ROAD TO MERITISSIMUS

Written by: Dapoy Peralta, MD

Transcribed by: Angiegenesis

ANAPHYLAXIS

Definition
- Anaphylaxis is an acute, potentially life-threatening, multisystem syndrome
caused by sudden release of mast cell mediators into the systemic circulation.
- It is an IgE-dependent reaction involving 2 or more organ systems
1. Cutaneous
2. Respiratory
3. Cardiovascular
4. Gastrointestinal
- On the other hand, anaphylactoid reaction is a. non-IgE dependent reaction
which does not require previous sensitization
- This involves direct mast cell activation, complement activation or alteration in
arachidonic acid metabolism by Aspirin and NSAIDs
- In terms of statistics, the lifetime prevalence of these reactions are estimated to
be between 0.05 to 2 % in the general population

Etiology
ü Some of the common causes of ANAPHYLAXIS include:
1. FOOD
• Peanuts, walnuts, cashew, pistachio, milk, eggs, chicken, fish, shellfish,
sesame seeds, wheat, food preservatives
2. DRUGS
• B-lactam antibiotics, sulfonamides, monoclonal antibodies
3. VACCINES
• Tetanus toxoid, MMR, DPT, influenza
4. HYMENOPTERA VENOM
• Honeybee, wasp, hornet, fire ant
5. RUBBER LATEX
• gloves
ü It also important to know the different causes of ANAPHYLACTIOD REACTIONS
since more or less, they will require the same management
1. PHYSICAL FACTORS
 • Exercise, cold, heat, sunlight
2. DRUGS
• Aspirin, COX inhibitor, NSAIDs, opiates, radiocontrast media (iodine),
ethylene oxide (vancomycin), dialysis tubing
3. IVIg

Pathogenesis

ü The classical mechanism associated with allergic diseases is initiated by an

allergen, interacting with an allegro-specific IgE antibody bound to mast cell
ü It begins with allergic sensitization which occurs when an allergen is first
encountered
ü These allergens are internalized by Antigen-presenting cells (APC) and
expressed on their cell surface through HLA MHC
ü The products are then presented to other cells involved in the immune
response, particularly the T cells and B cells (T cell CD40 ligand binds to CD40
receptors in the B cells
ü Through a series of specific cell interactions, B cells are then transformed into
plasma cells, undergo class switching, and are able to synthesize IgE antibodies
specific to an allergen
ü IgE antibodies then bind to the Fc receptors of mast cells and basophils leaving
their Fab portion available for future interaction with the specific allergen
ü Once an allergen is reencountered, it binds to the Fab portion of the bound IgE
initiating a process of intracellular signaling, leading to degranulation if mast cell
with subsequent release of inflammatory mediators
o Histamine
§ Vasodilation and decreased peripheral vascular resistance
-> Hypo
o Proteases
§ Contraction and separation of endothelial cells -> edema
o Prostaglandins
§ Bronchoconstriction
o leukotrienes
§ Increased gastric acid output

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 Clinical Manifestation

ü Symptoms usually begin within seconds to minutes and can be divided into early
and late phase reactions
EARLY PHASE REACTIONS
1. Early phase symptoms usually occur within 15 minutes and may present as:
§ CUTANEOUS
• Generally, hives, pruritus, flushing, swollen lips, periorbital
edema, conjunctival swelling (chemosis)
§ RESPIRATORY
• Rhinorrhea, hoarseness, stridor, shortness of breath, wheeze,
cough, reduced PEFR, hypoxemia
§ GASTROINTESTINAL
• Nausea, vomiting diarrhea, crampy abdominal pain
§ CARDIOVASCULAR
• Syncope, dizziness, palpitations, chest pains, decreased BP
§ NEUROLOGIC
• Anxiety, irritability, sense of impending doom, confusion,
incontinence
LATE PHASE REACTIONS
2. Late phase reactions account for the biphasic anaphylaxis seen when
epinephrine administration is delayed.
3. It occurs 4-6 hours for as long as 24 hours after the disappearance of the
early phase symptoms and can last for days to weeks.
4. This is brought about by remaining cellular mediators and tissue
destruction from sustained allergic response
5. There may be increased bronchial reactivity, edema, and further
inflammatory cell recruitment
ü The primary endangering manifestations of anaphylaxis must be immediately
recognized. This includes:
1. Laryngeal edema (sudden death)
2. Severe bronchial obstruction
3. Cardiac dysfunction (arrhythmias)
4. Hypotension

