To the Editor:—

We report a case of intraoperative fatal anaphylaxis. The chronology of the event and the subsequent evaluation strongly point to a role of the aprotinin contained in the fibrin glue locally applied to the operating field.

This letter is accompanied by an Editorial View. Please see: Moss J: Allergic to anesthetics. Anesthesiology 2003; 99:521-3.

A 52-yr-old man underwent surgery for a painful lumbar disc herniation. His past medical history included a rhinoplasty, and his only other medical problem was a glaucoma treated with carteolol. After premedication with hydroxyzine 100 mg, anesthesia was induced with midazolam, propofol, and rocuronium and maintained with sufentanil and desflurane. No event occurred for 2 h until application of 0.2 ml of fibrin glue (Tissucol® Kit 500 U/ml; Baxter, Maurepas, France) on a dural tear. Blood pressure decreased immediately (60 mmHg), accompanied by a bronchospasm and a skin rash. The anesthetic agents were discontinued. The patient received hydroxyethyl-starch and intravenous epinephrine, but cardiac arrest developed. Cardiac massage was started and was soon followed by defibrillation. Stabilization of hemodynamic parameters was achieved with epinephrine infusion (epinephrine 3 mg/h). Right heart and pulmonary artery catheterism performed in the intensive care unit showed a low cardiac output with low left and right filling pressure. Despite intensive inotropic support, the patient died 48 h later from multiorgan failure.

The plasma levels of histamine and tryptase were increased 2 h after initial symptoms, confirming anaphylaxis. Antiaprotinin immunoglobulin (Ig) E and antiquaternary ammoniums immunoglobulins were identified in the preoperative serum of the patient (table 1).

Table 1. Allergologic Workup

IgE = immunoglobulin E antibodies; RAST = radio-allergosorbent assay; RIA = radioimmunologic assay.

Table 1. Allergologic Workup
Table 1. Allergologic Workup

No drugs other than those cited above had been given during the 2 h preceding the shock, except for Tissucol®. The chronology does not point to a role of neuromuscular blocking agents, because a 2-h interval had elapsed between the injection of rocuronium and the shock. Our patient had specific IgE against quaternary ammoniums (detected on his preoperative stored plasma), but this has little predictive value because antiquaternary ammoniums IgE are present in 10% of the population without allergic reaction to neuromuscular blocking agents. 1An allergic reaction to latex may occur at any time during surgery, but the negativity of antilatex IgE in the preoperative serum does not support this hypothesis in our case. The chronology of events and the presence of antiaprotinin IgE in the preoperative serum strongly argue in favor of an allergic mechanism induced by fibrin glue.

Fibrin glue is effective for hemostasis and sealing of tissue wounds but has been associated with severe anaphylactic reactions. 2Since 1990, Tissucol® has been composed of human coagulation factors and bovine aprotinin. The aprotinin role is to delay the destruction of the glue by fibrinolysis. None of the allergic cases following exposure to fibrin glue related to human coagulation factors. Bovine aprotinin was therefore held responsible. 3More than 100 cases of allergy to intravenous aprotinin have been published, essentially after reexposure to the drug. 4,5In our patient, the antiaprotinin IgE level was moderately positive, indicating previous sensitization. Cases of allergy after local application of the product are rare, and our case is the first related death reported. A case similar to ours was described after neurosurgery with local injection of fibrin glue for closure of a liquor fistula, which resulted only in a generalized skin rash. 6After further enquiry, we discovered that fibrin glue had been applied during the previous rhinoplasty 5 yr before. It has been demonstrated in cardiovascular surgery that locally given aprotinin results in a 10% 12-month prevalence of IgG antibodies. 7On the other hand, it has been observed in cardiovascular surgery that even a careful research of exposure history is not very sensitive to identify patients with aprotinin-specific antibodies. 8In case of known previous exposure to aprotinin, a preoperative allergologic workup is usually performed. However, the predictive value of the tests (prick-test, specific antiaprotinin IgG or IgE) has not been studied for aprotinin local application. Because the prevalence of reactions to aprotinin is higher in patients with a reexposure interval less than 6 months, such a short interval should be considered a relative contraindication to fibrin glue application. 5 

This is the first report of a fatal case of intraoperative anaphylactic shock related to local aprotinin. Because the preoperative questioning to investigate previous exposure to fibrin glue is difficult, and because an allergologic workup cannot be performed in every patient, the liberal use of fibrin glue must be weighed in relation to the risk of allergy.

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