Antihistamine prophylaxis permits rapid vancomycin infusion

Objective: To determine whether pretreatment with intravenous antihistamine s attenuates the symptoms of red-man syndrome associated with rapid vancomy cin administration, Design: Prospective, randomized, double-blinded, placebo-controlled study o f patients undergoing elective arthroplasty, Setting: Preoperative unit in a tertiary care center. Patients: Forty preoperative patients (American Society of Anesthesiologist s status I-III, receiving vancomycin prophylaxis for elective prosthetic jo int replacement or revision. interventions: Elective orthopedic patients were randomly allocated to rece ive intravenous antihistamines (diphenhydramine, 1 mg/kg, and cimetidine, 4 mg/kg) or placebo before rapid vancomycin infusion (1 g over 10 mins), Hem odynamic measurements, symptoms of histamine release, and plasma histamine levels were obtained in each patient during vancomycin administration. Rapi d vancomycin infusion was discontinued in cases of decreases in mean blood pressure of greater than or equal to 20% or intolerable itching. Measurements and Main Results: Clinical symptomatology of red-man syndrome and histamine levels were assessed using Fisher's exact test or Student's t -test. Comparison of baseline and peak histamine levels for both the treate d (mean +/- SD, 0.2 +/- 0.2 vs. 4.7 +/- 2.4 ng/mL; p < .0001) and placebo p atients (mean +/- SD, 0.2 +/- 0.1 vs. 3.5 +/- 3.4 ng/mL; p = .0002) was sta tistically significant. Although there was a significant increase in plasma histamine levels during vancomycin infusion, it did not differ between the treatment groups, Only two (11%) of the treated patients developed hypoten sion, vs. 12 (63%) of the placebo patients (p =,.002), Rash was partially a ttenuated. Twelve (63%) of the treated patients developed rash, compared wi th 19 (100%) of the placebo patients (p = .008). The rapid infusion was dis continued in two (11%) of the treated patients, compared with 11 (58%) of t he placebo patients (p = .005), Four treated patients had no symptoms of hi stamine release, Conclusions: Pretreatment with intravenous H-1, and H-2, antihistamines per mitted rapid vancomycin administration in 89% of treated patients. Although protection was incomplete, rash did not predict a need to stop the rapid i nfusion of vancomycin in our patients.