomes
• Likelihood of recurrence & resolution • Room air SaO2 >90%
• Intervention Complications: intercostal vessel hemorrhage, lung
• Need for positive-pressure ventilation • Absence of hemothorax
parenchymal injury, empyema, tube malfunction (may lead to air
leak / tension pneumothorax)
• Selection of catheter or chest tube size is based on the flow rate • Recurrence Prevention: pleurodesis
of air that the device can accommodate o First spontaneous pneumothorax with a persistent air leak
o Large-bore tubes: anticipated big leaks (mechanical ventilation) o Second ipsilateral spontaneous pneumothorax
o Small-bore tubes or catheters cannot handle the air flow o First contralateral pneumothorax
o Bilateral spontaneous pnemumothoraces
o First episode of a secondary pneumothorax
o Recurrent high-risk activities (flying or diving)

SPECIAL CONSIDERATIONS
Needle Decompression
• 14G (adults); 18G (children); 2 inches long needle
• 2 locations are recommended:
o 2nd ICS MCL just above the rib (avoid intercostal artery)
o 4th ICS AAL just above the rib
• A rush of air exiting the plural space may be audible and is
diagnostic of a pneumothorax
• Converts tension pneumothorax into an open pneumothorax
o Needle decompression is a temporizing measure and should be
followed promptly with tube thoracostomy
• If patient’s hemodynamics fail to improve following decompression,
consider other causes of hypoperfusion (pericardial tamponade)
• Iatrogenic pneumothorax: subset of traumatic pneumothorax
o Causes: transthoracic needle procedures (½ of cases);
subclavian vein catheterization (¼ of cases)
o Ultrasound guidance for central venous catheter insertion for
thoracentesis reduces the pneumothorax complication rate
o Chest radiograph may not identify a pneumothorax if supine or
if there is inadequate time for the pneumothorax to develop
o Bedside US: excellent rapid alternative to CXR to detect central
venous catheter misplacement & iatrogenic pneumothorax
o Treatment: Observe / simple catheter aspiration
▪ For small pneumothorax after a needle puncture
▪ Those not requiring positive-pressure ventilation
• Air transport with pneumothorax: ↑ elevation causes increase in
gas volume, ↑ risk for tension pneumothorax (Boyle’s law)
o High-altitude flying is not recommended for at least 7 to 14 days
after pneumothorax resolution
• Diving: development of pneumothorax at depth may lead to tension
pneumothorax with ascent (Boyle’s law)
o A history of spontaneous pneumothorax is a contraindication to
underwater diving unless treated by surgical pleurectomy and
normal lung function exists

DISPOSITION
• Discharge patients with a primary spontaneous pneumothorax
treated with observation or with catheter aspiration if
o Pneumothorax does not increase in size over 3 to 6 hours
o Symptoms resolve or do not worsen
• Other patients may need to be observed longer or admitted based
on size, therapy, and clinical condition

Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8 th edition (2016)

19. PNEUMOTHORAX | 93
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Small-size catheters
Description Placing a small catheter
Insertion • Anteriorly at 2nd ICS MCL
site • Laterally at 4th or 5th ICS AAL
• Local anesthesia & sterile
preparation
• Attach three-way stopcock & use
60-mL syringe to aspirate pleural
fluid until resistance is met
(triggering a cough)
• Close stopcock, secure tube, &
obtain follow-up CXR to ensure
Procedure
lung re-expansion
• Aspiration of >4 L suggest
continued air leak & failure of
simple aspiration
• Failure of lung to fully expand
warrants another aspiration
attempt or formal tube
thoracostomy & admission
94 | 19. PNEUMOTHORAX
Pigtail Catheters using Seldinger Technique
• Advantages
o Smaller incision
o Less tissue dissection
o Smaller scar
Ensure needle placement in “triangle of safety”
• Base: 5th intercostal space
• Medial: lateral border of pectoralis major
• Lateral: anterior border of latissimus dorsi
• Aspirate fluid or air to verify location in pleural
space, & advance a guidewire though needle
• Place dilator over guidewire until pleural space
is entered
• Remove dilator & place chest tube over wire
into pleural space
• Remove stylet, secure tube, & attach to suction
Tube Thoracostomy with underwater seal drainage
Indications
• Large pneumothorax
• Recurrent or bilateral pneumothorax
• Coexistent hemothorax
• Abnormal vital signs or dyspnea
• Small spontaneous secondary pneumothoraces where large
air leak is anticipated or noted
Choice of chest tube
• Non-trauma: 10- to 14-French chest tube
• Probable large air leak: 14- to 22-French chest tubes
5th ICS AAL at level of nipple in men or inframammary crease
in women
• Oblique skin incision 1-2 cm below interspace insertion site
• Insert large clamp through skin incision & muscles in next
higher intercostal space, just above rib, avoiding
neurovascular bundle
• Resulting oblique tunnel through subcutaneous tissue &
intercostal muscles usually closes promptly after chest tube
is removed, reducing chances of recurrent pneumothorax
• Once clamp reaches internal intercostal fascia, open to
enlarge hole to ~2.0 cm
• Insert finger along top of clamp through hole to verify position
within thorax & to verify that lung is not adhering to chest wall
• Chest tube insertion: advance tube at least until last side
hole is 2.5 to 5.0 cm (1 to 2 inches) inside the chest wall
o Pneumothorax: direct the tube towards the apex, away
from the hilum and mediastinum
o Hemothorax: direct the tube posteriorly & laterally
• Connect to suction: attach open end of tube to a
combination fluid-collecting water-seal suction device, with
20-30 cm H2O of suction
• Document tube placement and function
o Serial chest auscultation
o Serial chest radiographs
o Record volume of blood loss & amount of air leakage
• Leave chest tubes in place on suction at least 24 hours after
all air leaks have stopped (if placed for a simple
pneumothorax) or until drainage is serous and <200 mL/24
hours (if placed on hemothorax)

20. ACUTE RESPIRATORY FAILURE
• One of the most common reasons for ICU admission
• ≥75% of ICU patients require mechanical ventilation
CATEGORIES OF RESPIRATORY FAILURE
TYPE I: ACUTE HYPOXEMIC RESPIRATORY FAILURE
• Occurs with alveolar flooding and subsequent intrapulmonary shunt
physiology
• Alveolar flooding
o May be a consequence of pulmonary edema, lung injury,
pneumonia, or alveolar hemorrhage
o Pulmonary edema can be further categorized as:
▪ Elevated pulmonary microvascular pressures (heart failure)
▪ Intravascular volume overload or ARDS (“low-pressure
pulmonary edema”)
• Occurs in clinical setting such as sepsis, gastric aspiration,
pneumonia, near-drowning, multiple blood transfusions, and
pancreatitis
• Mechanical ventilation of patients may propagate lung injury
o Stretching and overdistention of injured alveoli during
mechanical ventilation can further injure the lung (ventilator-
induced “volutrauma”)
o Dramatic reduction in mortality rate in low tidal volume ventilator
(6 mL/kg IBW) than high tidal volume ventilator (12 mL/kg IBW)
• Neuromuscular blockade and prone positioning have been shown to
improve survival in those with severe ARDS
• “Fluid conservative” management strategy
o Maintaining a low central venous pressure (CVP) or pulmonary
capillary wedge pressure (PCWP) is associated with fewer days
of mechanical ventilation
• Avoid intubation in patients with ARDS
o Use of a variety of devices such as masks, high flow oxygen
delivery systems, and helmets for respiratory support
TYPE II RESPIRATORY FAILURE
• Consequence of alveolar hypoventilation
• Results from the inability to eliminate carbon dioxide effectively
• Mechanisms
o Impaired/Diminished CNS drive to breathe
▪ Drug overdose, brainstem injury, sleep-disordered
breathing, severe hypothyroidism
o Impaired/Reduced strength
▪ Impaired neuromuscular transmission (myasthenia gravis,
Guillain-Barré syndrome, amyotrophic lateral sclerosis)
▪ Respiratory muscle weakness (myopathy, electrolyte
derangements, fatigue)
o Increased load(s) on the respiratory system
▪ Resistive loads (bronchospasm)
▪ Loads due to reduced lung compliance (alveolar edema,
atelectasis, intrinsic positive end-expiratory pressure [auto-
PEEP])
▪ Loads due to reduced chest wall compliance
(pneumothorax, pleural effusion, abdominal distension)
▪ Loads due to increased minute ventilation requirements
(pulmonary embolus with increased dead-space fraction,
sepsis)
• The mainstays of therapy are directed at reversing the underlying
cause(s) of ventilatory failure
o Noninvasive positive-pressure ventilation with a tight-fitting
facial or nasal mask (avoid endotracheal intubation)
▪ Beneficial in treating exacerbations of COPD
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
TYPE III RESPIRATORY FAILURE
• Results from lung atelectasis
• Also called perioperative respiratory failure
o After general anesthesia, decreases in functional residual
capacity lead to collapse of dependent lung unit
• Can be treated by frequent changes in position, chest
physiotherapy, upright positioning, and control of incisional and/or
abdominal pain
• Noninvasive positive-pressure ventilation may also be used to
reverse regional atelectasis
TYPE IV RESPIRATORY FAILURE
• Results from hypoperfusion of respiratory muscles in patients in
shock
• Patients in shock often experience respiratory distress due to
pulmonary edema (cardiogenic shock), lactic acidosis, and anemia
o Up to 40% of cardiac output may be distributed to the respiratory
muscles (normal: <5% of total cardiac output)
• Intubation and mechanical ventilation can allow redistribution of the
cardiac output away from the respiratory muscles and back to vital
organs while the shock is treated
CARE OF THE MECHANICALLY VENTILATED PATIENT
• Daily spontaneous breathing trials can identify patients ready for
extubation
• All intubated, mechanically ventilated patients should undergo daily
screening of respiratory function
• Screening test for spontaneous breathing trial
o Stable (PaO2/FIO2 >200 & PEEP ≤5 cmH2O)
o Cough and airway reflexes are intact
o No vasopressor agents or sedatives are being administered
• Spontaneous breathing trial
o Period of breathing though the endotracheal tube without
ventilator support for 30-120 minutes
▪ Continuous positive airway pressure (CPAP) of 5 cmH2O
with or without low level pressure support
▪ Open T-piece breathing system
o Trial is declared a failure and stopped if any of the following:
▪ Respiratory rate >35/min for >5 minutes
▪ O2 saturation <90%
▪ Heart rate >140/min or a 20% increase/decrease from
baseline
▪ Systolic blood pressure <90 mmHg or >180 mmHg
▪ Increased anxiety or diaphoresis
o Indications for extubation
▪ None of the above events has occurred
▪ Ratio of respiratory rate and tidal volume (f/VT) is <105
• Up to 10% of patients develop respiratory distress after extubation
and may require resumption of mechanical ventilation.
o Many of these patients will require reintubation
• Mechanically ventilated patients frequently require sedatives and
analgesics
o Opiates are the mainstay of therapy for analgesia
o Additional indications for sedation:
▪ Anxiolysis
▪ Treatment of subjective dyspnea
▪ Reduction of autonomic hyperactivity (may precipitate
myocardial ischemia)
▪ Reduction of total O2 consumption (VO2)
o Non-benzodiazepine sedatives are preferred since
benzodiazepines are associated with worse patient outcomes
o Neuromuscular blocking agents (cisatracurium) typically are
used as a last resort when aggressive sedation fails to achieve
patient-ventilator synchrony (may result in postparalytic
syndrome)
o Amnesia can be achieved reliable with propofol and
benzodiazepines (lorazepam and midazolam) when
neuromuscular blocking agents are used to induce
pharmacologic paralysis
20. ACUTE RESPIRATORY FAILURE | 95
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS)
• Clinical syndrome of severe dyspnea of rapid onset, hypoxemia, and diffuse
pulmonary infiltrated leading to respiratory failure
• Caused by diffuse lung injury from underlying medical and surgical disorders
• “ARDS is an acute diffuse, inflammatory lung injury, leading to increased
pulmonary vascular permeability, increased lung weight, & loss of aerated
lung tissue, with hypoxemia & bilateral radiographic opacities, associated with
increased venous admixture, increased physiological dead space, &
decreased lung compliance.” (Berlin Definition, 2013)
Epidemiology
• Annual incidence: 60 cases/100,000 population
• Approximately 10% of all ICU admissions involve ARDS patients
Etiology
• Risks of developing ARDS are increased in patients with more than one
predisposing medical or surgical condition
• Several other clinical variables have been associated with ARDS
o Older age
o Chronic alcohol abuse
o Metabolic acidosis
o Pancreatitis
o Severity of critical illness
• Trauma patients with APACHE II score of ≥16 have a 2.5-fold increased risk
of developing ARDS
Clinical Course and Pathophysiology
• Exudative Phase
o Alveolar capillary endothelial cells and type I pneumocytes (alveolar
• Proliferative Phase
epithelial cells) are injured, with consequent loss of the normally tight
alveolar barrier to fluid and macromolecules
o Protein-rich edema accumulates in interstitial & alveolar spaces
o Pro-inflammatory cytokines (IL-1, IL-8, TNF-α) and lipid mediators (LTB4)
are increased, leading to recruitment of leukocytes (neutrophils) into the
pulmonary interstitium & alveoli
o Condensed plasma proteins aggregate in air spaces with cellular debris
and dysfunctional pulmonary surfactant to form hyaline membrane whorls
o Pulmonary vascular injury also occurs early in ARDS, with vascular
obliteration by microthrombi & fibrocellular proliferation
o Alveolar edema predominantly involves dependent portions of the lung
with diminished aeration
o Collapse of large sections of dependent lung can contribute to decreased
lung compliance
o Consequently, intrapulmonary shunting and hypoxemia develop and the
work of breathing increased, leading to dyspnea
• Fibrotic Phase
o Pathophysiologic alterations in alveolar spaces are exacerbated by
microvascular occlusion that results in reductions in pulmonary arterial
blood flow to ventilated portions of lung (and thus in increased dead
space) and in pulmonary hypertension
o In addition to severe hypoxemia, hypercapnia secondary to increase in
pulmonary dead space can be prominent
96 | 20. ACUTE RESPIRATORY FAILURE
o Encompasses 1st 7 days of illness after exposure to a precipitating ARDS
risk factor, with patient experiencing onset of respiratory symptoms
o Symptoms usually present within 12-36 hours after the initial insult, and
can be delayed by 5-7 days
o Dyspnea develops, with a sensation of rapid shallow breathing and an
inability to get enough air
o Tachypnea and increased work of breathing result frequently in
respiratory fatigue and ultimately in respiratory failure
o Chest radiograph: opacities consistent with pulmonary edema and often
involves at least ¾ of the lung fields
▪ Characteristic, but not specific for ARDS
▪ Indistinguishable from cardiogenic pulmonary edema, except for
cardiomegaly, pleural effusions, or pulmonary vascular redistribution
▪ If no ARDS risk factor, cardiac etiology must be excluded
(echocardiography) for hydrostatic edema
o Chest CT: bilateral pulmonary infiltrates; extensive heterogeneity of lung
involvement
o Differential diagnosis of early ARDS
▪ Cardiogenic pulmonary edema
▪ Bilateral pneumonia
▪ Alveolar hemorrhage
▪ Acute interstitial lung disease (acute interstitial pneumonitis)
▪ Acute immunologic injury (hypersensitivity pneumonitis)
▪ Toxin injury (radiation pneumonitis)
▪ Neurogenic pulmonary edema
o Usually lasts from day 7 to day 21
o Most patients recover rapidly and are liberated from mechanical
ventilation during this phase
o Despite improvement, many patients still experience dyspnea,
tachypnea, and hypoxemia
o Some patients develop progressive lung injury and early changes of
pulmonary fibrosis during the proliferative phase
o Histologically, the first signs of resolution are often evident in this phase
▪ Initiation of lung repair
▪ Organization of alveolar exudates
▪ Shift from neutrophil- to lymphocyte-predominant infiltrates
o As part of the reparative process, type II pneumocytes proliferate along
alveolar basement membranes
▪ These specialized epithelial cells synthesize new pulmonary
surfactant and differentiate into type I pneumocytes
o Many patients recover lung function 3-4 weeks after initial injury
o Some enter a fibrotic phase that may require long-term support on
mechanical ventilators and/or supplemental oxygen
o Histologically
▪ The alveolar edema and inflammatory exudates of earlier phases
convert to extensive alveolar-duct and interstitial fibrosis
▪ Marked disruption of acinar architecture leads to emphysema-like
changes, with large bullae
▪ Intimal fibroproliferation in the pulmonary microcirculation causes
progressive vascular occlusion and pulmonary hypertension
o Physiologic consequences
▪ increased risk of pneumothorax
▪ reductions in lung compliance
▪ increased pulmonary dead space
o Patients in this phase experience substantial burden of excess morbidity
o Lung biopsy evidence for pulmonary fibrosis in any phase of ARDS is
associated with increased mortality risk
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

TREATMENT Glucocorticoids
General Principles • Goal: reducing potentially deleterious pulmonary inflammation
• Recognition and treatment of underlying medical and surgical disorders (e.g., • Few studies have shown any significant mortality benefit
pneumonia, sepsis, aspiration, trauma) • Current evidence does not support the routine use of glucocorticoids in the
• Minimization of unnecessary procedures and their complications care of ARDS patients
• Standardized “bundled care” approaches for ICU patients
o Venous thromboembolism prophylaxis
o Gastrointestinal bleeding
o Aspiration
o Excessive sedation
o Prolonged mechanical ventilation
o Central venous catheter infections
• Prompt recognition of nosocomial infections
• Provision of adequate nutrition via the enteral route when feasible

Management of Mechanical Ventilation

• Minimizing Ventilator-Induced Lung Injury
o 2 principles mechanisms of ventilator-induced lung injury
▪ “Volutrauma” from repeated alveolar overdistention from excess VT
▪ “Atelectrauma” from recurrent alveolar collapse
o Attempts to fully inflate the consolidated lung may lead to overdistention
of and injury to the more normal areas
o Mortality rate was significantly lower in the low VT, low airway pressure
PROGNOSIS
patients (6 mL/kg of predicted body weight; ≤30 cm H2O) than in the
• Mortality
conventional VT patients (12 mL/kg predicted body weight; ≤50 cm H2O)
o Hospital mortality estimates for ARDS range from:
• Minimizing Atelectrauma by Prevention of Alveolar Collapse
▪ Mild ARDS: 34.9%
o With marked reduction of lung compliance, significant alveolar collapse
▪ Moderate ARDS: 40.3%
can occur at end-expiration, with consequent impairment of oxygenation
▪ Severe ARDS: 46.1%
o Positive end-expiratory pressure (PEEP) is adjusted to minimize FIO2 and
o Substantial variability; trend toward improved ARDS outcome over time
provide adequate PaO2 without causing alveolar overdistention
o Morality in ARDS is largely attributable to nonpulmonary causes
▪ Promotes alveolar recruitment
▪ Sepsis & nonpulmonary organ failure accounting for >80% of deaths
▪ Minimizes alveolar overdistention and hemodynamic instability
o Improvement in survival is likely secondary to advances in the care of
▪ Provides adequate PaO2 while minimizing FIO2
septic/infected patients and those with multiple organ failure
• Prone Positioning
o Major risk factors for ARDS mortality are nonpulmonary
o Significant reduction in 28-day mortality with prone positioning (32.8% to
▪ Advanced age is an important risk factor
16%) for patients with severe ARDS (PaO2/FIO2 <150 mmHg).
• >75 years have a substantially higher mortality risk (~60%) than
o Requires a critical-care team experienced in “proning”, as repositioning
those <45 (~20%)
critically ill patients can be hazardous, leading to accidental endotracheal
• >60 years of age with ARDS and sepsis have a three-fold higher
extubation, loss of central venous catheters, and orthopedic injury
mortality risk than those <60
Other Strategies in Mechanical Ventilation ▪ Preexisting organ dysfunction from chronic medical illness
• Recruitment maneuvers • Chronic liver disease
o Transiently increase PEEP to high levels to “recruit” atelectatic lung can • Cirrhosis
increase oxygenation, but a mortality benefit has not been established • Chronic alcohol abuse
• Alternate modes of mechanical ventilation • Chronic immunosuppression
o airway pressure release ventilation ▪ ARDS arising from direct lung injury (pneumonia, pulmonary
o high-frequency oscillatory ventilation contusion, aspiration)
• Lung-replacement with extracorporeal membrane oxygenation (ECMO) • Nearly twice as likely to die as those with indirect causes
o May have utility in select adults with severe ARDS as rescue therapy ▪ Surgical & trauma patients with ARDS (especially those without
direct lung injury)
Fluid Management • Generally have a higher survival rate than other ARDS patients
• Maintaining a low left atrial filling pressure minimizes pulmonary edema and o Increasing severity of ARDS, as defined by the consensus Berlin
prevents further decrements in arterial oxygenation and lung compliance; definition, predicts increased mortality.
improves pulmonary mechanics; shortens ICU star and the duration of • Functional Recovery in ARDS Survivors
mechanical ventilation o Majority of patients who survive regain nearly normal lung function
• Aggressive attempts to reduce left atrial filling pressures with fluid restriction o Patients usually recover maximal lung function within 6 months
and diuretics should be an important aspect of ARDS management, limited o 1 year after endotracheal intubation, more than 1/3 of ARDS survivors
only by hypotension and hypoperfusion of critical organs such as the kidneys have normal spirometry values and diffusion capacity
o Most others have only mild abnormalities in pulmonary function
Neuromuscular Blockade
o Recovery of lung function is strongly associated with the extent of lung
• In severe ARDS, sedation alone can be inadequate for the patient-ventilator
injury in early ARDS
synchrony required for lung-protective ventilation
o Less recovery of pulmonary function
• Early neuromuscular blockade (cisatracurium besylate) for 48 hours in ▪ Low static respiratory compliance
patients with severe ARDS had increased survival and ventilator-free days
▪ High levels of required PEEP
without increasing ICU-acquired paresis
▪ Longer durations of mechanical ventilation
▪ High lung injury scores

20. ACUTE RESPIRATORY FAILURE | 97

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

MECHANICAL VENTILATORY SUPPORT Principles of MV

Mechanical ventilation (MV)
• Used to assist or replace spontaneous breathing
• Implemented with special devices that can support ventilatory function and
improve oxygenation through the application of high-oxygen-content gas and
positive pressure
• 2 basic type of respiratory failure
o Hypoxemic respiratory failure (SaO2 <90% despite increased FiO2)
▪ V/Q mismatch or shunt
o Hypercarbic respiratory failure (PaCO2 >50 mmHg)
▪ Conditions that ↓ minute ventilation or ↑ physiologic dead space
• Basic goals of MV (“protective ventilatory strategy”)
o Optimize oxygenation while avoiding ventilator-induced lung injury due to
overstretch and collapse/re-recruitment
• High airway pressures and volumes & overstretching of the lung as well as
collapse/re-recruitment are inked to poor clinical outcomes (barotrauma and
volume trauma)
• Permissive hypercapnia has been accepted to avoid the risk of lung damage
associated with large volume and high pressures needed to eliminate CO 2 to
normalize pH

Indications
• Acute respiratory failure with hypoxemia (~65% of all cases)
o ARDS, heart failure with pulmonary edema, pneumonia, sepsis,
complications of surgery and trauma
• Hypercarbic ventilatory failure
o Coma (15%); COPD exacerbations (13%); neuromuscular diseases (5%)
• Primary objectives of MV
o Decrease work of breathing (avoiding respiratory fatigue)
o Reverse life-threatening hypoxemia and progressive respiratory acidosis
• MV as an adjunct to other forms of therapy
o Reduce cerebral blood flow in increased ICP
o Airway protection to prevent aspiration of gastric contents in otherwise
unstable patients during gastric lavage for suspected drug overdose or
during gastrointestinal endoscopy
o In critically ill patients before essential diagnostic or therapeutic studies if
it appears that respiratory failure may occur during those maneuvers

Types of Mechanical Ventilation

• Noninvasive Ventilation (NIV)
o Fewer complications (pneumonia, tracheolaryngeal trauma)
o Usually provided with a tight-fitting face mask
o Modes of NIV (preset positive pressure during inspiration and a lower
pressure during expiration)
▪ Bilevel positive airway pressure ventilation
▪ Pressure-support ventilation (PSV)
o WTolerated by conscious patient & optimize patient-ventilator synchrony
o Major limitation: patient intolerance (physical & psychological discomfort)
o Most important group of patients who benefit from a trial of NIV
▪ COPD exacerbations
▪ Respiratory acidosis (pH <7.35)
o Disadvantages of NIV
▪ Not useful in the majority of cases of respiratory failure
▪ Can delay lifesaving ventilatory support in contraindicated cases,
and can result in aspiration or hypoventilation
o Contraindications for Noninvasive Ventilation
▪ Cardiac or respiratory arrest
▪ Severe encephalopathy
▪ Severe gastrointestinal bleed
▪ Hemodynamic instability
▪ Unstable angina and myocardial infarction
▪ Facial surgery or trauma
▪ Upper airway obstruction
▪ High-risk aspiration and/or inability to protect airways
▪ Inability to clear secretions
o Monitoring of patients in NIV
▪ Clinical indicators of therapeutic benefit
• Reduction in respiratory frequency
• Decrease in the use of accessory muscles
▪ Arterial blood gases (within hours of therapy to ensure desired effect)
• Conventional MV
o Implemented once a cuffed tube is inserted into the trachea to allow
conditioned gas (warmed, oxygenated, humidified) to be delivered to the
airways and lungs at pressures above atmospheric pressure
o Care should be taken during intubation to avoid brain-damaging hypoxia
▪ Administration of mild sedation may facilitate the procedure
• Opiates & benzodiazepines (CI: ↓ cardiac function, ↓ SVR)
• Morphine (↑ histamine release; bronchospasm in asthma)
• Fentanyl, sufentanil, alfentanil (acceptable alternatives)
• Ketamine (↑ systemic arterial pressure, hallucinations)
▪ Shorter-acting agents (etomidate & propofol)
• Induction & maintenance of anesthesia in ventilated patients
• Fewer adverse hemodynamic effects
• Significantly more expensive than older agents
▪ Avoid using neuromuscular paralysis during intubation of patients
with renal failure, tumor lysis syndrome, crush injuries, medical
conditions associated with elevated serum potassium levels, and
muscular dystrophy syndromes
MODES OF VENTILATION
• Mode: the manner in which ventilator breaths are triggered, cycled, & limited
• Trigger: defines what the ventilator senses to initiate and assisted breath
(either an inspiratory effort or a time-based signal)
• Cycle: factors that determine the end of inspiration
• Limiting factors: operator-specified values (such as airway pressure) that are
monitored by transducers throughout the respiratory cycle
o If the specified values are exceeded, inspiratory flow is terminated, and
the ventilator circuit is vented to atmospheric pressure or the specified
pressure at the end of expiration (PEEP)
Other Modes of Ventilation
• Pressure-Control Ventilation (PCV)
o Time-triggered, time-cycled, pressure-limited
o A specified pressure is imposed at the airway opening through inspiration
o Since inspiratory pressure is specified by the operator, tidal volume and
inspiratory flow rate are dependent, rather than independent, variables
and are not operator-specified
o Preferred mode of ventilation for patients in whom it is desirable to
regulate peak airway pressures, (preexisting barotrauma, post-thoracic
surgery patients)
o Minute ventilation is altered through changes in rate or in the pressure-
control value, with consequent changes in tidal volume
• Inverse-Ratio Ventilation (IRV)
o Variant of PCV that incorporates the use of a prolonged inspiratory time
with the appropriate shortening of the expiratory time
o Used in patients with severe hypoxemic respiratory failure
o Increases mean distending pressures without increasing peak airway
pressures
o It is thought to work in conjunction with PEEP to open collapsed alveoli
and improve oxygenation
• Continuous Positive Airway Pressure (CPAP)
o Not a true support mode of ventilation because all ventilation occurs
though the patient’s spontaneous efforts
o The ventilator provides fresh gas to the breathing circuit with each
inspiration and sets the circuit to a constant, operator-specified pressure
o Used to assess extubation potential in patients who have been effectively
weaned and who require little ventilatory support and in patients with
intact respiratory system function who require an endotracheal tube for
airway protection

98 | 20. ACUTE RESPIRATORY FAILURE


Assist-Control Ventilation (ACMV)
• Most widely used mode of ventilation
• An inspiratory cycle is initiated either by patient’s inspiratory effort or, if none
is detected within a specified time window, by a timer signal within ventilator
• Every breath delivered, whether patient- or timer-triggered, consists of the
operator-specified tidal volume
• Ventilatory rate is determined by the patient or by the operator-specified
backup rate, whichever is of higher frequency
• Commonly used for initiation of MV because:
o Ensures a backup minute ventilation in absence of intact respiratory drive
o Allows for synchronization of ventilator cycle with inspiratory effort
• Problems can arise when ACMV is used in patients with tachypnea due to
nonrespiratory or nonmetabolic factors (anxiety, pain, airway irritation)
o Respiratory alkalemia may develop and trigger myoclonus or seizures
o Dynamic hyperinflation leading to increased intrathoracic pressures
(auto-PEEP) may occur if the patient’s respiratory mechanics are such
that inadequate time is available for complete exhalation between
expiratory cycles
o Auto-PEEP can limit venous return, cardiac output, and increase airway
pressures, predisposing to barotrauma
Intermittent Mandatory Ventilation
• Operator sets number of mandatory breaths of fixed volume to be delivered
by ventilator; between those breaths, patient can breathe spontaneously
• Synchronized mode (SIMV) – mandatory breaths are delivered in synchrony
with the patient’s inspiratory efforts at a frequency determined by the operator
o If the patient fails to initiate a breath, the ventilator delivers a fixed-tidal-
volume breath and resets the internal timer for the next inspiratory cycle
• Only a preset number of breaths are ventilator-assisted
• Allows patients with an intact respiratory drive to exercise inspiratory muscles
between assisted breaths (for both supporting & weaning intubated patients)
• May be difficult to use in patients with tachypnea because they may attempt
to exhale during the ventilator-programmed inspiratory cycle
o Airway pressure may exceed the inspiratory pressure limit, the ventilator-
assisted breath will be aborted, and minute volume may drop below that
programmed by the operator
o If tachypnea represents a response to respiratory or metabolic acidosis,
a change in ACMV will increase minute ventilation and help normalize pH
while the underlying process is further evaluated and treated
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Pressure-Support Ventilation
• Patient-triggered, flow-cycled, and pressure-limited
• Provides graded assistance and differs from the other two modes in that the
operator sets the pressure level (rather than the volume) to augment every
spontaneous respiratory effort
o Level of pressure is adjusted by observing patient’s respiratory frequency
• Inspiration is terminated when inspiratory airflow falls below a certain level; in
most ventilators, this flow rate cannot be adjusted by the operator
• Patients receive ventilator assistance only when the ventilator detects an
inspiratory effort
• Used in combination with SIMV to ensure volume-cycled backup for patients
whose respiratory drive is depressed
• Well tolerated by most patients who are being weaned from MV
• PSV parameters can be set to provide full ventilatory support and can be
withdrawn to load the respiratory muscles gradually
PROTECTIVE VENTIALTORY STRATEGY
• Safe and offers the best chance of a good outcome:
o Set a target tidal volume close to 6 mL/kg IBW
o Prevent plateau pressure (static pressure in the airway at the end of
inspiration) exceeding 30 cm H2O
o Use lowest possible fraction of inspired oxygen (FiO2) to keep SaO2 ≥90%
o Adjust PEEP to maintain alveolar patency while preventing overdistention
and closure/reopening
• With application of these techniques, mortality rate among patients with acute
hypoxemic respiratory failure has decreased to ~30% from close to 50% a
decade ago
Patient Management
• Once patient’s gas exchange has been stabilized, definitive therapy for the
underlying process responsible for respiratory failure is continued
• Subsequent modifications in ventilator therapy must be provided in parallel
with changes in the patient’s clinical status
• As improvement in respiratory function is noted, the first priority is to reduce
the level of mechanical ventilatory support
• Patients on full ventilatory support should be monitored frequently, with the
goal of switching to a mode that allows for weaning as soon as possible
• Patients whose condition continues to deteriorate after ventilatory support is
initiated may require increased O2, PEEP, or one of the alternative modes of
ventilation
20. ACUTE RESPIRATORY FAILURE | 99
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

GENERAL SUPPORT DURING VENTILATION

• Usually require sedation and analgesia to maintain acceptable level of comfort
o Combination of benzodiazepine and an opiate by IV
o Lorazepam, midazolam, diazepam, morphine, fentanyl
• Venous thrombosis should be prevented with the use of subcutaneous
heparin, fractionated LMWH, and/or pneumatic compression boots
• To help prevent decubitus ulcers, frequent changes in body position and the
use of soft mattress overlays and air mattresses are employed
• Early mobilization is recommended for patients on MV
• Prophylaxis against diffuse gastrointestinal mucosal injury is indicated
o H2-receptor antagonists, antacids, cytoprotective agents (sucralfate)
• Nutritional support by enteral feeding (nasogastric or orogastric tube)
• Delayed gastric emptying is common in critically ill patients taking sedative
medications but often responds to promotility agents such as metoclopramide
• Parenteral nutrition is an alternative to enteral nutrition in patients with severe
gastrointestinal pathology needing prolonged MV

COMPLICATIONS OF MECHANICAL VENTILATION

• Pulmonary complications
o Barotrauma & volutrauma
▪ Overdistend and disrupt lung tissue
▪ Clinically manifest by pneumomediastinum, interstitial and
subcutaneous emphysema, or pneumothorax
o Nosocomial pneumonia
o Oxygen toxicity
o Tracheal stenosis
o Deconditioning of respiratory muscles
• Intubated patients are at high risk for ventilator-associated pneumonia
o Aspiration from the upper airways through small leaks around the
endotracheal cuff
o Most common organisms: Pseudomonas aeruginosa, enteric gram-
negative rods, Staphylococcus aureus
o Early initiation of empirical antibiotics is recommended
• Hypotension resulting from elevated intrathoracic pressures with decreased
venous return is almost always responsive to intravascular volume repletion Prolonged MV and Tracheostomy
• Hemodynamic monitoring with a pulmonary arterial catheter may be of value • 5-13% of patients undergoing MV will require prolonged MV (≥21 days)
in helping to clarify cause of edema • Individualized & is based on the risk and benefits of tracheostomy & prolonged
o Patients who are judged to have respiratory failure on basis of alveolar intubation as well as the patient’s preference and expected outcomes
edema but in whom cardiac or pulmonary origin of edema is unclear • In general, if a patients needs MV for >10-14 days, a tracheostomy, planned
• Gastrointestinal effects of positive-pressure ventilation under optimal conditions, is indicated
o Stress ulceration • Advantages:
o Mild to moderate cholestasis o More comfortable
o Requires less sedation
WEANING FROM MECHANICAL VENTILATION
o Provides a more secure airway
The Decision to Wean o May reduce weaning time
• Consider discontinuation of MV once underlying respiratory disease begins to • Complications (5-40% of these procedures):
reverse o Bleeding
• Conditions indicating amenability to weaning (daily “wean screen”): o Cardiopulmonary arrest
o Lung injury is stable or resolving o Hypoxia
o Gas exchange is adequate, with low PEEP (<8 cmH2O) and FiO2 (<0.5) o Structural damage
o Hemodynamic variables are stable, and the patient is no longer receiving o Pneumothorax
vasopressors o Pneumomediastinum
o Patient is capable of initiating spontaneous breaths o Wound infection
• If patient is deemed capable to beginning to wean, the recommendation is to • Long-term complex complications
perform a spontaneous breathing trial (SBT) o Tracheal stenosis
o Integrated patient assessment during spontaneous breathing with little or o Granulation
no ventilatory support o Erosion of the innominate artery
o Implemented with a T-piece using 1-5 cmH2O CPAP with 5-7 cm H2O or • 5-10% of patients are deemed unable to wean in the ICU, and may benefit
PSV from the ventilator to offset resistance from the endotracheal tube from transfer to special units with a multidisciplinary approach (successful
• Once it is determined that the patient can breathe spontaneously, a decision weaning rates up to 30%):
must be made about the removal of the artificial airway o Nutrition optimization
o Undertaken only when patient has the ability to protect the airway, is able o Physical therapy with rehabilitation
to cough and clear secretions, and is alert enough to follow commands o Slower weaning methods (including SIMV with PSV)
o Other factors must be taken into account such as the possible difficulty of • Close to 2% of ventilated patients may ultimately become dependent on
replacing the tube if that maneuver is required ventilatory support to maintain life
• If upper airway difficulty is suspected, an evaluation using a “cuff-leak” test o Most of these patients remain in chronic care institutions
(assessing presence of air movement around deflated endotracheal tube cuff) o Some with strong social, economic, and family support may live a
o If “cuff-leak test” suggests a risk of post-extubation stridor, administration relatively fulfilling life with at-home ventilation
of systemic corticosteroids should be considered prior to extubation
o Despite all precautions, ~10-15% of extubated patients require
reintubation
o Several studies suggest that NIV can be used to obviate reintubation,
particularly in patients with ventilatory failure secondary to COPD
exacerbation or congestive heart failure; in this setting, earlier extubation
with the use of prophylactic NIV has yielded good results

Reference: Harrison’s Principles of Internal Medicine, 20 th edition (2018)

100 | 20. ACUTE RESPIRATORY FAILURE

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

21. ADRENAL CRISIS • Gonadocorticoids (androgen hormones and estrogen)

Adrenal insufficiency o Androgens: testosterone, dehydroepiandrosterone,
• Deficiency of adrenal gland hormone production in the cortex dehydroepiandrosterone sulfate (present in both men & women)
Primary adrenal insufficiency (Addison’s disease) ▪ Women: produced in the adrenal glands and ovaries
• Due to intrinsic adrenal gland dysfunction • Promote the development of sex characteristics (axillary
• Results in decreased cortisol, aldosterone, and sex hormone and pubic hair and libido)
production ▪ Men: most (testosterone) are produced in the testes
• Rare, with prevalence ranging from 39 to 144 cases per million o Androgen made by the adrenal glands are less important for
Secondary adrenal insufficiency normal sexual function
• Due to hypothalamic-pituitary dysfunction with failure to secrete
corticotropin-releasing hormone (CRH) and/or adrenocorticotropic PRIMARY ADRENAL INSUFFICIENCY (Addison’s Disease)
hormone (ACTH) • Approximately 90% of the gland must be destroyed for clinical
• Results in cortisol deficiency only adrenal insufficiency to develop
Adrenal crisis • Autoimmune disorders are responsible for most cases of PAI
• Life-threatening exacerbation of adrenal insufficiency when an (autoimmune adrenalitis)
increased demand fails to increase hormone production o May occur as an isolated process (30-40%) or as a component
of autoimmune polyglandular syndromes types I and II (60-70%)
EPIDEMIOLOGY o Autoimmune polyglandular syndrome type I (APS1)
• Well-documented, permanent adrenal insufficiency: 5 in 10,000 ▪ Also termed autoimmune polyendocrinopathy-candidiasis-
o Hypothalamic-pituitary origin: most frequent (3 in 10,000) ectodermal dystrophy (APECED)
o Primary adrenal insufficiency (2 in 10,000) ▪ In 10% of patients affected by APS
▪ ½ of cases: acquired (autoimmune destruction of adrenals) ▪ Autosomal recessive inheritance
▪ ½ of others: genetic, most commonly caused by distinct ▪ Mutations in the autoimmune regulator gene AIRE
enzymatic blocks in adrenal steroidogenesis affecting ▪ Associated with chronic mucocutaneous candidiasis (in
glucocorticoid synthesis (i.e., CAH) childhood), primary hypoparathyroidism, and adrenal failure
(by years or decades); may include total alopecia, and in
ADRENAL GLAND PHYSIOLOGY rare cases, lymphoma
• Adrenal gland o Polyglandular autoimmune syndrome type II
o Cortex: producing steroid hormones ▪ Addison’s disease plus either an autoimmune thyroid
▪ Zona fasciculata: glucocorticoids (cortisol) disease or type I diabetes mellitus
▪ Zona glomerulosa: mineralocorticoids (aldosterone) ▪ Associated with premature ovarian failure, pernicious
▪ Zona reticularis: gonadocorticoids (sex hormones) anemia caused by vitamin B12 deficiency, celiac disease, or
o Medulla: producing catecholamines in response to stimulation primary biliary cirrhosis, vitiligo
by sympathetic preganglionic neurons ▪ Polygenic inheritance
▪ Adrenaline ▪ Associations with the HLA-DR3 gene region in MHC and
▪ Noradrenaline distinct gene regions involved in immune regulation (CTLA-
▪ Dopamine (small amounts) 4, PTPN22, CLEC16A)
• Cortisol • Tuberculosis is the most common infectious cause of PAI
o Secreted in response to direct stimulation by ACTH (tuberculous adrenalitis)
▪ ACTH secretion: stimulated by CRH from hypothalamus • HIV may cause adrenal insufficiency through
o Secretion occurs in a diurnal rhythm o Opportunistic infections (principally cytomegalovirus)
▪ Higher levels secreted in the morning o Use of medications (ketoconazole)
▪ Lower levels in the evening • Infiltrative diseases (amyloidosis, hemosiderosis, bilateral
o Daily cortisol equivalent: 20 mg/day of hydrocortisone metastasis from cancer) can also cause PAI
o Plasma cortisol suppresses the release of ACTH through • Thrombosis and/or hemorrhage of the adrenals may occur as a
negative feedback inhibition complication of:
o Facilitates the stress response by affecting o Anticoagulation therapy
▪ Heart o Sepsis
▪ Vascular bed o Disseminated intravascular coagulation
▪ Water excretion o Meningococcemia (Waterhouse-Friderichsen syndrome)
▪ Electrolyte balance o Antiphospholipid syndrome
▪ Potentiation of catecholamine action Causes of Primary Adrenal Insufficiency
▪ Control of water distribution Primary Adrenal Insufficiency Examples
o Affects fat, protein, and carbohydrate metabolism • Isolated adrenal insufficiency or associated with
Autoimmune polyglandular insufficiencies (APS type I or II)
▪ Stimulating glycogenolysis and gluconeogenesis Adrenal hemorrhage or • Necrosis caused by meningococcal sepsis
• Coagulation disorders
o Involved in immunologic and inflammatory responses thrombosis • Overwhelming sepsis (Waterhouse-Friderichsen syndrome)
o Affects calcium metabolism • Adrenal enzyme inhibitors (affect those with limited pituitary
or adrenal reserve)
o Promotes growth and development o Etomidate
Drugs o Aminoglutethimide (can be used by body builders)
o In excess, interferes with the GI tract mucosa maintenance, o Mitotane (orphan drug used to treat adrenocortical
carcinoma)
leading to peptic ulcer o Ketoconazole
• Aldosterone • Tuberculosis
• Fungal, bacterial sepsis
o Secretion is controlled primarily by RAAS and serum potassium Infections • Acquired immunodeficiency syndrome involving adrenal
▪ RAAS: controls aldosterone levels in response to changes glands
• Sarcoidosis
in volume, posture, and sodium intake • Hemochromatosis
Infiltrative disorders • Amyloidosis
▪ Serum potassium (hyperkalemia): influences adrenal cortex • Lymphoma
• Metastatic cancer
directly to increase aldosterone secretion • Bilateral adrenalectomy
Surgery
o Maintains sodium and potassium plasma concentrations • Bariatric surgery
• Adrenal hypoplasia
o Regulates extracellular volume • Congenital adrenal hyperplasia
Hereditary • Adrenoleukodystrophy
o Controls sodium and water balance
• Familial glucocorticoid deficiency

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

SECONDARY ADRENAL INSUFFICIENCY CLINICAL FEATURES

• Consequence of dysfunction of the hypothalamic-pituitary Differences between Primary and Secondary Adrenal Insufficiency
component of the HPA axis
• Usually characterized by depressed ACTH secretion
o Reduces cortisol production
o Aldosterone levels remain normal (preserved stimulation by
RAAS and potassium)
o Adrenal sex hormone production is also preserved
• Intracranial disorders may affect hypothalamic-pituitary function
(pituitary or hypothalamic tumors)
o Brain tumor
o Pituitary disease
o Postpartum pituitary necrosis (Sheehan’s syndrome)
o Major head trauma
• Long-term therapy with pharmacologic doses of
glucocorticoids
o Most common cause of SAI • Primary adrenal insufficiency
o Severity of adrenal suppression is variable and depends on o Loss of both glucocorticoid and mineralocorticoid secretion
▪ Dose and potency of the glucocorticoid o Symptoms of diminished cortisol, aldosterone, and
▪ Time of the day the drug was taken (suppression is grater gonadocorticoids, & increased ACTH (skin hyperpigmentation)
when taken in the evening) o Hyperpigmentation: distinguishing feature of PAI
o Recovery of the hypothalamus-pituitary-adrenal axis may take a ▪ Caused by excess ACTH stimulation of melanocytes
few months to 1 year after steroid cessation ▪ Most pronounced in skin areas exposed to increased friction
or shear stress and is increased by sunlight
• Some critically ill patients demonstrate reduced cortisol clearance
• Secondary adrenal insufficiency
and suppression of ACTH release
o Only glucocorticoid deficiency is present
Causes of Secondary Adrenal Insufficiency ▪ Adrenal gland is intact & amenable to regulation by RAAS
Secondary Adrenal Insufficiency Examples ▪ Symptoms of diminished cortisol only
Sudden cessation of prolonged • Chronic use of steroid inhibits CRH and ACTH o Possible with related symptoms of intracranial lesions
glucocorticoid therapy production
Pituitary necrosis or bleeding • Postpartum pituitary necrosis (Sheehan’s syndrome)
(headache, visual changes, galactorrhea)
Exogenous glucocorticoid • Causes decreased production of CRH at hypothalamus o Hypothalamic-pituitary disease can lead to additional clinical
administration and ACTH at pituitary
manifestations
• Pituitary tumor
Brain tumors • Hypothalamic tumor ▪ Involvement of other endocrine axes (thyroid, gonads,
• Local invasion (craniopharyngoma)
Pituitary irradiation
growth hormone, prolactin)
• Disrupts CRH and ACTH production capacity in
Pituitary surgery hypothalamic-pituitary axis
▪ Visual impairment with bitemporal hemianopia caused by
Head trauma involving pituitary chiasmal compression
• Sarcoidosis
• Hemosiderosis o Iatrogenic adrenal insufficiency
Infiltrative disorders of the pituitary • Hemochromatosis
or hypothalamus • Histiocytosis X ▪ Exogenous glucocorticoid suppression of HPA axis
• Metastatic cancer ▪ May result in all symptoms associated with glucocorticoid
• Lymphoma
• Tuberculosis deficiency, if stopped abruptly
CNS infections involving •
hypothalamus or pituitary •
Meningitis
Fungus
▪ Patients will appear clinically cushingoid as a result of the
• Human immunodeficiency virus preceding overexposure to glucocorticoids
o Skin: alabaster-like paleness due to lack of ACTH secretion
ADRENAL CRISIS • Chronic adrenal insufficiency
• Shock refractory to volume resuscitation and pressors o Relatively nonspecific signs and symptoms (fatigue and loss of
• Occurs after a prolonged period of nonspecific complaints energy), often resulting in delayed or missed diagnoses (e.g., as
• More frequently observed in patients with PAI due to the loss of both depression or anorexia)
glucocorticoid and mineralocorticoid secretion
• Can result from
o Acute destruction of the hypothalamic-pituitary axis or the
adrenal glands
o Acute stressors in the setting of underlying primary or secondary
adrenal insufficiency
▪ Acute infection (GI infection)
▪ Surgery or other stress
▪ Extreme physical activity
▪ Acute severe injury or burns
▪ Cessation of chronic glucocorticoid replacement
▪ Increased glucocorticoid inactivation (e.g., hyperthyroidism)

