Effect of aprotinin on renal dysfunction in patients undergoing on-pump and off-pump cardiac surgery: a retrospective observational study.
BACKGROUND
Aprotinin 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.


METHODS
Our 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.


RESULTS
In 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).


CONCLUSIONS
Our 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.
Mouton
Ronelle
R
Department of Anaesthesia, Bristol Royal Infirmary, Bristol, UK. Ronelle.Mouton@nbt.nhs.uk
Finch
David
D
Davies
Ian
I
Binks
Andrea
A
Zacharowski
Kai
K
D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D007611:Aprotinin / Q000009:adverse effects* / Q000494:pharmacology; D016063:Blood Loss, Surgical / Q000517:prevention & control; D001026:Coronary Artery Bypass; D047549:Coronary Artery Bypass, Off-Pump; D004347:Drug Interactions; D005260:Female; D006490:Hemostatics / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000139:chemically induced; D051437:Renal Insufficiency / Q000139:chemically induced*; D012189:Retrospective Studies; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014148:Tranexamic Acid / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000933:Antifibrinolytic Agents; D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D014148:Tranexamic Acid; D007611:Aprotinin