Anaphylactic reactions to aprotinin reexposure in cardiac surgery - Relation to antiaprotinin immunoglobulin G and E antibodies

Background: Aprotinin, a serine proteinase inhibitor, reduces bleeding duri ng cardiac surgery. As aprotinin is derived from bovine lung, it has antige nic properties. This investigation examined the incidence of anaphylactic r eactions in patients reexposed to aprotinin and the relation to preformed a ntiaprotinin immunoglobulin (Ig)G and IgE antibodies. Methods: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to a protinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurem ents, using a noncommercial enzyme-linked immunosorbent assay and an inmuno fluorescence assay, respectively, were performed preoperatively and postope ratively. An anaphylactic reaction was defined as major changes from baseli ne within 10 min of aprotinin administration of systolic pressure 20% or gr eater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2 O, or a skin reaction. Results: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative a ntiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioaller gosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respec tively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score greater than or equal to 3) were detected in five patients. Thre e patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphy lactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-n egative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable In two of three react ive patients and in three nonreacting patients. Conclusions: Quantitative detection of antiaprotinin IgE and IgG lacks spec ificity for predictive purposes; however, quantitation of antiaprotinin Ige may identify patients at risk for developing an anaphylactic reaction to a protinin reexposure.