102 | 21. ADRENAL CRISIS


• Acute Adrenal Insufficiency / Adrenal Crisis
o Characterized by severe hypotension refractory to vasopressors
▪ Postural hypotension may progress to hypovolemic shock
o Other symptoms: severe abdominal pain/tenderness, nausea,
vomiting, fever (mimicking an acute abdomen)
o CNS symptoms: confusion, disorientation, lethargy, decreased
responsiveness, progressing to stupor and coma
o There may be associated sepsis, even without fever
o Consider adrenal crisis in situations of:
▪ Unexplained hypotension, especially in patients with a
history of glucocorticoid therapy
▪ AIDS, TB, autoimmune disease, or severe head trauma
▪ History of chronic fatigue and hyperpigmentation
▪ Disorders known to cause acute adrenal crisis
LABORATORY STUDIES AND IMAGING
• Bedside glucose determination: identify hypoglycemia
• CBC, full chemistries, hepatic function studies, ECG, urinalysis
• TSH: slightly increased; normalize within days to weeks after
initiation of glucocorticoid replacement
• Additional studies are determined by the presumptive underlying
source (sepsis, hemorrhage, CNS abnormality)
• Primary adrenal insufficiency
o Hyponatremia: 80% of patients (mineralocorticoid deficiency)
o Hyperkalemia 40% of patients
• Secondary adrenal insufficiency
o Hypernatremia: functioning aldosterone (sodium reabsorption)
o Hyponatremia: water retention (diminished inhibition of ADH
release by cortisol, resulting in SIADH)
o Hypokalemia
• Both PAI and SAI:
o Cortisol deficiency is a common sequela
o Hypotension or hypoglycemia may be present
• Mild metabolic acidosis: tissue hypoxia (hypovolemia, hypotension)
• ECG changes are generally related to potassium imbalances
Hyperkalemia (in PAI) Hypokalemia (in SAI)
• Prolonged QT • Inverted T waves
• Peaked T waves • Presence of U wave
• Heart block
• Abdominal CT scan: adrenal gland hemorrhage or infarction
• Serum cortisol or ACTH are not usually readily available at the ER
o Serum cortisol >18 μ/dL generally rules out adrenal insufficiency
o ACTH stimulation test (cosyntropin test): measures serum
cortisol after stimulation by synthetic ACTH
▪ Serum cortisol rises significantly in SAI, but not in PAI
▪ Cut-off for adrenal failure: cortisol levels of <450-500 nmol/L
(16-18 ug/dL) 30-60 minutes after ACTH stimulation
o Random serum cortisol measurements are of limited diagnostic
value, because baseline cortisol levels may be coincidentally
low due to the physiologic diurnal rhythm of cortisol secretion
o Tests for adrenal insufficiency should never delay treatment
o In a patient with suspected adrenal crisis, it is reasonable to
draw baseline cortisol levels, provide replacement therapy, and
defer formal stimulation testing until a later time
o Once adrenal insufficiency is confirmed, measurement of
plasma ACTH is the next step
▪ High ACTH: primary adrenal insufficiency
▪ Low ACTH: secondary adrenal insufficiency
• In primary adrenal insufficiency, increased plasma renin will
confirm the presence of mineralocorticoid deficiency
• At initial presentation, patients with PAI should undergo screening
for steroid autoantibodies as a marker of autoimmune adrenalitis
o If negative, adrenal imaging by CT is indicated to investigate
possible hemorrhage, infiltration, or masses
• In inappropriately low ACTH, in presence of confirmed cortisol
deficiency, should undergo hypothalamic-pituitary imaging by MRI
o Features suggestive of preceding pituitary apoplexy (sudden-
onset severe headache/history of previous head trauma) should
be carefully explored, particularly if no obvious MRI lesion
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
TREATMENT
Adrenal Insufficiency
• Primary insufficiency
o Daily dosing of glucocorticoid & mineralocorticoid, usually for life
o Androgen replacement may be recommended for women
o Goals of treatment:
▪ Stabilize hormone levels
▪ Relieve symptoms
o Mineralocorticoids are replaced with an oral, synthetic
mineralocorticoid drug (fludrocortisone 100-150 μg)
▪ Dose is tailored to manage blood pressure and fluid balance
• Secondary insufficiency
o Only glucocorticoid replacement is required
Adrenal Crisis
• Begin therapy immediately in any suspected case of adrenal crisis
o Prognosis is related to the rapidity of treatment onset
• Give IV fluids early to treat hypotension
o If hypoglycemia is present, give dextrose-containing solutions
o Initial rates of 1 L/h with continuous cardiac monitoring
• Hydrocortisone is the steroid drug of choice for cases of adrenal
crisis or insufficiency
o Provides both glucocorticoid and mineralocorticoid effects
o IV hydrocortisone (100 mg bolus, followed by 200 mg over 24
hours by continuous infusion or by bolus IV or IM injections)
o IV dexamethasone (4 mg bolus) may be given rapidly if ACTH
test is contemplated as part of diagnostic strategy
o Give vasopressor only after steroid therapy in patients
unresponsive to fluid resuscitation
• Mineralocorticoid replacement (fludrocortisone 100-150 μg)
o Initiated once daily hydrocortisone been reduced to <50 mg
▪ ↑ hydrocortisone doses provide sufficient stimulation of MRs
▪ Dose should be increased by 50-100 μg during the summer
o Adequacy of treatment can be evaluated by
▪ BP (sitting & standing): detect postural drop (hypovolemia)
▪ Regular serum sodium, potassium, and plasma renin
▪ Renin levels should be kept in upper normal reference range
o Changes in glucocorticoid dose may also impact on
mineralocorticoid replacement (cortisol also binds to MR)
▪ 40 mg hydrocortisone = 100 μg fludrocortisone
o Adjusted during pregnancy due to anti-mineralocorticoid activity
of progesterone (less often required than in hydrocortisone)
• Glucocorticoid replacement for the treatment of chronic adrenal
insufficiency
o Administered at a dose that replaces physiologic daily cortisol
production (oral hydrocortisone 15-25 mg in 2-3 divided doses)
o Pregnancy may require an increase in hydrocortisone dose by
50% during the last trimester
o In all patients, at least one-half of the daily dose should be
administered in the morning
o Long-acting glucocorticoids (prednisolone or dexamethasone)
are not preferred: increased glucocorticoid exposure (extended
GR activation at times of physiologically low cortisol secretion)
o 1 mg hydrocortisone = 1.6 mg cortisone acetate = 0.2 mg
prednisolone = 0.25 mg prednisone = 0.025 mg dexamethasone
o Monitored mainly based on history & examination of signs &
symptoms suggestive of glucocorticoid over/underreplacement,
including assessment of body weight and blood pressure
• Adrenal androgen replacement (DHEA 25-50 mg once daily)
o Option in patients with lack of energy, despite optimized
glucocorticoid and mineralocorticoid replacement
o May also be indicated in women with features of androgen
deficiency, including loss of libido
o Monitored by measurement of DHEAS, androstenedione,
testosterone, & SHBG 24 hours after the last DHEA dose
• Determine the underlying cause
o Primary adrenal insufficiency
▪ Abdominal CT scan: evaluate the adrenal glands
▪ Retroviral screening: if HIV is under consideration
▪ Chest radiography: assess for bronchopneumonia or TB
21. ADRENAL CRISIS | 103
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
o Secondary adrenal insufficiency
▪ Head CT or MRI
▪ Blood tests for pituitary hormones
• For patients receiving chronic steroids, increase the maintenance
dose during periods of stress (illness, surgery, trauma, GI upset)
o To satisfy the increased physiologic need for cortisol
o Dosage recommendations vary and are based on expert opinion
o Typical stress dose: 3 times daily maintenance dose of
glucocorticoid
o Mineralocorticoid dosage generally stays the same
o Endocrinology consultation can be helpful for further
recommendations
104 | 21. ADRENAL CRISIS
DISPOSITION AND FOLLOW-UP
• Admit patients with adrenal crisis to ICU for
o Careful clinical monitoring
o IV steroid administration
o Confirmation of diagnosis and identification of etiology
• Discharge can only be considered for
o Mild cases of adrenal insufficiency with identified etiologies
o After a clear plan of management is established, often with
endocrinology consultation
SPECIAL POPULATIONS
Patients on Chronic Corticosteroids
• Hypothalamus-pituitary-adrenal axis function is inhibited with
chronic use of steroids
• Always consider adrenal insufficiency in patients with chronic steroid
use presenting with any acute illness
• Hypothalamus-pituitary-adrenal axis function should recover within
about 1 month after the last dose of steroid intake, but may be longer
in some cases
• Patients who receive steroids by topical, intranasal, inhalational, or
PR routes are not at risk for hypothalamus-pituitary-adrenal axis
suppression
Patients with Chronic Adrenal Insufficiency with Acute Illness of
Injury
• Require special attention to steroid dosing
• In normal circumstances, about 20 mg/d of hydrocortisone is
equivalent to the daily production of cortisol
• For a minor illness or injury, triple the daily glucocorticoid dose for
24-48 hours until symptoms improve
• Increasing the mineralocorticoid dose, if the patient is receiving one,
is usually not necessary
• Arrange follow-up care in 24 hours with the primary care physician
or endocrinologist
• Patients should return to the ER if: nausea, vomiting, fever,
weakness, or any untoward symptoms, or if they cannot retain their
medications
Pregnancy with Adrenal Insufficiency
• Most women with PAI are able to undergo healthy pregnancy, labor,
and delivery
• They need to take medications on schedule with close monitoring of
mother and fetus
• Some may require adjustment of glucocorticoid doses, especially
during the third trimester and during labor
• Women with hyperemesis gravidarum may need to switch from oral
medication to parenteral medication until symptoms subside
Sepsis
• IV hydrocortisone is not necessary to treat septic shock if adequate
fluid resuscitation and vasopressor therapy restore hemodynamic
stability
• IV hydrocortisone 200 mg/d is only recommended if these are not
achievable
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

22. DIABETIC KETOACIDOSIS • Ketogenesis: favored by the depletion of hepatic glycogen stores
• Acute, life-threatening complication of diabetes mellitus • Low/absent insulin levels decrease ability of brain & cardiac &
skeletal muscle to use ketones as energy source (↑ ketonemia)
EPIDEMIOLOGY • Osmotic diuresis: due to persistently elevated serum glucose
• Occurs predominantly in patients with type 1 (insulin-dependent) o Resulting volume depletion worsens hyperglycemia & ketonuria
diabetes mellitus o Renal potassium loss by osmotic diuresis is exacerbated by
• 10-30% of cases occur in newly diagnosed type 2 (non-insulin- activation of RAAS brought about by volume depletion
dependent) diabetes mellitus • In the kidney, chloride is retained in exchange for the ketoanions
• Mortality is high in the elderly due to underlying renal disease or being excreted (loss of ketoanions: potential loss of bicarbonate)
coinfection and in the presence of coma or hypotension o Marked ketonuria: superimposed hyperchloremic acidosis
• Adipose tissue breakdown: prostaglandins I2 and E2 are produced
PATHOPHYSIOLOGY o Paradoxical vasodilation despite profound volume depletion
• DKA is a response to cellular starvation brought about by
o Relative insulin deficiency (underutilization of glucose)
o Counterregulatory or catabolic hormone excess (excess
production of glucose)
• Effects of DKA
o Hyperglycemia
o Osmotic diuresis
o Prerenal azotemia
o Worsening hyperglycemia
o Ketone formation
o Wide-anion gap metabolic acidosis
Insulin
• Only anabolic hormone produced by β cells of endocrine pancreas
• Primary stimulant of insulin release: ingested glucose
• Responsible for metabolism & storage of carbohydrates, fat, protein
• 3 principal tissues of energy storage and metabolism:
• Facilitates uptake of glucose & its conversion to glycogen
• Inhibits glycogen breakdown (glycogenolysis) and
Liver
suppressing gluconeogenesis
• Net effect: promote storage of glucose (glycogen)
• Produces triglycerides from free fatty acids and glycerol
Liver &
(lipogenesis)
adipose cells
• Inhibits breakdown of triglycerides
• Stimulates uptake of amino acids with subsequent
Skeletal incorporation into muscle protein
muscle • Prevents the release of amino acids from muscle and
hepatic protein sources
• Deficiency in insulin secretion due to loss of islet cell mass is the
predominant defect in type 1 diabetes mellitus Causes of DKA
o Initial stages: secretory failure of β cells impair fuel storage and
may be evident only during a glucose tolerance test
o As insulin levels decrease, fuel stored are mobilized during
fasting, resulting in hyperglycemia
o When pancreatic β-cell reserve is present, hyperglycemia may
trigger an increase in insulin and a return to normal glucose level
o With further disease progression, hyperglycemia can no longer
trigger an increase in insulin activity (insulin deficiency)
▪ Cells are unable to use glucose as a fuel source
▪ Body responds by breaking down protein and adipose
stores to try to produce a useable intracellular fuel
▪ Leads to secretion of catabolic (counterregulatory)
hormones and resulting hyperglycemia and ketonemia
Ketoacidosis
• Cellular starvation
o Increased levels of counterregulatory hormones (glucagon,
catecholamines, cortisone, and growth hormone)
o Glucagon: primary counterregulatory hormone
o Catabolic effects:
▪ Increased gluconeogenesis and glycogenolysis
▪ Breakdown of fats intro free fatty acids and glycerol
▪ Proteolysis with increased levels of amino acids
o Increased levels of glucogenic precursors (glycerol and amino
acids) facilitate gluconeogenesis, worsening hyperglycemia • Additional risk factor
• Free fatty acids: bound to albumin and transported to the liver, o Poor economic background
where they undergo conversion to ketone bodies o Lack of insurance of minority status
• Primary ketone bodies: β-hydroxybutyrate (βHB) & acetoacetic o Drug abuse
acid (AcAc) [account for the metabolic acidosis seen in DKA] o Depression
o In equilibrium: AcAc + NADH ↔ βHB + NAD o Presence of an eating disorder
o AcAc is metabolized into acetone, another ketone body • In many patients, no clear precipitating cause is found

22. DIABETIC KETOACIDOSIS | 105

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
CLINICAL FEATURES
• Related directly to hyperglycemia, volume depletion, and acidosis
• Metabolic alterations of DKA tend to evolve within 24 hours
• Osmotic diuresis
o Volume loss
o Renal losses of Na+, Cl-, K+, P, Ca2+, Mg+
o Initial compensation: increasing fluid intake
▪ Polyuria & polydipsia are usually the only symptoms until
ketonemia and acidosis develop
• As acidosis progresses, ventilation is stimulated physiologically by
acidemia to diminish the PCO2 and to counter metabolic acidosis
• Acidosis + PGI2 and PGE2 = peripheral vasodilation despite
profound levels of volume depletion
o Prostaglandin release: unexplained nausea, vomiting,
abdominal pain seen at presentation, especially in children
o Vomiting: maladaptive physiologic response to diminish the
acid load; exacerbates potassium losses
• As volume depletion progresses, poor absorption of SC insulin
renders administration ineffective
• Impaired mental status may develop; most likely multifactorial:
o Metabolic acidosis
o Hyperosmolarity (>320 mOsm/L or >320 mmol/kg)
o Low extracellular fluid volume
o Poor hemodynamics
• Effects of volume depletion
o Tachycardia
o Orthostasis or hypotension
o Poor skin turgor
o Dry mucous membranes
• Kussmaul respiration: increased rate and depth of breathing
• Fruity odor of breath: due to acetone
• Absence of fever does not exclude infection
o Hypothermia is present occasionally (peripheral vasodilation)
• Abdominal pain and tenderness: correlate with level of acidosis
o Pain can be due to gastric dilatation, ileus, or pancreatitis
o Serum amylase & lipase are elevated in both DKA & pancreatitis
DIAGNOSIS
• Criteria for diagnosis
o Blood glucose level >250 mg/dL (13.9 mmol/L)
o Anion gap >10-12 mEq/L (>10 mmol/L)
o Bicarbonate <15 mEq/L (<15 mmol/L)
o pH <7.3
o Moderate ketonuria or ketonemia
• Euglycemic ketoacidosis (glucose <250 mg/dL/<13.9 mmol/L)
o Shortly after receiving insulin
o Type I diabetics who are young and vomiting
o Impaired gluconeogenesis (alcohol abuse or liver failure)
o Low caloric intake/starvation
o Depression
o Pregnant
o Adverse effect of SGLT-2 inhibitors
DIFFERENTIAL DIAGNOSIS (any cause of a high anion gap metabolic acidosis)
• Hyperosmolar, nonketotic coma
o Older, more prolonged, prominent mental status changes
o Glucose levels higher (>600 mg/dL or >33.3 mOsm/L)
o Little to no anion gap metabolic acidosis
• Alcoholic acidosis and starvation ketosis
o Ketosis tend to be milder (βHB <3 mmol/L; HCO3 >18 mmol/L)
o Serum glucose level is usually low or normal
o βHB predominates in alcoholic ketoacidosis
• Ingestion: serum osmolarity or drug-level testing is required
• Acetaminophen toxicity: renal failure, anion gap acidosis, liver
function abnormalities
• Lactic acidosis (poor perfusion): simultaneously with DKA
o Serum lactate level is indicated
o Type B (aerobic) lactic acidosis: patients on metformin with a
new-onset renal insufficiency are at risk
106 | 22. DIABETIC KETOACIDOSIS
LABORATORY TESTING
• Initial: glucose (CBG), urine test strip, ECG (hyperkalemia)
• Routine: CBC, serum electrolytes, BUN, creatinine, urinalysis,
venous blood gas, phosphate/magnesium/calcium levels, anion gap
• Ketone Bodies
o Elevated serum βHB & AcAc: acidosis & ketonuria (ketonemia)
o NADH accumulation in mitochondria (lactic acidosis or alcohol
metabolism) favors βHB formation (AcAc + NADH ↔ βHB + NAD)
o Nitroprusside reagent (unreliable for diagnosis/monitoring DKA)
▪ Only detects AcAc; acetone: weakly reactive; βHB: negative
▪ As patient is treated & clinically improves, ketone levels
increase (converts the more acidic βHB to AcAc)
• Acid-Base Abnormalities
o DKA leads to wide-anion-gap metabolic acidosis
o Hyperchloremic acidosis also occurs
▪ Basis: ketoanion exchange for chloride in the urine
▪ Common in patients who maintain good hydration status
and GFR despite ketoacidosis
o Metabolic alkalosis
▪ May occur secondary to vomiting, osmotic diuresis or
concomitant diuretic use
▪ Rarely, normal [HCO3-] or even elevated [HCO3-] if severe
enough to mask acidosis
• Elevated anion gap may be the only clue to the
presence of an underlying metabolic acidosis
• Venous pH
o Strong correlation between venous & arterial pH in DKA
o Venous pH is about 0.03 lower than arterial pH
o Low PCO2: respiratory compensation for metabolic acidosis
▪ If lower than expected: primary respiratory alkalosis
• Early indication of pulmonary disease (pneumonia,
pulmonary embolus) or sepsis as a possible trigger
• Potassium
o Total-body potassium is depleted by renal losses
o Measured serum potassium: normal/elevated in most patients:
▪ Extracellular shift of potassium secondary to acidemia
▪ Increased intravascular osmolarity (hyperglycemia)
o Hypokalemia in 4-6% of patients
o Decrease in serum potassium during therapy: about 1.5 mmol/L
▪ Parallels the drop in glucose and the dose of insulin
o ECG changes of hyperkalemia or hypokalemia may be seen
▪ Evaluate for ischemia (MI may precipitate DKA)
• Sodium and Other Electrolytes
o Osmotic diuresis leads to excessive renal losses of NaCl
▪ Hyperglycemia tends to artificially lower serum sodium
▪ Corrected serum sodium during hyperglycemia:
1.6 × (𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝑁𝑎 − 100)
𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑒𝑑 𝑁𝑎 = + 𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝑁𝑎
100
▪ Corrected serum sodium for hyperglycemia >400 mg/dL
2.4 × (𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝑁𝑎 − 100)
𝑐𝑜𝑟𝑟𝑒𝑐𝑡𝑒𝑑 𝑁𝑎 = + 𝑚𝑒𝑎𝑠𝑢𝑟𝑒𝑑 𝑁𝑎
100
▪ Urinary losses & total-body depletion of P, Ca2+, Mg2+
o Hemoconcentration: initially elevated serum electrolytes
▪ As therapy progresses, lower serum levels will be evident
• Other laboratory values
o Serum creatinine
▪ May be elevated factitiously if the laboratory assay for
creatinine is interfered by the nitroprusside assay
▪ Some elevation is expected due to prerenal azotemia
o Liver function studies
▪ May be elevated because of fatty infiltration of the liver
▪ Gradually corrects as the acidosis is treated
o Leukocytosis
▪ Often present because of hemoconcentration and stress
▪ WBC >25,000 mm3 and/or an absolute band count of 10,000
mm3 or more is suggestive of infection
o C-reactive protein
▪ Elevated: reflect the proinflammatory state found in DKA
▪ Elevated levels of cytokines may also be present

TREATMENT
• Initial Management
o Place patients on a cardiac monitor
o IV access
▪ At least 1 large-bore (16G-18G) IV infusion of normal saline
▪ Second line can be considered: 0.45% normal saline KVO
• Goals of therapy
o Volume repletion
o Reversal of the metabolic consequences of insulin insufficiency
o Correction of electrolyte and acid-base imbalances
o Recognition and treatment of precipitating causes
o Avoidance of complications
• Order of therapeutic priorities
o Volume
o Correction of potassium deficits
o Insulin administration
• Monitoring: every 2 hours of electrolytes (glucose, potassium,
anion gap), vital signs, level of consciousness, and volume
input/output until recovery is well established
• Goal of treatment
o Glucose <200 mg/dL (<11.1 mmol/L)
o Bicarbonate ≥18 mEq/L (≥18 mmol/L)
o Venous pH >7.3
Volume Repletion
• Fluids
o Help restore intravascular volume and normal tonicity
o Perfuse vital organs
o Improve glomerular filtration rate
o Lower serum glucose and ketone levels
• Rehydration improves the response to low-dose insulin therapy
• Average adult patient has
o Water deficit: 100 mL/kg (5 to 10 L)
o Sodium deficit: 7 to 10 mEq/kg (7 to 10 mmol/L/kg)
• Normal saline is the most frequently recommended fluid for initial
volume repletion even though the extracellular fluid of the patient is
initially hypertonic
o Does not provide “free water” to correct intracellular fluid loss
o Prevent an excessively rapid fall in extracellular osmolarity and
the potential devastating transfer of excessive water into CNS
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• In general, first 2 L are given over 0-2 hours, next 2 L over 2-6
hours, and then additional 2 L over 6-12 hours
o Replaces 50% of the total water deficit over the first 12 hours
o Remaining 50% water deficit over subsequent 12 hours
• Initial fluid bolus: isotonic crystalloid at 15-20 mL/kg for the 1st hour
o Based on clinical suspicion and before initial electrolyte results
▪ Hemodynamic stability
▪ Hydration status
▪ Urine output
▪ Serum electrolytes
• After the initial bolus
o Normal saline at 250-500 mL/h in hyponatremic patients
o 0.45% normal saline at 250-500 mL/h for eunatremic and
hypernatremic patients
• When the blood glucose level is 250 mg/dL (13.9 mmol/L), change
to 5% dextrose in 0.45% normal saline
• Patients without extreme volume depletion: more modest fluid
replacement regimen (250-500 mL/h for 4 hours)
• Consider CVP or PCWP monitoring in elderly or heart/renal disease
• Excess fluid: adult respiratory distress syndrome & cerebral edema
Potassium Replacement
• Patients with DKA usually present with profound total-body
potassium deficit (3-5 mmol/kg) created by insulin deficiency,
metabolic acidosis, osmotic diuresis, and frequent vomiting
• Initial serum concentration is usually normal or high due to:
o Intracellular exchange of potassium for hydrogen ions (acidosis)
o Total-body fluid deficit
o Diminished renal function
• Correction of the acidosis predicts the change in serum potassium
o For 0.1 increase/decrease in pH, serum K falls/rises 0.5 mmol/L
o Guide for estimating the serum potassium when pH is restored
Hypokalemia
• Initial serum potassium level 3.3-5.2 mmol/L before fluid resuscitation and
insulin, coupled with urine output
o Dose: 20-30 mmol/L for at least 4 hours
o Goal: Keep K between 4-5 mmol/L
o Monitoring of plasma K: every 2 hours
o Oliguria/renal insufficiency: withhold/decrease replacement
• Initial hypokalemia (<3.3 mmol/L)
o Indicates severe total-body potassium deficit
o Necessitates more aggressive replacement before insulin
o Give potassium IV at 20-30 mmol/h in the first 24-36 hours
o Hold insulin until K+ is ≥3.5 mmol/L
• During initial therapy for DKA, serum potassium may fall rapidly due to:
o Action of insulin promoting reentry of potassium into cells
o Dilution of extracellular fluid
o Correction of acidosis
o Increased urinary loss of potassium
• Precipitous severe hypokalemia: most life-threatening electrolyte
derangement during treatment of DKA; may result in:
o Fatal cardiac arrhythmias
o Respiratory paralysis
o Paralytic ileus
o Rhabdomyolysis
• No advantage to potassium phosphate (K2PO4) over KCl
o K2PO4: hypocalcemia & metastatic Ca 3(PO4)2 in tissues
• Oral potassium replacement: safe and effective; preferred route of
replacement as soon as patient can tolerate oral fluids
• In DKA, initial potassium replacement is usually by IV line
o <10 mmol/h via peripheral IV; <20 mmol/h via central line
• Continuous ECG monitoring is generally recommended while replacing
potassium in the severely hypokalemic patient
• First 24 hours: 100-200 mmol of KCl is usually required
Hyperkalemia
• Obtain an ECG immediately (check for signs of hyperkalemia)
o Giving potassium to a patient in a hyperkalemic potentiating state (i.e.,
acidemia, insulin deficiency, volume contraction, renal insufficiency) may
dangerously increase extracellular potassium level & precipitate fatal
dysrhythmias
• Initial potassium therapy is determined by
o Initial measurement of serum electrolytes
o ECG review for signs of hyperkalemia
o Presence of urine output
• Initial serum potassium level >5.2 mmol/L
o Reflects more profound acidemia, volume depletion, renal insufficiency
o Fluid and insulin therapy alone: will lower serum K quickly
o Albuterol nebulization: additional quick-K-lowering effect
22. DIABETIC KETOACIDOSIS | 107
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Insulin
• Low-dose regular insulin administration by an infusion pump
o Simple and safe
o Ensures a steady blood concentration of insulin
o Allows flexibility in adjusting the insulin dose
o Promotes a gradual fall in serum glucose and ketone body levels
• Half-life of IV insulin: 4-5 minutes
• Effective biological half-life at the tissue level: 20-30 minutes
IV Insulin
• If with a second IV line (after initial fluid bolus & hypokalemia excluded)
o Dose: 0.10-0.14 unit/kg/h with no bolus
• If no second IV line or difficult to establish another IV line
o Dose: 0.1 unit/kg bolus IM, followed by 0.1 unit/kg/h drip
o IV loading dose is not recommended in children and new-onset young
adult diabetics and is optional in adults
• Plasma glucose concentration typically decreases by 50-75 mg/dL/h
o If blood glucose fails to drop by 10% 1 hour after initial therapy, or by 3
mmol/L/h (assuming adequate hydration)
▪ Give a 0.14 unit/kg bolus and resume insulin drip rate
▪ Another option: increase insulin infusion rate by 1 unit/h
• Incidence of nonresponse to low-dose continuous IV insulin is 1-2%
o Infection: primary reason for failure to respond
• Resolution of hyperglycemia occurs earlier than resolution of anion gap
o Once serum glucose is 200 mg/dL, add dextrose to the IV fluids and
reduce the insulin drip rate to 0.02-0.05 unit/kg/h
o Maintain serum glucose 150-200 mg/dL until the resolution of DKA
o Occasionally a 10% dextrose solution may be needed to maintain glucose
• Continue the insulin infusion until the resolution of DKA
o Glucose <200 mg/dL (<11 mmol/L) and 2 of the following:
▪ Serum bicarbonate >15 mEq/L
▪ Venous pH >7.3
▪ Normal calculated anion gap
• Monitor labs every 1-2 hours to ensure insulin being given in desired amount
Transition from IV Infusion After DKA Correction
• To avoid relapse to hyperglycemia/DKA when the insulin infusion is stopped
• Relapse can occur quickly (within an hour after IV insulin is stopped) due to
the short duration of action of IV insulin
• Once the patient eats, the glucose infusion can be stopped
o Transition: short-acting & long-acting insulin when DKA has resolved
▪ 10 units regular insulin SC 30-60 mins before stopping insulin infusion
▪ 80% of usual long-acting insulin 1-2 hrs before discontinuing IV insulin
o Alternate: 50% of usual long-acting insulin 2 hrs before IV insulin stopped
• Newly diagnosed diabetic: start long-acting insulin at 0.1-0.2 unit/kg
o Additional glucose coverage with short-acting insulin as needed
• Continue glucose checks every hour for 2 hours
SC Insulin
• In uncomplicated mild to moderate DKA, rapid-acting SC insulin may be
another option, although standard treatment remains continuous IV insulin
• Initial dose of SC rapid-acting insulin (until blood glucose is <250 mg/dL)
o Initial injection of 0.2 unit/kg followed by 0.1 unit/kg/h, or
o Initial dose of 0.3 unit/kg followed by 0.2 unit/kg every 2 hours
• Dose is decreased by half & given every 1-2 hours until resolution of DKA
• Advantage: can avoid intensive care admissions and lower hospital costs
• Disadvantage: still requires close nursing monitoring that is difficult to
accomplish in the ER or in a regular hospital bed
Hypophosphatemia
• Phosphate (similar to glucose & potassium) reenters intracellular
space during insulin therapy (low phosphate concentrations)
• Most severe 24-48 hours after the start of insulin therapy
• Acute phosphate deficiency (<1.0 mg/dL) can result in:
o Hypoxia
o Skeletal muscle weakness
o Rhabdomyolysis
o Hemolysis
o Respiratory failure
o Cardiac dysfunction
• Do not give IV phosphate unless PO4 <1.0 mg/dL early in therapy
o IV K2PO4 2.5-5 mg/kg (0.08-0.16 mmol/kg)
o Monitor serum calcium level if giving supplemental phosphate
• Undesirable side effects from IV phosphate administration
o Hyperphosphatemia
o Hypocalcemia
o Hypomagnesemia
o Metastatic soft tissue calcifications
o Hypernatremia
o Volume loss from osmotic diuresis
108 | 22. DIABETIC KETOACIDOSIS
Hypomagnesemia
• Osmotic diuresis may deplete magnesium stores from bone
• May inhibit PTH secretion (hypocalcemia and hyperphosphatemia)
• If serum Mg <2.0 mEq/L or symptoms of hypomagnesemia
o Give magnesium sulfate 2 g IV over 1 hour
o Obtain serum Mg & Ca on presentation & 24 hours into therapy
o Monitor levels every 2 hours if:
▪ Initial hypomagnesemia or hypocalcemia or if
▪ Symptoms suggestive of hypomagnesemia/hypocalcemia
Bicarbonate
• Acidotic patients routinely recover from DKA without alkali therapy
o Fluid & insulin therapy inhibit lipolysis and resolve ketoacidosis
without added bicarbonate
• Give bicarbonate if initial pH is ≤6.9
o NaHCO3 100 mmol in 400 mL water + KCl 20 mmol at 200 mL/h
for 2 hours until the venous pH >7.0
o If pH remains <7.0 despite infusion, repeat infusion until pH >7.0
o Check [K+] every 2 hours
• Severe metabolic acidosis: associated with numerous complications
o Cardiovascular: impaired contractility, vasodilation, hypotension
o Neurologic: cerebral vasodilation, coma
• Theoretical advantages of bicarbonate
o Improved myocardial contractility
o Elevated ventricular fibrillation threshold
o Improved catecholamine tissue response
o Decreased work of breathing
• Disadvantages of bicarbonate
o Worsening hypokalemia
o Paradoxical CNS acidosis
o Worsening intracellular acidosis
o Impaired (shift to left) oxyhemoglobin dissociation
o Hypertonicity and sodium overload
o Delayed recovery from ketosis
o Elevation of lactate levels
o Possible precipitation of cerebral edema
• During treatment, H+ production ceases when ketogenesis stops;
excess H+ are eliminated through urine & respiratory tract
o Ketone metabolism results in endogenous production of alkali
• Decision to use bicarbonate in DKA patients should be based on
the clinical condition and pH (≤6.9) of the patient
o Potential benefits must be balanced against potential
disadvantages in elderly with cardiovascular instability
o Selected patients who benefit from cautious alkali therapy
▪ Decreased cardiac contractility and peripheral vasodilation
▪ Life-threatening hyperkalemia and coma
• Severe acidosis (pH <7.0) and worsening pH despite aggressive
therapy for DKA: investigate for other causes of metabolic acidosis
DISEASE COMPLICATIONS
• Complications Related to Acute Disease
o In general, greater mortality is associated with
▪ Greater initial serum osmolality, BUN, & blood glucose
▪ Lower serum bicarbonate level (<10 mEq/L)
o Infection & myocardial infarction: main contributors to mortality
o Additional factors that increase morbidity: old age, severe
hypotension, coma, underlying renal & cardiovascular disease
o Severe volume depletion leaves elderly at risk for DVT
• Complications Related to Therapy
o Hypoglycemia, hypokalemia, hypophosphatemia, acute
respiratory distress syndrome, cerebral edema
o Gradual return to normal metabolic balance will diminish
likelihood of such outcomes
o Acute respiratory distress syndrome
▪ Rare complication of therapy, particularly in the elderly &
those with impaired myocardial contractility
▪ Overly aggressive fluid therapy decreases plasma oncotic
pressure & raises left atrial end-diastolic pressure, favoring
a shift of fluid across the pulmonary capillary membrane
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

o Cerebral edema SPECIAL POPULATIONS

▪ Most common & feared cause of mortality in very young • Recurrent DKA patients
children, new-onset diabetics, and adolescents with DKA
▪ Potential risk factors:
• Young age
• New-onset diabetes (particularly in young adolescents)
▪ Often seen when the patient appears to be improving
clinically and biochemically, and carries a high mortality
▪ One hypothesis: during therapy with IV fluid and insulin,
water moves into brain cells faster than osmotically active • Patients with Insulin Pumps
particles can dissipate, promoting cellular swelling
▪ Gradual replacement of water and sodium deficits and slow
correction of hyperglycemia may lessen the risk
▪ Premonitory symptoms: severe headache, incontinence,
change in arousal or behavior, pupillary changes, blood • DKA in pregnancy
pressure changes, seizures, bradycardia. disturbed
temperature regulation
▪ Any change in neurologic function early in therapy
• IV mannitol (1-2 g/kg): given before respiratory failure
or obtaining confirmatory CT scans
• Hypertonic saline (3%) 5-10 mL/kg over 30 minutes
▪ Intubation and fluid restriction are generally necessary
o Address barriers to care access while in ER or hospital stay
▪ In urban setting, insulin noncompliance is a major trigger
▪ Cocaine is an independent risk factor for DKA
o Interventions that can promote improved glycemic control
▪ Social workers: assist with drug access & affordability
▪ Drug rehabilitation when indicated (illicit drug use)
▪ Education provided by the diabetic care team
o Should have their pumps disconnected and turned off
o Should be treated just like any other patient
o Reinstitution of pump therapy should start in the same time
frame as switching over to SC insulin in the non-pump user
o Leading cause of fetal loss (fetal mortality rate: 30%)
o Physiologic changes in diabetic pregnant women prone to DKA
• Relative insulin deficiency
Maternal FBS • Increased baseline free fatty acid levels in the blood
normally lower • DKA is triggered at lower sugar levels in pregnancy
• Normally have ↑ counterregulatory hormones
Chronic
• Decreased bicarbonate levels due to a compensatory
respiratory
renal response (decrease in buffering capacity)
alkalosis
Vomiting & UTI • Can precipitate DKA
Maternal • Fetal hyperglycemia
hyperglycemia • Osmotic diuresis
• Fetal acidosis
Maternal
• Decreased uterine blood flow and fetal oxygenation
acidosis
• Shifts O2-hemoglobin dissociation curve to the right
Maternal • Fetal dysrhythmias
hypokalemia • Death
o Correction of maternal hyperglycemia, acidosis, and electrolyte
balance are the first priorities

• Later Complications
Metabolic acidosis • Unrecognized infection (lactic acidosis)
refractory to routine • Insulin antibodies (rare)
therapy • Improper preparation/administration of insulin
Shock unresponsive to • Gram-negative bacteremia
aggressive fluid therapy • Silent myocardial infarction
• Rapid volume expansion in the face of ↓ HCO3
• HCO3 equivalents excreted in urine as
Hyperchloremic non-
ketones & replaced with Cl- in normal saline
anion gap metabolic
• Important to monitor anion gap during therapy
acidosis
• Resolves during recovery as HCO3 is
regenerated & excess Cl- is excreted in urine
• May occur in any muscular artery
o Cerebral vessels: most susceptible
• Elderly are predisposed due to:
o Volume depletion
o Low cardiac output
Late vascular o Increased blood viscosity
thrombosis o Underlying atherosclerosis
• May occur several hours/days after institution
of therapy & after resolution of ketoacidosis
• No studies support prophylactic anticoagulant
use (heparin may be beneficial if no
associated bleeding disorder)
• Elderly: sepsis/pulmonary & CV complications
Mortality in DKA
• Children & young adults: fatal cerebral edema

DISPOSITION AND FOLLOW-UP

Hospitalization in a • Great majority of patients
monitored setting • Initial care in an intensive or intermediate care unit
• Anion gap <25
Inpatient unit • Glucose level <600 mg/dL (33.3 mmol/L)
• No comorbidity at time of disposition decision
• Early in course of illness, can tolerate oral liquids
ER/observation unit
• Discharged after 6-12 hours of therapy

References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)

22. DIABETIC KETOACIDOSIS | 109

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

23. THYROID STORM CLINICAL FEATURES

Thyroid hormone History and Comorbidities
• Affects virtually all organ systems • Patient may only complain of constitutional symptoms (generalized
• Responsible for increasing metabolic rate, heart rate, and ventricular weakness and fatigue)
contractility, as well as muscle and CNS excitability • Common historical features: heat intolerance, diaphoresis, fever,
• Two major types: voracious appetite but poor weight gain, anxiety, emotional lability,
o Thyroxine (T4): major form of thyroid hormone palpitations, diarrhea, hair loss
▪ Peripherally, converted to the active triiodothyronine • History of hyperthyroidism: treatment & medication compliance
▪ Ratio of thyroxine to triiodothyronine = 10:1
o Triiodothyronine (T3): 3-4 times more potent than thyroxine Physical Examination
Hyperthyroidism • Often appear toxic and agitated
• Excess circulating hormone only from thyroid gland hyperfunction • Fever is often present in thyroid storm and may be quite high
• Primary hyperthyroidism: caused by excess production of thyroid o May herald onset of thyrotoxic crisis in previously uncomplicated
hormones from the thyroid glands • Palpitations, tachycardia, and dyspnea are common
• Secondary hyperthyroidism: caused by excess production of TRH or • A pleuropericardial rub may be heard
TSH in hypothalamus & pituitary, respectively • Direct inotropic and chronotropic effects on the heart:
Thyrotoxicosis o Increased blood volume
• Excess circulating thyroid hormone originating from any cause o Increased contractility: ↑ SBP & pulse pressure (dicrotic or
(including thyroid hormone overdose) water-hammer pulse)
Thyroid Storm o Increased cardiac output
• Extreme manifestation of thyrotoxicosis • Widened pulse pressure: ↑ cardiac output & ↓ PVR
• Acute, severe, life-threatening hypermetabolic state of • Atrial fibrillation: 10-35% of thyrotoxicosis cases
thyrotoxicosis caused either by: • Exophthalmos: reflects the responsible autoimmune process
o Excessive release of thyroid hormones: adrenergic hyperactivity o Severity not parallel to magnitude of thyroid dysfunction
o Increased peripheral response to thyroid hormone in response • Not all hyperthyroidism patients present with goiter
to one or more precipitants o Absent: exogenous thyroid hormone & apathetic thyrotoxicosis
• Graves’ disease: most common underlying cause of o Presence of goiter does not confirm diagnosis of thyrotoxicosis
hyperthyroidism in thyroid storm • Thyroid tenderness: inflammatory conditions (subacute thyroiditis)
o Caused by TSH receptor antibodies: stimulate excess &
uncontrolled thyroidal synthesis & secretion of thyroid hormones Symptoms and Signs of Thyrotoxicosis
o Occurs most frequently in young women (10 times more Affected System Symptoms Signs
common in women compared to with men) at any age group Constitutional Lethargy Diaphoresis
Weakness Fever
• Mortality rate of thyroid storm: 8-25% Heat intolerance Weight loss
Neuropsychiatric Emotional lability Fine tremor
Anxiety Muscle wasting
Confusion Hyperreflexia
Coma Periodic paralysis
Psychosis
Ophthalmologic Diplopia Lid lag
Eye irritation Dry eyes
Exophthalmos
Ophthalmoplegia
Conjunctival infection
Endocrine: thyroid Neck fullness Thyroid enlargement
gland Tenderness Bruit
Cardiorespiratory Dyspnea Widened pulse pressure
Palpitations Systolic hypertension
Chest pain Sinus tachycardia
PATHOPHYSIOLOGY Atrial fibrillation or flutter
• Pathophysiologic mechanisms underlying the shift from High output heart failure
Gastrointestinal Diarrhea Hyperactive bowel sound
uncomplicated thyrotoxicosis to thyroid storm are not entirely clear
Yellowish sclera Jaundice
o Involve adrenergic hyperactivity Reproductive Oligomenorrhea Gynecomastia
▪ ↑ release of thyroid hormones (with or without ↑ synthesis) Decreased libido Telangiectasia
▪ ↑ receptor sensitivity Gynecologic Menorrhagia Sparse pubic hair
o Relatively higher level of free thyroid hormones as opposed to Irregularity
Hematologic Pale skin Anemia
those with uncomplicated thyrotoxicosis Leukocytosis
▪ Total thyroid hormone level may or may not be increased Dermatologic Hair loss Pretibial myxedema
• Excess thyroid hormones: circulating T4 & T3 taken into cytoplasm Warm, moist skin
o T4 is converted to its active form, T3 Palmar erythema
Onycholysis
o T3 → nucleus → binds to thyroid hormone receptors or thyroid
hormone-responsive elements → gene activation & transcription
o Receptors: stimulate changes specific to the tissue
• T3, T4 → pituitary gland (negative feedback) → TSH suppression
• Thyroid storm: precipitants multiply effect of thyroid hormones by:
o Freeing thyroid hormones from their binding sites
o Increasing receptor sensitivity

110 | 23. THYROID STORM

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

DIAGNOSING THYROID STORM ECG

• Clinical diagnosis for patients with preexisting hyperthyroidism • Sinus tachycardia: approximately 40% of cases
• Atrial fibrillation: 10-35% of patients, more common in >60 years
Burch and Wartofsky Point Scale (BWPS) old with underlying structural heart disease
Diagnostic Parameters Scoring Points
• Premature ventricular contractions & heart blocks may be present
Thermoregulatory dysfunction (Temperature, °C)
37.2 – 37.7 5 • Atrial premature contractions & atrial flutter may also occur
37.7 – 38.3 10 • Institute cardiac monitoring
38.3 – 38.8 15
38.9 – 39.4 20 TREATMENT
39.4 – 39.9 25
≥40 30
• Treatment aims are as follows:
CNS effects o Supportive care
Absent 0 o Inhibition of peripheral adrenergic effects
Mild (agitation) 10 o Inhibition of new hormone synthesis
Moderate (delirium, psychosis, extreme lethargy) 20 o Inhibition of thyroid hormone release
Severe (seizures, coma) 30
o Preventing peripheral conversion of T4 to T3
GI-hepatic dysfunction
Absent 0 o Preventing free thyroid hormone reabsorption
Moderate (diarrhea, nausea/vomiting, abdominal pain) 10 o Treating the precipitant
Severe (unexplained jaundice) 20 o Definitive care
CV dysfunction (Tachycardia, beats/min) • The order of therapy in treating thyroid storm is very important with
90 – 109 5
regard to the use of thionamide and iodine therapy
110 – 119 10
120 – 129 15 o Obtain pregnancy testing before beginning treatment
≥140 25 o Obtain consultation for treatment if pregnant or breastfeeding
Congestive heart failure o If not pregnant, inhibit thyroid hormone synthesis of new thyroid
Absent 0 hormone with a thionamide should be initiated before iodine
Mild (pedal edema) 5 therapy to prevent stimulation of new thyroid hormone synthesis
Moderate (bibasilar rales) 10
Severe (pulmonary edema) 15 if iodine is given too soon
Atrial fibrillation
Absent 0 Treatment Aim 1: Supportive Care
Present 10 • Fluid losses: from fever + diaphoresis + vomiting, and diarrhea
• Scoring system: • Check blood glucose (high metabolic rate in thyroid storm)
o ≥45: highly suggestive of thyroid storm o If relatively low: IV fluids with dextrose (isotonic saline with 5%
o 25–44: suggestive of impending storm or 10% dextrose) may be given to replenish glycogen stores
o <25: unlikely to represent thyroid storm
Treatment Aim 2: Inhibition of Peripheral Adrenergic Effects
DIFFERENTIAL DIAGNOSIS • Thyroid storm is a hyperadrenergic state with risk of high-output HF
• Infection and sepsis • Reducing afterload and heart rate with a β-blocker is essential
• Sympathomimetic ingestion (e.g., cocaine, amphetamine, ketamine) • Inotropic agents may have to be considered carefully as they may
• Heat exhaustion worsen the hyperadrenergic state
• Heat stroke • Propranolol
• Delirium tremens o IV: slow 1-2 mg bolus, may be repeated every 10-15 minutes
• Malignant hyperthermia until desired effect (clinical improvement or HR <100 bpm)
• Malignant neuroleptic syndrome o Oral: 20-120 mg or 160-320 mg/day in divided doses
• Hypothalamic stroke o IV: 0.5-1 mg over 10 minutes, increased to 1-2 mg over 10
• Pheochromocytoma minutes each time; adjust dose every few hours to VS
• Medication withdrawal (e.g., cocaine, opioids o Oral: 60-80 mg every 4 hours (for the less toxic patient)
• Psychosis o Advantage: also prevents T4 to T3 conversion as well as being a
• Organophosphate poisoning nonselective β-blocker
• Esmolol (alternative short acting β-blocker)
LABORATORY TESTING o IV: 250-500 μg/kg, then 50-100 μg/kg/min, titrated based on VS
• CBC, electrolytes, glucose, renal & liver function tests to identify o Preferable for patients with HF because the drug’s action could
comorbidities be curtailed if patient deteriorates
• Obtain a pregnancy test in women of childbearing age o Alternatives: IV landiolol or oral bisoprolol
• Except for pregnancy testing, start treatment upon suspicion of • If contraindicated to β-blockers (reactive airway disease)
diagnosis without waiting for laboratory results o Cardioselective β-blockers (atenolol or metoprolol)
CBC • Leukocytosis with shift to the left o Calcium channel blockers
Hyperglycemia • Catecholamine-induced inhibition of insulin release • Alternative Drugs for Peripheral Blockade of β-Receptor
& increased glycogenolysis o Indications: severe asthmatics, β-blockers contraindicated, no
• Rapid intestinal absorption of glucose hypotension/CNS-associated mental status changes
Mild hypercalcemia • Hemoconcentration & enhanced thyroid hormone-
& elevated ALP
o Side effects: hypotension & diarrhea
stimulated bone resorption
Liver enzymes • Elevated: liver enzyme metabolism induced o Contraindications: CHF, hypotension, cardiogenic shock
Serum cortisol • High: normal reaction of adrenal gland under stress o Reserpine 2.5mg IM q4-6 h, then 1mg test dose (monitoring BP)
• Low: suspicion of coincidental adrenal insufficiency ▪ Alkaloid agent that depletes catecholamine stores in
sympathetic nerve terminals and the CNS
IMAGING ▪ Can have CNS depressant effects
• Chest radiograph: rule out infection as precipitant o Guanethidine (dose: 30-40 mg PO every 6 hours)
• Bedside 2D-echo: tachycardia, enhanced LV contractility, dilated ▪ Inhibits the release of catecholamines
inferior vena cava in the presence of high-output cardiac failure • Contraindications are same as those for other medical conditions
• CT of the brain: exclude conditions if diagnosis is uncertain (CNS o Caution in patients with CHF and thyrotoxic cardiomyopathy
abnormalities with altered mental status precipitate thyroid storm) o Tachydysrhythmia + CHF: rate control first

