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  • Potentially lethal allergic reaction
  • Rapid onset, from minutes to hours after exposure
  • Generally requires a prior sensitization to antigen; can occur on first exposure due to cross-reactivity among drugs/products
  • Pathophysiology: type I hypersensitivity reaction involving multiple organ systems
    • IgE-mediated mast cell degranulation with release of stored histamine, proteases, proteoglycans, and platelet-activating factor (PAF); followed by production of proinflammatory prostaglandins and leukotrienes
    • Histamine, prostaglandin, and leukotriene receptors elicit changes in vascular permeability and tone, bronchial smooth muscle contraction, and coagulability, and may produce angioedema, urticaria, bronchoconstriction, and DIC; PAF can further contribute to anticoagulation and constriction of bronchial smooth muscle
  • Clinically indistinguishable from anaphylactoid reactions, that is, “pseudoanaphylaxis” (non-IgE-mediated, no prior sensitization, nonspecific histamine release)
  • Incidence 1/3,500–20,000 anesthetic procedures; higher mortality rate in perioperative anaphylaxis than anaphylaxis in other settings
  • Early signs often unrecognized and undertreated in anesthetized patients; cutaneous signs masked by surgical draping
  • May be biphasic with recurrence of symptoms 8–10 and up to 72 hours after initial occurrence
  • Requires immediate treatment and resuscitation
  • Death from upper airway edema, bronchial obstruction, circulatory collapse
  • Comorbidities with high risk of poor outcomes: asthma/COPD and CV disease
  • Four grades:
    1. Cutaneomucosal generalized signs: rash, urticaria

    2. Moderate multivisceral involvement: hypotension, tachycardia, bronchial hyperreactivity

    3. Severe, life-threatening multivisceral involvement: MI, severe bronchospasm

    4. Cardiorespiratory arrest

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NB: Cutaneous signs can be delayed or absent.

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Clinical Features of Anaphylaxis/Anaphylactoid Reactions and Differential Diagnosis
SystemClinical featuresDifferential
MucocutaneousPruritus, flushing, erythema, acute urticaria, angioedemaCarcinoid syndrome, contact or cholinergic urticaria, medication-induced vasodilation
RespiratoryLaryngeal edema, hoarseness, bronchospasm, hypersecretion, increased peak airway pressure, decreased O2 saturationMalignant hyperthermia, asthma, aspiration, mucous plug, mainstem intubation, recurrent laryngeal nerve injury, post-extubation stridor
Cardiovascular(Pre)syncope, tachycardia/bradycardia, hypotension, dysrhythmia, cardiovascular collapse, cardiac arrestVasovagal reaction, arrhythmia, MI, PE, tension pneumothorax, tamponade, shock
HematologicDisseminated intravascular coagulation (DIC)Transfusion reaction, hemorrhage
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Causative Agents
NMBAs50–70% of perioperative anaphylaxis; 60–70% cross-reactivity (no absolute contraindication to all NMBAs, if allergy testing available); more common in females (75% of NMBA-related reactions)
LatexHigher risk of sensitivity in health care workers and with multiple past surgeries (prior exposures to antigen), history of spina bifida, allergy to tropical fruits (bananas, kiwi, avocado, papaya, mango, passion fruit), chestnut allergy
AntibioticsPenicillins, cephalosporins, carbapenems, monobactams, vancomycin, sulfonamides
Local anestheticsRare and occurring mostly with amino ester local anesthetics (reaction to amino ester local anesthetic metabolite para-aminobenzoic acid [PABA])
OthersColloids, protamine (diabetics receiving NPH insulin), radiology contrast dye (not an iodine allergy, no correlation to seafood allergy), hypnotics (primarily barbiturates), opioids
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  • Elicit risk factors for allergy to medications, latex, foods
  • If patient had an anaphylactic reaction during a prior anesthetic:
    • Prefer regional if possible
    • If GA, avoid NMBAs and histamine-releasing medications (e.g., morphine); use propofol, inhalation agents; prefer non-histamine-releasing opioids (fentanyl, hydromorphone)
    • No preoperative tests have been shown to reliably identify medications to avoid
    • ...

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