Diagnosis

ü Since there are no definite laboratory work-ups locally available to diagnose or

confirm anaphylaxis, diagnosis is CLINICAL and relies on prompt recognition of the
syndrome

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 ü There are 3 diagnostic criteria for anaphylaxis each reflecting a different clinical
presentation
1. CRITERION 1
• Acute onset of an illness (minutes to several hours) involving the
skin, mucosal tissue, or both (ex. Generalized hives, pruritus,
flushing, swollen lips-tongue-uvula) and at least one of the following:
o Respiratory compromise (ex. dyspnea,
wheeze/bronchospasm, stridor, reduced PEFR, hypoxemia)
o Reduced blood pressure or associated symptoms and signs
of end-organ malperfusion (ex. Hypotonia (collapse),
syncope, incontinence)
2. CRITERION 2
• Two or more of the following that occur rapidly after exposure to a
likely allergen for that patient (minutes to several hours)
• Involvement of skin-mucosal tissue
• Respiratory compromise
• Reduced BP or associated symptoms and signs of end-organ
malperfusion
• Persistent gastrointestinal symptoms and signs (ex. Crampy
abdominal pain, vomiting)
3. CRITERION 3
• Stand alone criteria
• Reduced BP after exposure to a KNOWN ALLERGEN for that
patient (minutes to hours)
o SBO <90 mmHg
o Greater than 30% decrease from person’s baseline
• Infants and children
o Low SBP (age specific)
§ 1 month – 1 year : <70 mmHg
§ 1 year – 10 years: <70 mmHg [2 x age]
§ 11 years – 17 years: <90 mmHg
o Greater than 30% decrease from person’s baseline

Differential Diagnosis
1. Vasovagal collapse
§ Pallor, nausea and diaphoresis with slow pulse but maintained BP
2. Hereditary angioedema
§ Strong FH, laryngeal edema, deep localized swelling (hand and
foot), cutaneous non-pitting, non-pruritic edema, abdominal pain
§ C1 esterase inhibitor deficiency

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 3. Arrhythmias, Myocardial infarction
4. Aspiration
5. Pulmonary embolism
6. Seizure disorders
7. Flushing disorders
§ Alcohol ingestion, mastocytosis, carcinoid syndrome
8. Scombroid poisoning
§ Unfresh fish products contaminated with Morganella Morgagni
(histidine decarboxylase: histidine -> histamine)
9. And other causes of shock (ex. Cardiogenic, septic)

Management

ü Prompt assessment and treatment are critical in anaphylaxis as respiratory and

cardiac arrest can occur within minutes
ü The cornerstone of initial management are the following:
1. Removal of inciting allergen if possible
2. IM injection of epinephrine at the earliest opportunity
3. Proper positioning placement of patient in a supine position with lower
extremities elevated unless there is upper airway swelling wherein patient
must be upright
4. Supplementation of oxygen and airway management
5. Volume resuscitation with IV fluids
6. Continuous monitoring
ü Patients on beta blockers may be resistant to epinephrine and can develop
refractory hypotension (shift to CCBs)
ü Glucagon 1-5 mg IV over 5 minutes should be administered because it has
inotropic and chronotropic effects not mediated through beta-receptors
ü This is followed by infusion titrated (5-15 ug/min) to clinical response
ü Most patients with minor signs and symptoms who show marked resolution with
emergency treatment can be sent home with regular oral antihistamines and
follow-up instructions after 4 hours observation
ü Those who present with life-threatening anaphylaxis should be admitted and
observed for another 24 to 48 hours even if their symptoms were easily managed
or reversed because of high risk of late phase reactions.