23. THYROID STORM | 111

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Treatment Aim 3: Inhibition of New Thyroid Hormone Synthesis Treatment Aim 6: Preventing Reabsorption or Removal of Thyroid
• Thionamides: inhibits thyroid hormone synthesis by: Hormones
o Preventing organification and trapping of iodide to iodine • Cholestyramine 4 g every 6 hours
o Inhibiting coupling of iodotyrosines o Used to inhibit thyroid hormone reabsorption
o Also has immunosuppressive effects o Anion exchange resin that decreases reabsorption of thyroid
• Methimazole 20 mg PO q6h (total dose: 60-80 mg/day) hormone form the enterohepatic circulation
o If given PR: similar dose crushed in aqueous solution o Normal: thyroid hormone is metabolized mainly in the liver
o Presents in free form in serum (conjugated to glucuronides and sulfates) and excreted in bile
o Carbimazole: prodrug of methimazole (alternative) ▪ Free hormones are released in the intestine and finally
▪ Dose: 40-60 mg, then 5-20 mg/day reabsorbed, completing the enterohepatic circulation
o Advantage: longer half-life than PTU (less frequent dosing) o Thyrotoxicosis: ↑ enterohepatic circulation of thyroid hormone
o Disadvantage: category D (teratogenic in 1st trimester) o Cholestyramine + methimazole or PTU: more rapid decline in
▪ Can be used during 2nd and 3rd trimester thyroid hormones than standard therapy with thionamides alone
• Propylthiouracil (PTU) 500-1000 mg PO, then 250 mg q4h • Thyroid Hormone Removal
o 80-90% of PTU is bound to albumin o If contraindicated to PTU & methimazole (prior severe reaction)
o Can be given by nasogastric tube or PR o Direct removal of thyroid hormone may be effectively used to
o Advantages: can inhibit peripheral conversion of T4 to T3 rapidly reduce thyroid hormone levels in thyroid storm patients
▪ Reserved for patients who cannot tolerate methimazole who respond poorly to traditional therapeutic measures
▪ Preferred in cases of 1st trimester pregnancy ▪ Plasmapheresis, charcoal hemoperfusion, resin
o Disadvantages: ↑ risk of hepatotoxicity vs. methimazole hemoperfusion, plasma exchange
▪ Signs and symptoms of liver injury should be closely
monitored, especially in 1st 6 months of therapy initiation Treatment Aim 7: Identify Precipitating Factors
▪ May cause increased liver enzymes • Search for infection in febrile thyrotoxic patients
▪ Should not be used as therapy if transaminase levels reach • ECG: identify MI, ischemia, or arrhythmia
>3x ULN or if elevated at the onset of therapy • If precipitated by DKA, MI, PE, or other acute processes: appropriate
o Should not be used in children unless patient is allergic or management of underlying problem with treatment of thyrotoxicosis
intolerant of methimazole & no other options are available
Treatment Aim 8: Definitive Therapy
Treatment Aim 4: Inhibition of Hormone Release • Radioactive iodine ablation or surgery: may not be possible for
• Iodine several weeks/months after treatment with iodine for thyroid storm
o Lugol solution, potassium iodide, ipodate, or lithium carbonate • Close follow-up & monitoring should continue, with plans for
o Thionamide therapy must be instituted first with these drugs only definitive therapy to prevent future recurrence
given at least 1 hour later
o MOA: blocks the release of prestored hormone & decreases Adverse Side Effects from Antithyroid Drugs
iodide transport and oxidation in follicular cells
o Lugol solution can be given as 8-10 drops PO, then q6-8h
▪ Provides 8 mg of iodide per drop
o Iodinated radiographic contrast dyes that contain
▪ Iodate 0.5-3 g/day orally
▪ Iopanoic acid IV 1 g q8h for 1st 24 h, then 500 mg BID
▪ Added property to effectively prevent conversion of T4 to T3
o Contraindications
▪ Iodine hypersensitivity
▪ Iodine overload or iodine-induced hyperthyroidism
▪ Amiodarone-induced thyrotoxicosis
• Alternative Drugs if Iodine Intake is Contraindicated
o Potassium perchlorate (dose: 0.5 g/day)
▪ MOA: blocks thyroid uptake of iodine
▪ Perchlorate (CIO4-): competitive inhibitor of iodide transport
▪ Side effects: aplastic anemia & nephrotic syndrome
o Lithium (dose: 300 mg every 8 hours)
▪ MOA: inhibits thyroid hormone release from thyroid gland
▪ Has effects on thyroid gland that ↓ hormone synthesis
• ↑ intrathyroidal iodine content & inhibits coupling of RAPID PREPARATION OF THYROTOXIC PATIENTS FOR
iodotyrosine residues that form T4 and T3 EMERGENCY SURGERY
▪ In severe thyroid storm: can be used with PTU/methimazole
▪ To avoid lithium toxicity: maintain at 0.6-1.0 mmol/L
▪ Frequent monitoring is mandatory because serum lithium
may change as patient is rendered more euthyroid
▪ Avoid in pregnancy (teratogenic effects)

Treatment Aim 5: Preventing Conversion of T4 to T3

• Glucocorticoids (hydrocortisone or dexamethasone)
o Hydrocortisone 300 mg IV, then 100 mg q8h until stable
o Dexamethasone 2 mg IV q6h
o Use in thyroid storm also improves survival rates
o Standard practice in severe thyrotoxicosis + hypotension
(possibility of relative adrenal insufficiency)

112 | 23. THYROID STORM


DISPOSITION AND FOLLOW-UP
• Typically requires admission to ICU
• Patients often have concomitant diseases precipitating attack &
require close monitoring
• Complete recovery may take 1 week until circulating levels of
thyroid hormones are depleted
• Stable hyperthyroid patients with minimal symptoms can only be
discharged for follow-up if patient is already on medication with a
clear plan of follow-up
SPECIAL POPULATIONS
• Pregnancy and Lactation
o Avoid methimazole during the 1st trimester of pregnancy in
thyrotoxic patients in view of its teratogenic effects
o PTU should be used during the 1st trimester
▪ This can be converted back to methimazole from 2 nd
trimester onward
o Lithium is contraindicated in pregnancy
▪ Effects on breastfeeding infants are not well documented
• Elderly Patients
o Older patients may present with “apathetic” thyrotoxicosis
▪ Atypical symptoms: weight loss, palpitations, weakness,
dizziness, syncope, memory loss
▪ Physical findings: sinus tachycardia or atrial fibrillation
o Signs & symptoms are few and subtle
o Initial appearance of disease may be single-organ failure (e.g.,
CHF), producing diagnostic confusion by pointing to diagnosis
other than thyrotoxicosis
• Thyrotoxic Patients with Atrial Fibrillation
o β-blockers can provide rate control
▪ Propranolol can be used if the patient is not in failure
▪ Esmolol, with short-acting effect, is a safer choice
▪ If β-blockers are contraindicated, digoxin can be used
o Calcium channel blockers can also be cautiously used
▪ Can induce severe hypotension & reduce SVR
o Amiodarone can be considered
▪ Note that is has 37% organic iodine by weight
▪ Ensure thionamides have been given to avoid synthesis of
new thyroid hormones
o Thrombosis may ensue & heparinization should be instituted
▪ Thyrotoxic patients may require a lower maintenance dose
of warfarin than euthyroid patients (increased clearance of
vitamin K-dependent clotting factors)
• Congestive Cardiac Failure in Thyroid Storm
o Avoid vasodilators such as nitrates
▪ Thyrotoxicosis is associated with vasodilation and
decreased systemic vascular resistance
o Avoid β-blockers when cardiac failure is associated with
underlying ischemic, hypertensive, or valvular heart disease
▪ Short-acting β-blocker (esmolol) is a safer choice
• Drug Interactions in Thyrotoxic Patients
o Many drugs interfere with protein binding
▪ Heparin
▪ Furosemide
▪ Phenytoin
▪ Carbamazepine
▪ Diazepam
▪ Salicylates
▪ Opiates
▪ Estrogens
▪ NSAIDs
o Free hormone concentrations are preferable in diagnosis
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
SUMMARY: Treatment for Thyroid Storm
Supportive care
General: oxygen, cardiac monitoring
Fever: external cooling; acetaminophen 325-650 mg PO/PR every 4-6 hours
(aspirin is contraindicated: may increase free thyroid hormone)
Dehydration: IV fluids, IV isotonic saline with 5% dextrose may be used to
replace glycogen depletion if blood sugar is low
Nutrition: glucose, multivitamins, thiamine, and folate can be considered
(deficient secondary to hypermetabolism)
Inhibition of peripheral adrenergic effects
Propranolol 0.5-1 mg IV over 10 minutes, then 1-2 mg every few hours
adjusted to vital signs. For less toxic patient, PO dose of 60-80 mg every 4
hours (for reactive airway disease, cardioselective β-blockers, such as atenolol
or metoprolol, or calcium channel blockers can be considered)
OR
Esmolol 250-500 μg/kg IV load, then 50-100 μg/kg/min titrated doses to VS
OR
Reserpine 2.5-5.0 mg IM every 4-6 hours, preceded by 1 mg test dose while
monitoring blood pressure (use if β-blocker contraindicated but avoid in
congestive heart failure or hypotension and cardiac shock)
OR
Guanethidine 30-40 mg PO every 6 hours (use if β-blocker contraindicated
but avoid in congestive heart failure, hypotension, and cardiac shock)
Inhibition of new thyroid hormone synthesis with thionamides
Methimazole 20 mg every 6 hours PO
(Avoid methimazole for pregnant women. Teratogenic risk is highest in 1st
trimester. FDA pregnancy category D. Obtain consultation if breastfeeding)
OR
PTU, loading dose of 500-1000 mg PO and followed by 250 mg every 4 h
(PTU is used for pregnant women in 1st trimester. PTU also has a boxed
warning regarding rare but severe hepatic dysfunction. There are case reports
of hepatic failure in mother/fetus.) Obtain consultation if breastfeeding
Inhibition of thyroid hormone release (at least 1 hour after step 3)
Lugol solution 8-10 drops PO every 6-8 hours
OR
Potassium iodide (SSKI) 5 drops (0.25 mL or 250 μg) PO every 6 hours
OR
IV iopanoic acid 1 g every 8 hours for first 24 hours, then 500 mg BID
(FDA pregnancy category C)
OR
Ipodate 0.5-3.0 g/day PO (useful with thyroiditis/thyroid hormone overdose)
OR
Lithium carbonate (if allergic to iodine or agranulocytosis occurs with
thionamides), 300 mg PO every 6 hours (1200 mg/day) and subsequently to
maintain serum lithium at 1 mEq/L
(Lithium is contraindicated for use in pregnant mothers; effects in breastfeeding
uncertain, so obtain consultation.)
Preventing peripheral conversion of T 4 to T3
Hydrocortisone 300 mg IV initially, then 100 mg 3 times a day until stable
(also for adrenal replacement due to hypermetabolism)
OR
Dexamethasone 2 mg IV every 6 hours
Prevention of free thyroid hormones reabsorption
Cholestyramine 4 g every 6 hours
Treat precipitating event
All triggers of thyroid storm should be searched and treated accordingly
(infection, myocardial infarct, diabetic ketoacidosis, etc.)
Definitive therapy
Radioactive iodine ablation therapy or surgery may be necessary
Note: Replacement therapy: dialysis and plasmapheresis are last resorts for patients who do
not respond to treatments 1-5
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
23. THYROID STORM | 113
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
24. UREMIA
End-Stage Renal Disease (ESRD)
• Irreversible loss of renal function, resulting in the accumulation of
toxins and the loss of internal homeostasis
Uremia
• Clinical syndrome resulting from ESRD
• Uremia: contamination of the blood with urine
• Azotemia: buildup of nitrogen in the blood
• Universally fatal without some form of renal replacement therapy
Renal Replacement Therapy (RRT)
• Renal Transplant: most children receive transplants
• Dialytic Therapy:
o Hemodialysis (HD): initial therapy in most new adult ESRD
o Peritoneal Dialysis (PD)
• HD patients: 1-year mortality: 20-35%; 5-year mortality: 35%
o Cardiac causes accounting about ½ of all deaths
o Infections trigger death in up to ¼ of patients
o Cerebrovascular events and malignancy being other causes
PATHOPHYSIOLOGY
• Excretory failure
o Leads to elevated levels of >70 chemicals in uremic plasma
▪ May cause uremic organ dysfunction
▪ Produce symptoms of uremia
o Urea is not the major toxin
o Potential uremic toxins: cyanate, guanidine, polyamines, β2-
microglobulin (many are highly protein bound & nondialyzable)
• Biosynthetic failure
o The kidneys are primarily responsible for secretion of:
▪ Erythropoietin (85% of EPO is produced in the kidneys)
▪ 1α-hydroxylase (necessary to produce active vitamin D3)
o Loss of renal hormones 1,25(OH)2-vitamin D3 & erythropoietin:
▪ Erythropoietin deficiency: anemia
▪ Vitamin D3 deficiency: decreased GI calcium absorption →
secondary hyperparathyroidism → renal bone disease
• Regulatory failure
o Results in oversecretion of hormones, leading to uremia by
disruption of normal feedback mechanisms
o Uremic state produces excess free oxygen radicals
▪ React to carbohydrates, lipids, and amino acids to create
advanced glycation end products, linked to progressive
atherosclerosis and amyloidosis in ESRD patients
CLINICAL FEATURES OF UREMIA
• Uremia is a clinical syndrome
• No single symptom, sign, or laboratory result reflects all aspects
o Correlation between uremia & low GFR (8-10 mL/min/1.73 m2)
o BUN and serum creatinine levels are inaccurate markers
• The decision to start long-term dialysis is based on the severity of
the patient’s symptoms related to uremia
• Most common reasons for emergency dialysis:
o Fluid overload (51%)
o Hyperkalemia (18%)
o Severe acid-base disturbances
• Uremia is the most common indication for nonemergent dialysis
Neurologic Complications
• Stroke: approximately 6% of hemodialysis patients
o ½ being hemorrhagic; ½ being ischemic
• Subdural hematomas: 10 times more frequently in dialysis patients
o Headache, focal neurologic deficits, seizure, coma
• Uremic encephalopathy
o Constellation of nonspecific CNS symptoms associated with
renal failure: cognitive defects, memory loss, decreased
attentiveness, slurred speech, reversal of sleep-wake cycle,
asterixis, seizure, coma, symptomatic improvement with dialysis
o Best diagnosed after eliminating structural, vascular, infectious,
toxic, and metabolic causes of neurologic dysfunction
o Neurologic findings improves with dialysis
114 | 24. UREMIA
• Dialysis dementia
o Nonspecific in presentation from other encephalopathies
o Progressive: 2- to 4-year survival for these patients being 24%
o Becomes evident after at least 2 years of dialysis therapy
o Fails to respond to ↑ dialysis frequency or renal transplantation
• Peripheral neuropathy
o One of the most frequent neurologic manifestations of ESRD
o Singultus (hiccups), restless leg syndrome (RLS), sensorimotor
neuropathy, autonomic neuropathy
o Greater lower than upper limb involvement
o Reflect large-fiber involvement: paresthesias, reduction in DTR,
impaired vibration sense, muscle wasting, weakness
o Autonomic dysfunction: impotence, postural dizziness, gastric
fullness, bowel dysfunction, reduced sweating
▪ ↓ HR variability & baroreceptor control impairment occur
o Nerve conduction studies: generalized axonal neuropathy
o Daily short hemodialysis and long nocturnal hemodialysis may
reduce the elevated sympathetic activity
Cardiovascular Complications
• Mortality: 10-20 times higher in dialysis patients
• CAD, LVH, CHF are common
• Etiology of cardiovascular disease in ESRD is multifactorial
o Preexisting conditions: hypertension, diabetes
o Uremia: uremic toxins, hyperlipidemias, homocysteine level,
hyperparathyroidism
o Dialysis-related conditions: hypotension, dialysis membrane
reactions, hypoalbuminemia
• Elevated troponin I & T are common even in asymptomatic patients
o Reflect LVH and microvascular disease
o Associated with long-term risk for CAD
• Hypertension
o Present in most patients starting dialysis
o Essential hypertension, glomerulonephritis, renal artery
stenosis, fluid overload
o Depends mostly on increased total peripheral resistance
▪ Increases in blood volume, decreased vascular compliance,
vasopressor effects on native kidneys, RAAS, SNS also
play roles in ESRD hypertension
o Management: control of blood volume
▪ If unsuccessful: adrenergic blocking agents, ACE inhibitors,
or vasodilators (hydralazine or minoxidil)
▪ Bilateral nephrectomy is rarely necessary for BP control
• Heart failure
o From hypertension, followed by CAD and valvular defects
o Fluid overload, uremic cardiomyopathy, high-output AV fistula
o Natriuretic peptide levels are elevated in hemodialysis patients
▪ Often from LVH or systolic dysfunction
▪ Correlates with higher short-term mortality rates (no reliable
thresholds to identify fluid overload)
• Uremic cardiomyopathy
o Diagnosis of exclusion (all other causes of CHF excluded)
o LVH is related to IHD, hypertension, & hypoalbuminemia
o Dialysis rarely improves LVH in uremic patients with CHF
• Pulmonary edema
o Commonly ascribed to fluid overload
o AMI can also trigger depressed LV function
o Cornerstone of therapy: supplemental oxygen (if needed),
bilevel positive airway pressure, nitrates, ACE inhibitors
▪ Loop diuretics (furosemide 60-100 mg IV) may aid even in
minimal urine output (short-lived vasodilatory actions)
o Hemodialysis: ultimate treatment for fluid overload in ESRD
▪ In low-resource situations: preload reduction by:
• Inducing diarrhea with sorbitol
• Phlebotomy: improved oxygenation offsets decrease in
O2-carrying capacity due to decrease in hemoglobin
o RBCs transfused back later during dialysis
o Removing as little as 150 mL of blood is safe and
effective in some with pulmonary edema

• Cardiac tamponade
o Critically ill ESRD patient; presents without classic findings
▪ Mental status changes, hypotension, shortness of breath
o Other warning signs suggesting tamponade: ↑ interdialytic
weight gain, ↑ edema, intradialytic hypotension
▪ ↑ heart size (CXR) suggest effusion & potential tamponade
o Bedside US: best to detect pericardial effusion & tamponade
o Pericardiocentesis under fluoroscopic or US guidance:
hemodynamically significant pericardial effusions
o Bedside pericardiocentesis: only in hemodynamically unstable
patients because of its high complication rate
• Uremic pericarditis
o Linked to fluid overload, abnormal platelet function, and
increased fibrinolysis and inflammation
o Pericardial contents are sterile unless infected and are abundant
with fibrin and inflammatory cells
o Pericardial friction rubs: louder than in most other forms of
pericarditis, often palpable, and frequently persist for some time
after metabolic abnormalities have been corrected
o BUN level is nearly always >60 mg/dL
o ECG changes: typical findings of acute pericarditis are absent
(inflammatory cells does not penetrate the myocardium)
▪ Associated abnormalities: hyperkalemia & hypocalcemia
▪ Findings of acute pericarditis: infection should be suspected
• Dialysis-related pericarditis
o During periods of ↑ catabolism (trauma & sepsis) or inadequate
dialysis (missed sessions or vascular access problems)
o Due to buildup of middle molecules & hyperparathyroidism
o More common during hemodialysis than during PD
o Fever & malaise more common & severe (vs uremic pericarditis)
o Pericardial effusion: most important complication; recurrent
▪ Adhesions & fluid loculations common
o Management
▪ Hemodynamically stable: intensive dialysis (HD> PD)
• HD: Higher clearance rates, recognizing the risks of
tamponade from heparin and rapid fluid shifts
▪ Hemodialysis: effective in majority cases (after 10-14 days)
• Indomethacin, colchicine, & steroids are not useful
▪ Anterior pericardiectomy: if persists for >10-14 days
▪ Total pericardiectomy: reserved for constrictive pericarditis
Hematologic Complications
• Anemia
o ↓ EPO, dialysis blood loss, frequent phlebotomy, ↓ RBC survival
o Factitious anemia: wide fluctuations in plasma blood volume
o Without treatment: Hct 15-20%; normocytic normochromic RBC
o Bone marrow: erythroid hypoplasia, with little effect on
leukopoiesis or megakaryocytopoiesis
o Treatment: regular human recombinant erythropoietin infusions
▪ Replacement therapy improves the quality of life for ESRD
patients (increases exercise capacity & tolerance)
• Bleeding diathesis
o Increases the risks of GI tract bleeding, subdural hematomas,
subcapsular liver hematomas, and intraocular bleeding
o Uremic bleeding: decreased platelet function, abnormal platelet-
vessel interactions, altered von Willebrand factor, anemia,
abnormal cGMP-dependent production of nitric oxide
o Skin bleeding test: best predictor of clinical hemostatic defects
o Aspirin or warfarin intake: greater risk of major bleeding
o Improvement in bleeding times with infusion of desmopressin
(benefit in 1 hour), cryoprecipitate (benefit in 4 hours), or
conjugated estrogens (benefit in 6 hours) is an option
• Immunologic deficiency
o Results in high morbidity and mortality from infectious diseases
o Key feature: depressed leukocyte chemotaxis and phagocytosis
from many causes, along with abnormal T-cell activation
o Dialysis does not improve immune function; may exacerbate
immunodeficiency (complement activation after exposure to HD
filter membrane)
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Gastrointestinal Complications
• Anorexia, nausea, and vomiting are common symptoms of uremia
o Used to initiate and monitor dialysis adequacy
• Increased incidence of gastritis and upper GI bleeding
• Incidence of gastric & duodenal ulcers same with general population
• Chronic constipation is common secondary to decreased fluid intake
and the use of phosphate-binding gels
• Increased incidence of diverticular disease and colonic perforation,
especially patients with polycystic kidney disease
• Dialysis-related ascites: secondary to fluid overload, portal
hypertension from polycystic liver disease, & osmotic disequilibrium
o Treatment of refractory ascites: peritoneovenous shunts
Renal Bone Disease
• As GFR falls, phosphate excretion decreases, which results in
increased serum phosphate levels
• Metastatic calcification
o Calcium-phosphate product [Ca2+ (mg/dL) x PO4 (mg/dL]
o If >70-80: metastatic calcification can ensue
▪ Joint pain (pseudogout): calcification of synovial membrane
▪ Skin and finger necrosis: calcification in small vessels
▪ Life-threatening calcifications can occur in cardiac &
pulmonary systems
o >72: short-term mortality rate is higher
o Treatment: low-calcium dialysate & phosphate-binding gels
• Hyperparathyroidism
o Increased production of PTH due to ↓ ionized calcium due to the
calciphylaxis + vitamin D3 deficiency as ESRD progresses
o High bone turnover & weakened bones susceptible to fracture
o Bone pain and muscle weakness are other symptoms
o Diagnosis: high ALP and PTH
o Treatment: control of serum PO4 with binding gels, vitamin D3
replacement, and, if necessary, subtotal parathyroidectomy
• Osteomalacia
o Defect in bone calcification
o Signs and symptoms: weakened bones, bone pain, muscle
weakness (similar to hyperparathyroidism)
o Diagnosis: low to normal ALP & low PTH
▪ ↑ serum & bone aluminum levels confirm diagnosis
o Treatment: desferrioxamine helps aluminum bone disease
β2-Microglobulin Amyloidosis (dialysis-related amyloidosis)
• In dialysis patients >50 years of age & on dialysis for >10 years
• Advanced glycation end products appear central to the chronic
inflammatory condition, leading to amyloidosis
• Amyloid deposits are found in the GI tract, bones, and joints
• Complications: GI perforation, bone cysts with pathologic fractures,
arthropathies (carpal tunnel syndrome, rotator cuff tears)
• Higher mortality rates than do those without this disorder
24. UREMIA | 115
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
HEMODIALYSIS
Technical Aspects of Hemodialysis
• Substitutes a filter for glomerulus to produce ultrafiltrate of plasma
• IV heparin 1000-1000 U: prevent thrombosis at vascular access site
• Hemodialysis sessions typically take 3-4 hours
• Adjustment of pressure gradient across hemodialyzer filter during
hemodialysis controls amount of fluid removal (ultrafiltration)
• Solute removal (clearance) during hemodialysis depends on:
o Filter pore size
o Amount of ultrafiltration (solute drag)
o Concentration gradient across the filter (diffusion)
• During hemodialysis, blood is
o Removed from vascular access by large-bore needles (15G)
o Circulated through dialysis machine at rates of 300-500 mL/min
o Returned to the patient
• Dialysate: flows at a rate of 500-800 mL/min through the dialysis
filter in the direction opposite to blood flow
Complications of Vascular Access
• Account for more hospital days than any other HD complication
• Thrombosis and stenosis of the vascular access
o Most common causes of inadequate dialysis flow
o Grafts generally have a higher rate of stenosis than fistulas
o Presents with loss of bruit and thrill over the access
o Treatment:
▪ Within 24 hours: angiographic clot removal or angioplasty
▪ With vascular surgeon: direct injection of alteplase
• Vascular access infections (2-5% of AV fistulas; 10% of AV grafts)
o Presents with fever, hypotension, or an elevated WBC count
o Classic signs of infection are often missing
o Dialysis catheter-related bacteremia
▪ Very common & potentially life-threatening
▪ After 6 months, approx. ½ of patients develop bacteremia
▪ Serious complications (death, endocarditis, osteomyelitis,
septic arthritis, epidural abscess) in 5-10% of patients
▪ Trial of IV antibiotics: attempt to maintain the dialysis access
▪ Removal of catheter: if still fever after 2-3 days of antibiotics
▪ Peripheral & catheter blood cultures: potential sources
• 4-fold higher colony count in catheter vs. peripheral
• Most common organisms: S. aureus, gram-negatives
▪ Usually require hospital admission
• Vancomycin 15 mg/kg or 1 g IV: against MRSA
o Long half-life (5-7 days) in dialysis patients
• Gentamicin 100 mg IV initially & after each dialysis:
added if gram-negative organisms suspected
• Alternatives or adjuncts to IV antibiotics
o Removal and delayed replacement of the catheter
o Catheter exchange over a guidewire
o Use of antimicrobial/citrate lock solutions
• Hemorrhage from a vascular site
o Rare but life-threatening complication
o Causes: aneurysms, anastomosis rupture, overanticoagulation
o Control bleeding immediately with manual pressure on puncture
site for 5-10 minutes, & observe patient for 1-2 hours if ceased
116 | 24. UREMIA
• Vascular access aneurysms
o From repeated puncture; true aneurysm very rare; rarely rupture
o Most are asymptomatic, with patients occasionally complaining
of pain or an associated peripheral impingement neuropathy
• Vascular access pseudoaneurysms
o From subcutaneous extravasation of blood from puncture sites
o Signs: bleeding & infection at access site
o Arterial Doppler US identifies any aneurysm/pseudoaneurysm
• Vascular insufficiency of extremity distal to vascular access (1%)
o “Steal syndrome”: preferential shunting of arterial to venous side
o Features: exercise pain, nonhealing ulcers, cool pulseless digits
o Doppler US or angiography is the best diagnostic approach
o Treatment: surgical
• High-output heart failure (>20% of CO diverted through access)
o Branham sign: heart rate drop after temporary access occlusion
o Doppler US: measure access flow rate & establish diagnosis
o Treatment: surgical banding of the access (↓ flow & treat HF)
Complications During Hemodialysis
• Hypotension (most frequent complication; 50% of treatments)
o Fluid removal during HD: 1-3 L over 4 hours (up to 2 L/hour)
o Maintenance of a normal BP during ultrafiltration depends on:
▪ Cardiovascular compensatory mechanisms
▪ Refilling of vascular space (fluid shifts from interstitial &
intracellular compartments)
• Hypotension early in the dialysis session
o Usually due to preexisting hypovolemia
o Suspected when patient start HD at weight below dry weight
o GI bleeding, sepsis, vomiting, diarrhea, ↓ salt & water intake
• Intradialytic hypotension
o Most common cause: excessive ultrafiltration due to
underestimation of patient’s ideal blood volume (dry weight)
▪ Optimal dry weight is often clinically defined when
hypotension prevents further fluid removal
o Can occur from blood tubing or hemodialyzer filter leaks
o Produces nausea, vomiting, and anxiety
o Orthostatic hypotension, tachycardia, dizziness, syncope
o Treatment: halting hemodialysis & Trendelenburg position
▪ If persists, give salt by mouth (broth) or IV (100-200 mL)
▪ If conservative measures fail: more extensive evaluation
• Adequacy of volume status, cardiac dysfunction,
pericardial disease, infection, & GI bleeding
o Further volume expansion or vasopressors to support BP may
require invasive hemodynamic monitoring in ICU
• Dialysis disequilibrium (clinical syndrome at end of dialysis)
o Features: nausea, vomiting, hypertension
▪ Can progress to seizure, coma, & death
o Occurs when large solute clearances occur during hemodialysis
(first dialysis session or hypercatabolic states)
o Cause: believed to be cerebral edema from an osmolar
imbalance between brain and blood
▪ High solute removal: osmolality in blood < brain, favors
water movement into brain & causes cerebral edema
o Prevention: limit solute clearance when initiating hemodialysis
o Treatment: stop dialysis & give mannitol IV to ↑ serum osmolality
• Air embolism
o Always a risk when blood is pumped through extracorporeal unit
o Clinical presentation depends on the patient’s body position:
▪ Sitting: increased ICP & neurologic symptoms (air →
internal jugular vein → cerebral circulation)
▪ Recumbent: pulmonary hypertension & systemic
hypotension (air → RV → pulmonary circulation)

▪ Arterial air embolism: myocardial infarction or stroke (air →
right-to-left shunt [PFO] → coronary/cerebral circulation)
o Symptoms: acute dyspnea, chest tightness, loss of
consciousness, and sometimes full cardiac arrest
o Signs: cyanosis, churning sound in heart (air bubbles in blood)
o If suspected: clamp venous blood line & place patient supine
▪ Give 100% oxygen to aid reabsorption of the air
▪ Other therapies: percutaneous aspiration of air from RV, IV
steroids, full heparinization, hyperbaric oxygen treatment
• Electrolyte abnormalities
o Due to errors in mixing the dialysate concentrate with water
o Results in rapid osmolar shifts and hemolysis
o In some communities, water contains calcium & magnesium
▪ Produces a final dialysate high in these minerals
▪ Use of this dialysate can result in “hard water syndrome”
• Significant hypercalcemia & hypermagnesemia
• Symptoms: nausea, vomiting, headaches, burning skin,
muscle weakness, lethargy, hypertension
• Treatment: properly filtering dialysis water to lower
calcium and magnesium concentration
• Hypoglycemia
o In diabetic and nondiabetic ESRD patients
o Causes: drugs, malnutrition, sepsis
ER Evaluation of Hemodialysis Patients
• Medical history is very important
o Many of the same diseases that caused ESRD (hypertension,
diabetes) persist after the patient’s kidneys have failed
o Repeated episodes of intradialytic hypotension: important early
clues to pericardial tamponade or myocardial ischemia
o Repeated access infections: worsening immunologic status
o Hemodialysis schedule (note all missed sessions & reasons)
o Hemodialysis details: dry weights, baseline laboratory test
results, average interdialytic weight gains, recent complications
o Uremic symptoms: markers of inadequate hemodialysis
o Retained native kidneys: can be sources of hypertension,
infection, and nephrolithiasis
• Physical Examination
o Access site: examine flow (presence of bruit & thrill)
o Classic signs of infection (erythema, swelling, tenderness,
purulent discharge) often limited until infection is far advanced
o Look for CHF, effusion, or high-output fistula-related HF
o Peripheral edema, hepatojugular reflux, & jugular venous
distention: present in both fluid overload & cardiac tamponade
o Loud cardiac murmur: represent ↑ flow (anemia or AV access)
o Neurologic dysfunction: generally diffuse & nonfocal
▪ Any focal neurologic findings require neuroimaging
o Seek GI bleeding with rectal examination & occult blood testing
o Doppler US examination if any question about vascular
insufficiency, aneurysm, or pseudoaneurysm exists
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
PERITONEAL DIALYSIS
Technical Aspects of Peritoneal Dialysis
• Peritoneal membrane is the blood-dialysate interface
• Relies on the separate processes of clearance (solute removal) and
ultrafiltration (fluid removal) to replace the functions of the nephron
o Solute removal: diffusion down chemical gradients established
by altering dialysate electrolyte concentrations
o Ultrafiltration: determined by osmotic pressure differences
between blood & dialysate (manipulated by changing dialysate
glucose concentration in 1.5% & 4.25% glucose formulations,
alternated to increase or decrease ultrafiltration)
• Typical PD regimens use 4 exchanges daily, with 2 L of dialysate
infused and left in place for several hours before draining
o During the day, approximately 8 L is infused and about 10 L is
drained, for a removal of approximately 2 L/day of fluid
• PD can be accomplished:
o In an acute setting
o Continuous ambulatory PD: over long term via exchanges of
solution throughout the day
o Continuous cyclic PD: through multiple exchanges at night while
the patient sleeps
Complications of Continuous Ambulatory Peritoneal Dialysis
• Peritonitis
o Most common complication of PD (mortality rate: 2.5-12.5%)
o Symptoms & signs: fever, abdominal pain, rebound tenderness
o Peritoneal fluid analysis: cloudy effluent suggests peritonitis
▪ Cell count: >100 WBC/mm3, with >50% neutrophils
▪ Gram stain: positive in 10-40% of culture-proven cases
▪ Organisms isolated: S. epidermidis (40%), Streptococcus
spp. (15-20%), gram-negative bacteria (15-20%), anaerobic
bacteria (5%), fungi (5%)
o Empiric therapy
▪ Few rapid exchanges of fluid lavaged to decrease number
of inflammatory cells in the peritoneum, with added heparin
(500-1000 units/L dialysate) to decrease fibrin clot formation
▪ First-generation cephalosporin can be mixed with dialysate
(500 mg/L: first exchange; 200 mg/L: subsequent changes)
▪ Penicillin-allergic patients: vancomycin 500 mg/L,
maintenance dose: 50 mg/dL per exchange
▪ Gram-negative coverage: add gentamicin 100 mg/L,
maintenance dose: 4-8 mg/L per exchange
o Most recommend treating for 7 days after the first negative
culture results, usually resulting in a total of 10 days of therapy
o Admission decisions: based on patient’s clinical appearance
o Parenteral antibiotics are not used
• Infections around a PD catheter
o Pain, erythema, swelling, & discharge around catheter exit site
o Most common bacteria: S. aureus, Pseudomonas aeruginosa
o Empiric therapy: oral first-generation cephalosporin or
ciprofloxacin for outpatient therapy
o Refer patients to their continuous ambulatory PD centers for
follow-up the next day
• Abdominal wall hernia (10-15% of PD patients)
o Immediate surgical repair of pericatheter hernias is common
because of the high risk of incarceration
ER Evaluation of Peritoneal Dialysis Patients
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
24. UREMIA | 117
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
25. RABIES
• Rapidly progressive, acute infectious disease of the CNS in humans
and animals that is caused by infection with rabies virus
• The infection is normally transmitted from animal vectors
• Rabies hass encephalitic and paralytic forms that progress to death
ETIOLOGY: Rabies virus
• Family Rhabdoviridae; Genus Lyssavirus; single-strand RNA virus
• Non-segmented, negative-sense (antisense) genome, encodes for:
o Nucleocapsid protein
o Phosphoprotein
o Matrix protein
o Glycoprotein
o Large polymerase protein
EPIDEMIOLOGY
• Rabies is a zoonotic infection that occurs in a variety of mammals
throughout the world except in Antarctica and on some islands
• Transmission: contaminated saliva of an infected host is passed to
a susceptible host, usually by the bite of a rabid animal
• Worldwide, most human rabies is transmitted from dogs in countries
with endemic canine rabies and dog-to-dog transmission
o Endemic canine rabies: ~59,000 human deaths annually (rural
populations and children most frequently affected)
o Endemic in wildlife species: bats, racoons, skinks, foxes
o Domestic animals: cats, dogs, cattle
• Transmission from non-bite exposures is relatively uncommon
o Contamination of mucous membranes (i.e., eyes, nose, mouth)
o Aerosol transmission during spelunking in bat-infested caves
o Exposure while working in the laboratory with rabies virus
o Infected organ transplantation (e.g., cornea, liver, kidney,
vascular graft, lung)
PATHOGENESIS
• Incubation period: 20-90 days (a few days or >1 year)
o Thought to be present at or close to the site of inoculation
o Shorter when the bite is near the head than on an extremity
• In muscles, the virus is known to bind to nicotinic acetylcholine
receptors on postsynaptic membranes & neuromuscular junction
• Rabies virus spreads centripetally along peripheral nerves toward
the spinal cord or brainstem via retrograde fast axonal transport
(~250 mm/d), with delays at intervals of ~12 hours at each synapse
• Once the virus enters CNS, it rapidly disseminates to other regions
of CNS via fast axonal transport along neuroanatomic connections
o Neurons are prominently infected, astrocytes unusual
• After CNS infection becomes established, there is centrifugal
spread along sensory and autonomic nerves to other tissues
o Salivary glands, heart, adrenal glands, skin
• Rabies virus replicates in acinar cells of salivary glands and is
secreted in saliva of rabid animals (vectors of the disease)
o No well-documented evidence for hematogenous spread
118 | 25. RABIES
PATHOLOGY
• Mild mononuclear inflammatory infiltration in the CNS
o Leptomeninges, perivascular regions, and parenchyma,
including microglial nodules called Babes nodules
• Degenerative neuronal changes usually are not prominent
o There is little evidence of neuronal death
o Neuronophagia is observed occasionally
• Pathologic changes are surprisingly mild in light of the clinical
severity and fatal outcome of the disease
• Negri body: most characteristic pathologic finding in rabies (75%)
o Eosinophilic cytoplasmic inclusions in brain neurons
o Composed of rabies virus proteins and viral RNA
o Commonly observed in Purkinje cells of the cerebellum and in
pyramidal neurons of the hippocampus
o Less frequently seen in cortical and brainstem neurons
o Not observed in all cases of rabies
• Lack of prominent degenerative neuronal changes has led to the
concept that neuronal dysfunction (rather than neuronal death) is
responsible for clinical disease in rabies
• Behavioral changes (aggressive behavior) not well understood
o May be related to infection of serotonergic neurons in brainstem
CLINICAL MANIFESTATIONS
• The disease generally presents as atypical encephalitis with
relative preservation of consciousness
Prodromal Features
• Nonspecific: fever, malaise, headache, nausea, vomiting
• Anxiety or agitation may occur
• Earliest specific neurologic symptoms: paresthesias, pain, or
pruritus near site of the exposure (≥1 occurs in 50-80% of patients)
o Wound has usually healed by this point
o Probably reflect infection with associated inflammatory changes
in local dorsal root or cranial sensory ganglia
Encephalitic Rabies (“furious rabies”; 80% of cases)
• Fever, confusion, hallucinations, combativeness, seizures
o May be seen in other viral encephalitides as well
• Autonomic dysfunction is common and may result in
o Hypersalivation
o Hyperthermia
o Tachycardia
o Hypertension
o Gooseflesh (piloerection)
o Cardiac arrhythmia
o Priapism
• Episodes of hyperexcitability are typically followed by periods of
complete lucidity that becomes shorter as the disease progresses
• Distinguished by early brainstem involvement
o Results in the classic features of:
▪ Hydrophobia (involuntary, painful contraction of diaphragm
& accessory respiratory, laryngeal, & pharyngeal muscles in
response to swallowing liquids)
▪ Aerophobia (same feature by stimulation from a draft of air)
▪ Foaming mouth: hypersalivation + pharyngeal dysfunction
o Probably due to dysfunction of infected brainstem neurons that
normally inhibit inspiratory neurons near nucleus ambiguous,
results in exaggerated defense reflexes that protect airway
o Brainstem dysfunction progresses rapidly, & coma (followed by
death) is rule unless prolonged course by supportive measures
▪ With such measures, late complications can include:
• Cardiac and/or respiratory failure
• Disturbances of water balance (SIADH, DI)
• Noncardiogenic pulmonary edema
• Gastrointestinal hemorrhage
• Cardiac arrhythmias may be due to dysfunction
affecting vital centers in the brainstem of to myocarditis
• Multiple-organ failure is common in patients treated
aggressively in critical care units
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Paralytic Rabies (“dumb rabies; 20% of cases) Rabies Virus-Specific Antibodies

• Muscle weakness predominates • Unimmunized: serum neutralizing antibodies are diagnostic
• Cardinal features of encephalitic rabies (hyperexcitability, • May not develop until late in the disease
hydrophobia, aerophobia) are lacking o Rabies virus infects immunologically privileged neuronal tissues
• Early and prominent flaccid muscle weakness, often beginning in • Detected within few days after onset of symptoms (5-14 days)
the bitten extremity and spreading to produce quadriparesis and o Some patients die without detectable antibodies
bilateral facial weakness • (+) CSF suggests rabies encephalitis, regardless of immunization
• Sphincter involvement is common • Questionable in patients who recover from their illness without
• Sensory involvement is usually mild developing serum neutralizing antibodies to rabies virus
• Commonly misdiagnosed as Guillain-Barré syndrome
• Generally survive a few days longer than those with encephalitic RT-PCR Amplification
rabies, but multiple-organ failure nevertheless ensues • Detection of rabies virus RNA is highly sensitive and specific
• Specimen: fresh saliva, skin biopsy, CSF, brain tissues
Death occurs due to a variety of complications: • RT-PCR with genetic sequencing: distinguish among rabies virus
• Pituitary dysfunction variants, permitting identification of probable source of an infection
• Seizures
• Respiratory dysfunction with progressive hypoxia Direct Fluorescent Antibody (DFA) Testing
• Cardiac dysfunction with dysrhythmias and arrest • Use of rabies virus antibodies conjugated to fluorescent dyes is
• Autonomic dysfunction highly sensitive & specific for rabies virus antigen in tissues
• Renal failure • Can be performed quickly and applied to skin biopsy and brain tissue
• Secondary bacterial infections • Skin biopsy: detected in cutaneous nerves at base of hair follicles

DIFFERENTIAL DIAGNOSIS
• Encephalitic rabies
o Herpes simplex encephalitis
o Arboviral encephalitis
o Anti-NMDA encephalitis
o Autoimmune encephalitis
o Postinfectious (immune-mediated) encephalitis
o Psychiatric disorders (rabies hysteria)
• Paralytic rabies
o Guillain-Barré syndrome
o Poliomyelitis
• Other considerations
o Tetanus
o Botulism
o Transverse myelitis
LABORATORY INVESTIGATIONS o Postvaccinal encephalomyelitis
• Most routine laboratory tests in rabies yield normal results or show o Intracranial mass lesions
nonspecific abnormalities (CBCs are usually normal) o Cerebrovascular accidents
• CSF analysis: mild mononuclear pleocytosis with mildly ↑ protein o Poisoning with atropine-like compounds
o Severe pleocytosis (>1000 WBC/μL) is unusual and should
prompt a search for an alternative diagnosis TREATMENT
• Imaging: exclude other diagnostic possibilities • No established treatment for rabies
o CT head scans: usually normal • Aggressive management with supportive care in critical care units
o MRI brain scans: signal abnormalities in brainstem or other • Palliative approach may be appropriate for many patients
gray-matter areas (variable & nonspecific)
• EEG: nonspecific abnormalities PROGNOSIS
• Important tests in suspected cases of rabies include those that may • Uniformly fatal
identify an alternative, potentially treatable diagnosis • Nearly always preventable after recognized exposures with
appropriate postexposure therapy during the early incubation period
DIAGNOSIS • Most patients die within several days of the onset of illness despite
• Rabies should usually be suspected based on clinical presentation aggressive care in a critical care unit
o Considered in patients presenting with acute atypical
encephalitis or acute flaccid paralysis, including those in
whom Guillain-Barré syndrome is suspected
o Important clues to diagnosis include:
▪ History of an animal bite or bat exposure
▪ Development of the pathognomonic signs of hydrophobia
and aerophobia (lack of hydrophobia is not unusual)
• Once rabies is suspected, rabies-specific laboratory tests should
be performed to confirm the diagnosis
o Diagnostically useful specimens: serum, CSF, fresh saliva,
nuchal skin biopsy, brain tissue (rarely obtained before death)
o Skin biopsy: from hairy skin at nape (demonstration of rabies
virus antigen in cutaneous nerves at the base of hair follicles)
• Negative antemortem rabies-specific laboratory tests never exclude
a diagnosis of rabies, and tests may need to be repeated after an
interval for diagnostic confirmation

25. RABIES | 119

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
PREVENTION
Postexposure Prophylaxis
• Based on exposure history and local epidemiologic information
o Healthy dogs, cats, or ferrets: confined & observed for 10 days
▪ Animal remains healthy: PEP not necessary
▪ Animal develops signs of rabies during observation period:
• Euthanized immediately
• Head transported to laboratory under refrigeration
• Rabies virus sought by DFA testing
• Viral isolation by cell culture and/or mouse inoculation
o Any animal other than a dog, cat, or ferret: euthanized
immediately & head submitted for laboratory examination
o In high-risk exposures and in endemic canine rabies areas:
rabies prophylaxis initiated without waiting for laboratory results
▪ If laboratory results are negative
• Animal’s saliva considered no rabies virus
• Immunization discontinued
▪ If animal escapes after exposure, consider it rabid
• PEP must be initiated
• Local Wound Care
o Essential; may greatly decrease the risk of rabies virus infection
o Should not be delayed, even if immunization is postponed
o Assess wounds for presence of a life-threatening condition
(arterial laceration or pneumothorax)
o Provide proper wound care
▪ Devitalized tissues should be debrided
▪ Tetanus prophylaxis
▪ Wound cleansing with soap and water
▪ Dilute solution of povidone-iodine (1 mL povidone-iodine in
9 mL water or normal saline)
▪ Antibiotics (if indicated) to prevent bacterial infection
▪ Rabies prophylaxis
• Active and Passive Immunization
o Rabies immune globulin (RIG) [Passive Immunity]
▪ Indication: previously unvaccinated persons (Category III)
▪ Schedule: immediately (Day 0) or within first 7 days
• After day 7, endogenous antibodies are being produced,
& passive immunization may be counterproductive
▪ Route: local infiltration at the site of the bite
• Entire dose of RIG (20 IU/kg)
• Any RIG remaining should be given IM at a distal site
• Caution when injecting into a tissue compartment (finger
pulp): excessive RIG can increase compartment
pressure & lead to necrosis
• Multiple/large wounds: diluted to obtain a sufficient
volume for adequate infiltration of all wound sites
• Involves mucous membrane: entire dose given IM
▪ Considerations:
• Rabies vaccine & RIG should never be administered at
the same anatomic site or with the same syringe
• If human RIG is unavailable, purified equine RIG can
be used in the same manner at a dose of 40 IU/kg
o Incidence of anaphylactic reactions and serum
sickness has been low with recent equine RIG
▪ Commercially available RIG in the US is purified from the
serum of hyperimmunized human donors
• Much better tolerated than equine-derived preparations
• Adverse effects uncommon: local pain, low-grade fever
• Contraindications: IgA deficiency, anti-IgA antibodies
120 | 25. RABIES
o Rabies Vaccines [Active Immunity]
▪ Highly immunogenic & remarkably safe
▪ 2 purified inactivated rabies vaccines
• Human diploid cell vaccine/HDCV (Imovax ®)
• Purified chick embryo cell vaccine/PCECV (RabAvert ®)
Route & Site Dose Schedule
Intramuscular (IM)
1 mL or
• Deltoid muscle Days 0, 3, 7, 14
0.5 mL
• Anterolateral thigh (<1 year old)
Intradermal (ID)
0.1 mL Days 0, 3, 7, 28
• 2 sites: deltoid & thigh
▪ Active antibody response requires approximately 7-10 days
to develop, and detectable rabies virus-neutralizing
antibodies generally persist for several years
▪ DO NOT:
• Administer via gluteal injections: may not always reach
the muscle; associated with rare vaccine failures
• Administer glucocorticoids & other immunosuppressive
medications: may interfere with the development of
active immunity UNLESS essential
▪ Side effects:
• Local: pain, erythema, edema, pruritus (10-90%)
• Systemic: fever, myalgias, headache, nausea,
abdominal pain, dizziness (5-40%)
• Serum sickness-like reactions (type III hypersensitivity):
~6% receiving booster doses of HDCV; occur 2-21 days
• Severe egg allergy: contraindication to use of PCECV
▪ Rabies prophylaxis should not be interrupted/discontinued
because of local or mild systemic adverse reactions
• Can be managed with anti-inflammatory & antipyretics
• Systemic allergic reactions are uncommon, but
anaphylaxis does occur rarely and can be treated with
epinephrine and antihistamines
▪ Routine measurement of serum neutralizing antibody titers
is not required, but titers should be measured 2-4 weeks
after immunization in immunocompromised persons
▪ Pregnancy is not a contraindication
WHO Postexposure Prophylaxis Guidelines
Category Degree of contact Action
• Touching or feeing animals
Category • Licks on intact skin (i.e., no exposure) NO prophylaxis
I • Casual contact with patient with signs &
symptoms of rabies
• Nibbling of uncovered skin
Category
• Minor scratches or abrasions without Immediate vaccination
II
bleeding (not in the head/neck area)
• Single/multiple transdermal bites/scratches
• Contamination of mucous membranes with
Category
saliva from licks
Immediate vaccination +
• Licks on broken skin, exposure to bats
III
• Wounds with spontaneous bleeding
rabies immunoglobulin
• All category II exposure in head/neck area
• Consumption of contaminated meat
Preexposure Rabies Vaccination
• Indications
o Occupational or recreational risk of rabies exposures
o Certain travelers to rabies-endemic areas
o Ex. veterinarians, animal handlers, field biologists, spelunkers,
missionaries, certain laboratory workers
• Schedule: Days 0, 7, and 21 or 28 (3 doses)
• Previously immunized individual: 2 booster doses (days 0 and 3)
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)

