SHORT COMMUNICATIONS AND BRIEF CASE NOTES Fatal Intraoperative Anaphylaxis After Aprotinin Administration

Aprotinin is a 6512-dalton bovine peptide antifi brinolytic agent. Due to its inhibitory effect on proteolytic enzymes (trypsin, plasmin, kallikrein), it is used to reduce blood loss and transfusion requirements and to limit the systemic infl ammatory response in major surgery under extracorporeal circulation (cardiac surgery, lung and liver transplantation, hip replacement). The frequency of allergic reactions to aprotinin has been estimated at 2.8 % when patients are re-exposed to this peptide within a 6-month period [1, 2]. We present the case of a 76-year-old man with no history of previous allergic diseases who underwent aortic valve replacement due to prosthetic valve endocarditis. Remifentanil, fentanyl, etomidate, midazolam, atracurium, and cefazolin were given during anesthesia. Sixty minutes after induction, intravenous aprotinin (Trasylol, Bayer AG, Levercusen, Germany) was administered; it induced immediate hypotension, pulmonary hypertension, ventricular fi brillation and cardiorespiratory arrest. The patient died after 2 hours of advanced cardiopulmonary resuscitation. When aprotinin had been administered intravenously 2 months earlier, tolerance had been good. Serum tryptase levels measured 167 g/L and 3.8 g/L (CAP Pharmacia, Uppsala, Sweden ) at the time of the adverse reaction and 1 day before surgery, respectively. A peroxidasebased enzyme-linked immunosorbent assay demonstrated the presence of specifi c immunoglobulin (Ig) E to aprotinin in serum. The absorbance measured at 495 nm was 0.728 optical density (OD) in contrast with 0.090 OD for the mean of the control sera from 3 patients. This is a case of fatal anaphylaxis due to aprotinin demonstrated by the presence of serum specifi c IgE. Serum tryptase measurement was essential for the diagnosis of anaphylaxis. It has been recommended to avoid re-exposure to aprotinin for at least 6 months, since it has been proven to be a main risk factor for anaphylactic reactions [1-3]. Re-exposure to aprotinin within a 2-month period may have been a determinant for this fatal reaction. Standardized enzyme immunoassay kits are commercially available for the quantitative determination of antiaprotinin IgG antibodies (CellTrend, Luckenwalde, Germany). We propose that the determination of specifi c IgE, and especially IgG, to aprotinin should be evaluated in patients with prior contact with this peptide. Patients with high antibody titers should be considered at risk, whereas the absence of aprotinin-specifi c IgG has been reported to indicate low risk of a hypersensitivity reaction [1-3]. Recently, the Spanish Drug Agency has issued an offi cial bulletin recommending that IgG specifi c antibodies be determined prior to aprotinin administration. They also stress that aprotinin administration is contraindicated in patients in whom specifi c-IgG antibodies are detected as well as in patients possibly exposed to aprotinin within the last 12 months. Recent publications indicate that the use of aprotinin is associated with a dose-dependent higher risk of renal failure and multiorgan damage, including heart and brain injury. The risk of long-term mortality is also higher after the use of aprotinin in comparison with the use of lysine analogs aminocaproic acid and tranexamic acid. It has therefore been suggested to use those safer and cheaper alternatives and to withdraw aprotinin from human use [4-6].