• Ronelle Mouton, David Finch, Ian Davies, Andrea Binks, and Kai Zacharowski.
• Department of Anaesthesia, Bristol Royal Infirmary, Bristol, UK. Ronelle.Mouton@nbt.nhs.uk
• Lancet. 2008 Feb 9;371(9611):475-82.

BackgroundAprotinin is used during cardiac surgery for its blood-saving effects. However, reports suggest a possible association between use of this drug and increased renal dysfunction and mortality. We investigated the effect of aprotinin on renal dysfunction in cardiac surgery, considering the cofactors on-pump versus off-pump surgery and co-medication with angiotensin-converting enzyme (ACE) inhibitors.MethodsOur analysis included 9875 patients undergoing on-pump or off-pump cardiac surgery from Jan 1, 2000, to Sept 30, 2007. Of these patients, 9106 were included in the retrospective observational study analysis. With propensity-adjusted, multivariate staged logistic regression, we analysed separately the incidence of renal dysfunction in patients receiving aprotinin, tranexamic acid, or no antifibrinolytic treatment in the presence or absence of preoperative ACE inhibitor treatment, for both on-pump and off-pump surgical techniques.FindingsIn 5434 patients undergoing on-pump cardiac surgery, the odds ratio (OR) between aprotinin and an increased risk of renal dysfunction without ACE inhibitor was 1.81 (95% CI 0.79-4.13, p=0.162) and with ACE inhibitor 1.73 (0.56-5.32, p=0.342). In the 848 patients taking ACE inhibitors and undergoing off-pump cardiac surgery, aprotinin was associated with a greater than two-fold increase in the risk of renal dysfunction after off-pump cardiac surgery (OR 2.87 [1.25-6.58], p=0.013).InterpretationOur results have shown that aprotinin seems to be safe during on-pump cardiac surgery. However, the combination of aprotinin and ACE inhibitors during off-pump cardiac surgery is associated with a significant risk of postoperative renal dysfunction.

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