26. TETANUS
• Acute disease manifested by skeletal muscle spasm and autonomic
nervous system disturbance
• In any setting, established tetanus is a severe disease with a high
mortality rate (mortality rate of 35-40%)
DEFINITION
• Tetanus is diagnosed on clinical grounds (sometimes with
supportive laboratory confirmation of the presence of C. tetani)
• Probable tetanus (CDC): acute illness with muscle spasms or
hypertonia in the absence of a more likely diagnosis
• Neonatal tetanus (WHO): an illness occurring in a child who has
the normal ability to suck and cry in 1st 2 days of life but who loses
this ability between days 3-28 of life & becomes rigid & has spasms
• Maternal tetanus (WHO): tetanus during pregnancy or within 6
weeks after conclusion of pregnancy (birth, miscarriage, or abortion)
EPIDEMIOLOGY
• C. tetani is found throughout the world, and tetanus commonly
occurs where the vaccination coverage rate is low
o Approximately 100,000 cases per year worldwide
• In developed countries, the disease is seen occasionally in
individuals who are incompletely vaccinated
CLINICAL MANIFESTATIONS
• Tetanus is a rare disease in the developed world
• Persons >60 years of age are at greater risk of tetanus because
antibody levels decrease over time
• People who inject drugs (subcutaneous heroin injection or “skin-
popping”) are increasingly recognized as a high-risk group
ETIOLOGY
• Caused by a powerful neurotoxin produced by the bacterium
Clostridium tetani and is completely preventable by vaccination
• Clostridium tetani: motile, non-encapsulated, anaerobic, gram-
positive, spore-forming rod
o Spores: ubiquitous in soil and animal feces; highly resilient; can
survive on environmental surfaces for years
▪ Resist boiling and many disinfectants
▪ Found in many places, including skin/contaminated heroin
o Spores & bacilli survive in intestinal systems of many animals
o Produces 2 exotoxins
▪ Tetanolysin: facilitates growth of the bacterial population
▪ Tetanospasmin: powerful neurotoxin responsible for all
clinical manifestations of tetanus
• Highly potent (minimal lethal human dose: 2.5 ng/kg)
• Only those producing tetanospasmin can cause tetanus
• Spores/bacteria enters body through abrasions, wounds, or
umbilical stump (in neonates)
o Crushed/devitalized tissue, foreign body, or development of
infection favors growth of toxin-producing form of C. tetani
o Once in a suitable anaerobic environment, the organism grow,
multiple, and release tetanospasmin
• No puncture entry wound is found in 20-30% of cases
o Superficial abrasions to limbs: most common sites in adults
o Deeper infections (open fracture, abortion, or drug injection) are
associated with more severe disease and worse outcomes
o Infection of the umbilical stump in neonates
▪ From inadequate umbilical-cord care
▪ In some cultures, for example, the cord is cut with grass or
animal dung is applied to the stump
o Circumcision or ear-piercing also can result in neonatal tetanus
PATHOGENESIS
• Tetanospasmin undergoes retrograde transport into CNS
o Intra-axonally transported to motor nuclei of the cranial nerves
or ventral horns of the spinal cord
o Produced as a single 150-kDa protein that is cleaved to produce
▪ Heavy (100-kDa) chain
▪ Light (50-kDa) chain
▪ Linked by a disulfide bond and noncovalent forces
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Process Mechanism
Carboxy terminal of the heavy chain binds to
Toxin internalization specific membrane components in presynaptic α-
& uptake into nerves motor nerve terminals (both polysialogangliosides
& membrane proteins)
Transported in a carefully regulated pH-neutral
Retrograde transport
environment that prevents an acid-induced
pathway (carried
conformational change that would result in light-
proximally to the motor
chain expulsion into the surrounding cytosol
neuron body)
Escaping lysosomal degradation processes
Translocation across synapse to GABA-ergic presynaptic inhibitory
interneuron terminals (less clearly understood)
Prevents transmitter Light chain (zinc-dependent endopeptidase)
release and cleaves vesicle-associated membrane protein 2
blocks inhibitory (VAMP2, or synaptobrevin) necessary for
interneuron discharge presynaptic binding & release of neurotransmitter
End result: unregulated activity in the motor nervous system
• Similar activity in autonomic system accounts for characteristic
features of skeletal muscle spasm & autonomic system disturbance
o Increased circulating catecholamine levels in severe tetanus are
associated with cardiovascular complications
• Relatively little is known about processes of recovery from tetanus
o Recovery can take several weeks
o CNS sprouting may occur in tetanus
o Other evidence suggests toxin degradation as a mechanism
• Occur only after tetanus toxin reached presynaptic inhibitory nerves
o There may be little can be done to affect disease progression
• Tetanus results in generalized muscular rigidity, violent
muscular contractions, & autonomic nervous system instability
• Incubation period: <24 hours to >1 month
o Shorter incubation periods: severe disease & a poor prognosis
• Local tetanus
o Only isolated areas of the body are affected
o Only small areas of local muscle spasm/rigidity may be apparent
o Usually resolves completely after weeks to months
o May progress to the generalized form of the disease
o Approximately 1% of these cases are fatal
• Cephalic tetanus
o Follows injuries to the head or occasionally otitis media
o Involvement of the cranial nerves (poor prognosis)
▪ Pharyngeal or laryngeal muscles may spasm
▪ Consequent aspiration or airway obstruction
▪ Results in cranial nerve dysfunction (facial nerve)
• Generalized tetanus (about 80% of cases)
o Most common initial symptoms: trismus (lockjaw), muscle pain
and stiffness, back pain, and difficulty swallowing
o Nerves with short axons are involved first
▪ Symptoms in the facial muscles & jaw
▪ Progression to muscles of neck, trunk, & extremities
o The transition from muscle stiffness to rigidity leads to
▪ Trismus (lockjaw)
▪ Risus sardonicus (sardonic smile)
o As the disease progresses, muscle spasm develops
▪ Generalized muscle spasm can be very painful
▪ Spasms can last for 3-4 weeks
o Reflex convulsive spasms & tonic muscle contractions
▪ Dysphagia
▪ Opisthotonic flexing of arms
▪ Clenching of fists
▪ Extension of lower extremities
o Complications of tetanus
▪ Rhabdomyolysis
▪ Long-bone fractures from violent muscle contractions
▪ Tendon avulsions & crush fractures in strong spasm (rare)
▪ Aspiration pneumonia (50-70% of autopsy cases)
▪ Complete airway obstruction (laryngeal muscle spasms)
▪ Respiratory failure (spasms; most common cause of death)
o Mental status is normal (differentiates tetanus from others)
▪ Remain conscious & alert unless laryngospasm/contraction
of respiratory muscles results in respiratory compromise
o Recovery: regrowth of axonal nerve terminals (months)
26. TETANUS | 121
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Neonatal tetanus (a form of generalized tetanus)
o Develops in infants born to inadequately immunized mothers,
frequently after unsterile treatment of the umbilical cord stump
o Usual presentation: difficulty in feeding
o Weak, irritable, and have an inability to suck
o Symptoms are evident by the 2nd week of life
o The younger the infant at onset, the worse the prognosis
• Autonomic dysfunction
o Maximal during the 2nd week of severe tetanus
o Hypersympathetic state: tachycardia, labile hypertension,
profuse sweating, hyperpyrexia, increased urinary excretion of
catecholamines, episodes of bradycardia & heart block, GI
stasis, ↑ tracheal secretions, acute (high-output) renal failure
o Death due to cardiovascular events becomes the major risk
DIAGNOSIS
• Diagnosis of tetanus is based on clinical findings
• Culture of C. tetani from a wound provides supportive evidence
o May be cultured from wounds in absence of clinical disease
o May not be recovered in patients with documented tetanus
• Serum anti-tetanus IgG may also be measured in a sample taken
before the administration of antitoxin or immunoglobulin
o Levels >0.1 IU/mL (by standard ELISA) are deemed protective
and do not support the diagnosis of tetanus
o If levels are below this threshold, a bioassay for serum tetanus
toxin may be helpful, but a negative result does not exclude the
diagnosis and these levels are not generally performed
• PCR also has been used for detection of tetanus toxin, but its
sensitivity is unknown
DIFFERENTIAL DIAGNOSIS
• Generalized tetanus
o Strychnine poisoning
o Dystonic reactions to antidopaminergic drugs
o Malignant neuroleptic syndrome
o Serotonin syndrome
o Stiff person syndrome
o Peritonitis
o Rabies
• Cephalic tetanus
o Peritonsillar abscess
o Temporomandibular joint disease
• Neonatal tetanus
o Hypocalcemia
o Meningoencephalitis
TREATMENT
• Should not be delayed while laboratory tests are awaited
• Management strategies aim to neutralize remaining unbound toxin
and support vital functions until the effects of the toxin have worn off
• If possible, the entry wound should be identified, cleaned, and
debrided of necrotic material in order to remove anaerobic foci of
infection and prevent further toxin production
o Metronidazole (400 mg rectally or 500 mg IV every 6 hours for
7 days) is preferred for antibiotic therapy
o Alternative: penicillin (100,000-200,000 IU/kg per day), although
may exacerbate spasms & may increase mortality
o Failure to remove pockets of ongoing infection may result in
recurrent or prolonged tetanus
122 | 26. TETANUS
Tetanus Immunoglobulin (TIG)
• Neutralizes circulating tetanospasmin and toxin in the wound but not
toxin already fixed in the nervous system
• 2 preparations are available
o Human tetanus immune globulin (HTIG)
▪ Preparation of choice
▪ Less likely associated with anaphylactoid reactions
▪ Dose: 3000-5000 IU single IM dose, with a portion injected
around the wound
o Equine antitoxin
▪ Available widely; used in low-income countries
▪ After hypersensitivity testing: 10,000-20,000 U administered
IM as a single dose or as divided doses
• For postexposure prophylaxis
o Single dose of 250 units (4 units/kg in children) IM given in the
anterolateral thigh or deltoid
• For treatment of clinical tetanus
o 3000-6000 units IM administered in a separate syringe and
opposite the site of tetanus toxoid
o A portion of the dose is optimally given in and around the wound
• Give tetanus immunoglobulin before wound debridement
o Exotoxin may be released during wound manipulation
• Repeat doses of tetanus immunoglobulin are unnecessary because
the half-life is 28 days
Muscle Relaxants
• Spasms are controlled by heavy sedation with benzodiazepines
o Benzodiazepines: centrally acting inhibitory agents
o Diazepam is the preferred benzodiazepine
o Another option is midazolam, a water-soluble agent, as
continuous infusion if requiring large doses of benzodiazepines
• Chlorpromazine and phenobarbital are commonly used
• IV magnesium sulfate has been used as a muscle relaxant
• Disadvantage: doses necessary to control spasms also cause
respiratory depression
• Infusions of propofol also have been used successfully to control
spasms and provide sedation
Intensive Care
• Establish secure airway (tracheostomy) early in severe tetanus
o Tracheal secretions are increased in tetanus
o Dysphagia (pharyngeal involvement) + hyperactivity of laryngeal
muscles makes endotracheal intubation difficult
o Patients may need ventilator support for several weeks
• Ideally, patients should be nursed in calm, quiet environments
o Light and noise can trigger spasms
Neuromuscular Blockade
• Prolonged neuromuscular blockade aids in control of ventilation,
muscular spasms, secondary fractures, and rhabdomyolysis
• Succinylcholine can be given early for emergency airway control
• Vecuronium is a good option for prolonged blockade because of
minimal cardiovascular side effects
Treatment of Autonomic Dysfunction
• Magnesium sulfate reduces autonomic instability & muscle spasm
o Reduces urinary catecholamine excretion in severe tetanus
o Plasma concentration 2-4 mmol/L or titrated against
disappearance of the patella reflex
• Adrenergic blocking agents
o Short-acting β-blocker (esmolol) or a combined α- and β-
adrenergic blocking agent (labetalol)
• Morphine sulfate
o Reduces sympathetic α-adrenergic tone & central sympathetic
efferent discharge
o Produces peripheral arteriolar and venous dilatation
• Clonidine (central α2-receptor agonist)
o May reduce sympathetic hyperactivity that causes autonomic
dysfunction and thereby provide better control of crises

PROGNOSIS
• Recovery from tetanus may take 4-6 weeks
o Recovery is typically complete unless periods of hypoventilation
have been prolonged or other complications have ensued
• Incubation period & period of onset are of particular significance
o Rapid development of tetanus is associated with more severe
disease and poorer outcome
• Children & neonates have higher incidence of neurologic sequelae
o Neonates may be at increased risk of learning disabilities,
behavioral problems, cerebral palsy, and deafness
PREVENTION
• Tetanus is prevented by good wound care and immunization
• In neonates, use of safe, clean delivery and cord-care practices as
well as maternal vaccination are essential
• WHO guidelines for tetanus vaccination
o Primary course: 3 doses in infancy, boosters at 4-7 and 12-15
years of age, 1 booster in adulthood
o Catch-up schedules: 3-dose primary course with 4 weeks
between doses, followed by 2 boosters 6 months apart
o Complete primary course in childhood but no further boosters: 2
doses at least 4 weeks apart are recommended
• Standard WHO recommendations for prevention of maternal
and neonatal tetanus
o Previously unimmunized pregnant women: 2 doses of tetanus
toxoid at least 4 weeks apart
o High-risk areas (more intensive approach): all women of
childbearing age receiving a primary course along with
education of safe delivery and postnatal practices
• It is recommended that tetanus toxoid given with diphtheria
toxoid in a preparation with or without acellular pertussis:
o DTaP for children <7 years old
o Td for 7-9 years old
o Tdap for children >9 years old and adults
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
TETANUS IMMUNIZATION
• Patient who recover from tetanus must receive active immunization
o Infection does not confer immunity
o Vaccination is the only means of disease prevention
• Adsorbed tetanus toxoid (0.5 mL) IM at the time of presentation
and at 4 weeks and 6 months after injury
• Give a dose of Tdap during each pregnancy
o Irrespective of prior history of receiving Tdap
o To maximize maternal antibody response & passive antibody
levels in the newborn
o May be given at any point during pregnancy, with optimal timing
at 27-36 weeks of gestation unless treating a specific wound
o For women who have never received Tdap, it should be given
to the mother immediately postpartum
• Patients with HIV infection or severe immunodeficiency who
have contaminated wounds should also receive tetanus
immunoglobulin (TIG) regardless of tetanus immunization history
• Adverse reactions following tetanus immunization
o Erythema
o Induration
o Pain at injection site
• Local reactions are common and usually self-limited
• Exaggerated local reactions (Arthus reaction)
o Occur occasionally
o Extensive pain and swelling of the entire extremity
o Occur most often in adults with high serum tetanus antitoxin
levels who have received frequent doses of tetanus toxoid,
which is the reason this therapy is limited to 10-year intervals
• Contraindications to tetanus-diphtheria or Tdap
o History of serious allergic reaction (respiratory compromise or
cardiovascular collapse) to vaccine components
o History of encephalopathy (e.g., coma or prolonged seizures)
not attributable to an identifiable cause within 7 days of
administration of a pertussis vaccine
• Reasons to defer tetanus-diphtheria or Tdap include
o Guillain-Barré syndrome ≤6 weeks after a previous dose of
tetanus toxoid-containing vaccine
o Moderate to severe acute illness
o Unstable neurologic condition
o History of an Arthusx reaction to a tetanus toxoid-containing
vaccine administered <10 years previously
• If tetanus toxoid is contraindicated
o Consider passive immunization with tetanus immunoglobulin
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
26. TETANUS | 123
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
27. INCREASED INTRACRANIAL PRESSURE
PHYSIOLOGY
• Average intracranial volume: 1,700 mL
o Brain: 1,200-1,400 mL
o CSF: 70-160 mL (<10% of intracranial & intraspinal spaces)
o Blood: 150 mL
o Spinal subarachnoid space: 10-25 mL CSF
• CSF Flow
o Choroid plexuses: main sites of CSF formation
▪ Located in the floor of the lateral, 3rd, and 4th ventricles
▪ Average rate of CSF formation: ~20 mL/h (0.35 mL/min)
▪ Approximately 500 mL/d (renewed 4-5 times daily)
o Arachnoid villi: main site of CSF drainage
▪ Microscopic excrescences of arachnoid membranes that
penetrate dura & protrude into superior sagittal sinus & other
venous structures (pacchionian granulations or bodies)
▪ Thought to act as functional valves that permit unidirectional
bulk flow of CSF into the vascular lumen
• CSF Volume and Pressure
o Normal CSF pressure: 8 mmHg or 110 mmH2O
o Elevations in systemic arterial pressure: little or no increase of
pressure because of cerebral autoregulation
o Increased venous pressure: immediate effect on CSF pressure
by increasing blood volume in cerebral veins, venules & sinuses
▪ If jugular veins are compressed: rise in ICP transmitted to
lumbar subarachnoid space
▪ Valsalva maneuver, coughing, sneezing, & straining (↑
intrathoracic pressure): transmitted to jugular → cerebral &
spinal veins→ CSF compartment (intervertebral foramina)
▪ Mediastinal tumors (SVC obstruction) has the same effect
o Acidification of CSF acts as a potent cerebral vasodilator
▪ ↑ CBF & blood volume→ intracranial hypertension
▪ Hyperventilation (reduces PCO2) increases pH and cerebral
vascular resistance and thereby decreasing CSF pressure
INTRACRANIAL DYNAMICS
First Principle: Monro-Kellie doctrine
• Cranial cavity: has a fixed volume composed of brain tissue
(parenchyma), CSF, and blood vessels and intravascular blood
• Increase in one component must be accompanied by an equal and
opposite decrease in one or both remaining components
• Stage of compensation: volume of other compartments can be
reduced to avoid elevations in the ICP
Second Principle: CSF is produced at a constant rate (~20 mL/hr)
• Production is little affected by any intracranial backpressure
• CSF production continues unabated, even to lethal elevations of ICP
• Derangement of CSF dynamics almost always involves some
aspect of CSF obstruction along CSF pathways
• Only exceptions to the almost constant CSF production
o Excess: choroid plexus papilloma
o Decreased: gram-negative bacterial meningitis with ventriculitis
124 | 27. INCREASED INTRACRANIAL PRESSURE
Third Principle: CBF normally varies over a wide range
• Cerebral blood flow: 30-100 mL/100 g brain tissue per minute
o Depends on metabolic demand from neuronal activity within a
particular area of the brain
• Blood flow to any brain area generally exceeds demand by a wide
margin, so that oxygen extraction ratios are often low
• Cerebral autoregulation: CBF maintains perfusion despite wide
variations in systemic blood pressure (50-150 mmHg)
o Brain vasculature matches blood flow to metabolic demand
• Changes in PaCO2 shift the curve as indicated
o Traumatic brain injury: curve becomes more pronounced
(smaller changes in BP or PaCO2) and affects CBF dramatically
• If tissue demand exceeds autoregulation, or if CBF declines for
pathologic reasons, the first defense is to increase oxygen extraction
o 0.25 mL/g brain tissue/min: begins to experience dysfunction
o 0.15-0.20 mL/g brain tissue/min: reversible ischemia
o 0.10-0.15 mL/g brain tissue/min: infarction within a few minutes
Fourth Principle: Injured tissue swells
• Potential for a cascading injury by a vicious circle mechanism
• Cerebral perfusion pressure (CPP) [CPP = BP – ICP]
o Difference between ICP and mean BP within cerebral vessels
o ↑ ICP close to BP: widespread reduction in cerebral blood flow
▪ May result in global ischemia, widespread cerebral
infarction (like cardiac arrest), & ultimately brain death
o Brain edema (swelling) within closed cranium: further ↑ in ICP
with even further ↓↓ in CPP in a stage of decompensation
• When the capacity for autoregulation is exceeded or damaged so
that it can no longer play a role, CBF is linked directly to the CPP
Fifth Principle: Focal mass effect and its progression
• Complex anatomy of the cranial cavity
o Falx & tentorium: projections of folded dura that divide cavity:
▪ Supratentorial compartment (right and left)
▪ Infratentorial compartment (posterior fossa)
o Sphenoid wing: prominent, mostly bony ridge; separates:
▪ Anterior fossa containing the frontal lobe
▪ Middle fossa containing the temporal lobe
o Incisura: narrow opening that surrounds midbrain
▪ Only passage between the supratentorial & infratentorial
o Foramen magnum: only sizable opening from cranial cavity as
a whole (apart from small opening for cranial nerves & arteries)
• Rostrocaudal decay: reflects early and late stages of progression
o Focal distortion only
o Effacement of gyri and sulci
o Compression of the lateral (or other) ventricle
o Midline shift
o Subfalcine herniation
o Temporal lobe tentorial herniation
▪ 3rd nerve compression (unilateral dilated pupil)
▪ Obliteration of basal cisterns
▪ Midbrain compression
▪ Midbrain infarction, Duret hemorrhages (both pupils dilate,
with irreversible damage to midbrain)
o Further brainstem compression
▪ Loss of brainstem reflexes: flexor to extension posturing;
vestibulo-ocular & oculocephalic reflexes; corneal reflexes
▪ Medullary compression syndrome: respiratory reflexes;
vasomotor reflexes, Cushing reflex
o Foramen magnum herniation

ETIOLOGY OF INCREASED INTRACRANIAL PRESSURE
• Localized mass lesions with deformation of brain parenchyma
o Cerebral/extracerebral mass (brain tumor); cerebral infarction
with edema; traumatic contusion; parenchymal, subdural, or
extradural hematoma; or abscess
o Brain deformation is compartmentalized, or constrained by rigid
dural partitions surrounding compartment containing the mass
• Generalized brain swelling
o Ischemic-anoxic states, acute hepatic failure, hypertensive
encephalopathy, hypercarbia, Reye hepatocerebral syndrome
o Increase in pressure can reduce cerebral perfusion
o Tissue shifts are minimal: effect of addition of mass to the brain
is uniformly distributed throughout the cranial contents
• Increased venous pressure
o Cerebral venous sinus thrombosis
o Heart failure
o Obstruction of superior mediastinal or jugular veins
• Obstruction to the flow and absorption of CSF
o Hydrocephalus: obstruction within ventricles or in subarachnoid
space at the base of the brain
o Extensive meningeal disease from several potential causes
(infectious, carcinomatous, granulomatous, hemorrhagic)
• Increased CSF levels
o CSF volume expansion: meningitis, subarachnoid hemorrhage
o Increased CSF production: choroid plexus tumor
CLINICAL MANIFESTATIONS
• Normal ICP varies over a wide range (0-20 mmHg)
o Diffuse increased ICP: headache, nausea, vomiting, double
vision, obscuration of vision
• Papilledema
o Develops within 12-24 hours: brain trauma and hemorrhage
o If with coma: brain tumor or abscess (lesion of longer duration)
o May result in periodic visual obscurations: vision temporarily
fades or becomes gray, in combination with headache
o If prolonged, optic atrophy and blindness may follow
o Absence of papilledema does not exclude the presence of
increased intracranial pressure, particularly in the elderly
• False localizing signs (neurologic signs of “intracranial mass”): due
to displacement of brain tissue (not a direct effect of ↑ ICP)
Pupillary dilatations • Mass in medial temporal lobe compress CN III with
(CN III compression) little elevations of ICP (28-34 mmHg)
• Lateral rectus weakness & side-by-side diplopia,
initially worse on far vision or gaze directed toward
6th cranial nerve
the side of palsy
(abducens) palsy
• Due to diffusely distributed brain swelling,
hydrocephalus, meningitis, pseudotumor cerebri
Cushing’s triad • Hypertension, bradycardia, irregular respiration
Drowsiness • Impediment in global cerebral blood flow
• Coma: generally cannot be attributed to elevated ICP alone (only
at extremely high levels)
• Retains mental alertness with normal BP
25-40 mmHg • Unless there is countercurrent shift of brain tissue
that compresses the brainstem
40-50 mmHg • CBF diminish; results in loss of consciousness
Further elevations • Global ischemia and brain death
• Slowly growing lesions (raise ICP slowly): allow for compensation &
causes few clinical signs
• In infants and small children whose cranial sutures have not closed,
the head enlarges, and the eyes may bulge
• Patient with these symptoms should undergo an immediate head CT
and rapid neurosurgical evaluation
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
MONITORING INTRACRANIAL PRESSURE
• Indications: warn of impending deterioration in patients that:
o Cannot be examined because of induced paralysis or sedation
o Subjected to a procedure that risks further elevating ICP
o GCS 3-8 with abnormalities on CT scan
o No abnormality on CT but the patient has any 2 of:
▪ Age >40; posturing; systolic blood pressure <90 mmHg
o Not necessary if only drowsy or minimal mass effect on CT
• ICP & CPP: highly practical surrogates for CBF (easy to measure
continuously) with targets of:
o CPP: 60 mmHg (50-70 mmHg) and ICP: <20 mmHg
• Gold standard: ventricular catheter
o Directly coupled to the CSF compartment (best reflect
summated pressures within cranium)
o Advantages:
▪ Therapeutic drainage of CSF to reduce ICP
▪ Avoid excessive fluid administration
▪ Refine amount of osmotic agent & hypertonic saline used to
reduce pressure
▪ Establishes the ideal level of hyperventilation
o Complications: bacterial meningitis (3%)
MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE
General Measures
• Emergent intubation and ventilation
o “Crashing patient”: lethargic/obtunded with ↓ respiratory drive
(↑PaCO2) → cerebral vasodilation & worsening ↑ ICP
▪ Rapidly loses airway protection, becomes apneic, herniates
o Goal: reduce PaCO2 to ~35 mmHg
• Control incidental factors that are known to raise pressure
o Hypoxia, hypercarbia, hyperthermia, awkward head positions
that compress jugular veins, ↑ mean airway pressures (PPV)
o Treatment of brain edema and elevated ICP is governed by the
underlying disease (excision of a tumor, treatment of intracranial
infection, placement of a shunt, etc.)
• Avoid hyponatremia and serum hypoosmolarity
o Prevent water to enter the brain and increase its volume
o Diffusible solutes (5% dextrose in water, 0.5 normal saline, 5%
dextrose in 0.5 normal saline) are avoided (hypotonic solutions)
o Lactate Ringer solution (289 mOsm/L) is acceptable
o Normal saline (314 mOsm/L) ± dextrose, is ideal
Hyperosmolar therapy
• Basis: creates a water gradient (shifts water from brain to plasma)
o Effective means of rapidly reducing brain volume & lowering ICP
o Useful in urgent circumstances but diminishes effect in days
o Repeated use on a regular schedule can lead to a reduction in
headache & stabilization of some of deleterious effects of tumor
• Mannitol 20% 0.25-1 g/kg bolus given every 3-6 hours
o MOA: produces serum hyperosmolarity initially
▪ Causes diuresis that sustains hyperosmolality
▪ Secondarily causes hypernatremia and hypovolemia
o Targets: sodium >142 mmol/L & osmolarity of 290-315 mOsm/L
o Disadvantage: effect delayed by ~20 minutes & is transient
o Adverse effect: renal failure (>200 g/d) almost always reversible
• Hypertonic saline (3% given 150 mL bolus; 7.5% given 75 L bolus;
23% given approximately 30 mL)
o Comparable effect to mannitol in the treatment of increased ICP
o MOA: Raises sodium directly & expands intravascular volume
o Advantage: avoids severe dehydration because it increases
osmolarity directly rather than through diuresis
o Disadvantage: patients with poor cardiac output may be subject
to CHF in high volumes (use diuretics to mitigate this effect)
• Disadvantage of both: can produce hyperglycemic, hyperosmolar
state in diabetics, particularly in elderly & receiving corticosteroids
• Diuretic drugs (acetazolamide and furosemide)
o May be helpful in interstitial edema, pseudotumor cerebri
o MOA: creates hyperosmolar state & by reducing CSF formation
o Effects are usually mild and transient
27. INCREASED INTRACRANIAL PRESSURE | 125
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Hypocarbia by hyperventilation
• MOA: produces respiratory alkalosis & cerebral vasoconstriction
with a corresponding reduction in cerebral blood volume and ICP
o Single-step reduction in PCO2 typically ↓ ICP for ~20-40 minutes
• Indications: mainly in cases of head trauma with high ICP
o During intracranial surgery
o Acutely comatose from the mass effect of a tumor
• Disadvantage: effective for a limited period of time
o CSF pH equilibrates over hours by releasing NH4+ in choroid
plexus (cerebral blood volume returns to its previous level)

Glucocorticoids
• MOA: probably act directly on endothelial cells (↓ permeability)
o Shrink normal brain tissue, thus reducing overall ICP
• Advantage: beneficial effect on vasogenic edema associated with
tumors (primary & metastatic), sometimes beginning within hours
• Disadvantages:
o Does not improve the clinical outcome of severe head injury
▪ Dexamethasone also reduce vasogenic edema associated
with brain abscess and head injury, but their usefulness in
these cases and in large cerebral infarctions, contusions,
and hemorrhage is less clear
o No evidence for response in cytotoxic or cellular edema
• For brain tumors: dexamethasone 4 mg q6h
o A dose with meals and at bedtime usually suffices to suppress
headache and focal tumor signs
o Extremely high doses (≥100 mg/d) for a brief time: in patients
with large tumors and marked secondary edema

Blood pressure management

• Posttraumatic systemic hypertension within hours after head injury
o Sympathoadrenal response and elevation of blood pressure
recedes spontaneously in a matter of a few hours or days
• Elevated BP control must be balanced against
o Risk of reducing cerebral perfusion pressure
o Brief period of mild hypotension may provoke a cycle of cerebral
vasodilatation, ↑ cerebral blood volume, & ↑ ICP
• Avoid both severe hypertension and any degree of hypotension
o In lowering high levels of BP: diuretics, β-blockers, or ACEI
are used rather than agents that potentially dilate cerebral
vasculature (nitroglycerin, nitroprusside, hydralazine, CCBs)
o Hypotension: vasopressors (phenylephrine, norepinephrine)
• Goal: maintain CPP of 60-80 mmHg and previous blood pressure
o Evidence of organ failure from either hyper- or hypotension
(cardiac or renal ischemia) must also be considered
Surgical Decompression
• A renewed search for a late-occurring cerebral hemorrhage if:
o Patient did not respond to medical management
o Condition & vital signs begin to deteriorate
▪ Rising HR
▪ Rising or falling temperature
▪ Worsening mental status
▪ Hemiplegia
▪ Plantar reflexes more clearly extensor
• Ventriculostomy and/or craniectomy may be needed or definitive
decompression
o Greatly reduces mortality in traumatic brain injury or in cerebral
swelling from stroke
o Has been presumed that this is the result of a reduction of ICP
COMPLICATIONS OF INCREASED INTRACRANIAL PRESSURE
• Focal mass lesions cause shift and herniation
• Temporal lesions push the uncus medially and compress the
midbrain (uncal herniation)
o Posterior cerebral artery passes between the uncus and
midbrain and may be occluded, leading to an occipital infarct
o Oculomotor nerve may be compressed at end of tentorium,
leading to ophthalmoparesis with pupillary enlargement
• Masses higher up in the hemisphere can push the cingulate gyrus
under the falx cerebri (subfalcine herniation)
o Anterior cerebral artery branches run along the medial surface
of the cingulate gyrus and may be occluded in this case, leading
to medial frontal and parietal infarcts
• Diffuse increases in pressure in the cerebral hemispheres can
lead to central, or transtentorial, herniation
• Increased pressure in the posterior fossa can lead to upward
central herniation or downward tonsillar herniation through the
foramen magnum
• Uncal, transtentorial, and tonsillar herniation can cause direct
damage to the brainstem

References:
• Adams and Victor’s Principles of Neurology, 11 th edition (2019)
• Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 20 th edition (2017)
• Schwartz’s Principles of Surgery, 11th edition (2019)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)

126 | 27. INCREASED INTRACRANIAL PRESSURE


28. STROKE
STROKE (CEREBROVASCULAR ACCIDENT)
• Abrupt onset of a neurologic deficit that is attributable to a focal
vascular cause
• Stroke is generally defined as any disease process that interrupts
blood flow to the brain
EPIDEMIOLOGY
• Stroke is the second leading cause of death worldwide
o 6.2 million dying from stroke in 2015
• Declining among the affluent and rising among those with less
access to medical care
ANATOMY
• Vascular supply is divided into anterior & posterior circulations
o Clinical findings in stroke are determined by the location of the
lesion(s), but the degree of collateral circulation may cause
variations in the specific clinical symptoms and their severity
ETIOLOGY
• Ischemic strokes (87% of all strokes)
o Thrombosis of the cerebral vessels themselves
o Emboli from a proximal arterial source or the heart
o Hypoperfusion-related
• Hemorrhagic strokes
o Intracerebral (10% of all strokes): bleeding directly into the brain
▪ Clinically indistinguishable from ischemic infarction
▪ Distinct clinical entity in terms of management (higher levels
of morbidity and mortality)
▪ Headache, nausea, and vomiting often precede neurologic
deficit, & patient’s condition may quickly deteriorate
o Nontraumatic subarachnoid hemorrhage (3% of all strokes):
bleeding around the brain
▪ Characterized by a severe occipital or nuchal headache
▪ Recent sudden onset of a maximal-intensity headache
▪ Activities associated with a Valsalva maneuver (defecation,
sexual activity, weightlifting, or coughing, at stroke onset)
o Produces neurologic symptoms by
▪ Producing a mass effect on neural structures
▪ Toxic effects of blood itself
▪ Increasing intracranial pressure
• The final common pathway is altered neuronal perfusion
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
PATHOPHYSIOLOGY
• Acute occlusion of an intracranial vessel causes reduction in
blood flow to the brain region it supplies
o Flow reduction depends on collateral blood flow based on:
▪ Individual vascular anatomy (may be altered by disease)
▪ Site of occlusion
▪ Systemic blood pressure
o Neurons are exquisitely sensitive to changes in cerebral blood
flow and die within minutes of complete cessation of perfusion
▪ <20 mL/100 g tissue/min: ischemia without infarction unless
prolonged for several hours or days
▪ <16-18 mL/100 g tissue/min: infarction within an hour
▪ 0: death of brain tissue within 4-10 minutes
• Cerebral ischemia: reduction in blood flow more than few seconds
o Neurologic symptoms are manifest within seconds
▪ Neurons lack glycogen, so energy failure is rapid
o Ischemic penumbra: ischemic but reversibly dysfunctional
tissue surrounding a core area of infarction
▪ Favor apoptotic cellular death (cells die days to weeks later)
▪ Saving ischemic penumbra is the goal of revascularization
o Transient ischemic attack (TIA): clinical syndrome associated
with only transient symptoms brought about by ischemia with
subsequent restoration of blood flow before significant infarction
▪ Blood flow is quickly restored, brain tissue can recover fully,
and the patient’s symptoms are only transient
▪ Definition of TIA requires that all neurologic signs and
symptoms resolve within 24 hours without evidence of brain
infarction on brain perfusion imaging (MRI or CT)
▪ Eventually progress to infarction if no change in flow occurs
• Infarction or death of brain tissue
o Cessation of flow lasting for more than a few minutes
o Focal cerebral infarction occurs via 2 distinct pathways
▪ Necrotic pathway: cellular cytoskeletal breakdown is rapid,
due principally to energy failure of the cell
▪ Apoptotic pathway: cells become programmed to die
o Necrosis occurs by starving neurons of glucose & oxygen
o Stroke has occurred if the neurologic signs and symptoms last
for >24 hours or brain infarction is demonstrated
28. STROKE | 127
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
STROKE SYNDROMES
Anterior Cerebral Artery Infarction: uncommon (0.5-3% of all strokes)
• Left-sided lesion: akinetic mutism & transcortical aphasia (a
nonfluent aphasia with greatly reduced spontaneous speech, but
with retained auditory comprehension and repetition ability)
• Right-sided infarction: can result in confusion & motor hemineglect
• Unilateral occlusion: contralateral sensory and motor symptoms in
the lower extremity, with sparing of the hands and face
• Bilateral occlusion: combination of the above symptoms but was
particularly associated with mutism, incontinence, & poor outcomes
Middle Cerebral Artery Infarction: most commonly involved in stroke
• Typically presents with hemiparesis, facial plegia, & contralateral
sensory loss (face & upper extremity > lower extremity)
• Clinical findings can be quite variable, depending on exactly where
the lesion is located, and which brain hemisphere is dominant
o In right-handed patients and in up to 80% of left-handed
patients, the left hemisphere is dominant
• Dominant hemisphere: aphasia (receptive, expressive, or both)
• Nondominant hemisphere: inattention, neglect, extinction on
double-simultaneous stimulation, dysarthria without aphasia, and
constructional apraxia (difficulty in drawing complex 2D/3D figures)
• Regardless of side of infarction: homonymous hemianopsia & gaze
preference toward the side of the infarct
128 | 28. STROKE
Posterior Cerebral Artery Infarction (Distal Posterior Circulation)
• Symptoms: unilateral limb weakness, dizziness, blurry vision,
headache, dysarthria
• Signs: visual field loss, gait ataxia, unilateral limb ataxia, CN 7 signs,
nystagmus, vertigo, lethargy, sensory deficits
o Visual field loss: contralateral homonymous hemianopsia &
unilateral cortical blindness
▪ Thought to be specific for distal posterior circulation stroke
▪ Visual centers are supplied by posterior cerebral artery
o Light-touch and pinprick sensation deficits, loss of ability to read
(alexia) without agraphia, inability to name colors, recent
memory loss, unilateral 3rd nerve palsy, and hemiballismus
o Motor dysfunction, although common, is typically minimal, which
can keep some patients from realizing they have had a stroke
• Crossed neurologic deficits (e.g., ipsilateral cranial nerve deficits
with contralateral motor weakness) may indicate a brainstem lesion
Basilar Artery Occlusion (Middle Posterior Circulation)
• Symptoms: unilateral limb weakness, dysarthria, diplopia, headache
o Dysphagia, nausea/vomiting, dizziness, Horner’s syndrome:
positively correlated with basilar artery occlusion
• Signs: oculomotor signs, cranial nerve VII signs, Babinski sign
• Can also rarely cause locked-in syndrome
o Occurs with bilateral pyramidal tract lesions in the ventral pons
o Complete muscle paralysis except for upward gaze and blinking
• High risk of death and poor outcomes
Vertebrobasilar Infarction (Proximal Posterior Circulation)
• Symptoms: dizziness, nausea or vomiting, headache, dysphagia,
unilateral limb weakness, and unilateral cranial nerve V symptoms
• Signs: unilateral limb ataxia, nystagmus, gait ataxia, cranial nerve V
signs, limb sensory deficit, and Horner’s syndrome
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Cerebellar Infarction History

• Nonspecific symptoms: dizziness (± vertigo), nausea, vomiting, gait • Time of onset: last known time when the patient’s condition was at
instability, headache, limb ataxia, dysarthria, dysmetria, nystagmus, their bedside (i.e., “last known well” time)
hearing loss, intractable hiccups • Timing of symptom onset, presence of associated symptoms, and
• Mental status: vary from alert to comatose medical history may point toward a mechanism of stroke
• Clinical presentation & course can be difficult to predict History Mechanism of stroke
o Possible rapid deterioration secondary to increased brainstem Sudden onset of symptoms Embolic or hemorrhagic stroke
Thrombotic or hypoperfusion-
pressure caused by cerebellar edema Stuttering or waxing and waning deficit
related stroke
o Extremely close serial examinations (especially looking for gaze Valsalva maneuver → thunderclap
Ruptured cerebral aneurysm
palsy and altered mental status) and prompt neurologic and headache or sudden onset of symptoms
neurosurgical bedside consultations are needed Neck trauma or manipulation Cervical artery dissection
• Cerebellar edema: rapid deterioration with herniation • Thrombotic vs. embolic stroke
Thrombotic stroke Embolic stroke
Stuttering or waxing and Sudden onset of
Lacunar Infarctions Onset
waning deficit symptoms
• Caused by infarction of small penetrating arteries Hypertension Atrial fibrillation
• Signs/symptoms: pure motor/sensory deficits Risk factors Diabetes mellitus Valvular replacement
• Presentation is variable based on the location and size of the lesions Coronary atherosclerosis Recent MI
Distribution of Same vascular Different vascular
• Commonly associated with chronic hypertension and increasing age neurologic deficits distribution distributions
• Prognosis: more favorable than for other stroke syndromes • Quickly exclude as many stroke mimics as possible
• Ongoing complex partial seizures without tonic-clonic
Carotid & Vertebral Artery Dissection (“cervical artery dissection”) activity can on occasion mimic stroke
Seizure
• Uncommon entity (2.6 to 2.9 per 100,000 annually) • No convulsive activity occurred at onset usually
excludes seizure
• Major cause of stroke (~20%) in young adults and the middle-aged
Intracranial • May present with acute neurologic symptoms due to
• Risk factor: history of minor neck trauma days to weeks prior tumor hemorrhage, seizure, or hydrocephalus
o Manipulative therapy of the neck or sport-related trauma • May develop in patients without any prior history of
o Other associated conditions: hypertension, large-vessel migraine even after age 65
arteriopathies, history of migraine, connective tissue disease • Sensory disturbance is often prominent
• Sensory & motor deficits tend to migrate slowly across
• Symptoms: unilateral headache (68%), neck pain (39%), or face Acephalic
a limb, over minutes rather than seconds as with stroke
migraine
pain (10%), can precede other symptoms by hours to days
(migraine without • Favors diagnosis of migraine:
o New-onset headache or neck pain of unclear etiology: imaging head pain) o Cortical disturbance cross vascular boundaries
of the neck vessels is recommended as part of initial evaluation o Classical visual symptoms (scintillating scotoma)
• Diagnosis of migraine impossible until there have been
o Symptoms may be transient or persistent multiple episodes with no residual symptoms/signs &
• Time between neck pain & other neurologic symptoms: 14 days no changes on brain MRI
o If headache is the first symptom: median time of 15 hours • Fluctuating mental status changes without focal
• Carotid Artery Dissection neurologic findings
Metabolic • Prior stroke/brain injury: patient with fever/sepsis may
o Headache in frontotemporal region (variable quality & severity) encephalopathy manifest a recurrent hemiparesis (clears rapidly when
▪ May mimic subarachnoid hemorrhage (i.e., “thunderclap” infection is treated)
headache), temporal arteritis, or preexisting migraine o Metabolic process serves to “unmask” a prior deficit
o Partial Horner’s syndrome (miosis & ptosis): about 25% of
patients (sign accompanying other disorders besides stroke)
o Cranial nerve palsies: 12% of carotid artery dissections
o Can progress to cerebral ischemia or rarely, retinal infarction
• Vertebral Artery Dissection
o Symptoms: dizziness/vertigo (58%), headache (51-65%), neck
pain (46-66%)
▪ Both headache and neck pain can be unilateral or bilateral
▪ Headache: occipital, but can rarely present with pain on an
entire side of the head or in the frontal region
o Other symptoms/signs: unilateral facial paresthesia, dizziness,
vertigo, nausea/emesis, diplopia & other visual disturbances, Physical Examination
ataxia, limb weakness, numbness, dysarthria, & hearing loss • Assessment of airway, breathing, and circulation is the top priority
o Cervical radiculopathy (peripheral motor deficit at C5 level): rare • Next, the goals of examination are to
presentation (1%); can involve multiple levels & sensory findings o Confirm the diagnosis of stroke
o Untreated vertebral artery dissection may result in infarction in o Exclude stroke mimics
regions of the brain supplied by the posterior circulation o Identify comorbidities
• Fever should prompt an investigation of potential infection
APPROACH TO DIAGNOSIS o CNS infections (meningitis, encephalitis) may mimic a stroke
Recognition of Stroke o Infection such as aspiration pneumonia or a urinary tract
• Essential for use of acute treatment (thrombolysis/thrombectomy) infection may be a complication of the stroke
• Sudden onset of any of the following: o Fever dramatically worsen brain injury during ischemia, as does
o Loss of sensory and/or motor function on one side of the body hyperglycemia (glucose >11.1 mmol/L [200 mg/dL])
(~85% of ischemic stroke patients have hemiparesis) • Evaluate for meningismus, signs of emboli (Janeway lesions and
o Change in vision, gait, or ability to speak or understand Osler nodes), and bleeding diatheses (ecchymoses or petechiae)
o Sudden, severe headache • A funduscopic examination may identify signs of
• FAST acronym o Papilledema: suggesting a mass lesion, cerebral vein
o Facial weakness thrombosis, or hypertensive crisis
o Arm weakness o Preretinal hemorrhage: subarachnoid hemorrhage
o Speech abnormality • Assess for findings suggesting of possible cardiac or vascular
o Time disease, such as rales, and S3 gallop, or carotid bruit

