Epidemiology:
* Most common cause of anaphylaxis during anesthesia- estimated as cause of 59-69% of cases.
* Incidence of anaphylaxis/anaphylactoid reaction during anesthesia estimated to be 1 in 10K-20K.
* Increased incidence in females (3:1); patients with a history of atopy or asthma; and a history of anaphylaxis during anesthesia.

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Pathophysiology:
* Immune mechanism: Type I hypersensitivity reaction (e.g. anaphylaxis, extrinsic asthma, and allergic rhinitis).
* IgE binds ?  mast cell and basophil degranulation ? mediator (histamine, leukotriene, etc.) release ? bronchoconstriction, vasodilation, increased vascular permeability, etc.
* Direct histamine release by muscle relaxant not sufficient to cause reaction.
* Sensitization from prior surgery.  Hypothesized that cosmetics and penicillin may cause cross-sensitization in cases where there has been no prior exposure to muscle relaxants.

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Symptoms/Signs:
* Onset may be delayed 2-20 minutes, which may make identification of the cause difficult.
* Respiratory: chest discomfort, dyspnea, wheezing, laryngeal edema, or pulmonary edema.
* Cardiovascular: dizziness, chest discomfort, hypotension, tachycardia, dysrhythmia, or cardiac arrest.
* Cutaneous: itching, burning, flushing, urticaria, diaphoresis, or periorbital edema.

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Treatment of Anaphylaxis During Anesthesia:
* Initial:
1. Stop antigen administration.
2. Maintain airway and administer 100% oxygen.
3. Discontinue anesthetic agents.
4. Volume expansion for treatment of hypotension.
5. Epinephrine (10mcg IV for hypotension; 0.1-1mg IV for cardiovascular collapse)
* Secondary treatments include: antihistamines (0.5-1.0mg/kg diphenhydramine); corticosteroids (0.25-1.0g hydrocortisone); catecholamine infusion (epi 4-8mcg/min, norepi 4-8mcg/min, isoproterenol 0.5-1.0mcg/min); and bicarbonate (if indicated for acidosis).

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Testing:
* Intradermal skin testing most reliable test.
* Important to test for all muscle relaxants as they may or may not cross-react.  Cross-reactivity may occur between succinylcholine and non-depolarizers as well as between the aminosteroid and bezylisoquinoline non-depolarizers.
* Other tests:
Radioallergosorbent test (RAST)- In vitro detection of IgE to specific antigens.
Enzyme-linked immunosorbent assay (ELISA)- Measures antigen specific antibodies and, with an
additional step, can measure IgE specifically.
* Due to low the incidence even in those at increased risk, routine preoperative testing is not recommended.

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Prevention:
* Testing to determine the cause of previous reaction is the most important step.  Strict avoidance of the causative agent in the anesthetic technique (for example, reliance on potent inhalation agent for muscle relaxation) is mandatory.
* Pretreatment with corticosteroids and antihistamines (H1 and H2).

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References:
Barash  P, et al: Clinical Anesthesia.  Philadelphia, Lippincott Williams and Wilkens, 2001.
Laxenaire MC, Mertes PM, et al: Anaphylaxis During Anaesthesia. Results of a Two-Year Survey in France.  Br J of Anaes 87: 549-58, 2001.
Malcolm M, Fisher MB Munro I: Life-Threatening Anaphylactoid Reactions to Muscle Relaxants.  Anesth Analg 62:559-64, 1983.

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