Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model.
OBJECTIVE
The efficacy of aprotinin in reducing blood loss after cardiopulmonary bypass is well established, although its neuroprotective potential is less well known. Furthermore, there is controversy regarding optimal dosing and possible renal complications.


METHODS
Fifty-four piglets were randomized to one of 3 cardiopulmonary bypass groups designed to carry the risk of postoperative cerebral and renal dysfunction: circulatory arrest at 25 degrees C and ultra-low flow bypass (10 mL x kg(-1) x min(-1)) at either 25 degrees C or 34 degrees C. Animals were randomized to the following groups: control (no aprotinin), low dose (30,000 KIU/kg into prime only), standard full dose (30,000 KIU/kg bolus administered intravenously into prime plus 10,000 KIU/kg infusion), and double full dose. The tissue oxygenation index was monitored by means of near-infrared spectroscopy. Neurologic functional and histologic scores and creatinine and blood urea nitrogen values were outcomes of interest.


RESULTS
Aprotinin significantly improved neurologic scores on postoperative day 1 after ultra-low-flow bypass at 25 degrees C or 34 degrees C (P < .01) but not after hypothermic circulatory arrest (P = .57). Linear regression indicated a strong dose-response relationship, with higher aprotinin doses having the best neurologic scores. During low-flow bypass, a higher tissue oxygenation index was correlated with a higher aprotinin dose (P < .05). Aprotinin dose had no significant effect on creatinine or blood urea nitrogen values on day 1. Low body weight was the only predictor of high blood urea nitrogen values (r = -0.39, P < .01).


CONCLUSIONS
Aprotinin significantly improves neurologic recovery without compromising renal function in the young piglet.
Iwata
Yusuke
Y
Division of Cardiac Surgery, Children's National Medical Center, Washington, DC 20010, USA.
Okamura
Toru
T
Ishibashi
Nobuyuki
N
Zurakowski
David
D
Lidov
Hart G W
HG
Jonas
Richard A
RA
D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage*; D001522:Behavior, Animal; D001806:Blood Urea Nitrogen; D001921:Brain / Q000473:pathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D050792:Circulatory Arrest, Deep Hypothermia Induced; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010100:Oxygen / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage*; D034421:Sus scrofa
D018696:Neuroprotective Agents; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D003404:Creatinine; D010100:Oxygen