Aprotinin and anaphylaxis: analysis of 12,403 exposures to aprotinin in cardiac surgery.
BACKGROUND
Hypersensitivity reactions to the nonspecific proteinase inhibitor aprotinin may occur. The present study evaluates the incidence of hypersensitivity reactions to aprotinin.


METHODS
Data were prospectively collected as part of the institution's quality assurance program. The database was screened for anaphylactic reactions, especially those against aprotinin. The definition of an allergic reaction was predefined. A severe reaction was defined as hemodynamic instability of more than 10 minutes despite high dosages of vasopressors and inotropic medication.


RESULTS
Of 13,315 cardiac operations, 12,403 were done with aprotinin, with 801 reexposures in 697 patients. Eleven reactions to aprotinin (11 of 11,602; 0.09%, 95% confidence interval: 0.05% to 0.16%) were recorded after primary exposure, of which none was severe, while 12 reactions (12 of 801; 1.5%; 95% confidence interval: 0.86% to 2.6%) occurred after reexposure, of which 5 were severe. All severe reactions were in patients reexposed to aprotinin within 6 months after previous exposure. There was no reaction observed in patients reexposed to aprotinin within 3 days after the last exposure (n = 42). The incidence of hypersensitivity reactions was 4.1%, 1.9%, and 0.4% in the less than 6 months, 6 to 12 months, and more than 12 months reexposure intervals, respectively.


CONCLUSIONS
The risk of hypersensitivity reactions is low after primary exposure to aprotinin. This risk after reexposure reaches a maximum between the fourth day and the 30th day after previous exposure and declines considerably after 6 months. Consequently, application of aprotinin carries a high risk between the fourth and the 30th day after previous exposure, and cannot be recommended for the first 6 months, but is justifiable in previously aprotinin-exposed patients with a high risk of bleeding after this interval.
Dietrich
Wulf
W
Department of Anesthesiology, German Heart Center Munich, Germany. wulf.dietrich@t-online.de
Ebell
Anna
A
Busley
Raimund
R
Boulesteix
Anna-Laure
AL
D000328:Adult; D017677:Age Distribution; D000368:Aged; D000707:Anaphylaxis / Q000453:epidemiology* / Q000276:immunology; D007611:Aprotinin / Q000009:adverse effects* / Q000276:immunology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000379:methods; D002675:Child, Preschool; D015331:Cohort Studies; D016001:Confidence Intervals; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D015842:Serine Proteinase Inhibitors / Q000009:adverse effects* / Q000276:immunology; D017678:Sex Distribution
D015842:Serine Proteinase Inhibitors; D007611:Aprotinin