title: Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions.
abstract: BACKGROUND
  Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin. A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues. Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions. A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay. Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects. 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 antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed 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 were 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-severe rash, and stopped infusion. Antihistamine pretreatment significantly decreased the incidence and severity of the reactions.
  
  
  CONCLUSIONS
  Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.
authors.affiliation: Department of Anesthesia and Critical Care, The University of Chicago, Illinois, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Renz
authors.forename: D
authors.initials: D
authors.lastname: Laroche
authors.forename: J D
authors.initials: JD
authors.lastname: Thurn
authors.forename: H A
authors.initials: HA
authors.lastname: Finn
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.forename: R
authors.initials: R
authors.lastname: Thisted
authors.forename: J
authors.initials: J
authors.lastname: Moss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000201:enzymology*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D053818:Chymases; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000097:blood*; D053802:Tryptases; D014640:Vancomycin / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D006632:Histamine; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases