TRYPTASE LEVELS ARE NOT INCREASED DURING VANCOMYCIN INDUCED ANAPHYLACTOID REACTIONS

Background: Anaphylaxis, mediated by immunoglobulin E, may be clinical ly indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, cu rare, and vancomycin. A test to distinguish anaphylactic from anaphyla ctoid reactions would clarify therapeutic and medicolegal issues. Tryp tase levels identify anaphylactic reactions but have not been evaluate d in vivo during anaphylactoid reactions. A prospective, randomized, d ouble-blinded, placebo-controlled trial of antihistamine chemoprophyla xis for rapid vancomycin infusion was performed, and plasma tryptase w as measured using a new immunoassay, Histamine release was established by measurement of plasma histamine and the ability of prophylactic H- 1 and H-2 antagonists to prevent common histamine-associated side effe cts. Tryptase levels were compared with histamine levels and clinical symptoms. Methods: Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either ant ihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placeb o. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms mere asse ssed using Fisher's exact test, the Student's t test, or the paired t test, as appropriate. Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels. Results: Plasma tryptase levels mere unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these. Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-sev ere rash, and stopped infusion. Antihistamine pretreatment significant ly decreased the incidence and severity of the reactions. Conclusion: Plasma tryptase levels were not significantly elevated in confirmed an aphylactoid reactions, so they can be used to distinguish chemical fro m Immunologic reactions.