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National Institutes of Health Stroke Scales [NIHSS])
• Most widely used scale for documenting the severity of a stroke
• 11-category (15-item) neurologic evaluation (score 0 to 42)
• Advantages: rapid (5 to 10 minutes); provides baseline score for
predicting patient outcomes
• Disadvantages:
o High interrater reliability
o Weighted toward the detection of anterior circulation strokes as
opposed to posterior circulation strokes
o Bias toward detection of left hemisphere strokes
• Important scoring rules for proper use of NIHSS:
o Score what you see, not what you think
o Score first response, not best response (except best language)
o Do not coach
130 | 28. STROKE
Brain Imaging
• Emergency non-contrast enhanced CT for suspected stroke
o Exclude intracranial bleeding, abscess, tumor, & stroke mimics
o Detect current contraindications to thrombolytics (e.g.,
“extensive regions of clear hypoattenuation”)
o Most readily available imaging study
o Only imaging study necessary prior to thrombolytics
o Disadvantage: infarct may not be seen reliably for 24-48 hours
• Diffusion-weighted MRI
o Superior to non-contrast-enhanced CT or other types of MRI in
the detection of acute infarction
o Reliably documents extent & location of infarction in all areas of
the brain, including the posterior fossa and cortical surface
o Identifies intracranial hemorrhage and other abnormalities
o Disadvantage: more expensive & time consuming than CT &
less readily available
• Vascular Imaging: CT angiography or MR angiography
o Can detect presence of intracranial large-vessel stenosis or
occlusion (important for therapeutic decisions)
o Recommended if patient is possible candidate for endovascular
therapy concurrently with the initial head CT
▪ Should not delay thrombotic administration
• Perfusion Studies: perfusion CT and diffusion-weighted MRI/fluid-
attenuated inversion recovery (FLAIR)
o Can be used to measure the size of the penumbra
o Guide further therapy for patients who
▪ Fall outside the time ranges for thrombolysis
▪ Time of symptom onset is unclear
o Not recommended for routine use in all stroke patients
TREATMENT (“Time is brain”)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Standard Medical Treatment IV Thrombolysis

• Fluids • Alteplase 0.9 mg/kg IV, maximum dose of 90 mg
o Dehydration can contribute to worsened outcomes secondary to o Administer 10% of the dose as a bolus over 1 minute
↑ blood viscosity, hypotension, renal impairment, and VTE o Remaining amount infused over 60 minutes
▪ Correct if present with IV crystalloid fluids
o For euvolemic patients, provide maintenance fluids
• Oxygen supplementation (keep oxygen saturation >94%)
o Not indicated in stroke, only in hypoxia
• Fever is associated with increased morbidity and mortality
o Due to fever-related inflammatory response, increased
metabolic demands, and free radical production
o Identify the source of fever and treat the underlying cause
o Should be treated with antipyretics and surface cooling
• Blood pressure control
o Hypotension & hypovolemia should be corrected with either
colloids or crystalloids to maintain organ perfusion
o Elevated BP should be reduced if
▪ >220/120 mmHg
▪ Malignant hypertension
▪ Concomitant myocardial ischemia
▪ >185/110 mmHg and thrombolytic therapy is anticipated
• Contraindication to thrombolytics if >185/100 mmHg
before and after thrombolysis (increased risk for
hemorrhagic transformation of ischemic stroke)
• If target arterial BP cannot be reached, patient is no
longer a candidate for thrombolytic therapy
o Routine lowering of blood pressure below the limits listed above
has the potential to worsen outcomes
o β1-adrenergic blocker (esmolol): lowers the HR to decrease
cardiac work and maintain BP when faced with the competing
demands of myocardium and brain

• Hyperglycemia
o Hypoglycemia & hyperglycemia are important stroke mimics
o Maintain blood glucose between 140-180 mg/dL (7.77-9.99
mmol/L) using an insulin infusion if necessary
o Avoid and treat hypoglycemia (<60 mg/dL [3.33 mmol/L])
• Brain edema
o 5-10% develop cerebral edema (obtundation or brain herniation)
o Peaks on 2nd or 3rd day; cause mass effect for ~10 days
o Larger infarct, greater likelihood of clinically significant edema
o Water restriction & IV mannitol may be used to raise serum
osmolarity, but hypovolemia should be avoided because this
may contribute to hypotension and worsening infarction
• Antiplatelet Therapy
o Oral (or by rectum if swallowing impairment is present) aspirin
300 mg within 24-48 hours after stroke onset
▪ No antiplatelet agent (including aspirin) should be given
within 24 hours of receiving thrombolytic therapy
▪ Benefit seems due mainly to reduction of recurrent stroke
▪ Cost-effective & adds no risk to outcome of ischemic stroke
o Contraindicated in acute hemorrhagic stroke
• Prevent common complications of bedridden patients
o Infections (pneumonia, urinary, skin)
o DVT & pulmonary embolism (heparin, compression stockings)

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Endovascular Therapy TRANSIENT ISCHEMIC ATTACK (TIA)

• Intra-arterial thrombolysis and mechanical clot disruption/extraction • May arise from emboli to the brain or from in situ thrombosis of an
• Potential advantages intracranial vessel
o Expanded treatment window o Occluded blood vessel reopens, & neurologic function restored
o Treatment for patients with non-time-based contraindications to • Risk of stroke after TIA is ~10-15% in the first 3 months, with most
IV thrombolysis events occurring in the first 2 days
o Ability to specifically evaluate the occluded vascular territory
o Use of lower total doses of thrombolytic drugs
o Possibility of mechanical clot disruption
• Although all eligible stroke patients should be considered for IV
thrombolysis as a first-line therapy, also consider emergent
consultation with a neurointerventionalist for adjunctive
endovascular therapy in eligible patients

Neuroprotection
• Concept of providing a treatment that prolongs the brain’s tolerance
tolerance to ischemia
• Mild theraputic hypothermia is a powerful neuroprotective
treatment in patients with cardiac arrest & is neuroprotective in
animal models of stroke
o Assoicated with improved neurologic outcomes in comatose
patients who survive cardiopulmonary arrest
o Efficacy has not been firmly established, and it may be
• Treatment: primarily focuses on prevention of subsequent stroke
associated with increased risk of pneumonia
o Antiplatelet agents: aspirin, clopidogrel, dipyridamole
o Anticoagulation: warfarin
Stroke Centers and Rehabiltiation
o Carotid endarterectomy: in TIA with medically treated high-
• Improves neurologic outcomes and reduces mortality
grade internal carotid artery lesions
• Early physical, occupational, and speech therapy
▪ Greatest surgical benefit within 2 weeks of TIA
o Educate patient & family about the patient’s neurologic deficit
▪ Alternative: carotid stenting (in patients <70 years old or with
o Prevent complications of immobility (e.g., pneumonia, DVT,
higher surgical risks)
pulmonary embolism, skin pressure sores, muscle contractures)
▪ Pneumatic compression stockings is of proven benefit in
PREVENTION OF STROKE AND TIA
reducing risk of DVT and is a safe alternative to heparin
• Identification and control of modifiable risk factors, and especially
o Provide encouragement & instruction in overcoming the deficit
hypertension, is the best strategy to reduce the burden of stroke
• Goal of rehabilitation
o Return patient home
o Maximize recovery by providing a safe, progressive regimen
suited to the individual patient
• Constrained movement therapy (immobilizing the unaffected size)
o Shown to improve hemiparesis following stroke, even years
after the stroke, suggesting that physical therapy can recruit
unused neural pathways

• Atherosclerotic Risk Factors

o Older age, DM, hypertension, tobacco smoking, abnormal blood
cholesterol (elevated LDL and/or low HDL)
o Risk of stroke is much greater in those with prior stroke or TIA
o Cardiac conditions: atrial fibrillation, recent MI
o Oral contraceptives and hormone replacement therapy
• Hypertension target BP: <130/80
• Statin therapy: atorvastatin 80 mg/d
• Tobacco smoking should be discouraged in all patients
• Diabetes prevention is likely the most effective strategy for primary
and secondary stroke prevention
• Antiplatelet Agents
o Low-dose daily aspirin
o ADP receptor antagonists: ticlopidine, clopidogrel
o Dual antiplatelet therapy: clopidogrel 300 mg load then 75 mg/d
+ aspirin 75 mg for the first 21 days
o Dipyridamole + aspirin
• Anticoagulation therapy and Embolic Stroke Prevention
o Goal: INR 2-3 (in chronic nonvalvular AF)
o Vitamin K antagonists: warfarin
o Novel oral anticoagulants (NOACs): dabigatran
o Oral factor Xa inhibitors: apixaban, rivaroxaban
o Clopidogrel + aspirin if cannot take anticoagulant medications

References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
• Adams and Victor’s Principles of Neurology, 11 th edition (2019)

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29. STATUS EPILEPTICUS MANAGEMENT

• Refers to continuous seizures or repetitive, discrete seizures with • Goal of treatment: seizure control as soon as possible and within
impaired consciousness in the interictal period 30 minutes of presentation
• A single seizure ≥5 minutes in length or ≥2 seizures without recovery • Initial management:
of consciousness between seizures o Attend to any acute cardiorespiratory problems or hyperthermia
• Situation in which the duration of seizures prompts the acute use of o Perform a brief medical and neurologic examination
anticonvulsant therapy (GCSE: seizures last >5 minutes) o Establish venous access
• A neurologic emergency, and treatment should be initiated in all o Send samples to laboratory to identify metabolic abnormalities
patients with continuous seizure activity lasting for >5 minutes • Examination, identification of potential causes, application of ABCs
(airway, breathing, circulation), & treatment all begin simultaneously
ETIOLOGY Focused history & PE Possible cause & subsequent injuries
• Occurs in patients with a history of seizures or as first epileptic event Administer normal saline
Avoid glucose-containing IV fluids
• Most common causes Establish large-bore IV access
(phenytoin is not compatible with
o Subtherapeutic antiepileptic levels glucose-containing solutions)
o Anticonvulsant withdrawal or noncompliance Bedside glucose
Administer glucose IV if hypoglycemia
o Preexisting neurologic conditions (CNS infection, CNS tumors, is suspected or confirmed
Oxygen, cardiac monitor, pulse Monitor cardiorespiratory status,
head trauma, stroke, refractory epilepsy) oximeter, end-tidal capnography especially during phenytoin infusion
o Acute stroke Airway protection, oxygenation, &
o Anoxia or hypoxia ventilation
o Metabolic abnormalities Endotracheal intubation in Short-acting paralytic agent: not mask
established status epilepticus ongoing seizure activity
o Alcohol or drug intoxication or withdrawal Continuous EEG monitoring after
paralytic agent use
PATHOPHYSIOLOGY Monitor temperature continuously Treat hyperthermia (passive cooling)
• As seizures surpass the 5-minute mark, dramatic changes occur at Urinary catheter Monitor urine output
To prevent aspiration
the cellular level that lead to a greatly diminished seizure threshold
If toxic ingestion is suspected as the
o Decreased expression & internalization of GABA receptors Nasogastric tube
cause of seizures, proceed with GI
o Increased expression of both glutamine & NMDA receptors decontamination (as appropriate)
o Blood-brain barrier is also compromised: CNS penetration of • Initial laboratory evaluation
potassium and albumin (both hyperexcitatory CNS chemicals) o Blood glucose
• After 5 minutes, seizures are: o Metabolic panel including calcium and magnesium
o Less likely to spontaneously terminate o Lactate
o Less likely to be controlled with antiepileptic drugs o If appropriate: pregnancy test, toxicology screen, &
o More likely to cause neuronal damage anticonvulsant levels
• GCSE is an emergency and must be treated immediately • Do not attempt lumbar puncture during status epilepticus
o Cardiorespiratory dysfunction, hyperthermia, and metabolic o If bacterial meningitis or encephalitis is suspected clinically, then
derangements can develop as a consequence of prolonged immediately start empiric antibiotic or antiviral therapy
seizures, and these can lead to irreversible neuronal injury • Radiographic studies, such as CT scan, will usually need to be
o CNS injury can occur even when paralyzed with neuromuscular delayed until seizures are controlled
blockade but continues to have electrographic seizures

CLINICAL MANIFESTATIONS
Generalized convulsive status epilepticus (GCSE)
• Obvious when the patient is having overt seizures
• After 30-45 minutes of uninterrupted seizures, signs may become
increasingly subtle
o Mild clonic movements of only fingers
o Fine, rapid movements of the eyes
o Paroxysmal tachycardia, hypertension, pupillary dilation
• EEG should be performed to rule out ongoing status epilepticus if:
o Patient stops having overt seizures, yet remains comatose
o Paralyzed with neuromuscular blockade in the process of
protecting the airway

Nonconvulsive status epilepticus

• Patient is comatose or has fluctuating abnormal mental status or
confusion, but no overt seizure activity is present
• Diagnosis is challenging and is typically made by EEG
• Findings suggestive of nonconvulsive status epilepticus
o Prolonged postictal period after a generalized seizure
o Subtle motor signs such as twitching, blinking, and eye deviation
o Fluctuating alterations in mental status
o Unexplained stupor and confusion

Subtypes Description
Generalized convulsive Persistent, generalized electrographic
status epilepticus (GCSE) seizures, coma, and tonic-clonic movements
Persistent absence seizures or focal seizures
Nonconvulsive status
with confusion or partially impaired
epilepticus
consciousness, & minimal motor abnormalities

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Anticonvulsant Drugs in Status Epilepticus

• Drugs most often used in the therapy: benzodiazepines, (lorazepam,
midazolam, diazepam) & phenytoin/fosphenytoin
• Benzodiazepines
o Used in patients with continuous or very frequent seizures
o Temporarily control the seizures prior to more specific agents
o IV lorazepam: initial agent of choice if IV access is available
▪ More effective than phenytoin or phenobarbital as first-line
▪ Dose: 2-4 mg IV
▪ Adverse effects: respiratory depression & hypotension
• Young children
• Intake of alcohol, barbiturates, narcotics, sedatives
▪ Equal efficacy with diazepam 5-10 mg in controlling SE
• Lorazepam has a slightly slower onset (3 vs. 2 mins) but
a significantly longer duration of action (12-24 hours vs.
15-60 minutes), & associated with fewer recurrences
o If with difficult IV access & emergent need for seizure control:
▪ IM midazolam: similar safety and effect as IV lorazepam
▪ Children: rectal diazepam gel or buccal midazolam
• In established status epilepticus, follow benzodiazepines with
longer-acting antiepileptic agents (within 20 min of diagnosis)
o Fosphenytoin (water-soluble prodrug of phenytoin)
▪ Converted to phenytoin in the plasma
▪ Similar onset, effectiveness, & cardiac effects as phenytoin
▪ Dosing: phenytoin equivalents to prevent confusion
• Loading dose: 20 phenytoin equivalents/kg infused at
150 phenytoin equivalents/min over 10-15 minutes
▪ Advantages: Refractory Status Epilepticus
• Much fewer infusion-site reactions due to the lack or • Persistent seizure activity despite IV administration of adequate
propylene glycol and ethanol as the diluents amounts of 2 antiepileptic agents and usually exceeds 60 minutes
• May be infused quickly (preferred over phenytoin) • Develops in 31% of patients with status epilepticus
• Can also be given IM, which may be useful if the patient • Treatment: propofol, midazolam, & barbiturates given as infusions
does not have IV access o Adverse effects: hypotension, sometimes requiring concomitant
o Phenytoin vasopressor use, and frequently require intubation
▪ Loading dose: 20 mg/kg IV (doses >1000 mg often required) • Propofol
• Infused <20 mg/min (taking about 1 hour to administer) o Widely used, lipophilic, general anesthetic
due to myocardial depression (propylene glycol diluent) o Dose: 2-10 mg/kg/h infusion, titrated up to seizure cessation
• Rate may be increased to 50 mg/min during status o Advantage: short half-life allowing for quicker neurologic
epilepticus as long as hypotension does not develop recovery after seizure control is achieved
▪ Monitoring: cardiac monitor with blood pressure assessment o Disadvantage: at higher doses (>40 mg/kg/h), patients are at
• During infusion: every 5-15 minutes increased risk for hemodynamic instability including hypotension
• After infusion: every 15 minutes for 1 hour as well as propofol infusion syndrome
▪ Disadvantages: • Midazolam
• Should not be mixed with glucose-containing IV fluid o Dose: 0.05-0.40 mg/kg/h, titrated up to seizure cessation
• Should not be given IM due to erratic absorption o Advantage: easily titrated, infusible benzodiazepine
▪ Adverse effects: infusion-site reactions, hypotension, o Disadvantage: can accumulate in peripheral soft tissues in renal
cardiac dysrhythmias (stop, then restart at lower rates) insufficiency, leading to prolonged recovery period
▪ Contraindications: 2nd or 3rd degree AV blocks • Barbiturates (phenobarbital 20 mg/kg IV or pentobarbital)
o Valproic acid (dose: 20-40 mg/kg IV) o May be considered as 3rd-line drugs in patients in uncontrolled
▪ Effective but has more serious side effects seizures despite doses of benzodiazepines and other agents
▪ Black box warning for hepatic failure and pancreatitis o Disadvantages:
▪ Should not be administered along with phenytoin ▪ Patients in refractory SE may not respond to barbiturates
o Levetiracetam (dose: 20-60 mg/kg IV) ▪ Respiratory depression & hypotension are more common,
▪ Effective, quick to administer, few interactions & side effects at higher doses or when diazepam or lorazepam is given
▪ Precise MOA is unknown; may inhibit voltage-dependent • Ketamine (N-methyl-D-aspartate receptor antagonist)
Ca2+ channels & facilitate GABA inhibitory transmission o Considered as a 3rd-line agent in refractory status epilepticus
o Lacosamide (dose: 200 mg IV given over 15 minutes) o Dose: 0.5-4.5 mg/kg bolus or 5 mg/kg/h infusion
▪ Potential alternative for status epilepticus with limited o Advantage: helps block the hyperexcitatory pathway, which is
availability and limited data on its use thought to be a greater culprit in refractory status epilepticus

PROGNOSIS
• Mortality dramatically increases with delayed diagnosis or initiation
of treatment, particularly:
o Nonconvulsive status epilepticus
o Age >60 years
o Patients with no documented seizure disorder

References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
• Harrison’s Principles of Internal Medicine, 20th edition (2018)
• Adams and Victor’s Principles of Neurology, 11 th edition (2019)

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30. SPINAL CORD COMPRESSION • Main features of transverse damage at each level of spinal cord
PATHOPHYSIOLOGY • Quadriplegia & weakness of diaphragm: upper cervical cord
• Weakness and reflex loss
• In a healthy spine, the spinal cord and nerve roots are suspended in Cervical o C5-C6: biceps
CSF, free of mechanical compression cord o C7: finger and wrist extensors and triceps
o C8: finger, and wrist flexion
• Pathologic processes that can lead to CSF space impingement and • Horner’s syndrome (miosis, ptosis, hypohidrosis): any level
neural compression • Sensory level: trunk & by the site of midline back pain
o Hypertrophic degeneration of intervertebral discs & facet joints o T4: nipples
o T10: umbilicus
o Expansion of epidural masses (tumors & abscesses) Thoracic
• Paralysis + leg weakness + bladder & bowel dysfunction
Cord
o Subluxation (i.e., slippage) of adjacent vertebral bodies o T9-T10: paralyze lower abdominal muscles
▪ Beevor’s sign: upward movement of umbilicus when abdominal
▪ Reduces area of central canal & neural foramina wall contracts
Myelopathy Radiculopathy • Lesions at L2-L4
• Due to reduced central canal area • Due to reduced neural foraminal area o Paralyze thigh flexion & adduction
• Compression of spinal cord: disturbance of • Compression of nerve roots: o Weaken knee extension
Lumbar
cord function disturbance of root function o Abolish patellar reflex
Cord
• Dysfunction may be secondary to • Characteristic features • Lesions at L5-S1
o Direct effects of compression o LMN signs/symptoms o Paralyze only foot & ankle, knee flexion, & thigh extension
o Cord ischemia (reduced perfusion) ▪ Hyporeflexia o Abolish the ankle jerks (S1)
o Repeated cord trauma ▪ Atrophy • Conus medullaris (tapered caudal termination of the spinal cord; sacral
• Lead to demyelination of corticospinal tracts ▪ Weakness & single coccygeal segments) syndrome
(long descending motor tracts): UMN o Sensory disturbances o Bilateral saddle anesthesia (S3-S5)
signs/symptoms ▪ Numbness/tingling sensations o Prominent bladder & bowel dysfunction (urinary retention and
▪ Hyperreflexia (paresthesias) incontinence with lax anal tone) & impotence
▪ Spasticity ▪ Burning sensations Sacral o Absent bulbocavernosus (S2-S4) & anal (S4-S5) reflexes
▪ Weakness (dysesthesias) Cord/ o Muscle strength is largely preserved
• Also cause damage to dorsal columns ▪ Shooting (radicular) pain Conus • Cauda equina (nerve roots from lower cord) syndrome
(ascending proprioception, vibration, & two- Medullaris o Low back and radicular pain
point discrimination) o Asymmetric leg weakness and sensory loss
o Loss of proprioception makes fine motor o Variable areflexia in the lower extremities
tasks and ambulation difficult o Relative sparing of bowel and bladder function
• Myelopathy and radiculopathy often present together in diseases • Mass lesions in lower spinal canal: mixed clinical picture of both cauda
equina and conus medullaris syndromes
that involve the central canal and the neural foramina
o Lower motor neuron dysfunction at the level of disease
Special Patterns of Spinal Cord Diseases
o Upper motor neuron dysfunction below that level
• Most fiber tracts (posterior columns & spinocerebellar & pyramidal
tracts) are situated on the side of body they innervate
APROACH TO DIAGNOSIS
• Afferent fibers for pain & temperature sensation ascend in the
Distinguishing Compressive from Noncompressive Myelopathy
spinothalamic tract contralateral to the side they supply
• First priority: exclude treatable compression of cord by a mass lesion
• Ipsilateral weakness (corticospinal tract) & loss of joint position and
o Common causes: tumor, epidural abscess or hematoma, Brown- vibration sense (posterior column)
herniated disk, spondylitic vertebral pathology Sequard • Contralateral loss of pain and temperature sense (spinothalamic
Hemicord tract) 1-2 levels below the lesion
Warning signs Syndrome • Segmental signs are unilateral
• Neck or back pain
• Partial forms more common than the fully developed
Malignancy or abscess • Bladder disturbances
• Selective damage to gray matter nerve cells & crossing
• Sensory symptoms that precede
spinothalamic tracts surrounding central canal
development of paralysis
• Lesion in the cervical cord
Spinal subluxation, hemorrhage, &
Myelopathy without antecedent symptoms o Arm weakness out of proportion to leg weakness
noncompressive causes (infarction) Central Cord
o “Dissociated” sensory loss:
• Once compressive lesions have been excluded, noncompressive Syndrome
▪ Loss of pain & temperature sense over shoulders, lower neck,
upper trunk (cape distribution)
causes of acute myelopathy intrinsic to the cord are considered ▪ Preservation of light touch, joint position, & vibration sense
o Vascular, inflammatory, and infectious etiologies • Spinal trauma, syringomyelia, intrinsic cord tumors
• Infarction of cord due to occlusion/diminished flow
Anterior Spinal
• Bilateral destruction at several levels that spares posterior columns
Determining the Level of Lesion Artery
• All spinal cord functions (motor, sensory, autonomic) are lost below
Syndrome
• Hallmark of a spinal cord lesion: presence of a horizontally defined • Striking exception of retained vibration and position sensation
level below which sensory, motor, & autonomic function is impaired • Interrupt decussating pyramidal tract fibers to the legs, which cross
caudal to those of the arms: weakness of the legs (crural paresis)
Sensory loss (loss of • Unilateral lesion: 1-2 segments higher Foramen • Compressive lesions near the foramen magnum
pinprick or cold o Due to the course of 2nd-order sensory fibers Magnum o “Around the clock” pattern (may begin in any 4 limbs): weakness
sensation): damage (DRG → ascend 1-2 levels crossing anterior to Syndrome of ipsilateral shoulder & arm → ipsilateral leg → contralateral leg
to spinothalamic tract central canal → opposite spinothalamic tract) → contralateral arm
• Suboccipital pain spreading to the neck and shoulders
on the opposite side • Bilateral lesion: at the same level
• Radicular pain is often prominent
• Upper motor neuron syndrome Extramedullary
• Early sacral sensory loss & spastic weakness in legs with
Motor impairment: lesions: lie
o Paraplegia or quadriplegia incontinence due to the superficial location of corresponding sensory
transection of outside cord &
o Heightened deep tendon reflexes & motor fibers in spinothalamic and corticospinal tracts
corticospinal & other compress spinal
o Babinski signs • Extradural masses: generally malignant
motor tracts cord or its
o Spasticity vascular supply • Intradural masses: generally benign (neurofibroma being a common
Autonomic • Absent sweating below the implicated cord level cause); long duration of symptoms
• Poorly localized burning pain rather than radicular pain
disturbances • Bladder, bowel, and sexual dysfunction Intramedullary
• “Sacral sparing”: spare sensation in perineal & sacral areas (reflects
• Segmental signs: uppermost level of a spinal cord lesion lesions: within
laminated configuration of spinothalamic tract with sacral fibers
the substance of
corresponding to disturbed motor or sensory innervation by an outermost)
the cord
• Corticospinal tract signs appear later
individual cord segment
o Can also occur with focal root or peripheral nerve disorders
▪ Segmental signs + signs of long tract damage = myelopathy
A band of altered sensation at the
Hyperalgesia or hyperpathia
upper end of the sensory disturbance
Transverse section through the spinal
In muscles innervated by one or
Fasciculations or atrophy cord, composite representation,
several segments illustrating the principal ascending (left)
Muted/absent deep tendon reflex May be noted at this level and descending (right) pathways. The
• “Spinal shock”: limbs initially may be flaccid rather than spastic with lateral and ventral spinothalamic tracts
severe and acute transverse lesions ascend contralateral to the side of the
body that is innervated. C, cervical; D,
o Lasts for several days, rarely for weeks distal; E, extensors; F, flexors; L,
o May be mistaken for extensive damage to the anterior horn cells lumbar; P, proximal; S, sacral; T,
over many segments of the cord or for an acute polyneuropathy thoracic.

30. SPINAL CORD COMPRESSION | 135

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
NEOPLASTIC SPINAL CORD COMPRESSION
Epidural Mass Lesions
• In adults, most neoplasms are epidural in origin
• Etiology: metastases to the adjacent vertebral column
o Reflects the high proportion of bone marrow in the axial skeleton
o Almost any malignant tumor can metastasize to spinal column
▪ Breast, lung, prostate, kidney, lymphoma, myeloma
o Thoracic spinal column is most commonly involved
▪ EXCEPT prostate & ovarian cancer (lumbosacral column)
• Probably from spread through Batson’s plexus, a
network of veins along the anterior epidural space
o Retroperitoneal neoplasms (lymphomas or sarcoma)
▪ Enter spinal canal laterally through intervertebral foramina
▪ Produce radicular pain with signs of weakness that
corresponds to the level of involved nerve roots
• Initial symptom of spinal metastasis: pain
o Quality: aching & localized or sharp & radiating
o Typically worsens with movement, coughing, or sneezing
o Characteristically awakens patients at night
o A recent onset of persistent back pain, particularly if in the
thoracic spine (which is uncommonly involved in spondylosis),
should prompt consideration of vertebral metastasis
o Rarely, pain is mild or absent
• Imaging: should be obtained in suspected spinal cord compression
o (+) radiculopathy but (-) myelopathy: defer for 24-48 hours
o MRI: excellent anatomic resolution of the extent of spinal tumors
▪ Able to distinguish malignant lesions from other masses
(epidural abscess/hemorrhage, tuberculoma, lipoma)
• Infections of the spinal column (osteomyelitis): often
cross the disk space to involve adjacent vertebral body
▪ Imaging of entire length of spine is important to define extent
• ~40% of patients with cord compression at one level
have asymptomatic epidural metastases elsewhere
▪ T1-weighted MRI: vertebral metastases are usually
hypointense relative to a normal bone marrow signal on
▪ Gadolinium contrast enhancement: may deceptively
“normalize” the appearance of the tumor by increasing its
intensity to that of normal bone marrow
o Plain spine X-ray & radionuclide bone scans have limited roles
▪ Cannot identify 15-20% of metastatic vertebral lesions
▪ Fail to detect paravertebral masses that reach the epidural
space through the intervertebral foramina
• Treatment
o Glucocorticoids (dexamethasone)
▪ 10 mg IV: before an imaging study if there is a clinical
suspicion of cord compression
▪ 4 mg every 6 hours orally: continued until definitive
treatment (radiotherapy and/or surgical decompression)
o Radiotherapy (30-40 Gy administered in 8-10 fractions)
▪ Alone: effective even for some radioresistant metastases
▪ Surgery + radiotherapy: more effective than radiotherapy
alone if single area of spinal cord compression
▪ Good response to therapy in ambulatory at presentation
▪ Treatment usually prevents new weakness, & some
recovery of motor function occurs in up to ⅓ of patients
▪ Paraplegia/quadriplegia for >12 hours do not improve
• >48 hours: substantial motor recovery is poor
▪ Recurrence becomes increasingly likely beyond 2 years and
can be managed with additional radiotherapy
▪ Stereotactic radiosurgery: can deliver high doses of focused
radiation with similar response to traditional radiotherapy
• Used particularly for patients with traditionally
radioresistant tumors or requiring re-irradiation
o Biopsy of epidural mass: if no history of underlying cancer
o Surgical decompression: laminectomy/vertebral body resection
▪ If cord compression worsens despite radiotherapy
▪ Maximum-tolerated radiotherapy dose previously delivered
▪ Vertebral compression fracture/spinal instability
136 | 30. SPINAL CORD COMPRESSION
Intradural Extramedullary (IDEM) Lesions (slow-growing and benign)
• Etiology: meningiomas & neurofibromas account for most
o Occasional cases: chordoma, lipoma, dermoid, or sarcoma
o Meningiomas: posterior to thoracic cord or near foramen
magnum (arise from meninges anywhere along spinal canal)
o Neurofibromas: benign tumors of nerve sheath that typically
arise from the posterior root (when multiple: neurofibromatosis)
• Symptoms: radicular sensory symptoms followed by an
asymmetric, progressive spinal cord syndrome
• Therapy: surgical resection
Primary Intramedullary Tumors (uncommon)
• Present as central cord or hemicord syndromes (cervical region)
• Symptoms: poorly localized burning extremity pain & sacral sparing
• Adults: ependymoma, hemangioblastoma, low-grade astrocytoma
o Ependymoma: complete resection (microsurgical techniques)
o Astrocytoma: debulking helpful (often slowly growing lesions)
• Secondary (metastatic) intramedullary tumors also occur
o Advanced metastatic disease (infrequent as brain metastases)
SPINAL EPIDURAL ABSCESS
• Midline back or neck pain, fever, and progressive limb weakness
o Prompt recognition may prevent permanent sequelae
o Aching pain: over the spine or in a radicular pattern
▪ Duration prior to presentation: ≤2 weeks
o Fever is typically but not always present + ↑ WBC, ESR, CRP
o As abscess expands, further spinal cord damage results from
venous congestion and thrombosis
o Once weakness & other signs of myelopathy appear,
progression may be rapid and irreversible
• Risk factors: impaired immune status (HIV, DM, renal failure,
alcoholism, malignancy), IV drug abuse, skin/soft tissue infections
• Etiology
o Most cases: Staphylococcus aureus (including MRSA)
o Gram-negative bacilli, Streptococcus, anaerobes, fungi
o Tuberculosis (Pott’s disease)
• Spread
o Hematogenous spread (⅔ of epidural infections)
▪ Skin (furunculosis)
▪ Soft tissue (pharyngeal or dental abscesses; sinusitis)
▪ Deep viscera (bacterial endocarditis)
o Direct extension of a local infection to the subdural space
▪ Vertebral osteomyelitis, decubitus ulcers, lumbar puncture,
epidural anesthesia, spinal surgery
• MRI: localizes abscess & excludes other causes of myelopathy
• Blood cultures: positive in >1/2 of cases (direct aspiration of the
abscess at surgery is often required for a microbiologic diagnosis)
• Lumbar puncture: only in encephalopathy or other clinical signs
leads to an associated meningitis (in <25% of cases)
o A high cervical tap is sometimes the safest approach
o CSF abnormalities in epidural & subdural abscess: pleocytosis
with predominance of PMN, ↑ protein, & ↓ glucose level
o Responsible organism not cultured unless with meningitis
• Treatment: decompressive laminectomy with debridement + long-
term antibiotic treatment
o Surgical evacuation: prevents development of paralysis
▪ May improve or reverse paralysis in evolution
▪ Unlikely to improve deficits of more than several days
o Broad-spectrum antibiotics: started empirically before surgery
then modified based on culture results; continued for 6-8 weeks
▪ Vancomycin 15-20 mg/kg q12h for MRSA, streptococcus
▪ Ceftriaxone 2 g q24h for gram-negative bacilli
▪ Metronidazole 30 mg/kg/d divided into q6h (anaerobes)
o Long-term systemic & oral antibiotics can be used if
▪ Surgery is contraindicated
▪ Fixed paraplegia/quadriplegia unlikely to improve in surgery
o Surgical management remains the treatment of choice unless
abscess is limited in size and causes few or no neurologic signs
• Prognosis: with prompt diagnosis and treatment of spinal epidural
abscess, up to ⅔ of patients experience significant recovery
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

SPINAL EPIDURAL HEMATOMA

• Hemorrhage into the epidural (or subdural) space
• Symptoms: acute focal or radicular pain followed by variable signs
of a spinal cord or conus medullaris disorder
• Predisposing conditions: therapeutic anticoagulation, trauma,
tumor, blood dyscrasias
• In rare cases, may complicate lumbar puncture/epidural anesthesia
o Because of risk of hemorrhage, lumbar puncture should be
avoided in severe thrombocytopenia or other coagulopathies
• MRI & CT: confirm clinical suspicion & delineate extent of bleeding
• Treatment: prompt reversal of underlying clotting disorder + surgery
o Surgical decompression: substantial recovery, especially in
patients with some preservation of motor function preoperatively

HEMATOMYELIA
• Hemorrhage into the substance of the spinal cord
• Causes: trauma, intraparenchymal vascular malformation,
vasculitis (polyarteritis nodosa/SLE), bleeding disorders, neoplasms
• Symptoms: acute painful transverse myelopathy
• With large lesions, extension into subarachnoid space results in
subarachnoid hemorrhage
• Diagnosis: MRI or CT
• Therapy is supportive
o Surgical intervention not useful EXCEPT vascular malformation
▪ Spinal angiography & endovascular occlusion
▪ Surgery: evacuate clot & remove underlying vascular lesion

References:
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
• Schwartz’s Principles of Surgery, 11th edition (2019)
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)

30. SPINAL CORD COMPRESSION | 137

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
31. VAGINAL BLEEDING IN PREGNANCY
BLEEDING IN THE FIRST HALF OF PREGNANCY
ABORTION
• Spontaneous/induced termination of pregnancy before fetal viability
• Pregnancy termination or loss <20 weeks’ gestation or with a fetus
delivered weighing <500 g
• Early pregnancy loss: nonviable, intrauterine pregnancy with either
an empty gestational sac or a gestational sac containing an embryo
or fetus without fetal heart activity within first 126/7 weeks of gestation
Etiology
• Fetal Factors: approximately half have a chromosomal abnormality
o Trisomies 13, 16, 18, 21, 22
o Monosomy X (45,X): Turner syndrome
o Triploidy: hydropic or molar placental degeneration
• Maternal Factors
Infect fetoplacental unit by blood-borne transmission
Infections or locally through genitourinary infection/colonization;
uncommonly cause early abortion
Medical disorders DM, obesity, thyroid disease, SLE
Therapeutic doses of radiation, methotrexate,
Cancer
abdominopelvic radiotherapy or chemotherapy
Surgeries Complicated surgeries, abdominal trauma
Nutrition Obesity
Social and Chronic & heavy use of legal substances (alcohol),
behavioral factors cigarette smoking, heavy caffeine intake (~500 mg)
Occupational and Bisphenol A, phthalates, polychlorinated bisphenols,
environmental dichlorodiphenyltrichloroethane (DDT), sterilizing
factors agents, x-rays. antineoplastic drugs, nitrous oxide
• Paternal Factors: increasing paternal age
Pathogenesis
• >80% occur within the first 12 weeks of gestation
• Demise of embryo/fetus precedes spontaneous expulsion
• Death is accompanied by hemorrhage into the decidua basalis
o Adjacent tissue necrosis → uterine contractions → expulsion
• An intact gestational sac is usually filled with fluid
Spontaneous Abortion Clinical Classification
• Threatened Abortion
o Bloody vaginal discharge/bleeding + closed cervical os
o May be accompanied by suprapubic discomfort, mild cramps,
pelvic pressure, or persistent low backache
▪ Bleeding: most predictive risk factor for pregnancy loss
o Diagnosis
▪ Serum β-hCG: 1500-2000 by 4.5 weeks
▪ TVS: gestational sac ± subchorionic hemorrhage
o Management: bed rest, paracetamol (relieve discomfort)
• Incomplete Abortion
o Partial/complete placental separation & dilation of cervical os
o <10 weeks: fetus and placenta are frequently expelled together,
but later, they deliver separately
o Tissue may remain in uterus or partially extrude through cervix
o Management: completion curettage, misoprostol, expectant
• Complete Abortion
o Complete expulsion of entire pregnancy (closed cervical os)
o History of heavy bleeding, cramping, and passage of tissue
o TVS: minimally thickened endometrium without gestational sac
• Missed Abortion
o Dead products retained in uterus with closed cervical os
o TVS: check for viability (fetal heart tone)
o Management: dilatation & curettage
• Inevitable Abortion
o Preterm premature rupture of membranes (PPROM) at a
previable gestational age (spontaneous or invasive procedure)
o Sterile speculum examination: gush of vaginal fluid pooling
o ± uterine contractions or infections (termination is typical)
o Management: expectant management (spontaneous passage)
138 | 31. VAGINAL BLEEDING IN PREGNANCY
ECTOPIC PREGNANCY (Tubal Pregnancy)
Epidemiology
• ~95% of ectopic pregnancies: ampulla (most frequent site, 70%);
isthmic (12%); fimbrial (11%); interstitial (2%)
• 5% of nontubal: ovary, peritoneal cavity, cervix, prior cesarian scar
Risks: abnormal fallopian tube anatomy
• Prior ectopic pregnancy
• STD/tubal infection: salpingitis, peritubal adhesions, endometritis
• Assisted reproductive technology: atypical implantations (cornual,
abdominal, cervical, ovarian, heterotopic pregnancy)
• Contraceptive method failures: tubal sterilization, copper and
progestin-releasing IUDs, progestin-only contraceptives
Pathophysiology
• Because fallopian tube lacks submucosal layer, fertilized ovum
promptly burrows through epithelium
o Zygote comes to lie near/within muscularis, which is invaded by
rapidly proliferating trophoblasts
o Embryo/fetus often absent or stunted
• Outcomes: tubal rupture, tubal abortion, pregnancy failure
o Rupture: invading expanding conceptus & associated
hemorrhage can tear rents in the fallopian tube
▪ Usually burst spontaneously but may occasionally rupture
following coitus or bimanual examination
o May pass out distal FT: distal implantations are favored
▪ Hemorrhage may cease & symptoms eventually disappear
• Can persist as long as products remain in tube
▪ Blood slowly trickles from tubal fimbria into the peritoneal
cavity and typically pools in the rectouterine cul-de-sac
▪ Occlusion of fimbriae: fallopian tube may gradually become
distended by blood, forming a hematosalpinx
▪ Aborted fetus implants on peritoneal surface & becomes
abdominal pregnancy
o Pregnancy failure with spontaneous reabsorption
Clinical Manifestations
• Unruptured: symptoms and signs are often subtle or even absent
o Classic triad: misses menses, pain, vaginal bleeding/spotting
• Tubal rupture
o Severe lower abdominal & pelvic pain (sharp, stabbing, tearing)
o Abdominal palpation: tenderness
o Bimanual pelvic examination: cervical motion tenderness
o Posterior vaginal fornix may bulge from blood in the rectouterine
cul-de-sac, or a tender, boggy mass may be felt beside uterus
o Uterus can also be slightly enlarged due to hormonal stimulation
o Symptoms of diaphragmatic irritation (neck or shoulder pain)
especially on inspiration: hemoperitoneum
• Vaginal spotting or bleeding (60-80%)
o Can lead to significant intraabdominal hemorrhage
o Moderate bleeding: no change in VS, slight rise in BP, vasovagal
response with bradycardia and hypotension
o ↓ BP & ↑ pulse: continued bleeding & significant hypovolemia
o Vasomotor disturbances: from vertigo to syncope
• Women with ectopic tubal pregnancy mas pass a decidual cast
o Entire sloughed endometrium taking form of endometrial cavity
Differential Diagnosis of Abdominal pain in pregnancy
• Uterine conditions: miscarriage, infection, degenerating or enlarging
leiomyomas, round-ligament pain
• Adnexal disease: ectopic pregnancy; hemorrhagic, ruptured, or
torsed ovarian masses; salpingitis; tuboovarian abscess
• Nongynecologic: appendicitis, cystitis, renal stone, gastroenteritis
Diagnosis
• CBC: even after substantial hemorrhage, Hb/Hct: slight reduction
o After acute hemorrhage: trending decline in Hb/Hct over several
hours is more valuable index of blood loss than initial level
o Varying levels of leukocytosis up to 30,000/μL (~50%)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

• Serum β-hCG Medical Management

o Discriminatory level (DL): ≥1500 mIU/mL or ≥2000 mIU/mL • Patient Selection
o Above DL but (-) IUP: ectopic pregnancy vs complete abortion o Asymptomatic, motivated, and compliant
o Below DL: serial β-hCG level assays identify patterns that o Hemodynamically stable
indicate either growing or failing IUP (rechecked 48 hours later) o Low initial serum β-hCG level (<1000 mIU/mL)
▪ Declining pattern: failing IUP o Small ectopic pregnancy size (<3.5 cm)
▪ Delay is balanced against the risk of rupture o Absent fetal cardiac activity
• Transvaginal sonography (TVS) • Methotrexate (MTX): folic acid antagonist
o Endometrial Findings: uterine vs. ectopic pregnancy o Tightly binds to dihydrofolate reductase, blocking the reduction
▪ Intrauterine gestational sac visible between 4.5-5 weeks of dihydrofolate to tetrahydrofolate (active form)
▪ Yolk sac: 5-6 weeks o De novo purine and pyrimidine synthesis is halted, which leads
▪ Fetal pole with cardiac activity: 5.5-6 weeks to arrested DNA, RNA, and protein synthesis
• Trilaminar endometrial pattern o Highly effective against rapidly proliferating tissue (trophoblast)
• Anechoic fluid collections: o Adverse effects: bone marrow, GI mucosa, respiratory epithelial
o Pseudogestational sac: fluid collection between
Ectopic damage; directly toxic to hepatocytes and is renally excreted;
endometrial layers; conforms to cavity shape
pregnancy potent teratogen (craniofacial and skeletal abnormalities and
o Decidual cyst: anechoic area within endometrium but
remote from canal & often at endometrial-myometrial fetal-growth restriction); excreted in breast milk and may
border; decidual breakdown prior decidual cast formation interfere with neonatal cellular metabolism
Uterine • Early gestational sac: anechoic sac eccentrically located o Given with folinic acid (leucovorin) to blunt BM depression
pregnancy within one of the endometrial stripe layers
o Adnexal Findings
• Extrauterine yolk sac, embryo, fetus (13%): if FT
& ovaries visualized & identified, then an ectopic
Adnexal mass pregnancy is confirmed
separate from • Hyperechoic halo or tubal ring surrounding an
ovary anechoic sac (20%)
• Inhomogeneous adnexal mass (60%):
hemorrhage within the ectopic sac
• Placental blood flow within the periphery of the
Ring of fire (color
complex adnexal mass
Doppler flow)
• Can also be seen with corpus luteum cyst
o Hemoperitoneum
▪ Anechoic or hypoechoic fluid initially collects in the
dependent retrouterine cul-de-sac, and then additionally
surrounds the uterus as it fills the pelvis
▪ As much as 50mL of blood can be seen in the cul-de-sac Surgical Management
▪ With significant intraabdominal hemorrhage, blood will track • Laparoscopy: preferred unless hemodynamically unstable
up the pericolic gutters to fill Morison pouch near the liver • Salpingostomy: used to remove a small unruptured pregnancy
(accumulated volumes reaching 400-700 mL) o Linear incision on antimesenteric border of FT, products extrude
▪ Peritoneal fluid + adnexal mass = highly predictive & removed, & incision left unsutured (secondary intention)
▪ Ascites from ovarian or other cancer is a notable mimic o Salpingotomy: essentially same procedure except incision is
• Laparoscopy closed with delayed-absorbable sutures
o Direct visualization of the fallopian tubes and pelvis • Salpingectomy: tubal resection for both ruptured and unruptured
o Permits a ready transition to definitive operative therapy o To minimize the rare recurrence of pregnancy in the tubal stump,
complete excision of the fallopian tube is advised

GESTATIONAL TROPHOBLASTIC DISEASE

• Encompass a group of tumors typified by abnormal trophoblast
proliferation (trophoblasts produces human chorionic gonadotropin)
• Histological division
o Hydatidiform moles: presence of villi
▪ Excessively edematous immature placentas
▪ Complete hydatidiform mole: benign
▪ Partial hydatidiform mole: benign
▪ Invasive mole: malignant
o Nonmolar trophoblastic malignant neoplasms: lack villi
▪ Choriocarcinoma
▪ Placental site trophoblastic tumor
▪ Epithelioid trophoblastic tumor

Hydatidiform Mole
• Classic histological findings of molar pregnancy: trophoblast
proliferation and villi with stromal edema
• Complete mole: abnormal chorionic villi; grossly appear as a mass
of clear vesicles (vary in size; often clusters from thin pedicles)
• Partial molar pregnancy: has focal and less advanced hydatidiform
changes and contains some fetal tissue
• Both forms of moles usually fill the uterine cavity, but they rarely may
be tubal or other forms of ectopic pregnancy
• Risk factors: age and prior hydatidiform mole
o Women at both extremes of reproductive age