I. IM Epinephrine
ü Epinephrine is the first and most important treatment for anaphylaxis
ü It should be administered as soon as anaphylaxis is recognized to prevent
progression of life-threatening symptoms

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 ü The pharmacologic actions of epinephrine address the pathophysiologic
changes that occur in anaphylaxis better than any other medication
ü Therapeutic actions of epinephrine include:
§ Alpha-1 receptor
• Increased vasoconstriction
• Increased peripheral vascular resistance
• Increased blood pressure
• Decreased mucosal edema
§ Beta-1 receptor
• Increased heart rate (chronotropy)
• Increased force of cardiac contraction
§ Beta-2 receptor
• Increased bronchodilation
• Decreased mediator release from mast cells and basophils
ü Recommended route of administration is IM on the lateral thigh (vastus
lateralis)
ü Dosing would be an aqueous dilution of 1:1000 at 0.01 mL/kg, maximum of
0.5 mL per dose
ü IM epinephrine may be repeated at 5-15 minutes intervals if there is no
response or even sooner if clinically indicated
II. POSITIONING
ü If without upper airway swelling -> SUPINE position with lower extremities
elevated to maximize perfusion to vital organs
ü If with upper airway swelling -> patient should remain UPRIGHT and often
leaning forward (neck is hyperextended maximize diameter of obstructed
airway)
ü For pregnant patients -> LEFT LATERAL DECUBITUS to minimize
compression of IVC by the gravid uterus (increased venous return)
III. AIRWAY and OXYGEN
ü Immediate intubation should be done if there is an evidence of impeding
airway obstruction from angioedema/laryngeal edema
ü Oxygen can be given 8-10 L/min via facemask or up to 100% oxygen as
needed
IV. FLUID
ü Two large-borne IV catheters should be inserted in preparation for rapid
administration of fluids and medications
ü ADULTS – 1-2 L of NSS at the most rapid flow rate possible in the first
minutes. Larger volumes of fluid (up to 7L) may be required
ü CHILDREN – 20 mL/kg bolus of NSS each over 5-10 minutes and repeated
as needed. Larger volumes of fluid (up to 100mL/kg) may be required
V. MONITORING

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 ü Continuous noninvasive hemodynamics monitoring and pulse oximetry
should be done
ü Urine output should also be monitored for severe hypotension or shock
VI. ADJUNCTIVE AGENTS
ü H1 receptor antagonist
o Mainly used to relieve pruritus and urticaria
o Does not relieve airway obstruction, hypotension or shock
o ADULTS: Diphenhydramine 25-50 mg IV over 5 minutes
§ Max dose 400 mg/day
§ Rapid administration may lead to HYPOTENSION
o CHILDREN: Diphenhydramine 1 mg/kg over 5 minutes
§ Max dose 50 mg/kg or 200 mg/day
ü H2 receptor antagonist
o Used to decrease gastric acid output, decrease vasodilation and
decrease mucus gland secretion
o ADULTS: Ranitidine 50mg in 20 mL fluid IV over 5 minutes
o CHILDREN: Ranitidine 1 mg/kg in 20 mL fluid IV over 5 minutes
o Ranitidine is preferred over cimetidine due to lower drug
interactions
§ Cimetidine:
• Anti-androgenic (gynecomastia, impotence)
• Inhibits microsomal enzymes
• Increased CHON binding
ü Glucocorticoids
o The onset of action of glucocorticoids take several hours. Therefore,
these medications do not relieve the initial symptoms and signs of
anaphylaxis.
o The rationale for giving them is to theoretically prevent biphasic
reactions, however RCTs have failed to confirm its effectiveness
o The only proven way to prevent biphasic reaction is timely
administration of epinephrine
o Nevertheless, a dose of Methyprednisolone 1-2 mg/kg/day is
sufficient
Prevention

ü Avoidance of known allergen

ü Keep an Adrenaline kit (EPIPEN) and instruct how and when to use it
ü Advise patient to wear and carry warning identification
ü Venom immunotherapy for insect-allergic individuals