Optimal dose of aprotinin for neuroprotection and renal function in a piglet model
Yusuke Iwata, Toru Okamura, David Zurakowski, Richard A. Jonas; Children's National Heart Institute, Children's National Medical Center, Washington, DC
Comment on this Abstract
Objective: Efficacy of aprotinin in reducing blood loss after CPB is well established, however its neuroprotective potential is less well known. Furthermore, there is controversy regarding optimal dosing and possible renal complications.
Methods: 54 piglets were randomly assigned to three CPB groups at risk for post-op cerebral and renal dysfunction: circulatory arrest at 25°C, ultra-low flow (10 ml/kg/min) at 25°C or 34°C. Animals were randomized to: control (no aprotinin), low dose (30,000 KIU/kg into prime only), full dose (30,000 KIU/kg bolus IV into prime plus 10,000 KIU/kg infusion), and double full dose. Tissue oxygenation index (TOI) was monitored by near-infrared spectroscopy. Neurologic functional and histological scores, creatinine and blood urea nitrogen (BUN) were outcomes of interest.
Results: Aprotinin significantly improved neurological scores on postoperative day 1 after ultra-low flow bypass at 25°C or 34°C (P<.01), but not after HCA (P=.57). Linear regression indicated a strong dose-response relationship with higher aprotinin doses having the best neurological scores. During LF, a higher TOI was correlated with a higher aprotinin dose (P<.05). Use of aprotinin and dose had no significant effect on creatinine, BUN, or BUN-to-creatinine ratio on day 1. Low body weight was the only predictor of high BUN (r = -0.39, P<.01).
Conclusion: Aprotinin significantly improves neurologic recovery without impairing renal function. Future studies are needed to examine the safety and efficacy of a double usual full dose strategy.
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