31. VAGINAL BLEEDING IN PREGNANCY | 139

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Pathogenesis: from chromosomally abnormal fertilizations
• Clinical Findings
o Amenorrhea for 1-2 months: precede diagnosis
o As gestation advances, symptoms tend to be more pronounced
with complete compared with partial moles
o Uterine bleeding (varies from spotting to profuse hemorrhage):
untreated molar pregnancies
▪ May precede spontaneous molar abortion, but more often,
it follows an intermittent course for weeks to months
▪ More advanced moles with considerable concealed uterine
hemorrhage, moderate iron-deficiency anemia develops
o Nausea and vomiting may be significant
o Physical findings: uterine growth more rapid than expected
▪ Enlarged uterus is comparatively softer
▪ Fetal heart motion is absent with complete moles
▪ Complete mole: ovaries can be fuller & cystic from multiple
theca-lutein cysts (ovarian overstimulation by ↑↑ hCG)
o Thyrotropin-like effects of hCG: ↑ serum free T4; ↓ TSH
o Severe preeclampsia, eclampsia: advanced molar pregnancy
• Diagnosis
Complete mole Partial mole
• ↑ above expected for AOG
• “Hook effect”: excessive β-
β-hCG hCG oversaturate urine • ↑ expected for AOG
assay’s targeting Ab (falsely ↓
reading); use serum β-hCG
• “Snowstorm” appearance:
• Thickened, multicystic
echogenic uterine mass +
Sonography placenta;
numerous anechoic cystic
• (+) fetus/ fetal tissue
spaces; (-) fetus/amniotic sac
• Management: Molar Pregnancy Termination
o Molar evacuation by suction curettage
o Preoperative cervical dilatation with an osmotic dilator is
recommended if the cervix is minimally dilated
o Others: hysterectomy with ovarian preservation (complete
moles who have finished childbearing)
Gestational Trophoblastic Neoplasia
• Malignant forms of GTD; develop weeks/years following pregnancy
o Invasive mole
o Choriocarcinoma
o Placental site trophoblastic tumor
o Epithelioid trophoblastic tumor
• ½: hydatidiform mole, ¼: miscarriage/tubal pregnancy, ¼:
preterm/term pregnancy
• Clinical Findings
o Irregular bleeding: uterine subinvolution; continuous or
intermittent, with sudden and sometimes massive hemorrhage
o Intraperitoneal hemorrhage: myometrial perforation from
trophoblastic growth
o In some women, lower genital tract metastases are evident
o In others: distant metastases with no trace of uterine tumor
• Diagnosis, Staging, and Prognostic Scoring
o Serum β-hCG, then diagnostic curettage
o Uterine size is assessed along with careful examination for
lower genital tract metastases (bluish vascular masses)
o Once diagnosis is verified, search for local disease and
metastases: CBC, liver and renal function, TVS, chest CT scan
or radiograph, brain and abdominopelvic CT or MR
• Treatment: chemotherapy
140 | 31. VAGINAL BLEEDING IN PREGNANCY
BLEEDING IN THE SECOND HALF OF PREGNANCY
ABRUPTIO PLACENTA
• Separation of the placenta (partially or totally) from its implantation
site before delivery
• Premature separation of the normally implanted placenta
• Frequency: 0.5% or 1 in 200 deliveries
Etiopathogenesis
• Initiated by hemorrhage into decidua basalis
o Decidua splits, leaving a thick layer adhered to myometrium
• Process begins as a decidual hematoma and expands to cause
separation and compression of the adjacent placenta
o Abruption likely begins with rupture of a decidual spiral artery
and then an expanding retroplacental hematoma
o External hemorrhage: bleeding typically insinuates itself
between membranes & uterus, ultimately escaping to cervix
o Concealed hemorrhage: less often, blood is retained between
detached placenta & uterus, leading to delayed diagnosis
▪ Likelihood of DIC is elevated: ↑ pressure within intervillous
space by expanding retroplacental clot forces more
placental thromboplastin into maternal circulation
• When clinically suspected, an abruption is seen on freshly delivered
placenta as a circumscribed depression on the maternal surface
o Usually measure a few centimeters in diameter and are covered
by dark, clotted blood
• Traumatic abruption
o External trauma (usually from motor vehicle accidents or
aggravated assault) can cause placental separation
o Fetomaternal hemorrhage is more common because of
concomitant placental tears or “fractures”
Clinical Findings and Diagnoses
• Sudden abdominal pain, vaginal bleeding, uterine tenderness
• Other findings: frequent contractions, persistent hypertonus
Complications
• Hypovolemic shock secondary to massive & torrential hemorrhage
• Consumptive coagulopathy/disseminated intravascular coagulation
• Couvelaire uterus: uteroplacental apoplexy (myometrial
hemorrhages leading to uterine atony)
• End-organ injury: AKI; Sheehan syndrome (pituitary apoplexy)
Management
• Prompt resuscitation with blood + crystalloid is begun to replace
blood lost from retroplacental and external hemorrhage
• Emergency cesarian section: living viable-aged fetus and with
vaginal delivery not imminent
• Vaginal delivery: if the fetus has died or if it is not considered
sufficiently mature to live outside the uterus
o May NOT be preferable even with a dead fetus in:
▪ Brisk hemorrhage that cannot be successfully managed by
vigorous blood replacement
▪ Obstetrical complications that prohibit vaginal delivery
• Close observation: if diagnosis of abruption is uncertain and the
fetus is alive and without evidence of compromise

PLACENTA PREVIA
• A placenta that is implanted somewhere in the lower uterine
segment, either over or very near the internal cervical os
Classification
• Placenta previa: placenta cover internal os partially/completely
• Low-lying placenta: implantation in lower uterine segment is such
that the placental edge lies within a 2-cm wider perimeter around os
Risk Factors
• Demographic factor
o Maternal age
o Multiparity
o Cigarette smoking
o Uterine leiomyomas
• Clinical factors
o Prior cesarian deliveries
o Prior uterine incision and placenta previa
o Abnormally elevated maternal serum α-fetoprotein (MSAFP)
o Assisted reproductive technology (ART)
Clinical Features
• Painless sentinel bleeding: begins without a warning and without
pain or contractions
o When uterine body remodels to form lower uterine segment,
internal os dilates & implanted placenta inevitably separates
o Bleeding is augmented by inherent inability of myometrial fibers
in lower uterine segment to contract & constrict torn vessels
o Frequently continues after placental delivery
o There may be lacerations in the friable cervix and lower segment
that becomes problematic following manual removal of a
somewhat adhered placenta
Complications
• Morbidly adherent placentas: frequent and serious complication
o Abnormally firm placental attachment derives in part from poorly
developed decidua that lines the lower uterine segment
o Previa overlying a prior cesarian incision conveys a particularly
high risk for morbidly adherent placenta
• Coagulation defects: rare complications
o Placental thromboplastin (incites intravascular coagulation) is
presumed to readily escape through the cervical canal rather
than be forced into the maternal circulation
Diagnosis
• Clinical examination using the double set-up technique
o A finger is passed through the cervix and the placenta palpated
o Done in OR & with preparations for immediate cesarian delivery
o Even the gentlest examination can cause torrential hemorrhage
o Rarely necessary because placental location can almost always
be ascertained sonographically
• Transabdominal Sonography: placenta clearly overlies the cervix
or lies away from the lower uterine segment
• Transvaginal Sonography: most accurate method of assessment
o If the placental location remains in question
o Safe even when there is bleeding
Management
• Close observation: if fetus is immature & active bleeding subsides
o Discharge instruction: “pelvic rest”
• Scheduled cesarian delivery: for near term & not bleeding
o Elective delivery at 36-37 weeks of gestation
o Suspected morbidly adherent placenta: 34-35 weeks
o Low transverse cesarian section (LTCS) preferred
o Classical incision (vertical laparotomy): if anteriorly located
except if prior CS is LTCS (employ the same scar)
• Peripartum hysterectomy: if more conservative methods fail and
bleeding is brisk, especially in an abnormally adherent plasma
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
MORBIDLY ADHERENT PLACENTA (ACCRETE SYNDROMES)
• Aberrant placentation characterized by abnormally implanted,
invasive, or adherent placenta
Pathophysiology
• Abnormal placental adherence to myometrium due to:
o Partial or total absence of decidua basalis
o Imperfect development of the fibrinoid or Nitabuch layer
• Microscopically, placental villi attach to smooth muscle fibers rather
than to decidual cells (prevents normal separation after delivery)
Classification
• Placenta accrete (80%): villi are attached to the myometrium
• Placenta increta (15%): villi actually invade the myometrium
• Placenta percreta (5%): villi that penetrate through the myometrium
and/or through the serosa
Incidence
• Direct relationship to rising cesarian delivery rate
• High recurrence in subsequent pregnancies in placenta accrete
Risk Factors
• Associated previa
• Prior cesarian delivery
• Classical hysterotomy incision
• Myometrial trauma (curettage or endometrial ablation)
Clinical Presentation
• 1st and 2nd trimester accrete syndromes: hemorrhage as a
consequence of coexisting placenta previa
• In some not associated with previa, accrete may not be identified
until third-stage labor when an adhered placenta is encountered
Diagnosis
• Transabdominal Sonography: for antepartum identification of
abnormal placental ingrowth
o Multiple and massive placental “lakes” or “lacunae”
o Interpreted along with clinical and operative findings
o Doppler color flow: highly predictive of myometrial invasion
• MRI: outline anatomy and to identify invasion of adjacent structures,
including possible ureteral involvement
o Used if sonography results are inconclusive or a posterior previa
Management
• Cesarian delivery
o Timing of delivery 34-35 weeks
o After fetal delivery, the extent of placental invasion is assessed
without attempts at manual placental removal
• Hysterectomy: confirmation of a placenta percreta or increta
Reference: Williams Obstetrics, 25th edition (2018)
31. VAGINAL BLEEDING IN PREGNANCY | 141
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

32. HYPERTENSION IN PREGNANCY HELLP Syndrome

CHRONIC AND GESTATIONAL HYPERTENSION • Important clinical variant of preeclampsia
• Chronic hypertension in pregnancy • More common in the multigravida
o SBP ≥140 mmHg or DBP ≥90 mmHg that either: • Epigastric or RUQ pain ± hypertension
▪ Existed prior to pregnancy o Differential diagnosis: gastroenteritis, cholecystitis, hepatitis,
▪ Diagnosed <20 weeks AOG pancreatitis, or pyelonephritis
▪ Persists >12 weeks after delivery • Complications of preeclampsia, HELLP syndrome, eclampsia:
o Severe chronic hypertension: SBP >160 or DBP >110 mmHg DIC, spontaneous hepatic & splenic hemorrhage, end-organ failure,
o Increased risk for placental abruption, preeclampsia, low birth abruptio placentae, intracranial bleeding, maternal death, fetal death
weight, cesarian delivery, premature birth, and fetal demise
• Gestational hypertension
o >20 weeks AOG or immediately postpartum but (-) proteinuria
• Treatment: (goal: 140-140/90-100 mmHg)
o All hypertensive drugs cross the placenta
Drug Starting dose Maintenance dose
Labetalol 100 mg PO BID 200-400 mg PO BID
250 mg every 6 hours 500 mg to 3 g divided
Methyldopa PO and titrated to into 2-4 doses per day,
achieve desired BP max. 3 g per day
Nifedipine: if BP is not Can be increased up to
controlled with 30 mg PO once daily 120 mg/day slowly if Treatment of Preeclampsia
methyldopa or labetalol needed • Mild preeclampsia: outpatient management after consultation with
o Hypertensive emergencies: hydralazine 5 mg IV or IM; OB, as long as arrangements are made for frequent clinical and
labetalol 20 mg IV; nifedipine 10-30 mg PO laboratory evaluation and close fetal surveillance
o ACE inhibitors and ARBs are contraindicated because of their o Headache, scintillating scotoma or other visual changes,
teratogenic effects on fetal scalp, lungs, and kidneys abdominal pain, vaginal bleeding, and decreased fetal
movement require immediate reevaluation
PREECLAMPSIA • Severe preeclampsia: antihypertensives + IV magnesium sulfate
• Presence of de novo hypertension (SBP >140 mmHg or DBP >90 o Only definitive resolution for preeclampsia is delivery
mmHg) after 20 weeks of gestation combined with proteinuria or • HELLP syndrome: IV magnesium, BP control, and hospital
other maternal organ dysfunction (renal, liver, neurologic) admission for stabilization
o In absence of proteinuria: thrombocytopenia, liver dysfunction, o Correct coagulopathy if clinically indicated
renal insufficiency, pulmonary edema, cerebral dysfunction o Definitive therapy: delivery (especially if ≥34 weeks AOG)
• Cause: unknown o Corticosteroid administration can help delay delivery and
• Histologic hallmark lesion: acute atherosis of decidual arteries improve fetal outcome in pregnancies <34 weeks AOG
o Atherosis & thrombosis: lead to placental ischemia & infarctions
o Poor placental perfusion: formation of free radicals, to oxidative ECLAMPSIA
stress, & to inflammatory responses that may influence the • New-onset seizures, coma or encephalopathy, superimposed upon
mechanistic development of preeclampsia preeclampsia, in a woman >20 weeks AOG & <4 weeks postpartum
• Associated with intrauterine growth retardation, premature labor, low • Can present with seizure in absence of BP elevation & proteinuria
birth weight, abruptio placentae, future risk of maternal CV disease • Management of eclampsia
• Risk factors: primigravid, maternal age >40, hypertension, DM, • Magnesium sulfate 4-6 g IV in 100-mL aliquot given over
renal disease, collagen vascular disease, multiple gestation 20-30 minutes followed by infusion of 2 g/h for ≥24 hours
• Prevention: low-dose aspirin therapy, bed rest, calcium • In renal insufficiency: reduce to 2 g IV bolus & obtain
Treatment of
serum magnesium before increasing dose
seizures
• Main side effects: flushing, diaphoresis, hypothermia,
Diagnosis hypotension, flaccid paralysis, respiratory depression
• Toxic levels: diminished patellar reflex & bradypnea
Treatment of • Antihypertensives
hypertension • Replace coagulation factors and platelets as indicated
Emergent OB
• to facilitate urgent delivery of fetus
consultation

Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

142 | 32. HYPERTENSION IN PREGNANCY


33. GYNECOLOGIC EMERGENCIES
PELVIC INFLAMMATORY DISEASE
• Spectrum of infections of the female upper reproductive tract
• Common & serious disease by ascending infection (vagina & cervix)
• Includes salpingitis, endometritis, myometritis, parametritis,
oophoritis, and tubo-ovarian abscess (TOA)
o May extend to produce peri-appendicitis, pelvic peritonitis, and
perihepatitis (Fitz-Hugh-Curtis syndrome)
Epidemiology
• Most common serious infection in sexually active women age 16-25
• Long term sequelae (11%): tubal factor infertility, implantation after
in vitro fertilization, ectopic pregnancy, chronic pain
• Most common cause of death: rupture of TOA (mortality: 5-10%)
Etiology
Sexually
Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes
transmitted
simplex virus (types 1 and 2), Trichomonas vaginalis
organisms
Endogenous
genital tract
Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma
urealyticum
Mycoplasma
Anaerobic Bacteroides spp., Peptostreptococcus, Prevotella bivia,
bacteria Leptotrichia sanguinegens/amnionii, Atopobium vaginae
Gardnerella vaginalis, Haemophilus influenzae,
Aerobic
Streptococcus agalactiae, Escherichia coli and other gram-
bacteria
negative rods, Actiomyces israelii, Campylobacter fetus
• Risk Factors for PID
o Multiple sexual partners
o History of sexually transmitted infection (STI) or PID
o History of sexual abuse
o Frequent vaginal douching
o Intrauterine device insertion within previous month
o Adolescence, younger adulthood
o Lower socioeconomic status
o Post-abortion
Pathophysiology
• Ascending infection
o Presumed to originate with sexually transmitted infections of
lower genital tract, with ascending infection of upper tract
▪ Original STI may be asymptomatic, as may ascending
infection (subclinical PID)
o Efficacy of cervical mucus as a functional barrier to ascending
infection decreases by a number of factors
▪ Enzymes from bacterial vaginosis-associated organisms
(degrade cervical mucus & antimicrobial peptides)
▪ Hormonal changes during menstruation and ovulation
▪ Retrograde menstruation
o Intercourse may contribute to the ascent of infection due to
rhythmic mechanical uterine contractions
▪ Bacteria also may be carried by, or along with, sperm into
the uterus and tubes
o Uterine infection usually is limited to the endometrium, but can
be more invasive in a gravid or postpartum uterus
o Tubal infection initially affects only the mucosa, but acute,
complement-mediated transmural inflammation may develop
rapidly and increase in intensity with repeated infection
o Inflammation may extend to uninfected parametrial structures,
including the appendix and bowel
▪ By direct extension of purulent material from fallopian tubes
▪ Via lymphatic spread beyond pelvis to involve hepatic
capsule with acute perihepatitis (Fitz-High-Curtis syndrome)
and produce acute peritonitis
• Complications of PID
o Tubo-ovarian abscess (TOA)
o Tubal factor infertility: scarring and adhesions with obstruction
o Ectopic pregnancy
• Sequelae: recurrence, chronic pelvic pain, menstrual disturbances,
chronic dyspareunia
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Clinical Features
• History: symptoms usually occur early in menstrual cycle or end of
menses (low progesterone + thinning of cervical mucosal barrier)
o Lower abdominal pain (bilateral and dull or crampy)
▪ Exacerbated by movement or by sexual activity
o Abnormal vaginal discharge
o Vaginal bleeding (increased or prolonged menstrual bleeding)
o Postcoital bleeding
o Irritative voiding symptoms
o Systemic signs: fever, malaise, nausea, vomiting
• Physical examination
o Lower abdominal tenderness
o Cervical motion tenderness
o Uterine or adnexal tenderness
o Peritonitis: involuntary guarding and rebound tenderness
o Mucopurulent cervicitis is common
• Fitz-Hugh-Curtis syndrome (perihepatitis)
o PID + RUQ tenderness, jaundice, slightly ↑ transaminases
Differential diagnosis: cervicitis, ectopic pregnancy, endometriosis,
ovarian cyst, ovarian torsion, spontaneous abortion, septic abortion,
cholecystitis, gastroenteritis, appendicitis, diverticulitis, pyelonephritis,
renal colic; look for signs of other STIs (herpes simplex, syphilis, HPV)
Diagnosis
• Based on history and clinical findings
• Laboratory Testing
• Any woman of childbearing age
Pregnancy test
• Consider ectopic pregnancy or septic abortion
KOH wet smear of • Leukorrhea (>1 PMN per epithelial cell)
vaginal secretions • Trichomonads
Test for bacterial
• ↑ WBC + clue cells: increases likelihood of
vaginosis (clue
cervicitis/PID
cells, pH, whiff test)
Endocervical • Gram stain + culture/sensitivity
swab specimens • NAAT & DNA probes (N. gonorrhoeae & Chlamydia)
Other STIs • VDRL/RPR, HIV & hepatitis profile
• Exclude UTI but not PID
Urinalysis
• Pyuria: inflammatory process in contiguous pelvis
• Imaging and Other Diagnostic Modalities
o Transvaginal sonography: helpful in ruling in/out causes in
differential diagnosis of pelvic pain (ectopic pregnancy, ovarian
torsion, hemorrhagic ovarian cyst, appendicitis, endometriosis)
▪ Acute severe PID: thickened (>5 mm), fluid-filled fallopian
tubes or free pelvic fluid
▪ Pelvic/tubo-ovarian abscesses: complex adnexal masses
with multiple internal echoes
▪ Power Doppler: ↑ blood flow (inflammation & infection)
o Abdominopelvic CT and MRI: may also be used to diagnose
PID and TOA & to exclude other important causes of pelvic pain
▪ Used if appendicitis or other surgical or GI diagnoses cannot
be excluded
▪ CT findings in PID: obscuration of pelvic fascial planes,
cervicitis, oophoritis, salpingitis, thickening of uterosacral
ligaments, and presence of simple or complex pelvic fluid or
abscess collections
▪ MRI: more specific and accurate than US to assess PID
o Laparoscopy: gold standard for the diagnosis of PID
▪ Invasive, high interobserver variability, may not detect
endometritis or early tubal inflammation
33. GYNECOLOGIC EMERGENCIES | 143
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Treatment ABNORMAL UTERINE BLEEDING

• Aims of treatment • Bleeding from the uterine corpus that is irregular in volume,
o Relieve acute symptoms frequency, or duration in absence of pregnancy
o Eradicate current infection
o Minimize risk of long-term sequelae
o Reduce risk of transmission of infection to other new partners
o Identify & treat sexual partner/s to prevent disease spread
• Supportive: adequate analgesia, control of emesis and fever, fluid
replacement in those with nausea, vomiting, and dehydration and in
those who appear toxic
o NSAIDs are very useful for management of pain of pelvic origin
• Empiric broad-spectrum antibiotic therapy

Clinical Features
• History
o Bleeding pattern, associated symptoms, past medical,
reproductive, and sexual history
o Determine whether bleeding is acute or chronic
o Family history of bleeding disorders or chronic illnesses
• Alternative Antibiotics
▪ Screening criteria: heavy menstrual bleeding since
o Spectinomycin: for severe cephalosporin allergy
menarche, postpartum hemorrhage, bleeding related to
o Azithromycin: provides intrinsic anti-inflammatory effects and surgery or dental procedure, and ≥2 of following
may reduce local tissue damage
• Bruising 1-2 times a month
Alternative to doxycycline for M. 500 mg IV daily for 1-2 doses, then
genitalium 250 mg once daily for 12-14 days • Epistaxis 1-2 times a month
In combination with metronidazole 250 mg once daily for 7 days or • Frequent gum bleeding
for anaerobic coverage 1 g once a week for 2 weeks • Family history
o Medications: hormonal contraceptives, anticoagulants, SSRIs,
Special Considerations tamoxifen, herbal supplements (e.g., ginseng)
• Treatment in HIV Infection
o More likely to have concomitant Candida, Mycoplasma hominis,
HPV, and streptococcal infection
o More severe symptoms irrespective of CD4 count and are more
likely to have sonographically diagnosed tubo-ovarian abscess
o Respond similarly to treatment for uncomplicated PID
• Tubo-Ovarian Abscess
o Most commonly a late complication of PID (2% of PID cases)
o Majority have associated peritonitis
o HIV infection: an increased incidence of tubo-ovarian abscess
due to slower resolution of PID
• Physical examination
o Clinical findings: disproportionate unilateral adnexal
o Evaluate for hemodynamic stability on initial assessment
tenderness or adnexal mass or fullness
▪ Significant signs of volume depletion may not be present
o Diagnosis: pelvic US
until bleeding is profuse
o Treatment: most (60-80%) resolve with antibiotics alone
o Focused physical examination
▪ Oral therapy continued with clindamycin 450 mg PO q6h or
▪ Endocrine cause: hirsutism, obesity, galactorrhea
metronidazole + doxycycline (for anaerobics) for 14 days
▪ Hematologic cause: petechiae, purpura, mucosal bleeding
o If no improvement after 72 hours of treatment: reevaluate for
o Pelvic examination
possible CT/US-guided percutaneous drainage, laparoscopic
▪ External exam: perineum, vulva, urethra, perianal region
drainage, posterior colpotomy with drainage, surgical
▪ Speculum exam: vaginal canal & cervix (potential bleeding)
intervention, or reconsideration of other possible diagnosis
▪ Bimanual exam of uterus & adnexal structures: assess size,
▪ Abscess ≥9 cm on imaging appear to have a higher
masses, or tenderness
likelihood of requiring surgical therapy
▪ An enlarging pelvic mass may indicate bleeding secondary
Causes of Vaginal Bleeding
to vessel erosion or a rupture abscess

Disposition & Follow-Up

• Admission considerations
o Cannot exclude surgical emergency from differential diagnosis
o Pregnancy
o Failure to respond to outpatient treatment
o Inability to tolerate or comply with outpatient treatment
o Severe toxicity, high fever, nausea, vomiting
o Tubo-ovarian abscess

144 | 33. GYNECOLOGIC EMERGENCIES


Structural Causes of Vaginal Bleeding (PALM)
• Polyps (endometrial & endocervical polyps)
o Epithelial proliferations that most often are benign
o Most are asymptomatic; can be cause of AUB in women ≥35 yrs
o Common symptom: intermenstrual bleeding
o Diagnosis: US or hysteroscopy
• Adenomyosis
o Presence of endometrial glands & stroma within myometrium
o Histopathology: diffuse within the uterus
o Adenomyomas: localized areas of growth
o Symptoms: painful, heavy periods most commonly seen in the
4th and 5th decade of life
o Diagnosis: MRI, US (alternative)
o Patients with severe bleeding unresponsive to medical
management often require surgical management
• Leiomyomas (uterine fibroids, leiomyoma, myoma)
o Most common benign tumors of the pelvis in women
o Cause is unclear, but fibroids increase with reproductive age
and decrease in size during menopause
▪ Thought to be dependent on genetic & hormonal factors
▪ May enlarge early in pregnancy & with OCP use
o Most are asymptomatic; ~30% experience pelvic pain & AUB
▪ Acute pain is rare, but severe pain may be experienced with
torsion or degeneration
▪ Degeneration results from rapid growth and loss of blood
supply, often seen during pregnancy
o Signs and symptoms vary depending on size and location
▪ Large fibroids may be palpated on abdominal or rectal exam
▪ Acute degeneration: tenderness, rebound guarding, fever,
and elevated WBC count
▪ Rapid growth at any age or growth after menopause is
highly suspicious for malignant transformation
o Diagnosis: ultrasonography (as sensitive as MRI)
o Management: treat complications associated with fibroids
▪ Blood transfusion: long-standing iron deficiency anemia
▪ NSAIDs: mainstay for analgesia
▪ Hormonal agents: initiated with gynecologic consultation
▪ Tranexamic acid: reduce menstrual blood loss
▪ Surgical removal: 25-30% rate of recurrence and significant
bleeding complications
▪ Uterine artery embolization: effective treatment for
symptomatic fibroids, resulting in decreased fibroid volume
and alleviation of symptoms
• Malignancy (endometrial or cervical cancer)
o Endometrial hyperplasia/cancer: women >45 years old or in
younger women with other risk factors
o Amount of bleeding does not correlate with severity of disease
o All patients with postmenopausal bleeding warrant prompt US
and endometrial biopsy
o Elderly patients may not be able to accurately describe location
of pain or bleeding in proximity of bladder, uterus, or rectum
▪ Adequately visualize urethra, vagina, & cervix on pelvic
examination
o Vaginal bleeding + atrophic vaginitis: use of pessaries and
douche solutions (irritate the mucosa)
o Cervical polyps can also cause vaginal bleeding
▪ Endometrial biopsy is ultimately required to rule out other
serious causes of bleeding
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Nonstructural Causes of Vaginal Bleeding (COEIN)
• Coagulopathies
o Adolescents: primary coagulation disorders (~20% of AUB)
▪ von Willebrand disease is the most common cause
▪ Others: myeloproliferative disorders, immune
thrombocytopenia
o Adults: anticoagulation agents or acquired bleeding disorders
▪ Cirrhosis: bleeding secondary to reduced capacity of liver to
metabolize estrogens
• Ovulatory Dysfunction
o AUB secondary to anovulation: 10-15% of gynecologic patients
▪ Signs: irregular and/or heavy menstruation
▪ Perimenarchal & perimenopausal women, endocrine
disorders, PCOS, exogenous hormones, liver/renal disease
▪ Anovulatory uterine bleeding in adolescents
• Due to immature hypothalamic-pituitary-ovarian axis
• Amount of bleeding is usually minimal and painless
• Severe anemia from heavy menstrual bleeding in early
adolescence should prompt evaluation for bleeding
disorders (vWD, factor VIII deficiency)
▪ Anovulatory bleeding in the reproductive-age female
• Often irregular because of fluctuating estrogen levels
• Present as prolonged amenorrhea with periodic heavy
menstrual bleeding (increases risk of endometrial
hyperplasia & adenocarcinoma)
o Hypothyroidism
▪ Heavy uterine bleeding or intermenstrual bleeding
▪ Eating disorders, excessive weight loss, stress, exercise
▪ Consider obtaining TSH in uterine bleeding of undetermined
origin or in those with thyroid nodule or goiter
• Endometrial Causes
o Abnormal uterine bleeding that occurs in the context of normal
ovulation with a structurally normal endometrial cavity
o Bleeding + breast tenderness, abdominal bloating, pelvic pain
o Diagnosis: HMB with no other identifiable abnormalities
o Treatment: oral contraceptives, NSAIDs, progestins
▪ NSAIDS: ↓ prostaglandin levels can ↓ menstrual bleeding
▪ Endometrial ablation: for unresponsive to medical therapy
▪ Hysterectomy: reserved for those who fail medical
management and have excessive blood loss
• Iatrogenic Causes
o Oral contraceptive pills: most common cause of
intermenstrual bleeding
o Medications (e.g., antiseizures medications) that increase
P450 system of liver may increase metabolism of endogenous
hormonal glucocorticoids and may cause withdrawal bleeding
o Hormone replacement therapy (relieves symptoms
associated with menopause): associated with vaginal bleeding
▪ 40% of women receiving continuous OCP therapy will
experience abnormal bleeding in the initial 4-6 months
o Bleeding >6 months of continuous combined HRT, unexpected
bleeding with cyclic HRT, or bleeding that recurs after
amenorrhea is established should prompt referral for evaluation
▪ Most common etiologies for bleeding while on HRT: poor
compliance, poor GI absorption, drug interactions, failure to
synchronize therapy with endogenous ovarian activity,
coagulation disorders
• Other Causes of Vaginal Bleeding (Not Otherwise Classified)
o PID or infections that cause endometritis can result in abnormal
vaginal bleeding
o Cervical erosions, polyps, and cervicitis may cause bleeding
from the cervix
o Vaginal infections, trauma, and foreign bodies may also present
with abnormal bleeding
33. GYNECOLOGIC EMERGENCIES | 145
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Laboratory Evaluation and Imaging
• Pregnancy test: in women of childbearing age (except those with
hysterectomy) to rule out pregnancy as a cause of bleeding
• CBC: identifies anemia
• Thyroid studies if they have not been recently obtained
• Coagulation studies only when indicated by history or PE
• Ultrasonography: first-line imaging modality for gynecologic
conditions (vaginal bleeding, adnexal or uterine masses, pelvic pain)
o Determine uterine size and endometrial characteristics
o Identify leiomyoma, ovarian cysts, hydrosalpinx, pelvic
adhesions, tubo-ovarian abscesses, endometriosis, tumors
o Transvaginal ultrasonography: further delineates ovarian
cysts and fluid in the cul-de-sac
• CT: evaluation of acute abdominal or pelvic pain
• MRI: for cancer staging
Treatment
• Massive Uterine Bleeding
o Do not attempt vaginal packing, because it increases the risk of
infection and may hide ongoing blood loss
o Assess for other potential causes of bleeding: trauma, bleeding
dyscrasia, infection, retained foreign bodies
o Hormonal agents (conjugated estrogen): first-line medical
management for massive uterine bleeding in patients without an
underlying bleeding disorder
▪ Short-term hormonal treatment allows the endometrium to
stabilize and slows acute bleeding
▪ Contraindicated in women with a history of blood clot or
cardiovascular disease
▪ Obtain TVS to identify anatomic causes of bleeding
o Tranexamic acid (lysine derivative; prevents fibrin degradation)
▪ Used for intraoperative gynecologic & obstetric hemorrhage
• Heavy or Anovulatory Menstrual Bleeding
o Oral contraceptive pills: for young healthy women with AUB
due to anovulation & no concern for endometrial pathology
o NSAIDS: effective in reducing pain and blood loss in 20-50% of
women with AUB secondary to ovulatory dysfunction
▪ Started on the 1st day of period and continued until bleeding
stops and pain resolves
▪ Less useful in patients with uterine leiomyomas
o Progestin-only therapy: for older patients or obese/
perimenopausal patients with concern for endometrial pathology
▪ Works by decreasing the number of available estrogen
receptors and stabilizing endometrium
o Nonmedical invasive management strategies
▪ Hysteroscopy: used to sample the endometrium and resect
polyps and myoma
▪ Endometrial ablation: in patients who do not desire fertility,
have no pathologic diagnosis, and failed medical therapy
▪ Myomectomy: in patients with symptomatic fibroids
▪ Uterine artery embolization: effective nonsurgical option
for the management of bleeding caused by fibroids
146 | 33. GYNECOLOGIC EMERGENCIES
Disposition and Follow-Up
• Stable patients can be discharged home with arrangements for
prompt follow-up
• Need for surgical management is based on clinical stability
o If medical management fails, surgical management is next step
o Surgical options are directed by suspected etiology
o Dilatation and curettage, hysteroscopy, endometrial balloon
tamponade, uterine artery embolization
o Hysterectomy: last resort in patients with acute life-threatening
bleeding unresponsive to other treatment measures
• Referral for endometrial biopsy
o At risk for endometrial cancer
o All women >45 years old
• Perimenopausal bleeding: associated with malignancy in 10%
o Risk factors: obesity, nulliparity, anovulation, tamoxifen use,
infertility, family history of endometrial/colon cancer
• Other diagnostic procedures at follow-up: sonohysterography,
hysterosalpingography, hysteroscopy with directed biopsy,
dilatation and curettage
Special Considerations
• Anticoagulants
o Anticoagulation for DVT, pulmonary embolism, artificial heart
valves, atrial fibrillation, and other conditions
o >70% report changes in their periods, >50% reporting heavy
menstrual bleeding
o Management is challenging because first-line treatments
(contraceptives & tranexamic acid) are contraindicated
o Progestin-only may be used with caution (potential increased
risk of thrombosis)
• Inherited Bleeding Disorders
o Abnormal uterine bleeding is the most common symptom
o Abnormal uterine bleeding is present in majority of women with
von Willebrand’s disease or factor XI deficiency and in carriers
of hemophilia
o Initial treatment options are similar to those without bleeding
disorder, except the use of NSAIDs is contraindicated
o Hormonal agents raise factor VIII and von Willebrand factor
levels and are an effective and popular form of therapy
o If standard treatment fails, consider desmopressin acetate to
stimulate endogenous release of factor VIII and vWF
▪ Patients must be typed and screened for antibodies before
administering because it may induce thrombocytopenia
o Antifibrinolytics (tranexamic acid, recombinant vWF) are other
treatment options
• Polycystic Ovary Syndrome
o One of the most common endocrine disorder
o Triad: obesity, hirsutism, oligomenorrhea
o Heavy and prolonged menses
o Acne, androgen-dependent alopecia, ↑ serum androgens,
hyperinsulinemia, hypersecretion of LH with normal or low FSH
o Management of menorrhagia who do not desire fertility includes
low-dose oral contraceptives or cyclic progestin administration
• Stress, Illness, and Rapid Weight Change
o Periods of physical or psychological stress, illness, malnutrition,
rapid weight gain or loss, and intense physical regimens affect
hypothalamus & disrupt normal pattern of gonadotropin release
▪ Usually cause amenorrhea but may result in irregular, heavy
bleeding
o In obese women, menorrhagia may be result of increased
circulating levels of estrogen from peripheral conversion of
androstenedione to estrone in fatty tissue
o Patients with liver and renal disease may also develop irregular
bleeding
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

34. HEAD TRAUMA
TRAUMATIC BRAIN INJURY (TBI)
• Brain function impairment that results from external force
• Clinical manifestations represent a broad constellation of symptoms
from brief confusion to coma, severe disability, and/or death
• Underlying pathology ranges form temporary shifts in cellular ionic
concentrations to permanent structural damage
CLASSIFICATION
• Mild (GCS 14-15): >80% of TBI
o May lead to significant, debilitating short- & long-term sequelae
• Moderate (GCS 9-13): ~10% of TBI
o Mortality rates for isolated moderate TBI: <20%
o 40% of patients with moderate TBI have an abnormal CT
o 8% will require neurosurgical intervention
• Severe (GCS 3-8)
o Mortality approaches 40%
o Most deaths occur in the first 48 hours after injury
o <10% of patients with severe TBI experience good recovery
EPIDEMIOLOGY
• Prevalence of TBI is twice as high in males as in females
• Distribution of age at injury is trimodal
o 0-4 years, 15-24 years, >75 years of age
• Mortality rate increases with age at time of injury
ETIOLOGY
• Motor vehicle collisions are the primary cause of blunt head injury in
young adults and children
• Falls are more common in the elderly
• TBI has been called a “signature injury” of modern-day warfare
PATHOPHYSIOLOGY
Cerebral Blood Flow
• Autoregulation regulates local cerebral blood flow to maintain
equilibrium between oxygen delivery and metabolism
o Other systemic factors (hypertension, hypocarbia, alkalosis) can
affect cerebral blood flow by causing vasoconstriction
o Can adjust to accommodate CPP from 50-150 mmHg
• In brain injury, autoregulation is often impaired
o Even modest drops in BP can decrease brain perfusion and
result in cellular hypoxia
o <60 mmHg: lower limit of autoregulation below which local
control of CBF cannot be adjusted to maintain flow
o Traumatic hypotension leads to ischemia within low-flow regions
of the injured brain, so aggressive fluid resuscitation may be
required to prevent hypotension and secondary brain injury
▪ Important to maintain MAP ≥80 mmHg
▪ ↓ BP + ↑ ICP = ↓ CPP (brain injury)
Primary Brain Injuries
• Initial insult associated with moderate & severe TBI imparts
mechanical forces that produce high levels of direct damage and
strain to the brain parenchyma
• Contusions: bruises to brain parenchyma
• Hematoma: subdural, epidural, intraparenchymal, subarachnoid
• Diffuse axonal injury: stress or damage to axons
• Direct cellular damage: neurons, axons, & other supportive cells
• Loss of the blood-brain barrier
• Disruption of the neurochemical homeostasis
• Loss of electrochemical function
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Secondary Brain Injuries
• Secondary neurotoxic cascade: wave of secondary damage
resulting in a series of deleterious cellular & subcellular events
o Massive release of neurotransmitters (glutamate) into
presynaptic space, with activation of NMDA receptors
o Ionic shifts activate cytoplasmic and nuclear enzymes, induce
mitochondrial damage, and lead to cell death and necrosis
o Proinflammatory cytokines and other enzymes are released in
an attempt to clean and repair damage
• Indiscriminate & produces extensive neuronal loss
• Many survivable cells undergo apoptosis during secondary injury
Brain Edema
• Cytotoxic edema (cellular swelling)
o Results from large ionic shifts and loss of cellular membrane
integrity from mitochondrial damage (loss of ATP, ion pump
productivity, and increased free radical production)
• Extracellular edema
o Results from direct damage to, or breakdown of, the blood-brain
barrier, ionic shifts, & alteration of water exchange mechanisms
• As intracellular & extracellular water content rises, brain swells and
ICP increases, leading to
o Direct compressive tissue damage
o Vascular compression-induced ischemia
o Brain parenchyma herniation
o Brain death
Brain Herniation
• Uncal transtentorial herniation: most common
o Occurs when the uncus of the temporal lobe is displaced
inferiorly through the medial edge of the tentorium
o Due to expanding lesion in temporal lobe or lateral middle fossa
o Leads to compression of parasympathetic fibers running with
the 3rd cranial nerve (oculomotor), causing an ipsilateral fixed
and dilated pupil due to unopposed sympathetic tone
o Further herniation compresses the pyramidal tract, which results
in contralateral motor paralysis
• Central transtentorial herniation: less common
o Occurs with midline lesions (frontal lobe, occipital lobes, vertex)
o Symptoms: bilateral pinpoint pupils, bilateral Babinski’s sign,
hypertonia, prolonged hyperventilation & decorticate posturing
• Cerebellotonsillar herniation
o Cerebellar tonsils herniate through foramen magnum
o May lead to pinpoint pupils, flaccid paralysis, sudden death
• Upward transtentorial (posterior fossa) herniation
o Leads to a conjugate downward gaze with absence of vertical
eye movements and pinpoint pupils
CLINICAL FEATURES
History
• Mechanism, place, date, time of injury (MOI, POI, DOI, TOI)
• Overall severity of TBI: height of fall, impact surface, condition,
damage sustained to vehicle, air bag deployment, seat belt use,
history of ejection from vehicle, report of fatalities at the scene)
• Premorbid medical history, medications (anticoagulants), drug use,
and/or alcohol intoxication
• Clues to underlying brain injury: focal neurologic deficit, seizures,
emesis, depressed level of consciousness
Glasgow Coma Scale (GCS)
• Objective measurement of clinical status, correlates with outcome,
measures patient recovery/response to treatment over time
• Intended to gauge disease progression over time
• Intubated: verbal component scored 1; total score marked with “T”
• Serial GCS: gives broader picture of neurologic recovery/worsening
• Limitations
o Measures behavioral response, not underlying pathophysiology
o May be confounded by drugs, alcohol, medications, paralytics,
ocular, spinal peripheral extremity injuries
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INITIAL TREATMENT
Primary goals of treatment
• Maintain cerebral perfusion and oxygenation by optimizing
intravascular volume and ventilation
• Prevent secondary injury by correcting hypoxia, hypercapnia,
hyperglycemia, hyperthermia, anemia, or hypoperfusion
• Recognize and treat elevated ICP
• Neurosurgical intervention to evacuate intracranial mass lesions
• Treat other life-threatening injuries

Physical Examination
• Advanced Trauma Life Support (ATLS) principles for trauma-
Airway and Breathing
focused examinations, with lifesaving procedures as needed
• Treat any condition that compromises ventilation (e.g., altered
o Airway, Breathing, Circulation, Disability, Exposure
mental status, facial/neck trauma, pneumothorax)
o Protect cervical spine during evaluation, treatment, & imaging
• Patients with severe injury (GCS ≤8) require intubation
• Obtain the GCS and classify severity
• Avoid nasotracheal intubation if facial trauma or basilar skill fracture
o Severe (GCS 3-8); moderate (GCS 9-13); mild (GCS 14-15)
is evident or suspected
• Determine pupillary response
Unresponsive + single
• Maintain oxygenation and use capnometry to control PCO2 and
Intracranial hematoma with uncal herniation avoid hyperventilation
fixed & dilated pupil
Bilateral fixed & dilated ↑ ICP with poor brain perfusion, bilateral uncal o Prolonged (>6 hours) hypocapnia causes cerebral
pupils herniation, drug effect (atropine), severe hypoxia vasoconstriction and worsens cerebral ischemia
Bilateral pinpoint pupils Opiate exposure or central pontine lesion
o Keep SaO2 >90%, PaO2 >60 mmHg, PCO2 35-45 mmHg
• Altered motor function: brain, spinal cord, peripheral nerve injuries
Circulation
o Assess movement in a coma patient by observing reaction to
• Provide aggressive fluid resuscitation to prevent hypotension and
noxious stimuli (pressure to a nail bed)
secondary brain injury
o Assessment of symmetry, as well as gradation of motor
o Normal saline is recommended for volume resuscitation
strength is important initially and upon serial neurologic exams
o Maintain SBP ≥100 mmHg for patients 50-69 years old
o Decorticate posturing (UE flexion & LE extension): severe
o Maintain SBP ≥110 mmHg for patients 15-49 or >70 years old
intracranial injury above level of midbrain
o A blood pressure within “normal” range may be inadequate to
o Decerebrate posturing (arm extension & internal rotation with
maintain adequate flow and CPP if ICP is increased
wrist & finger flexion; internal rotation & extension of lower
• If fluid and blood resuscitation is not effective, use vasopressors to
extremities): more caudal injury
preserve cerebral perfusion
o For completely unresponsive patients: respiratory pattern &
• Treat pain and assess for impending herniation (Cushing reflex)
eye movements provide information on brainstem function
o Pain and increased ICP can cause hypertension
▪ Pupillary reflex, corneal reflex, cough, gag reflexes
Patient positioning: raise head of bed by 30°
▪ DO NOT assess oculovestibular (cold caloric) and
• May improve cerebral blood flow by lowering ICP
oculocephalic (doll’s eyes) responses in a patient under
cervical spine precautions • Ensure BP is maintained at MAP >80 mmHg
• Elevation of 30° can drop mean ICP by up to 10-15 mmHg
Imaging • Can be safely accomplished even when spine has not been cleared,
• Head CT: sensitive to presence of blood as long as cervical spine is stabilized within a collar (reverse
o Do not delay; expanding hemorrhagic Trendelenburg)
lesions need emergency Glucose control: 100-180 mg/dL (5.55-9.99 mmol/L)
neurosurgical intervention • Tight glycemic control recommended in moderate to severe TBI
o If the patient is uncooperative or • Insulin drips may be required to achieve adequate control
combative, endotracheal intubation Seizure Treatment and Prophylaxis
and sedation are often the best • Treat acute seizures with midazolam or lorazepam
options to enable rapid CT imaging • If seizures continue, treat as for status epilepticus
(midazolam 1-2 mg IV, propofol 20 mg q10s) • Prophylaxis: phenytoin/fosphenytoin 18 mg/kg at 25 mg/min
o Adults with mild TBI will have an intracranial lesion up to 15% of o Used if GCS ≤10, abnormal head CT, or had acute seizure
the time; <1% will require neurosurgical intervention o Reduce occurrence of posttraumatic seizures within 1st wk
• Cervical CT Cerebral Herniation: manage increasing ICP
o Prevalence of cervical fractures in comatose TBI: ~8% • Measure neurologic deterioration by comparing sequential GCS
▪ ~4% of injuries are missed on initial assessment • Mannitol 0.25-1 g/kg in
o Perform in patients with altered mental status & who were repetitive bolus
injured by mechanism that increases risk of cervical spine injury • Hypertonic saline 3% 250
o Superior to plain radiography in patients with altered mental mL over 30 minutes
status and can be performed at the same time as head CT
• MRI
o Can detect subtle lesions missed by CT
o Can better define extent of contusions
o Cannot be performed if patient is unstable
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SPECIFIC HEAD INJURIES Diffuse Axonal Injury

Cerebral Contusion and Intracerebral Hemorrhage
• Contusions most commonly occur in the subfrontal cortex, in frontal
and temporal lobes, and occasionally, in occipital lobes
o Often associated with subarachnoid hemorrhages
o May occur at the site of the blunt trauma (coup injury) or on
opposite side of the brain (contrecoup injury)
• Intracerebral hemorrhage can occur days after significant blunt
trauma, often at the site of resolving contusions
o More common in patients with coagulopathy
o CT scan findings immediately after injury may be normal
o Obtain serial CTs if any change in mental status in patient with
coagulopathy until the clot is stable
• Disruption of axonal fibers in the white matter and brainstem
• MOI: shearing forces on neurons generated by sudden deceleration
o Seen after blunt trauma (motor vehicular crash)
o In infants, shaken baby syndrome is a well-described cause
• In severe diffuse axonal injury, edema can develop rapidly
o Underlying injury can result in devastating and often irreversible
neurologic deficits
• CT: may appear normal; punctuate hemorrhagic injury along gray-
white junction of cerebral cortex and within deep structures of brain
• Treatment options are very limited
o Attempt should be made to prevent secondary damage by
reducing cerebral edema & limiting pathologic increases in ICP

Subarachnoid Hemorrhage Penetrating Injury

• MOI: disruption of parenchyma and subarachnoid vessels • MOI: direct penetration of the bullet through the brain substance and
• Clinical findings: blood in the CSF the transfer of kinetic energy cause the majority of the destruction
• Isolated traumatic SAH: headache, photophobia, meningeal signs o Depending on the velocity, a bullet that passes through the brain
• Most common CT abnormality in moderate to severe TBI can create a cavity 3-4 times larger than its diameter
• CT scans performed 6-8 hours after injury are sensitive for detecting • GCS can be used to predict prognosis for non-intoxicated patients
traumatic subarachnoid hemorrhage with a gunshot wound to the brain
o GCS >8 and reactive pupils have a 25% mortality risk
Epidural Hematoma o GCS <5: mortality approaches 100%
• Results when blood collects in potential space between skull & dura • Management: require admission, broad-spectrum antibiotics, and
• Mechanisms of injury operative intervention
o Blunt trauma to the temporal or temporoparietal area with an o Intubate patients with a penetrating gunshot wound to brain
associated skull fracture & middle meningeal arterial disruption o Prophylactic antibiotics (vancomycin 1 g IV, ceftriaxone 2 g IV)
o Trauma to parieto-occipital region or posterior fossa causes o Leave impaled objects in place until controlled surgical removal
tears of venous sinuses is facilitated
o Traumatic blows to the thin temporal bone over the lateral • Stab wounds have a very low energy and impart only direct damage
aspect of the head carry the highest risk to the area contacted by the penetrating object
• Classic history: significant blunt head trauma with loss of
consciousness or altered sensorium, followed by a lucid period and
subsequent rapid neurologic demise
• Diagnosis: PE findings and CT scan
o CT: biconvex (football-shaped) mass, typically temporal region
• Complication: herniation within hours after an injury (due to high-
pressure arterial bleeding of an epidural hematoma)
• Prognosis: early recognition & evacuation = ↓↓ morbidity & mortality
o Underlying injury of brain parenchyma is often absent
o Full recovery may be expected if hematoma is evacuated prior
to herniation or development of neurologic deficits

Subdural Hematoma
• MOI: sudden acceleration-deceleration of brain parenchyma with
subsequent tearing of the bridging dural veins
• Hematoma formation between dura mater and arachnoid
o Tends to collect more slowly because of its venous origin
o Often associated with concurrent brain injury & underlying
parenchymal damage
• Brains with extensive atrophy (elderly, chronic alcoholics) are more
susceptible to development of acute subdural hematoma
o Even seemingly benign falls from standing position can result in
subdural bleeding in elderly
o Children <2 years old are also at increased risk
• Classification according to onset & active hemorrhage
o Acute: within 14 days of injury
▪ Immediately after severe trauma; often unconscious
▪ CT: hyperdense (white) crescent-shaped; cross suture lines
o Chronic subdural hematoma: >2 weeks
▪ In elderly and alcoholics, may result in vague complaints or
mental status changes; often, there is no recall of injury
▪ CT: hypodense (dark) [iron in blood has been metabolized]
• Definitive treatment depends on type, size, effect on underlying
brain parenchyma, and associated brain injury
o Acute & subacute subdural hematomas: mortality and need
for surgical repair are greater
o Chronic subdural hematomas can sometimes be managed
without surgery depending on severity of symptoms Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

