Can Anaphylactic Reaction to Aprotinin Be Predicted by Preoperative Antibody Measurements?

Can Anaphylactic Reaction to Aprotinin Be Predicted by Preoperative Antibody Measurements? Dietrich et al. (page 64)

Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. Because it is derived from bovine lung, aprotinin has antigenic properties in humans. Anaphylactic reactions have been described in patients receiving the drug, and the incidence of reactions after reexposure has been reported to be 2.8%. In a prospective, observational study at five German centers between 1995 and 1996, Dietrich et al.  monitored antiaprotinin immunoglobulin (Ig) G and IgE antibodies before and after a second exposure to aprotinin in patients undergoing repeat cardiac surgery.

An aprotinin prick test was administered before surgery, and positive reactions were defined as development of a local wheal (≥ 3 mm) with swelling. First, a 1 × 10⁴kallikrein inhibitor unit (KIU) aprotinin test dose was administered to all patients 10 min before administration of the first aprotinin bolus after skin incision. If there was no reaction to the test dose, treatment of adult patients (n = 71) was initiated with a 2 × 10⁶KIU loading dose, followed by continuous infusion. Weight-based dosage regimens without continuous infusion were administered to pediatric patients (less than 12 yr of age; n = 46). Histamine H1 and H2 receptor antagonists also were administered to all patients prophylactically at induction of anesthesia. Blood samples were obtained before induction of anesthesia and 5–7 days postoperatively. Samples were also collected at the time of arrival in the intensive care unit from those patients who had experienced adverse reactions perioperatively.

Preoperatively, antiaprotinin IgG antibodies were detected in 18 patients; nine patients had antiaprotinin IgE antibodies. Three patients in this series experienced anaphylactic reactions after aprotinin exposure, followed by full recovery. They also had the highest preoperative IgG concentrations of all the patients, and their reexposure intervals were less than 6 months (22, 25, and 25 days). None of the IgG-negative patients experienced anaphylactic reactions to aprotinin reexposure. The aprotinin prick test was not predictive of response to aprotinin treatment because none of the patients showed positive preoperative results to the test. All of the patients who had adverse reactions to second exposures to aprotinin had high concentrations of antiaprotinin IgG antibodies, but only two expressed high concentrations of IgE antibodies. When exposure to aprotinin is necessitated within 6 months or less, aprotinin should be used with caution, say the authors. Quantitation of antiaprotinin antibody concentrations could help identify those in whom an anaphylactic reaction to the drug is likely to develop.