Effect of infusion rate on amphotericin B-associated febrile reactions

Our objective was to prospectively study febrile and chill reactions associated with two amphotericin B (AB) infusion rates, slow (2-hour) versus rapid (45 minute). Seventeen consenting bone marrow transplant recipients in whom AB was to be initiated for documented or suspected fungal infections were recruited. After standardized premedication, patients received eight daily AB infusions (0.5 mg/kg/d, concentration 0.25 mg/ml). Rate was assigned using a randomized, crossover pair design. Axillary temperature, chills, and meperidine dose required to resolve chills were monitored for each infusion. For the first pair of infusions, fever (defined as a rise of 1 degree C) occurred frequently, in 12 of 17 (70.5 percent) and 13 of 17 patients (76.4 percent), with a mean rise of 1.7 degrees C (range 1.1-3.7) and 1.7 degrees C (1.1-3.5) degrees for the 45-minute and 2-hour infusions, respectively (p greater than 0.10). Chills were observed in 15 of 17 (88.2 percent) and 14 of 17 (82.3 percent) recipients of the 45-minute and 2-hour infusions, respectively. The time of onset (p greater than 0.10) and the duration of chills (p = 0.08) were similar for both infusion rates. Meperidine requirements for rapid and slow infusions were similar as well (p = 0.12). These data suggest that for patients free of preexisting renal and cardiac disease, rapid AB infusions are well tolerated and produce adverse reactions (fever and chills) similar in nature and severity to slower infusions.