35. MAXILLOFACIAL INJURY CLINICAL FEATURES

ETIOLOGY Secondary survey: localize injuries while simultaneously examine
• Assaults, motor vehicle crashes, falls, sports, and gunshot wounds patient from upper to lower face
account for the majority of facial fractures (in descending order of Any patient with visual complaints or evidence of
How is your vision?
incidence) periorbital injury requires thorough eye examination
Checks for anesthesia of forehead, lower eyelid,
• Lack of a seat belt or air bag increases the risk of facial fractures Is your face numb? cheek, and upper lip or chin (injury to supraorbital,
and panfacial fracture infraorbital, or mental nerves)
• Most common fractures: nasal bone, orbital floor, Do your teeth fit Malocclusion typically occurs in patients with
zygomaticomaxillary, maxillary sinuses, mandibular ramus together normally? mandibular or maxillary fractures
• Mandibular condyle injury: pain and tenderness near ear
EPIDEMIOLOGY • Zygomaticomaxillary complex fractures: pain over the cheek and
• Mechanisms and injury patterns vary with geography trismus from masseter spasm or mechanical impingement of either
o Urban setting: penetrating trauma and assaults result in temporalis muscle or coronoid process of mandible
midface and zygomatic fractures
o Rural setting: motor vehicle crashes and recreational injuries
result in fractures of the mandible and nose
• Males are more frequently affected than females
o Domestic violence and elder & child abuse must always be
considered in any patient presenting with facial trauma
o Majority of abused women and children will have injuries to the
head, face, and neck

PATHOPHYSIOLOGY
• The facial skeleton is designed to create effective mastication
o Vertical & horizontal buttresses: bony arches at suture lines
Vertical buttresses (stronger) Horizontal buttresses (weaker)
Medial: nasofrontal-maxillary From superior to inferior: frontal bone,
Lateral: frontozygomaticomaxillary nasal bones, infraorbital region,
Posterior: pterygomaxillary zygomatic arches, upper alveolus
o Orbit: comprised of 7 different bones
▪ Inferior & medial walls being particularly fragile
o Frontal, lateral, & oblique forces often result in facial fractures
• Le Fort Classification of facial fracture patterns
Location Resulting mobility
Transverse maxillary alveolus fractures
Le Fort I Mobile hard palate
above the teeth
Extends superiorly to include Includes palate,
nasofrontal buttress, medial orbital wall, nasal dorsum,
Le Fort II
& as high as infraorbital rim & inferomedial aspect
zygomaticomaxillary articulation of orbital rim
Disruption of frontozygomaticomaxillary, Craniofacial
Le Fort III
frontomaxillary, & frontonasal suture line disjunction

IMAGING
• Noncontrast CT is the imaging modality of choice
• Plain radiographs remain helpful when CT is not available or to
exclude injury in low-risk patients
• Goals of management
o Protect patient’s airway during primary survey (principal focus)
o Identify facial injury
o Restore normal appearance, sight, mastication, smell, sensation

• Evaluate facial injuries as part of secondary survey only after

managing life-threatening injuries

150 | 35. MAXILLOFACIAL INJURY


TREATMENT
Airway Management
• During primary survey of facial trauma, aggressively protect
airway from hemorrhage and mechanical obstruction
Mechanism of obstruction Causes
Significant hemorrhage Mandible and midfacial fractures
Loss of mechanical support Bilateral posterior mandible fractures
Significant edema of soft palate Midfacial injuries
Patient unable to maintain Concomitant traumatic brain injury,
damaged airway intoxication, other life-threatening injuries
• Reposition airway as needed with a jaw thrust of head tilt and chin
lift after cervical spine clearance
o Grasp an obstructing tongue with gauze, towel clip, or suture to
pull anterior and out of the airway with mandible fractures
o Remove avulsed teeth and foreign bodies
o Use nasal trumpets very carefully to avoid worsening of injury or
intracranial placement in severe midfacial injuries
o Bag-mask ventilation often requires a 2-person technique
because of loss of normal facial bony structures and the need to
suction airway secondary to significant hemorrhage
o When cervical spine has ben clinically cleared, allow the alert
patient without significant associated injury to remain in an
upright position of comfort, with suction in hand, to better handle
bleeding and secretions
• Rapid sequence intubation is the preferred method of airway
management in trauma
o Presence of mandible fractures occasionally makes intubation
easier than expected
o Do not administer paralytics unless a patient can be bagged
effectively, or alternative airway devices or plans are in place
o When intubation seems straightforward: proceed with intubation
o When intubation appears more difficult/impossible: primary
cricothyrotomy or alternate airway management techniques
o Laryngeal mask airway device may be a temporizing measure,
but does not protect airway from aspiration of stomach contents
and may not be possible with injuries involving pharynx
o Avoid nasal intubation to prevent worsening of injury,
hemorrhage, or intracranial placement
Hemorrhage
• Posterior nasal epistaxis: early nasal tampon, dual balloon device,
or Foley catheter placement with anterior layered gauze packing
o Avoid intracranial placement in severe midfacial fractures
• After intubation, oral packing may be needed in a patient with
significant mid- and lower-facial bleeding
• Reduction of significantly displaced nasal fractures and Le Fort
injuries may be needed to stop arterial bleeding
• Significant persistent bleeding: immediate operative intervention is
required for ligation of injured vessels or better reduction of fractures
• Arterial embolization may also be effective in controlling bleeding
from branches of external carotid artery
o Associated with a small risk of stroke and other complications
SPECIFIC FACIAL FRACTURES
Frontal Bone Fractures
• Uncommon; results from high-energy mechanisms (unrestrained
motor vehicle crashes or assaults with blunt objects)
• Severe frontal fractures may extend to temporal bones and require
hearing and facial nerve function evaluation (otorrhea = CSF leak)
• Ocular injuries in ~25% (most common finding: RAPD in ~10%)
• Frontal sinus fractures: overlying lacerations, palpable crepitus
o Oral antibiotics (1st-generation cephalosporin or co-amoxiclav)
o Operative repair of through-and-through frontal sinus fractures
to prevent pneumocephalus, CSF leak, and infection
• Rhinorrhea in frontal bone fracture: CSF leak until proven otherwise
o Mucopyoceles (collections of pus from obstructed nasal ducts)
and cranial empyema can result
• Isolated anterior table fracture: may be discharged with nasal and
oral decongestants and appropriate follow-up with a facial surgeon
• Depressed fractures: admit for IV antibiotics & surgery
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Zygoma Fractures
• Zygomatic arch fractures occur when an anterior and lateral force
is applied typically from a fist or blunt object
• Zygomaticomaxillary (“tripod”) fracture: results classically from
high-energy deceleration injury with disruption of zygomaticofrontal
suture, zygomaticotemporal junction, & infraorbital rim (considered
as orbital and sinus fractures)
• Physical examination
o Flattening of malar eminence in absence of significant swelling
o Eye appears tilted as lateral canthus is pulled inferiorly, often
with a large lateral subconjunctival hemorrhage
o Trismus from masseter spasm or mechanical impingement of
either temporalis muscle or coronoid process of mandible
o Tenderness or loss of space of posterior surface of zygomatic
arch adjacent to maxillary molars
o Diplopia, infraorbital anesthesia, crepitus: significant orbital and
sinus involvement
• Isolated temporal arch fractures: discharge with appropriate
medications and follow-up
• Zygomaticomaxillary fractures with any loss of vision or
significant displacement: admission for IV antibiotics & surgery
Midfacial Fractures
• Can be caused by motor vehicle crashes, sports, assault, and falls
due to seizures or intoxication or in the elderly
• Fractures of the maxilla require a significant force
o Unrestrained motor vehicle crash whose face strikes dashboard
o Severely battered patient
• Le Fort injuries often present with significant hemorrhage, requiring
airway protection and nasal packing
o Oral packing for control of fractures involving hard palate
o Require admission for management of significant associated
injuries, IV antibiotics, and surgical repair
Mandible Fractures
• 2nd most common facial fracture after nasal fractures
• Assaults, motor vehicle crashes, and falls
• Should be considered bilateral until proven otherwise
o Always look for multiple mandibular fractures with one injury at
site of impact & a second subtle injury on opposite side of ring
• Comminuted mandibular fractures could results in upper airway
obstruction due to the tongue being unsupported anteriorly
o Presume an open fracture until proven determine otherwise
• Symptoms: malocclusion + pain worsened by attempted movement
• Inspection: mandible may appear widened or displaced to one side
o Patients may present with trismus due to pain and swelling
• Palpation: loss of smooth counters of mandible, tenderness &
anesthesia in area of proximal inferior alveolar or distal mental nerve
• Intraoral examination: exclude small breaks in mucosa seen with
open fractures, sublingual hematoma or ecchymosis, and dental or
alveolar ridge fractures and to identify missing teeth
• Examine the ears for evidence of tympanic membrane perforation,
hemotympanum, or evidence of condyle displacement
o Place finger into external auditory canal and ask patient to open
and close the mouth to palpate for injury to the condyle
• In patients with stable airway: placement of a Barton’s bandage, an
ace wrap over the top of the head and underneath the mandible will
stabilize the fracture and help relieve pain
• Open fractures: admission for pain control, antibiotics, surgery
o Penicillin G 2-4 million units IV
o Clindamycin 600-900 mg (in penicillin-allergic patients)
• Closed fractures: urgent outpatient follow-up
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Schwartz’s Principles of Surgery, 11th edition (2019)
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36. MECHANICAL INTESTINAL OBSTRUCTION Large Bowel Obstruction

INTESTINAL OBSTRUCTION • Most common cause, especially in the elderly
• Inability of intestinal tract to allow regular passage of food & bowel • Cancer of descending colon & rectum is responsible for ~⅔
Neoplasms
of all cases, followed by diverticulitis & volvulus
contents secondary to mechanical obstruction or adynamic ileus
• Incidence is rising in younger patients (<40 years old)
Ileus Bowel Obstruction Diverticulitis • Significant mesenteric edema & secondary obstruction
Pain Mild to moderate Moderate to severe
Stricture
Location Diffuse May localize • Chronic inflammation and scarring
formation
Physical Mild distension, ± Mild distension, tenderness, Fecal
examination tenderness, ↓ bowel sounds high-pitched bowel sounds • Common in elderly or debilitated
impaction
Laboratory Possible dehydration Leukocytosis
• Occurs when bowel twists on its mesenteric axis
Imaging May be normal Abnormal
• Cause partial/complete obstruction & vascular insufficiency
Treatment Observation, hydration Nasogastric tube, surgery
• Sigmoid: most commonly affected (⅔ of cases; 4% of all
cases of large-bowel obstruction)
EPIDEMIOLOGY • Cecal: nonfixation of right colon; rotation occurs around the
• Accounts for ~1-3% of all hospitalizations a quarter of all urgent or ileocolic blood vessels & vascular impairment occurs early
o 10-30% of the cecum folds upon itself (cecal bascule)
emergent general surgery admissions Volvulus
o Has been reported in pregnant patients
• ~80% of cases involve the small bowel, about ⅓ of these show • Transverse colon: nonfixation of colon and chronic
evidence of significant ischemia constipation with megacolon
• Mortality rate for patients with strangulation who are operated on • Risk factors: institutionalization, neuropsychiatric
conditions requiring psychotropic medication
within 24-30 hours is ~8% but triples thereafter (anticholinergic medication), chronic constipation, aging
• Patients typically present in their 70s or 80s
ETIOLOGY
Duodenum Small Bowel Colon PATHOPHYSIOLOGY
• Stenosis • Adhesions • Carcinoma • Normal bowel contains gas as well as gastric secretions and food
• Foreign body • Hernia • Fecal impaction
(bezoars) • Intussusception • Ulcerative colitis o Intraluminal accumulation of gastric, biliary, and pancreatic
• Stricture • Lymphoma • Volvulus secretions continues even if there is no oral intake
• Superior mesenteric • Stricture • Diverticulitis o As obstruction develops, the bowel becomes congested and
artery syndrome (stricture, abscess) intestinal contents fail to be absorbed
• Intussusception o Vomiting and decreased oral intake follow
• Pseudo-obstruction
o Decreased absorption, vomiting, & reduced intake: volume
depletion with hemoconcentration & electrolyte imbalance
▪ May lead to renal failure or shock
• Bowel distension often accompanies mechanical obstruction
o Accumulation of fluids in bowel lumen + increase in intraluminal
pressure with enhanced peristaltic contractions + air swallowing
• Strangulated bowel obstruction: impaired intestinal microvascular
perfusion due to high intramural pressure
o Intraluminal pressure > capillary & venous pressure bowel wall
o Absorption and lymphatic drainage decrease, bowel becomes
ischemic, and septicemia and bowel necrosis can develop
o Shock ensues rapidly (mortality is high)
• Closed loop obstruction: a particularly dangerous form of bowel
obstruction in which a segment of intestine is obstructed both
proximally and distally
o Accumulating gas and fluid cannot escape either proximally or
distally from obstructed segment, leading to a rise in luminal
pressure and a rapid progression to strangulation
o Examples: incarcerated hernia, volvulus, complete colon
Small Bowel Obstruction: accounts for most bowel obstructions obstruction in the presence of a closed ileocecal valve
• Majority of cases of early postoperative obstruction
• Open operations of lower abdomen: appendectomy,
Adhesions
colorectal, gynecologic procedures
• Within 1st few weeks to several months to years postop
Carcinomatosis • From ovary, pancreas, stomach, colon
Internal • Risk is increased by abdominal procedures such as
herniation laparoscopic or open Roux-en-Y gastric bypass
• Polyps, lymphoma, adenocarcinoma
Primary small
• Hamartomatous polyps in Peutz-Jeghers syndrome
bowel lesions
• Between age 10-30 years
• A gallstone has eroded from gallbladder through bowel
Gallstone ileus wall and causes obstruction at ileocecal valve
• Signs: bowel obstruction and pneumobilia
Lymphomas • Leading point of intussusception
• Vegetable matter or pulp from persimmons
Bezoars • Patients undergone GI pyloroplasty or pyloric resection
are most susceptible to intraluminal obstruction
IBD • May obstruct the small bowel at various sites
Radiation • Possible cause of small bowel obstruction in patients
enteritis who have undergone radiation therapy
Blunt • May cause a duodenal hematoma
abdominal • Restrained solely by a lap belt or as a result of striking
trauma the handlebar of a bicycle
Capsule • May be complicated by capsule retention (1-20%): can
endoscopy lead to obstruction and perforation

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CLINICAL FEATURES
History
• Site and nature of the obstruction and the preexisting condition
of the patient will determine the clinical presentation
• Cardinal signs: colicky abdominal pain, abdominal distension,
nausea, emesis, obstipation
o More intraluminal fluid accumulates in patients with distal
obstruction, which typically leads to greater distension, more
discomfort, and delayed emesis
• Nearly universal: generally crampy & intermittent
Abdominal
• Small bowel obstruction: episodic; periumbilical or diffuse
pain
• Large bowel obstruction: usually hypogastric
Abdominal • Most pronounced if site of obstruction is in the distal ileum
distension • Absent if site of obstruction is in proximal small intestine
• More prominent with proximal obstructions than distal
Vomiting • Bilious: proximal obstruction
• Feculent: distal ileal/large bowel (bacterial overgrowth)
• Inability to have a bowel movement or pass flatus
• Partial obstruction: continued passage of flatus and/or
stool beyond 6-12 hours after onset of symptoms
Obstipation
• Complete: evacuate bowel contents beyond obstruction
• Additional risk factors: advanced age, anticholinergic or
tricyclic antidepressant use, which depress bowel motility
• Prior abdominal operations (suggesting presence of adhesions) &
presence of abdominal disorders (intraabdominal cancer or IBD)
Physical Examination
• General Survey
o Most patients appear to be critically ill
o Many may be oliguric, hypotensive, and tachycardic because of
severe intravascular volume depletion
o Fever is worrisome for strangulation or systemic inflammation
• Abdominal Examination
• All surgical incisions should be examined
Inspection
• Meticulous search for hernias (inguinal & femoral regions)
• Early: high-pitched “musical” tinkling hyperactive bowel
Auscultation:
sounds and borborygmi (peristaltic “rushes”)
bowel sounds
• Later: absent or hypoactive (peristaltic activity decreases)
Percussion • Tympanitic
• Tenderness: ischemia, necrosis, peritonitis
• Discomfort out of proportion to physical findings
mimicking acute mesenteric ischemia
Palpation: • Localized or rebound tenderness: gangrenous or
tenderness perforated bowel (immediate surgical intervention)
• Tender abdominal or groin mass: incarcerated hernia
• Severe pain with localization or signs of peritoneal
irritation: strangulated or closed-loop obstruction
• Rectal examination: may identify fecal impaction, rectal carcinoma,
occult blood, or stricture
• Pelvic examination in women to identify gynecologic pathology
o Vaginal pessary: colonic obstruction from extrinsic compression
• Strangulated obstruction
o Abdominal pain often disproportionate to degree of abdominal
findings (intestinal ischemia)
o Tachycardia, localized abdominal tenderness, fever, marked
leukocytosis, acidosis
• Colonic volvulus: classic manifestations of closed-loop obstruction
o Severe abdominal pain, vomiting, obstipation; asymmetrical
abdominal distension and a tympanitic mass
DIAGNOSIS
Laboratory Testing
• CBC & electrolyte levels: results vary widely depending on
duration and site of obstruction and presence of bowel necrosis
o Leukocytosis >20,000/mm3 or left shift: bowel gangrene, intra-
abdominal abscess, or peritonitis
o Leukocytosis >40,000/mm3: mesenteric vascular occlusion
• Serum amylase and lipase levels may be mildly elevated
• ↑ hematocrit, BUN, creatinine: volume depletion and dehydration
• Other indications of severity of obstruction/secondary complications:
o Increased urine specific gravity
o Ketonuria
o Elevated lactate levels
o Metabolic acidosis
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Imaging
• Abdominal series: supine and upright abdominal radiographs with
an upright chest radiograph or a lateral decubitus view
• Dilated small bowel loops (>3 cm in diameter)
Triad for small
• Air-fluid levels on upright films
bowel obstruction
• Paucity of air in the colon
Closed-loop • Bowel lumen is filled with fluid but no gas (no air-
obstruction fluid levels)
• Bent inner tube or coffee bean appearance:
Sigmoid volvulus convexity of the loop lying in RUQ (opposite the
site of obstruction)
• Demonstrates free air (pneumoperitoneum)
Rupture/Perforation
• CT scan with oral and IV contrast
o Presence, location, severity, and cause of obstruction
o In renal insufficiency or contrast allergy: oral contrast alone
• Discrete transition zone with dilation of bowel proximally
Small bowel • Decompression of bowel distally
obstruction • Intraluminal contrast not passing beyond transition zone
• Colon containing little gas of fluid
• Presence of U-shaped or C-shaped dilated bowel loop
Closed-loop
associated with a radial distribution of mesenteric vessels
obstruction
converging toward a torsion point
• Thickening of the bowel wall
• Pneumatosis intestinalis (air in bowel wall)
Strangulation • Portal venous gas
• Mesenteric haziness
• Poor uptake of IV contrast into the wall of affected bowel
• Small bowel series (small bowel follow-through) or enteroclysis
o Abdominal radiographs taken serially as contrast travels distally
▪ Small bowel series: contrast is swallowed or instilled into
the stomach through a nasogastric tube
▪ Enteroclysis: contrast is instilled into the proximal jejunum
via a long nasoenteric catheter
o Advantage: better assessment of mucosal surface & detection
of small lesions even through overlapping small bowel loops
o Disadvantage: more labor-intensive and less readily performed
than CT; rarely performed in the acute setting
• Contrast enema: for large bowel obstructions
o Sigmoid volvulus: bird’s beak (narrowing at site of volvulus)
TREATMENT AND DISPOSITION
• Admit patients with bowel obstruction with surgical consultation
o Vigorous IV fluid resuscitation (isotonic fluids)
▪ Monitor adequacy by BP, heart rate, and urine output
o Gastric decompression via nasogastric tube
▪ Continuous evacuation of air and fluid
▪ ↓ nausea, distension, & risk of vomiting & aspiration
Small bowel obstruction: most can be managed nonoperatively
Partial bowel • Close observation
obstruction • If no improvement within 48 hours: consider surgery
Complete • Early surgical intervention to minimize risk for bowel
bowel strangulation
obstruction • Goal: operate before the onset of irreversible ischemia
Most patients with large bowel obstruction will require surgery
• Tumor resection is the gold standard treatment
Malignancy • Self-expanding endoluminal stents can be used to relieve
the obstruction and avoid emergent surgery
• No signs of gangrene/peritonitis: fluid resuscitation
followed by endoscopic detorsion (rigid proctoscope)
o Risk of recurrence is high (~40%)
Sigmoid o Elective sigmoid colectomy after stabilized &
volvulus undergone an adequate bowel preparation
• With gangrene/perforation, necrotic mucosa, ulceration,
dark blood on endoscopy: immediate surgical exploration
o Sigmoid colectomy with end colostomy
Cecal • Surgical exploration is necessary when diagnosis is made
volvulus o Right hemicolectomy with ileocolic anastomosis
• Surgical emergencies: closed-loop obstruction, bowel necrosis,
and cecal volvulus
o Administer preoperative broad-spectrum antibiotics
▪ Piperacillin-tazobactam 3.375 g IV every 1 hours
▪ Ticarcillin-clavulanate 3.1 g IV every 6 hours
o Operative procedure: adhesions lysed, tumors resected,
hernias reduced & repaired, nonviable bowel resected
References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Schwartz’s Principles of Surgery, 11 th edition (2019)
• Harrison’s Principles of Internal Medicine, 20 th edition (2018)
36. MECHANICAL INTESTINAL OBSTRUCTION | 153
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
37. SPINE TRAUMA
• Can cause a vertebral column injury, a spinal cord injury, or both
• Annual incidence: 15-65 cases per 100,000
• Leading causes of spinal cord injury: vehicular (38%), falls (31%),
and violence (13%)
PATHOPHYSIOLOGY
Spinal Column Injuries
• Cervical spine (C1-C7): particularly vulnerable to injury
o Most exposed, flexible, and mobile portion of the spinal column
• Thoracic spine (T1-T10): rigid segment
o Its stiffness enhanced by articulation with rib cage
o Injury less common than in other regions
o Injury indicates the patient was subjected to severe traumatic
forces and is at high risk for intrathoracic injuries
o Narrower spinal canal: increases risk of cord injury, which is
often complete when it occurs
• Lower lumbar spine (L3-L5): more mobile
o Wider spinal canal: isolated fractures of lower lumbar spine
rarely injure spinal cord or result in neurologic injury
• Sacrum & coccyx: lower portion of the spinal column
o Sacral canal: vertebral foramina; contains the nerve roots of
lumbar, sacral, and coccygeal spinal nerves and filum terminale
o Coccyx: 4 vertebrae fused together
o Neurologic injuries: complete cauda equina lesions or isolated
nerve root deficits
o Sacral fractures that involve the central sacral canal can
produce bowel or bladder dysfunction
• Transition zones: locations where vertebral morphology changes;
sustain greatest amount of stress during motion & are most
vulnerable to injury
o Cervicothoracic junction (C7-T1)
o Thoracolumbar junction (T11-L2): serves as level of transition
from end of spinal cord (about L1) to nerve roots of cauda equina
▪ Wider spinal canal relative to thoracic spine: most do not
have neurologic deficits; if present, partial or incomplete
Fracture Stability
• Spinal stability: ability of the spine to limit patterns of displacement
under physiologic loads so as not to damage or irritate the spinal
cord or nerve roots
• Denis column system: anterior, middle, and posterior segments
o Unstable spine injury: ≥2 columns of a particular region involves
• Assume any spinal fracture is unstable, & maintain appropriate
precautions until expert consultation can be obtained
154 | 37. SPINE TRAUMA
Spinal Cord Injuries
• Primary injury: from mechanical forces that directly traumatize the
spinal cord and vasculature
• Secondary injury: result of series of processes from primary injury
o Initial phase: hemorrhage into cord and formation of edema at
the injured site and surrounding region
▪ Local spinal cord ischemia ensues secondary to vasospasm
& thrombosis of small arterioles within gray & white matter
▪ Edema extension: decrease blood flow & increase ischemia
o Tissue degeneration phase begins within hours of injury
▪ Neural membrane dysfunction: excitation of sodium ion
channels, influx of calcium ions, glutamine release
▪ Cell death ensues from electrolyte imbalances, cell edema,
& formation and release of oxidative substances
Spinal Cord Lesions
Complete • Absence of sensory & motor function below level of injury
neurologic • Loss of function to the level of the lowest sacral segment
lesion • Minimal chance of functional motor recovery
• Sensory and/or motor partially present below level of injury
o Sacral sensation at anal mucocutaneous junction or
Incomplete
voluntary contraction of external anal sphincter DRE
o Expected to have at least some degree of recovery
Spinal • Loss of all reflex activities below the area of injury
shock • Lesions not deemed complete until spinal shock resolved
• Descending and ascending tracts in the spinal cord
o Corticospinal tracts: descending motor pathway
▪ Origin: cerebral cortex (internal capsule & crus cerebri)
▪ Course: breaks up into bundles in pons and finally collects
into a discrete bundle, forming the pyramids of the medulla
▪ ~90% of fibers decussate at the lower medulla & descend
through spinal cord as the lateral corticospinal tract
• Synapse on the lower neurons in the spinal cord
▪ 10% of fibers descend in anterior funiculus of cervical &
upper thoracic levels as ventral corticospinal tract
▪ Damage: ipsilateral muscle weakness, spasticity, increased
deep tendon reflexes, Babinski’s sign
o Spinothalamic tracts: ascending pathway (pain & temperature)
▪ First-order neuron (sensory neuron): ascend 1-2 levels
before entering the dorsal gray matter
▪ Second-order neuron (DRG): crosses midline in anterior
commissure and ascends in anterolateral funiculus as the
lateral spinothalamic tract
▪ Damage: loss of pain & temperature sensation in
contralateral half of body; begins 1-2 segments below
o Dorsal (posterior) columns: ascending pathway (vibration and
proprioception)
▪ First-order neuron (sensory neuron): enter ipsilateral dorsal
column and do not synapse until they reach medulla
▪ Second-order neuron (gracile & cuneate nuclei): cross
midline & ascend in medial lemniscus to thalamus
▪ Injury: ipsilateral loss of vibration and position sense;
begins at the level of the lesion
• Light touch is not completely lost unless there is damage
to both spinothalamic tracts & dorsal columns

CLINICAL FEATURES
History
• Mechanism, place, date, time of injury (MOI, POI, DOI, TOI)
• Symptoms: midline spine pain, painful distracting injury,
paresthesias, loss of function, change in mental status (including
loss of consciousness), or other neurologic symptoms (especially
priapism or urinary or fecal incontinence)
• Symptoms of present/impending respiratory compromise: dyspnea,
palpitations, abdominal breathing, anxiety (high cervical spine injury)
Physical Examination
• Mental status & clinical evidence of intoxication
• Focus on delineating the level of spinal cord injury
• Level of sensory loss; investigate proprioception or vibratory
function to examine posterior column function
• Presence or absence of midline neck or back tenderness
• Motor function for muscle groups
0 No active contraction
1 Trace visible or palpable contraction
2 Movement with gravity eliminated
3 Movement against gravity
4 Movement against gravity plus resistance
5 Normal power
• Test for “saddle anesthesia”: sensory deficit in region of buttocks,
perineum, and inner aspect of thighs
• Test deep tendon reflexes along with anogenital reflexes
o “Sacral sparing” + preservation of anogenital reflexes:
incomplete spinal cord level, even if patient has complete
sensory and motor loss
• Test for bulbocavernosus reflex: squeeze penis to determine
whether anal sphincter simultaneously contracts
• Document anal sphincter tone and sensation around the anus
o “Anal wink reflex”: contraction of anal musculature when
perineal region is stimulated; indicates some sacral sparing
• Test cremasteric reflex: stroke medial thigh with a blunt instrument
o If scrotum rises: some spinal cord integrity exists
Incomplete Spinal Cord Syndromes
• Anterior Cord Syndrome
o Pathology: damage to corticospinal & spinothalamic pathways,
with preservation of posterior column function
o Clinical: loss of motor function, pain & temperature sensation
distal to lesion; vibration, position, & tactile sensation preserved
o Mechanism of injury
▪ Following direct injury to the anterior spinal cord
▪ Flexion of the cervical spine: results in cord contusion or
bone injury with secondary cord injury
▪ Thrombosis of anterior spinal artery: ischemic injury
▪ Extrinsic mass that is amenable to surgical decompression
o Prognosis for recovery of function is poor
• Central Cord Syndrome
o Usually seen in older patients with preexisting cervical
spondylosis who sustain a hyperextension injury
o Pathology: preferentially involves the centrally located fibers of
corticospinal & spinothalamic tracts more than the peripheral
▪ Upper extremity neural tracts: most medial in position
▪ Thoracic, lower extremity, sacral fibers: more lateral
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
o Clinical: decreased strength and, to a lesser degree, decreased
pain & temperature sensation, more in UE than LE
▪ Vibration and position sense are usually preserved
▪ Spastic paraparesis or spastic quadriparesis can be seen
▪ Majority will have bowel and bladder control, although this
may be impaired in the more severe cases
• Brown-Séquard Syndrome
o Pathology: results from hemisection of the cord
o Clinical: ipsilateral loss of motor, proprioception, & vibration
sense; contralateral loss of pain & temperature sensation
o Most common cause: penetrating injury
▪ Can also be caused by lateral cord compression secondary
to disk protrusion, hematomas, spine fractures, infections,
spinal cord, infarctions, multiple sclerosis, or tumors
American Spinal Injury Association (ASIA) Impairment Scale
A Complete: No motor/sensory function is preserved in sacral segments S4-S5
Incomplete: Sensory but not motor function is preserved below neurologic
B
level and includes sacral segments S4-S5
Incomplete: Motor function is preserved below neurologic level, and >1/2 of
C
key muscles below neurologic level have a muscle grade <3
Incomplete: motor function is preserved below neurologic level, and ≥1/2 of
D
key muscles below neurologic level have a muscle grade of >3
E Normal: motor and sensory function are normal
Cauda Equina syndrome
• Not a true spinal cord syndrome because the cauda equina is
composed entirely of lumbar, sacral, and coccygeal nerve roots
• Injuries to this region produce peripheral nerve injuries
• Clinical: bowel and/or bladder dysfunction, decreased anal
sphincter tone, saddle anesthesia, variable motor and sensory loss
in the lower extremities, decreased lower extremity reflexes, sciatica
o Bowel or bladder incontinence is not a universal finding
o Anal sphincter tone can be spared
o If the patient presented acutely, the patient’s bladder may not
yet be full enough to cause overflow urinary incontinence
Neurogenic Shock
• Type of distributive shock that can occur with CNS or spinal cord
injury that probably occurs in <20% of spinal cord-injured patients
• Pathology: loss of peripheral sympathetic innervation results in
extreme vasodilatation secondary to loss of sympathetic tone;
causes blood pooling in distal circulation with resultant hypotension
• If T1-T4 levels are compromised: loss of sympathetic innervation to
the heart leaves unopposed vagal parasympathetic cardiac
innervation, resulting to bradycardia or absence of reflex tachycardia
• Clinical: warm, peripherally vasodilated, ↓ BP, relative bradycardia
o Patients tend to tolerate hypotension relatively well because
peripheral oxygen delivery is presumably normal
o Loss of sympathetic tone and inability to redirect blood from
periphery to core may cause excessive heat loss & hypothermia
Spinal Shock
• Pathology: temporary loss or depression of spinal reflex activity that
occurs below a complete or incomplete spinal cord injury
• Clinical: flaccidity, loss of reflexes, loss of voluntary movement
o The lower the level of spinal cord injury, the more likely it is that
all distal reflexes will be absent
• Loss of neurologic function that occurs with spinal shock can cause
an incomplete spinal cord injury to mimic a complete cord injury
• Duration is variable; lasts for days to weeks, can persist for 6 months
o The delayed plantar and bulbocavernosus reflexes are among
the first to return as spinal shock resolves
37. SPINE TRAUMA | 155
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

DIAGNOSIS Orthotic Devices

Cervical Spine Imaging
• CT: initial imaging modality of choice; can visualize entire spine
o Particularly useful at craniocervical, cervicothoracic regions, &
thoracolumbar injuries in patients with significant trauma
o Reveal anatomy of osseous injury, grade extent of spinal canal
impingement by bone fragments, & assess stability of an injury
o Advantages: more sensitive and specific than plain radiography
for evaluating cervical spine; can be done quickly
• Plain Radiography: largely replaced by CT
o For bony cervical injury: lateral, AP, and odontoid views
o “Swimmer’s view”: image all 7 cervical vertebrae, along with the
superior border of the 1st thoracic vertebra
▪ Requires assistant to pull down shoulders during radiograph
o Advantages: quickly done at bedside; exposes patient to only
small amounts of ionizing radiation
o Disadvantage: misses injuries vs. CT; poor for imaging C1 & C2
• MRI: if a ligamentous or spinal cord injury is strongly suspected
o Excellent sensitivity for soft tissue and spinal cord injuries
o Disadvantages: requires the patient to be stable, availability,
cost, patient tolerance for the procedure
o For symptomatic patients with negative CT who have persistent
neurologic deficits that could be attributed to a spinal lesion and
for patients with a positive CT in order to evaluate the spinal cord
MANAGEMENT
• Goals of treatment
o Prevent secondary injury
o Alleviate cord compression
o Establish spinal stability
Spinal Immobilization
• Minimize forces transferred through the spine and therefore
decrease the chance of causing dislocation, subluxation
o Patient should be kept on a hard, flat board with straps and pads
o A hard-cervical collar is kept in place
• Patient is then moved from the board to a flat stretcher
Airway
• The higher the level of spinal injury, the more likely is the need for
early airway intervention
• Any patient with an injury at C5 or above should have the airway
secured by endotracheal intubation
o Unstable spine lesions above C3: immediate respiratory arrest
o Lesions affecting C3-C5 can affect the phrenic nerve and
diaphragm function
• Rigid external orthotic devices: stabilize the spine by decreasing
range of motion and minimizing stress transmitted through the spine
o Philadelphia, Miami-J collars
• Cervicothoracic orthoses: brace upper thorax and neck, improving
stabilization over the cervicothoracic region
o Minerva braces
• Halo vest assemblies: external cervical stabilization
o For cervical spinal cord injury + vertebral dislocation
o Substituted to a rigid collar after 4-6 weeks
• Thoracolumbosacral orthoses: provides lumbar stabilization
Surgery
• Goals of neurosurgical intervention
o Decompression of the spinal cord and nerve roots
o Stabilization of the spine
• Medical stabilization prior to surgery
o Complete neurologic deficit
o No signs of recovery
o No neurologic deficits with bony or ligamentous injury requiring
open fixation
Complications
• Greatest medical risks occur within the first 10 days when gastric
dilatation, ileus, shock, and infection are threats to life
Continued Care
• Prevention & treatment of DVT, autonomic hyperreflexia, decubitus
ulcer formation
• Prolonged ventilatory support for cervical/high thoracic cord injuries
• Permanent ventilatory support for higher injuries (C4 or above)
• Spinal cord injury rehabilitation centers after stabilization of medical
and surgical issues

Hypotension
• May be due to neurogenic shock, blood loss, cardiac injury, tension
pneumothorax, or other injuries
• Presume blood loss as the cause of hypotension in spinal injury
patients until proven otherwise
• Maintain MAP >85 mmHg for 7 days

Spinal-Dose Steroids (High-dose methylprednisolone)

• Dose: 30 mg/kg IV bolus over 15 minutes, followed by a 45-minute
pause, then continuous infusion at 5.4 mg/kg/h for 23 hours
• Indications: blunt trauma, neurologic deficit referable to the spinal
cord, treatment must be started within 8 hours of injury
• Associated with a higher rate of complications such a pneumonia,
severe sepsis, and poor wound healing
• Inconclusive results (NASCIS I, II, III)

References:
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Schwartz’s Principles of Surgery, 11 th edition (2019)
• Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 20th edition (2017)
• Adams and Victor’s Principles of Neurology, 11 th edition (2019)

156 | 37. SPINE TRAUMA

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

38. THERMAL BURNS Burn Depth

EPIDEMIOLOGY
• ~70% of burn victims are male
• Risk is highest between ages 18 and 35 years
• 77% of all injuries are accounted for by fire or scalding; 43% of scald
injuries occur in children <5 years of age
• Elderly patients have a disproportionately higher death rate
• Risk of death from a major burn increases with larger burn size, older
age, presence of inhalation injury, and female sex
• Superficial burn: skin is red, painful, & tender without blisters
• Superficial partial-thickness burn: blistered, exposed dermis is
red and moist
• Deep partial-thickness burn: skin may not be blistered, & exposed
dermis is pale white to yellow in color; burned area does not blanch;
absent capillary refill and absent pain sensation
• Full-thickness burns: skin is charred, pale, painless, and leathery

PATHOPHYSIOLOGY
• Depth and severity of thermal injury vary by both age of victim and
anatomic location exposed
o Relatively thinner skin at extremes of ages
o Thicker skin on palms, soles, and upper back
• Thermal injury results in a spectrum of local & systemic homeostatic
disorders that contribute to burn shock
o Disruption of sodium pump Burn Depth Features: American Burn Association Classification
Classification Burn Characteristics Disposition
o Intracellular influx of sodium and water
• Partial thickness >25% BSA, age 10-50 y
o Extracellular efflux of potassium • Partial thickness >20% BSA, age <10 or >50
o Depression of myocardial contractility (>60% of BSA burned) • Full-thickness >10% BSA in anyone
o Increased systemic vascular resistance • Burns involving hands, face, feet, or perineum
Burn
• Burns crossing major joints
o Metabolic acidosis Major
• Circumferential burns of an extremity
center
o Increase in hematocrit and increased blood viscosity treatment
• Burns complicated by inhalational injury
o Secondary anemia from erythrocyte extravasation & destruction • Electrical burns
o Local tissue injury • Burns complicated by fracture or other trauma
• Burns in high-risk patients
o Release of histamine, kinins, serotonins, arachidonic acids, and • Partial-thickness 15-25% BSA, age 10-50
free oxygen radicals • Partial-thickness 10-20% BSA, age <10 or >50 Admission
Moderate
• Cell damage occurs at >45°C: denaturation of cellular protein • Full-thickness burns ≤10% BSA in anyone to hospital
• No major burn characteristics present
o Size and depth of resulting burn depends on the burning agent,
• Partial-thickness <15% BSA, age 10-50
its temperature, and duration of exposure • Partial-thickness <10% BSA, age <10 or >50 Outpatient
Minor
• 3 zones of burn wounds • Full-thickness <2% in anyone treatment
o Zone of coagulation: tissue is irreversibly destroyed with • No major burn characteristics present
thrombosis of blood vessels
o Zone of stasis: stagnation of microcirculation
o Zone of hyperemia: ↑ blood flow; minimal damage to cells
▪ Can become progressively more hypoxemia and ischemic if
resuscitation is inadequate
▪ Spontaneous recovery is likely

CLINICAL FEATURES
Burn Size
• Determines fluid resuscitation needs; quantified as the percentage
of body surface area (BSA) involved
o Rule of Nines: divides the body into segments that are ~9% or
multiples of 9%, with perineum forming the remaining 1%
o The area of the back of patient’s hand is ~1% of their BSA, with
the number of “hands” approximate %BSA
o Lund-Browder burn diagram: allows an accurate age-adjusted
determination of burn size for a given depth

38. THERMAL BURNS | 157

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Burn Unit Referral Criteria
• Full-thickness/third-degree burns in any age group
• Partial thickness burns >10% total body surface area
• Burns involving face, hands, feet, genitalia, perineum, major joints
• Electrical burns, including lightning injury
• Chemical Burns
• Inhalational injury
• Burn injury in patients with preexisting medical disorders that could complicate
management, prolong recovery, or affect mortality
• Burn injury in any patient with concomitant trauma (e.g., fractures) in whom
burn injury poses the greatest risk of morbidity or mortality
• Burn injury in children in hospitals without qualified personnel or equipment to
care for children
• Burn injury in patients who will require special, social, emotional, or long-term
rehabilitative intervention
• Burn injury in children <10 y and adults >50 y of age
TREATMENT: Moderate to Major Burns
Prehospital Care
• Stop the burning process
o Extricate the patient from the burning environment
o Burning clothing must be immediately removed
o Remove rings, watches, jewelry, and belts: retain heat and produce a
tourniquet-like effect on extremity, causing ischemia
• Assess and, if necessary, secure the airway
o Primary survey: identify and treat immediately life-threatening conditions
(airway, breathing, circulation)
▪ Give oxygen by facemask
▪ Rapid deterioration may occur even when initial assessment judges
the airway to be acceptable
▪ Consider prophylactic intubation in patients with perioral burns
sustained in a closed-space fire
o Secondary survey: thorough head-to-toe evaluation
• Initiate fluid resuscitation: give IV isotonic crystalloid
• Relieve pain: provide analgesia
• Protect the burn wound: cover the patient with clean sheets
• Transport the patient to an appropriate facility
Initial Assessment
• Directed history
o Burning agent(s), involvement of chemicals, duration of exposure, injury
sustained in an open or enclosed space
o Assess for loss of consciousness, risk of blast injury from explosion,
contact with electricity, or other trauma
o Assess adequacy of, or need for, cervical immobilization
o General history: past medical and surgical illnesses, chronic disease,
allergies, medications, tetanus immunization status
• Physical examination
o Quickly assess respiration & circulation & initiate stabilization
o Examine for signs of inhalation injury: respiratory distress, facial burns,
carbonaceous sputum, singed nasal hair, soot in mouth
▪ Perform early endotracheal intubation if there is any evidence of
airway compromise with swelling of the neck, burns inside the mouth,
or wheezing
o Assess adequacy of circulation: BP, pulse rate, capillary refill time, mental
status, urinary output
▪ Heart rate of 100-120 bpm is considered normal due to
catecholamine response associated with burn injury
o Insert IV lines in unburnt areas
▪ If not possible, a burned area can be used, and resuscitation started
according to a burn fluid resuscitation formula
• Secondary examination: head-to-toe assessment
o Eye examination: corneal burns
• Estimate and record size and depth of burn injury
o In partial-thickness burns >20% BSA: nasogastric tube insertion is
routinely required due to frequent development of ileus
• Insert urinary catheter to measure urine output and prevent urinary retention
in perineal burns
• Routine laboratory tests
o CBC, electrolytes, BUN, creatinine, glucose
o Moderate to severe burns, or suspected inhalational injury: ABG,
carboxyhemoglobin level, serum creatine kinase, urinalysis (myoglobin),
chest radiograph, ECG
o Fiberoptic bronchoscopy: suspected inhalational injury and in intubated
patients (diagnostic and therapeutic)
Fluid Resuscitation
• Guided by monitoring cardiorespiratory status and urine output
o Frequent assessment of vital signs, cerebral and skin perfusion,
pulmonary status, and urinary output
o Target urine output: 0.5-1.0 mL/kg/h
158 | 38. THERMAL BURNS
Wound Care
• Initially, wounds are best covered with a clean, dry sheet
• Later, small burns can be covered with a moist saline-soaked dressing while
the patient is awaiting admission or transfer
• Soothing effect of cooling on burns: due to local vasoconstriction
• Cooling stabilizes mast cells and reduce histamine release, kinin, formation,
and thromboxane B2 production
• For large burns, sterile drapes are preferred, because application of saline-
soaked dressing to a large area can cause hypothermia
• Escharotomy
o Indication: vascular compromise of distal circulation due to
circumferential deep burns of limbs
o Monitoring: pulses, capillary refill, pulse oximetry, and skin temperature,
as well as Doppler flow
o Procedure: eschar is incised with a scalpel to the level of the fat on the
mid-lateral portion of the limb (avoid fasciotomy)
o Circumferential burns of chest & neck: may restrict ventilation
▪ Escharotomy of chest wall to allow adequate ventilation
▪ Incision on AAL from 2nd rib to 12th rib
o Disadvantage: may provoke substantial soft tissue bleeding
Pain Control
• Superficial partial-thickness burns are the most painful
• Burn injury can cause hyperalgesia, chiefly mediated by A
• Local cooling may be soothing but does not provide pain control and can
cause hypothermia
• During the acute phase, preferred route for most medication is IV
o Opioids (morphine, fentanyl, hydromorphone) are the mainstay of
treatment, and relatively large doses may be required
o Anxiolytic agents may also be given
• Ensure adequate analgesia for patients being discharged
TREATMENT: Minor Burns
• Minor burns should be isolated, should not cross joints or be circumferential,
and should not meet criteria for burn center care
• Managed as outpatients
• Topical antimicrobials (antiseptics or antibiotics)
o 1% silver sulfadiazine
▪ Advantages: easy application, minimal toxicity
▪ Do not use on the face: stains the skin gray
▪ Should not be used in infants <2 months
o 8.5% mafenide acetate cream
▪ Penetrated the eschar well
▪ Useful in treating patients with invasive infections
▪ Disadvantages: can cause metabolic acidosis (carbonic anhydrase
inhibitor); not used for large burns for outpatients
o 0.2% nitrofurazone
▪ Supplied in a polyethylene glycol vehicle: toxic if absorbed in patients
with compromised renal function
▪ Not good choices for large burns in an outpatient setting
• Dressings should ideally be changed twice daily, gently removing residual
ointment, for as long as the wounds continue to weep, then daily until healing
is complete
• Synthetic occlusive solid, or biological dressing
o Alternative methods of managing partial-thickness burns
o Wounds are cleansed and debrided prior to application
o Ex: clear occlusive synthetics, foam or hydro-fiber dressing impregnated
with antiseptics, treated biologic membranes
o Goal is for the dressing to act as artificial skin
• Reassess burn wounds at 24-48 hours: depth & extent of burn
• Discharge instructions
o Home burn care
o Pain control
o Symptoms and signs of infection
o Burned extremities: elevated for 24-48 hours to prevent edema
• Refer to plastic surgery or burn care specialist for patients with deep-partial
thickness, full-thickness, and mixed-thickness burns not requiring admission
in 2-4 days for reevaluation and consideration for skin grafting
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

39. FRACTURES
• Disruption of bone tissue
• May be caused by
o Application of force exceeding the strength of the bone
o Repetitive stress
o Invasive process that undermines the bone’s integrity
TYPES OF FRACTURES
• Result of significant trauma to healthy bone
“Common” • Bony cortex may be disrupted by a variety of forces: direct
Fractures blow, axial loading, angular (bending) forces, torque
(twisting stress), or a combination of these
• Result from relatively minor trauma to diseases or otherwise
abnormal bone
• Preexisting process has weakened the bone and rendered
it susceptible to fracture by forces that, under normal
circumstances, would not disrupt the cortex
Pathologic
• Examples: fractures through metastatic lesions, benign
Fractures
bone cysts, vertebral compression fractures in patients with
advanced osteoporosis, osteogenesis imperfecta, Paget’s
disease, osteomalacia
• Subtle pathologic fractures may go undetected unless there
is a clinical index of suspicion
• Bone may undergo a “fatigue” fracture by being subjected
to low-intensity trauma or repetitive forces before the bone
and its supporting tissues have had adequate time to
accommodate to such forces
• Often involve the lower extremity, common in athletes
(runners or dancers), and occurs in deconditioned
Stress
individuals who begin new exercise programs
Fractures
• “March fracture”: metatarsal shaft fracture in unconditioned
foot soldiers
• Diagnosis: history + point tenderness or localized swelling
• Differentials: muscle strain, bursitis, exertional
compartment syndrome, nerve entrapment
• Detected by triple-phase nuclear bone scans
• Fractures involving physis (cartilaginous epiphyseal plate
Salter near the ends of long bones of growing children)
(Epiphyseal • Cannot occur in fully grown adults
Plate) • Damage to epiphysial plate during a child’s growth may
Fractures
destroy part or all of its ability to produce new bone
substance, resulting in aborted or deformed growth of limb
ORTHOPEDIC EMERGENCIES
Open Fracture: associated with overlying soft tissue injury, creating
communication between fracture site and skin
• Any puncture wound extending to the depth of an underlying fracture
o By external forces or within (sharp bone fragment transiently
protrudes through skin before receding back beneath surface)
• Potential major complication: osteomyelitis
o May result in months or years of pain, disability, medical therapy,
surgical procedures, and in some cases, amputation
• Gustilo-Anderson Open Fracture Classification System
Low energy injury with an open wound <1 cm in length and no
Grade I
evidence of contamination
Moderate injury with communication of fracture and a 1-10 cm
Grade II
wound with some contamination
High-energy fracture pattern with a wound >10 cm and gross
Grade IIIA
contamination
High-energy fracture with >10 cm contaminated wound with
Grade IIIB
exposed bone
Grade IIIC Similar to grade IIIB with vascular involvement
Subluxation and Dislocation
• Subluxation: articular surfaces of joint nonconcentric to any degree
• Dislocation: most extreme form of subluxation
• Reduction is based on potential neurologic or circulatory
compromise & length of time of dislocation (more difficult to reduce)
• Hip dislocation: potential for avascular necrosis of femoral head
o Circulation to the femoral head is disrupted due to dislocation of
the joint (vessels emerge from the acetabulum)
Neurovascular Injury
• Should be addressed as soon as possible
• The longer such a deficit goes untreated, the longer it is likely to
persist and the greater the possibility that it will be irreversible
• In some cases, reducing a deformity by means of longitudinal
traction is all that is necessary to restore circulation/nerve function
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
CLINICAL FEATURES
History
• Mechanism, place, date, time of injury (MOI, POI, DOI, TOI)
Mechanism Possible Injury
Bilateral compression of the Anterior or posterior sternoclavicular
shoulders dislocation
Direct blow to the medial clavicle Posterior sternoclavicular dislocation
Fall, landing on apex of shoulder Acromioclavicular separation
Direct blow to anterior shoulder, fall
on outstretched arm, seizure or Posterior dislocation of shoulder
electroconvulsive muscular activity
Subluxed radial head (sometimes
Sudden traction force to a toddler’s
misdiagnosed as brachial plexus injury
arm
because of pseudoparalysis of arm)
Fall, landing on outstretched arm or Fracture of radial head (may be occult
with elbow beneath body on initial radiography)
Scaphoid fracture, lunate dislocation,
Forced dorsiflexion of wrist
perilunar dislocation, Colles’ fracture
Striking knee against dashboard in
Posterior dislocation of hip
high-speed collision
Calcaneus fracture; tibial plateau
Landing flat on fleet from a height fracture; acetabular fracture; vertebral
compression fracture, usually lumbar
Fracture of any of 3 malleoli, fracture of
Ankle inversion force
base of 5th metatarsal
Fracture of any of 3 malleoli, disruption
of anterior tibiofibular ligament with
Rotatory ankle force
proximal fibular fracture
(Maisonneuve’s injury)
Inversion or medial or lateral stress
to forefoot; axial load on metatarsal Midfoot dislocation (Lisfranc’s injury)
heads with ankle plantarflexed
• Indirect injury resulting to gradual and insidious onset of symptoms
o Occult fracture of hip in an osteoporotic individual
o Occult stress fracture of metatarsal in someone who has
recently done an unusual amount of walking
o Slipped capital femoral epiphysis in a preteenager or young
adolescent
• General medical history
o History of cancer
o Heart disease or neurologic disease
o Anticoagulant medication
o Falling due to syncope or transient hemiparesis
o Unsteady baseline gait that cannot withstand further impairment
Physical Examination
• Inspection and Range of Motion
o Preternatural mobility: pathognomonic of fractures
o Deformity at a joint, loss of range of motion, and severe pain at
rest suggest the presence of a dislocation or fracture near joint
▪ Exception: posterior dislocation of shoulder (may not
accompany obvious deformity; humeral head palpated)
• Palpation
o When gross deformity is not present, presumptive diagnosis
strongly depends on findings noted on palpation
o Areas of bony step-off, precise location of point tenderness
o Area palpated should extend well beyond the location of pain
described by patient (referred pain)
• Neurovascular Assessment
o When injury involves an extremity, sensorimotor testing should
be performed on the basis of peripheral nerve function rather
than nerve root and dermatomal distribution
o Upper extremity: radial, median, and ulnar nerves
▪ Anterior dislocation of shoulder: axillary (sensation to lateral
shoulder) & musculocutaneous (extensor forearm)
o Lower extremity: saphenous (sensory), peroneal, & tibial nerves
o Neurologic deficit is important to document early, particularly
before patient has undergone any significant manipulation or
reduction maneuvers
o Assess vascular status early
▪ Sooner circulatory compromise is identified & addressed,
better chance of avoiding tissue ischemia or necrosis
▪ Injuries such as knee dislocation, fracture-dislocation of
ankle, and displaced supracondylar fracture of elbow in
children may be associated with vascular disruption
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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
DIAGNOSIS
Imaging
• Plain Radiographs: mainstay for fracture diagnosis
o Joints above and below a fracture should generally be imaged
▪ Injury at proximal or distal joint may coexist with long-bone
fractures
o Also helpful in detecting foreign bodies, air, or gas
o Orthogonal views: at least 2 perpendicular views are necessary
when evaluating long bones
o Negative radiologic report does not exclude significant injury
• Soft Tissue and Musculoskeletal Ultrasound
o Noninvasive, quick, and allows for comparison of affected side
to an unaffected side
o Tendon evaluation, joint effusion evaluation, muscle evaluation,
foreign body identification, procedural guidance
o Used in conjunction with plain radiographs
160 | 39. FRACTURES
TREATMENT
Control Pain and Swelling
• Application of cold and elevation are often quite effective in keeping
swelling to a minimum or at least halting its progression
• Jewelry, watches, or rings that may cause compression or
constriction as extremity swells should be removed immediately
• Administer analgesics as necessary
o If relatively comfortable at rest, medication may not be required
o Consider alternative pain control methods: local injection,
hematoma blocks, regional blocks
Withhold Oral Intake
• Any possible candidate for prompt surgical fixation, manipulation, or
any procedure under general anesthesia or procedural sedation
Reduce Fracture Deformity
• Long-term purpose: restoration of normal appearance and function
• Short-term benefits
o Alleviate pain
o Relieve tension on nerves or vessels that may be stretched
o Eliminate/minimize possibility of inadvertently converting closed
fracture to open when skin is tented by sharp bony fragment
o Restoring circulation to a pulseless distal extremity
• After appropriate sedation, deformity at or near midshaft of a long
bone is usually reduced with gradual, steady, longitudinal traction
• Any rotational deformity should be corrected only after angular
component is addressed; performed while traction is maintained
• The nearer a deformity is to a joint, more difficult it may be to correct
& more specialized the reduction maneuver may have to be
• Deformity with circulatory deficit (true emergency): anticipated delay
until reduction should be considered
Reduce Dislocations
• Prereduction radiographs are advisable when there has been
significant trauma, unless time is crucial (circulation is threatened)
• Postreduction radiographs are valuable for confirming success of
procedure, as well as for providing documentation if redislocated
Initial Management of Open Fractures
• Tetanus prophylaxis, irrigation, debridement, and antibiotics
• Antibiotics: 1st-gen cephalosporin; add aminoglycoside when
wound >10 cm with severe soft tissue injury & loss of bone coverage
o Alternatives: ciprofloxacin, penicillin (or metronidazole,
clindamycin, or vancomycin) for anaerobic coverage
• Debridement & irrigation: ↓ bacterial contamination & colonization
o Expose wound in order to allow better identification if limits of
injury and facilitate inspection for foreign material
o Identify and remove clots, debris, and nonviable tissue
o Reduce bacterial contamination and make wound more
resistant to effects of any residual contamination
Indications for Referral to Orthopedics
• Compartment syndrome
• Irreducible dislocation
• Circulatory compromise
• Open fracture
• Injuries requiring surgical intervention
DISCHARGE INSTRUCTIONS
• Elevate injured part above heart to help minimize pain and swelling
• Watch out for excessive swelling, decreased sensation, or cyanosis
of fingers or toes, and significant increase in pain
COMPLICATIONS
• Hemorrhage, neurologic deficit, vascular injury, compartment
syndrome
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

40. ACUTE URINARY RETENTION CLINICAL FEATURES

• Common painful urologic emergency
• Characterized by an inability to pass urine, with lower abdominal
distension or pain
EPIDEMIOLOGY
• Most patients are elderly men with benign prostatic hyperplasia
o 1 in 10 men in their 70s had an episode of acute urinary retention
o 1 in 3 men had one in their 80s
o 20% recurrence rate within 6 months of an episode of urinary
retention due to benign prostatic hyperplasia
• Uncommon in women (3 out of 100,000 cases yearly)
o Causes: bladder masses, gynecologic surgery, pelvic prolapse
ETIOLOGY
History
• Most common presentation: elderly male with inability to void for
several hours & lower abdominal distension/pain, secondary to BPH
• Consider urinary retention:
o In lower abdominal pain, even if no urinary complaints
o As an underlying risk factor when finding a urinary tract infection
• Urinary symptoms:
o Urinary urgency, frequency, or hesitancy
o Decreased force and caliber of stream
o Terminal dribbling
o Nocturia
o Incontinence (typically due to overflow phenomena)
• Detailed neurologic history: look for causative lesion from high
cortical function to peripheral nerves (determine end-organ function)
o Possible spinal cord injury: recent activities including any trauma
• PMH: prostatism, prostate/urinary bladder cancer, nephrolithiasis,
indwelling urethral catheter/injury, prostate surgery, bladder
prolapse, pelvic radiation therapy, recent general/spinal anesthesia
o Inquire about Foley catheter insertion, cystoscopy, trauma,
radiation therapy, prior infection (urethral structure)
• Review medication list for anticholinergic, sympathomimetic,
nonsteroidal, and narcotic medications

Physical Examination
• Fever & hypotension: more suggestive of infection or
sepsis than active urinary retention
Vital Signs
• Hypertension, tachycardia, & tachypnea: pain related;
may resolve after bladder decompression
• Palpate or percuss from epigastric area to lower abdomen
Abdominal
to identify a painful mass (distended bladder) in the lean
examination
patient
External • Identify phimosis, paraphimosis, meatal stenosis or
genitalia stricture, or evidence of urethral or penile trauma
• Evaluate the anal-rectal area & prostate
Digital
• Assess anal tone, perineal sensation, prostate
rectal
enlargement, stool impaction, or evidence of malignancy
examination
• A nodular or hard prostate may suggest prostate cancer
Pelvic • Women with urinary retention for possible inflammatory
examination lesions or pelvic/adnexal masses
Neurologic
• Assess for a neurogenic cause
examination
• After successful drainage of distended bladder, repeat physical
examination of lower abdomen to evaluate for an unresolved
extraurinary bladder problem (e.g., appendicitis)

DIAGNOSIS
PATHOPHYSIOLOGY • Bedside ultrasound: easily identify bladder distension
• Micturition (voiding process): complex integration & coordination of o Measure bladder volume & assess possible hydronephrosis
o High cortical neurologic: sympathetic, parasympathetic, somatic • Urinalysis: assess for UTI which may be cause or result of retention
o Muscular functions: detrusor and sphincter smooth muscle
• Further diagnostic tests depend on nature of clinical presentation,
Voiding Urine Storage
Contraction Relaxation
precipitating factors, and patient’s comorbidities
Bladder detrusor • For massive hematuria or in those presenting as septic
(cholinergic muscarinic (β-adrenergic stimulation &
muscle CBC
receptors) parasympathetic inhibition) • Gross hematuria: infection, bladder calculi, neoplasm
Bladder neck & Relaxation Contraction Renal function • Prolonged retention
urethral sphincter (α-adrenergic inhibition) (α-adrenergic stimulation) tests & serum • Risk factors for kidney injury (DM, HTN, prior AKI)
• Urinary retention: inability to void voluntarily despite a distended electrolytes • Hydronephrosis
bladder resulting from dysfunction of detrusor muscle and/or • Identify pelvic or abdominal masses or bladder stones
Abdominal CT
coordination of bladder outlet • Not routine if symptoms resolve after catheterization
o Extrinsic compression (benign prostatic hyperplasia): history Spinal imaging • Concerns for cord compression or cauda equina
of weakened urine stream despite forceful and prolonged
TREATMENT
detrusor contraction
o Chronic decompensation of urination: diminished detrusor
muscle contractility more pronounced, with large amount of
residual urine volume compared to acute decompensation
• Postobstructive acute kidney injury: follows after prolonged
complete bladder outlet obstruction
• Postobstructive diuresis: upon relief of prolonged obstruction
o Occurs in 0.5-50% of acute urinary retention cases
o Represents normal physiologic response to excess volume and
solutes accumulated during period of prolonged obstruction
o Absence of diuresis in patients with significant elevation in
serum creatinine predicts poor kidney recovery

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Urethral Catheterization Technique

• Use a standard 14F to 18F Foley catheter
• Do not inflate the retention balloon until urine begins to flow through
the catheter
o Severe pain with catheter balloon inflation: inflated prior to
entering bladder and could cause urethral damage, in addition
to not effectively draining bladder
o Forceful attempts at catheter removal with balloon still inflated
can cause edema and tears to urethra
o Adequately secure catheter to the thigh after insertion
• Causes of unsuccessful passage of Foley catheter
o Stricture
o External urethral compression
o Kinking of catheter within urethra
o Creation of a false lumen (catheter tunnels through urethral wall
into surrounding soft tissue)

Suprapubic Catheterization Technique
• Can be performed in patients after failure of urethral catheterization
if no obvious pelvic trauma or abnormal anatomy in lower abdomen
• May be the only option to decompress an extremely painful,
distended bladder with urethral catheterization is not possible
• Ultrasound-guided suprapubic catheterization
o Visualize distended bladder, making sure no loops of bowel are
present between bladder and insertion site
o Insertion site: 3-4 cm superior to pubic symphysis in midline
o Asepsis & antisepsis (betadine or chlorhexidine)
o Anesthetize skin and soft tissue
o Advance needle posteriorly and caudally at 30° angle from true
vertical (or 60° from horizontal plane of abdomen)
o A small skin incision may be necessary to facilitate passage of
catheter into bladder
• Obturator Technique
o Insert needle obturator into urinary catheter and lock into port
o Ultrasound visualization of needle advancement into bladder
and return of urine indicate correct placement
o After entering bladder, advance obturator/catheter system
another 3 cm, then unlock obturator and advance catheter an
additional 5 cm before withdrawing obturator needle, leaving
catheter in the bladder
o Inflate balloon and pull back on catheter until slight resistance is
met as the balloon engages with anterior bladder wall
Postcatheterization Care
• Reassess after urinary catheter insertion: resolution of symptoms
o Long-standing obstruction: at risk for postobstructive diuresis
and postobstructive acute kidney injury (more common when
large urine volumes are drained: 800-1500 mL)
o Other risk factors for postobstructive diuresis: prior renal
insufficiency, heart failure, altered mental status, illness severity
requiring ICU admission
• Monitor for 4 hours minimum for significant hourly urinary output
(>200 mL/h over intake) after initial return
o If this degree of output continues, admit patient with volume
replacement adjusted hourly according to urine output
o Significant elevations of BUN or creatinine should be admitted
• Pharmacologic therapy with α-adrenergic receptor antagonists
o Alfuzosin 10 mg daily, tamsulosin 0.4 mg daily
o Exert effects on bladder neck and prostate
o May relax bladder smooth muscle, reducing outlet resistance to
urinary flow
o May shorten interval of time before a successful voiding trial and
prevent recurrent episodes
o Adverse effect: postural hypotension
DISPOSITION AND FOLLOW-UP
• Most are discharged home with a urinary catheter
• Watch out for fever, persistent vomiting, abdominal pain, decreased
urinary output, penile pain (migration of balloon to proximal urethra)

Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)

162 | 40. ACUTE URINARY RETENTION


41. OCULAR TRAUMA
BLUNT EYE TRAUMA
Clinical Findings and Diagnosis
• First steps: assessment of visual acuity, anterior chamber, and
integrity of the globe
• Eyelids frequently swell shut, making visualization of globe difficult
o Insertion of a paper clip bent in an appropriate shape or an
eyelid speculum provides a significantly improved view of the
cornea and anterior chamber
• If the anterior chamber is flat, a ruptured globe is certain
o Suspected due to loss of visual acuity, flat anterior chamber,
obvious full-thickness laceration, or intraocular foreign body
o DO NOT manipulate the eye or measure intraocular pressure
o Stop the examination, place a metal shield over the injured eye,
and consult ophthalmology
• If globe appears intact & vision is preserved, check ocular motility
o Restricted up gaze or lateral gaze suggests a blow-out fracture
with entrapment, and a CT scan of facial bones is obtained
o Head CT scan: assess for associated intracranial injury
• Feel the orbital rim above and below for step-off deformities
• Test for cutaneous sensation along the distribution of inferior
orbital nerve (below the eye and ipsilateral side of nose)
• Slit lamp examination with fluorescein staining: for abrasions,
lacerations, foreign bodies, hyphema, iritis, lens dislocation
o Traumatic iritis is common, causing cells and flare to be seen
o Pupil can be constricted or dilated after sustaining trauma
o Look for pupillary irregularity because the pupil often will peak
toward the site of a penetration or rupture
o If anterior chamber is normal (not shallow), apply mydriatic
o Nonwhite, brown-eyed individuals frequently will require an
additional drop of a mydriatic to achieve adequate dilation
• Measure intraocular pressure if no signs of a ruptured globe
• If vision, ocular anatomy & function is preserved, outpatient follow-
up by an ophthalmologist in the next 48 hours should be planned
Hyphema
• Blood or clots in the anterior chamber
• Traumatic hyphema: from bleeding from a ruptured iris root vessel
• Spontaneous hyphema: associated with sickle cell disease
• History: ask about anticoagulant or antiplatelet medication use or
history of bleeding diathesis
• A hyphema may layer out posteriorly when lying flat and may only
become grossly evident when sitting upright
• Complications: increased intraocular pressure, rebleeding,
peripheral anterior synechiae, corneal staining, optic atrophy,
accommodative impairment
o Patient with large hyphemas, sickle cell disease, and bleeding
tendency are more likely to develop vision loss
o High risk for complications: suspected ruptured globe, sickle cell
disease, anticoagulant intake, bleeding diathesis
• Microhyphema: suspension of RBCs in the anterior chamber
without formation of a layered blood clot
o Seen with a slit lamp and can progress into a hyphema
o Complication: rebleeding, increased intraocular pressure
o Patients with sickle cell disease are more likely to develop
complications
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Treatment: prevent rebleeding and intraocular hypertension
o Elevated patient’s head 45° to promote settling of suspended
RBCs inferiorly to prevent occlusion of trabecular meshwork
o Treatment modalities: antifibrinolytic agents (oral and systemic
tranexamic acid), corticosteroids (systemic and topical),
cycloplegics, miotics, aspirin
• Rebleeding can occur 3-5 days later in ~30% of cases, sometimes
causing severe elevation of intraocular pressure and necessitating
surgical anterior chamber “washouts”
• Disposition: admit all patients with significant hyphemas
o ≤⅓ of anterior chamber: followed closely as outpatients
o Topical steroids: prevent posterior synechiae & treat iridocyclitis
Orbital Blow-Out Fractures
• Most frequent sites
o Inferior wall: maxillary sinus
o Medial wall: ethmoid sinus through the lamina papyracea
• ~⅓ are associated with ocular trauma (abrasion, traumatic iritis,
hyphema, lens dislocation/subluxation, retinal tear, or detachment)
• Fractures of medial wall can be associated with subcutaneous
emphysema, sometimes exacerbated by sneezing or blowing nose
• Fractures of inferior wall with entrapment of inferior rectus muscle
can cause restriction of up gaze and diplopia
o Especially in children, tight entrapment of an ocular muscle or
swelling putting pressure on the globe may stimulate the
oculovagal reflex (oculocardiac reflex), yielding nausea,
vomiting, bradycardia, and hypotension of varying degrees
• Tight entrapment: oculovagal reflex + CT findings demonstrating
large tissue herniation through a narrow bone fragment separation
o All entrapment (diplopia, limitation of ocular motility, CT findings,
proptosis) should be referred to ophthalmology for management
• Suspected on clinical examination and confirmed by CT scan
• Management
o Isolated blow-out fractures without entrapment and without eye
injury do not require immediate surgery
▪ Refer to ophthalmology, plastic surgery, oral maxillofacial
surgery, or ENT for repair within 3-10 days
o Oral antibiotics (cephalexin 250-500 mg PO 4 times daily for
10 days): often recommended due to sinus wall fractures
• Watch out for new symptoms of diplopia, nausea, vomiting
• All blow-out fractures with normal initial eye examination should be
referred to an ophthalmologist for dilated examination to rule out
any unidentified retinal tears or detachments
o Complete eye exam can be done as outpatient in 24-48 hours if
no need for admission or immediate surgery
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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
Ruptured Globe
• Vision-threatening emergency that may be easily missed
• Patient will usually complain of eye pain ± decrease in visual acuity
• Periorbital ecchymosis and maxillofacial fractures, including blow-
out fracture with limitation of extraocular muscle movement, should
raise one’s suspicion for globe rupture
• Scleral rupture may occur from blunt or penetrating trauma
o Blunt trauma directly to eyeball (a blow by a fist): sudden
elevation of intraocular pressure
▪ Globe tends to rupture at the thinnest points of the sclera
(limbus & extraocular muscle insertions)
▪ Any object that impacts orbital rim at high velocity & causes
a seal around orbit (tennis balls) will also cause a sudden
peak in intraocular pressure and may result in rupture
▪ A history of ocular surgery or previous ocular injury may
predispose to globe rupture
o Penetrating trauma: bullets, pellets, knives, sticks, darts,
needles, hammering, lawn mower projectiles
▪ Any projectile injury has the potential for penetrating the eye
▪ Suspected with any puncture or laceration of the eyelid or
periorbital area
• Occult globe penetration
o The smaller the diameter of offending object, the higher is the
likelihood of occult injury
o Corneal abrasions occurring with hammering metal on metal,
associated with use of high-speed machinery (lawn mowers, line
trimmers, grinders, drills), sustained during explosions
• Management: cover eye with a metal eye shield or make a shield
from a paper cup whenever globe rupture is obvious or suspected
o Consult ophthalmology immediately (no further manipulation)
o Elevated head of bed to 45°
o Broad-spectrum IV antibiotics (vancomycin + ceftazidime)
o Give tetanus toxoid as appropriate
o Provide sedation and analgesia
o Administer antiemetics: prevent increased intraocular pressure
and extrusion of intraocular contents from vomiting
o Avoid any topical eye solutions
o Start NPO anticipating surgery
• Eye examination: decreased visual acuity, irregular or teardrop-
shaped pupil, afferent pupillary defect, shallow anterior chamber,
hyphema, positive Seidel test, lens dislocation
o Very suspicious: large subconjunctival hemorrhage involving
entire sclera or hemorrhagic chemosis (bullous, raised
subconjunctival hemorrhage)
o Uveal prolapse through a scleral wound: brownish-black
discoloration against white sclera
• Slitlamp examination: corneal laceration, intraocular foreign body
o ± Seidel test with small corneal laceration
• Funduscopic examination: poor view of optic nerve and posterior
pole due to vitreous hemorrhage
164 | 41. OCULAR TRAUMA
Orbital Hemorrhage
• Postseptal hemorrhage (retrobulbar hematoma)
o Vision-threatening, can cause an orbital compartment syndrome
o Abrupt increase in intraocular pressure, resulting in decreased
blood flow to optic nerve and its blood supply and loss of vision
• Clinical findings: eye pain, proptosis, impaired extraocular
movements, decreased vision, possibly an afferent pupillary defect,
and elevated intraocular pressure
• Diagnosis: PE, noncontrast orbital CT scan
• Refer to ophthalmology
CHEMICAL OCULAR INJURY
• True ocular emergency
• Complications: scarring of cornea with permanent loss of vision
and loss of the eye due to corneal perforation
• Management: immediate irrigation of the eyes with 1-2 L normal
saline before any examination
Alkali and Acid Injuries
• Alkali injuries occur more frequently than acid injuries
o Causes: ammonia (household cleaners), lye (drain cleaners)
o Liquefactive necrosis: denaturing of proteins and saponification
of fats, allowing deep penetration into tissue
• Acid causes coagulation necrosis: denaturing of protein forming a
coagulum that acts as barrier to further tissue penetration
• Treatment: irrigation should begin at the scene
o Instill topical anesthetic & continue irrigation for ≥30 minutes
o Check pH with litmus paper on inferior conjunctival fornix
▪ pH >7.4: continue irrigation until neutral pH 30 minutes later
o Irrigation: sterile normal saline or other isotonic solution
o After irrigation and maintenance of ocular pH >7.4
▪ Perform eye examination
▪ Inspect facial skin and eyelids for burns
▪ Evert eyelids and remove any particulate matter
• Refer to ophthalmology for all but minor burns
o Any patient with corneal clouding or an epithelial defect after
irrigation should receive prompt ophthalmology referral
o Topical cyclopegic agent (cyclopentolate 1%, 1 drop) 3 times
daily for pain reduction if an epithelial defect is present
o Erythromycin ophthalmic ointment 4 times/d to affected eyes
o Doxycycline 100 mg BID to reduce risk of corneal melting
o Tetanus toxoid as appropriate
o Topical corticosteroids after ophthalmology referral if
recommended to control inflammation
Cyanoacrylate (Super Glue)
• Can cause adherence of lids & clumps of adhesive to form on cornea
o Mechanical abrasive effect of hard, irregular glue aggregates,
rubbing against the cornea with eye movement and blinking may
cause corneal abrasions
• Treatment: generous amounts of erythromycin ointment onto eye
and on surface of eyelids to moisten, lubricate, & antibiotic coverage
o Clumps of glue on the surface should begin to loosen
o Remove only those pieces that are easily removable
o Gentle traction may separate the lids
o The glue will loosen and become easier to remove in a few days
• Refer to ophthalmology within 24 hours for complete removal
Reference: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th edition (2020)
 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

42. FOREIGN BODY IN THE ESOPHAGUS/AIRWAY Physiology of Swallowing

Case Oral • Oral preparatory: processing of bolus to render it soft to swallow
A 4-year-old female was seen by her mother to have swallowed a 5-peso coin. (voluntary) • Oral propulsive: propelling of food from oral cavity to oropharynx
Patient immediately displayed gagging, dysphagia, and drooling. There was no • Occurs in about a second
note of difficulty in breathing. This prompted consult at the emergency room. Pharyngeal
• Soft palate elevates, tongue pushes bolus posteriorly, larynx
Salient Features (involuntary)
elevates, epiglottis retroflexes
Subjective Objective Esophageal • Involves the cricopharyngeal and inferior constrictor muscle
• (-) dyspnea, coughing, cyanosis, • 4-year-old female (involuntary) relaxes, allow the food to pass into the esophagus
hoarseness • No stridor, wheezes, cyanosis
• (+) dysphagia, vomiting, drooling • Clear and equal breath sounds
Anatomy of the Esophagus
• (+) drooling
• Muscular tube about 25 cm long
Physiology of Swallowing • Begins at the lower border of the cricoid cartilage (C6)
Swallowing occurs in 2 stages, oropharyngeal and esophageal stages: • Descends in front of the vertebral column through the superior and
At the start of the swallow, a food posterior mediastina
bolus is voluntarily pressed by the • Passes through the diaphragm and enters the abdomen at the 10th
tongue up against the roof of the thoracic vertebra
mouth, and backwards towards the
pharynx • 2 Curvatures
o Cervical esophagus: curved to the left
Then response to activation of o Thoracic esophagus: convex to the right
pharyngeal pressure receptors, the • 4 points of narrowing
swallowing center in the medulla
initiates reflexes that prevent food o Cricopharyngeus
entry into respiratory passageways o Arch of the aorta
o Left mainstem bronchus
o Hiatus of the diaphragm
• The uvula contracts, which
blocks the nasal passages from 3 Clinical Phases of Foreign Body Ingestion/Aspiration
the pharynx • Dysphagia, choking, gagging and paroxysms
Initial stage (Impaction) of coughing, obstruction of the airway
occurring at the time of aspiration or ingestion
Second stage
• Foreign body lodges and reflexes grow weary
(Asymptomatic phase)
• Airway: obstruction, erosion or infection cause
Third stage pneumonia, atelectasis, abscess, or fever
• The laryngeal muscles contract, (Complication phase) • Esophagus: dysphagia, mediastinal abscess,
closing the glottis at the top of the perforation, or erosion
trachea by tightly aligning the
vocal folds Population at Risk
• Children (pre-school): size, poor reflexes, curiosity
• Adults: mentally impaired, elderly, edentulous
• Pre-existing structural or functional esophageal abnormalities

• The epiglottis swings down upon Causes

a closed glottis • Coins: most common cause (76%) in children
• Food bolus: adults
With all airways blocked off,
respiration is temporarily inhibited • 40% of foreign body ingestion in children are unwitnessed
• 50% with confirmed foreign bodies are symptomatic
• 92% present with dysphagia, 60% with neck tenderness
• Stridor, dyspnea, chronic respiratory symptoms in children (due to
As the upper esophageal sphincter tracheal compression)
relaxes, pharyngeal contractions • Sharp objects (fishbone): may perforate esophagus
drive the bolus into the esophagus
• Button batteries: erode esophageal mucosa, causing burns
The oropharyngeal stage is done and
breathing resumes Symptoms of Esophageal Foreign Bodies
• Blood in saliva • Irritability
• Coughing • Pain in neck, throat, or chest
• Drooling • Recurrent aspiration pneumonia
• Dysphagia/odynophagia • Respiratory distress
• Failure to thrive • Stridor
During the esophageal stage, a • Fever • Tachypnea
primary wave of peristalsis initiated by
the swallowing center pushes the
• Food refusal • Vomiting
bolus through the esophagus • Foreign body sensation in throat • Wheezing
• Gagging
In a patient suspected to have foreign body, what diagnostic
procedure would be helpful?
• Plain Radiographs (PA – Lateral view)
o Cost-effective
As the bolus travels through the o Non-invasive
esophagus, the lower esophageal o Readily available
sphincter relaxes, allowing the food to
enter the stomach o Speed of result
o Advantage: visualizing radiopaque foreign bodies
▪ Only 64% of ingested FOREIGN BODY are radiopaque
o Disadvantage: radiolucent foreign bodies are missed out

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 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Is the foreign body in the trachea or the esophagus?

• Inspiration & expiration chest radiography is commonly

employed series for inhaled foreign body in children
o If an inhaled foreign body is present, it can produce a one-way
or a ball-valve effect
o On inspiration (left), the 2 lungs tend to appear similar in terms
of degree of aeration
Trachea & bronchi normally widen on inspiration, allowing
passage of air into the affected lung past the foreign body
o On expiration (right), the foreign body can obstruct the bronchi
as the diameter of the bronchi decreases slightly on expiration
o The greatest difference in lung aeration will therefore be seen
on the expiration image (right) as air is exhaled from normal lung
▪ There will be hyperaeration (hyperlucency) on left lung,
signalling a possible obstruction in left mainstem bronchus
This is another radiograph showing a foreign body aspiration
• Based on its location and the tracheal air column, the foreign body is in
the right mainstem bronchus
Most foreign bodies are radiopaque, but wooden, plastic, & glass
objects, as well as fish & chicken bones may not be seen on radiographs
• Esophagograms help identify radiolucent foreign body not
visualized on plain films (Barium vs. Gastrografin)
Foreign Body Aspiration
• Larynx: 1-5%
• Trachea: 5-15%
• Left main bronchus: 30-35%
• Right main bronchus: 30-40%
• L lobar bronchus: 5-15%
• Right lobar bronchus: 5-15%
o Larynx & trachea: least common site,
except in children <1 year old
o Bronchus: most common location (80-90%)
o In adults, it is more common in the right
due to its more vertical and wider orientation

Management: Radiopaque Foreign Bodies

• Lateral Decubitus Films
o Young children who cannot cooperate with the timing of
respiration may be examined using the lateral decubitus
o In this position, when the child is placed on his side, the splinting
of the dependent hemithorax results in restriction of movement
of the thoracic cage on that side and underaeration of the lung
while the hemithorax on the opposite side is unrestricted
o Normally, the dependent lung collapses, the hemidiaphragm of
the dependent lung is higher than the other
Suspected radiopaque foreign body ingestion employs evaluation
o In presence of foreign body, dependent lung remains inflated
using radiography
Chest x-ray of the patient (case) (AP and lateral views) • If the object is in the esophagus
o Endoscopic removal
o Rigid esophagoscopy
o Sharp objects and batteries require urgent removal
o Blunt objects may be observed
o Objects lodged >2 weeks may be at risk of erosion and surgical
consultation should be done prior to attempt at removal
• If the object is distal to the esophagus
o Symptomatic: warrants removal & referral to surgery/GI
o If asymptomatic: warrants referral to surgery/GI

Foreign Body Ingestion

Foreign body (radiopaque circular object) en face
• The coin is perpendicular with the AP of the thoracic cage
• The foreign body is in the esophagus (ingestion)
Lateral views are used to confirm the number and possibly the shape of the
object (flat coin, how many coins are possible ingested)

166 | 42. FOREIGN BODY IN THE ESOPHAGUS/AIRWAY

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

Management: Radiolucent Foreign Bodies Esophagoscopy

Entering the right pyriform sinus

Passing the cricopharyngeal

constriction
• Force must not be used but
steady and moderately firm
pressure is made to avoid injuring
the cricopharyngeus muscle
• 1-3 cm of compressed lumen at
this level
For a suspected radiolucent foreign body ingestion
• Esophageal placement is suspected Passing thru the thoracic
esophagus
o Direct Laryngoscopy
• Lumen is seen to enlarge during
o Endoscopy inspiration and diminish during
o Barium esophagogram expiration
o If positive, attempt removal of foreign body or push into the • In some, pulsations of the aorta
stomach in selected patients at the discretion of the specialist may be seen
o It is important to note that foreign body that may have been
lodged for >2 weeks are at risk of necrosis Passing thru the diaphragmatic constriction
• Esophageal placement is NOT suspected
o Small blunt object (low risk): observe patient for symptoms Different foreign bodies have different techniques for extraction
o Large, sharp object (high risk): observe for symptoms and • Food bolus: suction or any forceps that would remove the foreign
consequently check for the stool body by a piecemeal approach
▪ Consider doing a contrast radiograph if the object is not • In some instances (coin), since it is solid, forceps can be used
seen in the stool for ≤2 weeks • Sharp object
o Forceps to enclose the sharp point/end of the foreign body
Upon diagnosis of foreign body: o Gently retract inside the esophagoscope
• Esophagoscopy o Retract the forceps and the esophagoscope together so that
o Procedure to remove foreign body in the esophagus mucosa of the esophagus is protected upon retrieval
o Measure average distance from maxillary incisors to specific
landmarks that help identify at what level in the esophagus Postoperative Care
• Oral or nasal airway
• After esophagoscopy: NPO for 4 hours
• Chest X-Ray
o Suspected iatrogenic trauma to airway or esophagus
o Rule out presence of pneumothorax or mediastinal changes
▪ Mediastinitis: fever, chest pain, crepitus, tracheal deviation
o Chronic airway foreign body
• Barium esophagogram
o Chronic esophageal foreign bodies
o Mucosal injury
o Contraindication: perforation
• If within 4 hours there are no symptoms, we can start the patient
on general liquids (subject to reevaluation)
In adults: o If the patient can tolerate, progress the diet
▪ General liquids → Soft diet → General diet
o If no complication, send the patient home

Reference: Foreign Body Ingestion by Department of Otolaryngology Head and Neck Surgery (recorded lecture)

42. FOREIGN BODY IN THE ESOPHAGUS/AIRWAY | 167

 Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies

43. APPENDICITIS DIAGNOSIS

EPIDEMIOLOGY • Acute appendicitis is largely a clinical diagnosis
• Lifetime incidence of 8.6% in men and 6.7% in women • Complete physical examination, including pelvic examination in
• Common in patients age 10-19 years & in 2nd and 3rd decade of life women of childbearing age
• Most frequent cause of atraumatic abdominal pain in children >1 y • Consider appendicitis in any patient with atraumatic right-sided
• Most common non-obstetric surgical emergency in pregnancy abdominal, periumbilical, or flank pain who has not previously
undergone appendectomy
PATHOPHYSIOLOGY • Diagnostic adjuncts: CBC, inflammatory markers (CRP, ESR),
• Luminal obstruction of the vermiform appendix urinalysis, pregnancy test
o Pediatric population: lymphoid hyperplasia • Diagnostic imaging: in atypical presentations of if significant
o Adults: fecalith, fibrosis, foreign bodies (food, parasites, calculi), diagnostic uncertainty exists after thorough history and examination
or neoplasia
o Early obstruction leads to bacterial overgrowth of aerobic Alvarado Scoring Sytem
organisms in early period, and subsequently leads to mixed flora Symptom/Sign/Labs Point
o Obstruction generally leads to increased intraluminal pressure Migratory pain 1
and referred visceral pain to periumbilical region Anorexia or urinary acetone 1
o Leads to impaired venous drainage, mucosal ischemia leading Nausea/vomiting 1
Tenderness of RLQ 2
to bacterial translocation, and subsequent gangrene and
Rebound tenderness 1
intraperitoneal infection Elevated temperature ≥38°C 1
o Escherichia coli & Bacteroides fragilis: most common aerobic Leukocytosis >10,000/mm3 2
and anaerobic bacteria isolated in perforated appendicitis Shift to the left neutrophils* 1
• Visceral innervation produces vague, hard to localized periumbilical Scoring (Alvarado Score)
or central abdominal discomfort frequently observed early in course • Score <3: low likelihood of appendicitis
o Progressive inflammation & subsequent irritation of somatically • Score 4-6: consider further imaging
innervated parietal peritoneum: classic migratory pain to RLQ • Score ≥7: high likelihood of appendicitis
o McBurney’s point: located ⅓ of the distance from the anterior Scoring (Modified Alvarado Score)
superior iliac spine to the umbilicus • Score of 1-4: low-risk appendicitis
• Score of 5-9: possible or probable appendicitis
• ~50% may have an atypical presentation due to anatomic variation *not included in Modified Alvarado Scoring System (MASS)
o Retrocecal appendix: right flank or pelvic pain
o Malrotation of colon (transposition of appendix): LUQ pain Laboratory Testing
o Gravid uterus (abdominal displacement): RUQ tenderness • Leukocytosis (>10,000/mm3): earliest marker (70%)
o Higher leukocytosis (~17,000 cells/mm3) associated with
CLINICAL FEATURES gangrenous and perforated appendicitis
History o “Left shift” is present in >95% of cases
• Early on, patients classically complain of nonspecific symptoms of o Normal WBC in 10%; leukopenic presentations possible
general malaise, indigestion, or bowel irregularity o Does not distinguish between simple vs. perforated appendix
o Anorexia is common but not universally present • CRP >10 mg/L in children <6 y may be of value in predicting
o Alterations in bowel function are highly variable: constipation, o CRP & ESR alone lack sensitivity and specificity
diarrhea, obstruction (late complication) o ↑ WBC ± ↑ CRP: sensitivity as high as 98%; elevated in a
o Periumbilical or central abdominal pain generally develops after number of other appendicitis mimics
nonspecific symptoms • Urinalysis: valuable in ruling out nephrolithiasis or pyelonephritis
o Nausea ± vomiting typically follows onset of pain o Isolated microscopic hematuria: support diagnosis of renal colic
o Subjective or objective fever is frequent o Pyuria: can be present in acute appendicitis
• As clinical course progresses, discomfort migrates to RLQ (12-24 h) • Pregnancy test in females of reproductive age to rule out ectopic
o Flank pain, dysuria, or hematuria can occur, given the typical or heterotopic pregnancy
proximity of the appendix to the urinary tract
• Aggravating and alleviating features Imaging
o Worsening with deep inspiration: peritoneal irritation • Goals: establish diagnosis of appendicitis, avoid a negative
o Sudden alleviation of pain: consider appendiceal perforation appendectomy, identify perforation, exclude other causes of
(release of intraluminal obstruction) abdominal pain
• Graded compression ultrasound
Physical Examination o Initial imaging modality of choice in pregnant females & children
o Typically appear ill; frequently lie still because of presence of o Sensitivity of 0.85 and specificity of 0.90
localized peritonitis, which makes any movement painful
o Normal appendix
o Tachycardia, mild dehydration, fever to varying degrees ▪ Oval in the axial plane, ends blindly in longitudinal plane,
o RLQ tenderness: progressive inflammation & peritoneal irritation compressible with a maximum diameter <6 mm
o Rebound tenderness & involuntary guarding suggest peritonitis ▪ Absent peristalsis and lack of change in configuration over
o Rovsing’s sign: pain over McBurney’s point after release of time; small size
gentle pressure on LLQ (normal position) o Features suggesting appendicitis
o Dunphy’s sign: pain with coughing (retrocecal appendix) ▪ Thickened, noncompressible appendix >6 mm diameter
o Psoas sign: pain at the hip with passive extension of the right ▪ Pain with compression
leg while the patient lies on the left side (retrocecal appendix) ▪ Presence of an appendicolith
o Obturator sign: pain with passive internal and external rotation ▪ Increased echogenicity of fat
of flexed right thigh at the hip (pelvic appendix) ▪ Periappendiceal fluid
o Abdominal rigidity, positive psoas sign, fever, rebound ▪ Doppler US: hyperemia
tenderness increases likelihood of acute appendicitis o Perforation may lead to disappearance of specific imaging
o Prior episodes of similar pain, absence of RLQ pain, absence of hallmarks and difficult visualization of appendix
classic pain migration make appendicitis less likely o Advantages: cheaper and more readily available than CT scan
o Disadvantages:
▪ Operator-dependent
▪ Retrocecal appendicitis or perforation
▪ Excessive abdominal guarding or bowel gas
▪ Gravid uterus or obese habitus
▪ Decompressed bladder
▪ Lack of patient cooperation

168 | 43. APPENDICITIS


• Abdominopelvic CT
o In most adult males & nonpregnant females for whom diagnosis
of appendicitis not sufficiently clear
o Contrast-enhanced CT: sensitivity of 0.96 and specificity of
0.96 in diagnosing acute appendicitis
▪ Contrast avoided in allergies or low eGFR <30 mL/min
o Typical CT findings
▪ Dilated appendix >6 mm & double wall thickness
▪ Wall thickening (>2 mm)
▪ Periappendiceal fat stranding (inflammation)
▪ Potential visualization of an appendicolith or abscess
o Perforation may lead to disappearance of specific imaging
hallmarks and difficult visualization of appendix
▪ Due to relief of luminal obstruction and dilation
TREATMENT
• MRI
o Another reliable imaging technology in the evaluation of acute
appendicitis, particularly in pregnant women
o Applicable to pediatric patients >5 years if with MRI capability
o Sensitivity of 0.95 and specificity of 0.92
o Disadvantages
▪ Expensive, requires expertise to perform & interpret
▪ IV gadolinium crosses the placenta and is not used in
pregnancy: teratogenic effects
• Not given to patients with renal insufficiency: may cause
nephrogenic fibrosing dermopathy
▪ Sedation may be required for small children
DIFFERENTIAL DIAGNOSIS
DISPOSITION AND FOLLOW-UP
References:
Merit Is A Must: A Clinical Clerk’s Guide to Oral Revalida Emergencies
• Immediate referral to Surgery for appendectomy
o Timing of surgery
▪ Emergent surgery is often performed in patients with
appendicitis
▪ Delaying surgery <12 hours is acceptable in patients with
short duration of symptoms (<48 hours) and in
nonperforated, nongangrenous appendicitis
o Approach to surgery
▪ Laparoscopic appendectomy: shorter length of stay,
faster return to work, lower superficial wound infection rates
▪ Open appendectomy: shorter operative times, lower intra-
abdominal infection rates
• Maintain on NPO to avoid operative delay
• Provide resuscitation and maintenance IV fluids with appropriate
antiemetics and analgesia
• Initiate perioperative antibiotics upon diagnosis or if patient
exhibits signs of peritonitis (broad-spectrum with aerobic and
anaerobic gram-negative coverage)
o Ampicillin-sulbactam 3 g IV (pediatric dose: 75 mg/kg IV)
o Piperacillin-tazobactam 4.5 g IV (pediatric dose: 100 mg/kg IV)
o Cefoxitin 2 g IV (pediatric dose: 40 mg/kg)
o Metronidazole 500 mg IV + ciprofloxacin 400 mg IV
• Surgery is the accepted standard of care for acute appendicitis
• Extended observation for patient whom diagnosis remains elusive
o Serial examinations, allowing for evolution of condition
• Stable, reliable patient without significant comorbidities may be a
candidate for discharge
o Return to hospital within 12 hours for repeat examination
o Must have adequate pain control & able to tolerate oral hydration
• Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9 th edition (2020)
• Schwartz’s Principles of Surgery, 11th edition (2019)
• Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice, 20 th edition (2017)
• Harrison’s Principles of Internal Medicine, 20th edition (2018)
43. APPENDICITIS | 169
 Hippocratic Oath
Classic Version

I swear by Apollo, the Physician and Aesculepius and Hygeia and Panacea and all the
gods and goddesses, making them my witnesses, that I will fulfill according to my
ability and judgment this oath and this covenant:

To hold him who has taught me this art as equal to my parents and to live my life in
partnership with him, and if he is in need of money to give him a share of mine, and to
regard his offspring as equal to my brothers in male lineage and to teach them this art -
if they desire to learn it - without fee and covenant; to give a share of precepts and oral
instruction and all the other learning to my sons and to the sons of him who has
instructed me and to pupils who have signed the covenant and have taken an oath
according to the medical law, but no one else.

I will apply dietetic measures for the benefit of the sick according to my ability and
judgment; I will keep them from harm and injustice.

I will neither give a deadly drug to anybody who asked for it, nor will I make a
suggestion to this effect. Similarly I will not give to a woman an abortive remedy. In
purity and holiness I will guard my life and my art.

I will not use the knife, not even on sufferers from stone, but will withdraw in favor of
such men as are engaged in this work.

Whatever houses I may visit, I will come for the benefit of the sick, remaining free of all
intentional injustice, of all mischief and in particular of sexual relations with both female
and male persons, be they free or slaves.

What I may see or hear in the course of the treatment or even outside of the treatment
in regard to the life of men, which on no account one must spread abroad, I will keep to
myself, holding such things shameful to be spoken about.

If I fulfil this oath and do not violate it, may it be granted to me to enjoy life and art,
being honored with fame among all men for all time to come; if I transgress it and
swear falsely, may the opposite of all this be my lot.
 Hippocratic Oath
Modern Version

I swear to fulfill, to the best of my ability and judgment, this covenant:

I will respect the hard-won scientific gains of those physicians in whose steps I walk,
and gladly share such knowledge as is mine with those who are to follow.

I will apply, for the benefit of the sick, all measures [that] are required, avoiding those
twin traps of overtreatment and therapeutic nihilism.

I will remember that there is art to medicine as well as science, and that warmth,
sympathy, and understanding may outweigh the surgeon's knife or the chemist's drug.

I will not be ashamed to say "I know not," nor will I fail to call in my colleagues when
the skills of another are needed for a patient's recovery.

I will respect the privacy of my patients, for their problems are not disclosed to me that
the world may know. Most especially must I tread with care in matters of life and death.
If it is given me to save a life, all thanks. But it may also be within my power to take a
life; this awesome responsibility must be faced with great humbleness and awareness
of my own frailty. Above all, I must not play at God.

I will remember that I do not treat a fever chart, a cancerous growth, but a sick human
being, whose illness may affect the person's family and economic stability. My
responsibility includes these related problems, if I am to care adequately for the sick.

I will prevent disease whenever I can, for prevention is preferable to cure.

I will remember that I remain a member of society, with special obligations to all my
fellow human beings, those sound of mind and body as well as the infirm.

If I do not violate this oath, may I enjoy life and art, respected while I live and
remembered with affection thereafter. May I always act so as to preserve the finest
traditions of my calling and may I long experience the joy of healing those who seek
my help.