Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest

Background-The technique of deep hypothermic circulatory arrest (DHCA) for cardiothoracic surgery is associated with increased risk for perioperative blood loss and renal dysfunction. Although aprotinin, a serine protease inh ibitor, reduces blood loss in patients undergoing cardiopulmonary bypass, i ts use has been limited in the setting of DHCA because of concerns regardin g aprotinin-induced renal dysfunction. Therefore, we assessed the affect of aprotinin on both blood transfusion requirements and renal function in pat ients undergoing cardiovascular surgery and DHCA. Methods and Results-We reviewed the records of 853 patients who underwent a ortic or thoracoabdominal surgery at Stanford University Medical Center bet ween January 1992 and March 2000. Two hundred three of these patients were treated with DHCA. and 90% (183) survived for more than 24 hours. Preoperat ive patient characteristics and intraoperative and postoperative clinical a nd surgical variables were recorded, and creatinine clearance (CRCl) was ca lculated for the preoperative and postoperative periods; renal dysfunction was prospectively defined as a 25% reduction in CRCl. The association betwe en perioperative variables, including aprotinin use. and renal dysfunction was assessed by ANOVA techniques. Total urine output was 1294 +/- 1024 mL a nd 3492 +/- 1613 mL during and after surgery, respectively. CRCl decreased significantly after DHCA from 86 +/-8 mL/min (before surgery) to 67 +/-4 mL /min (in the intensive care unit) (P <0.01). Thirty-eight percent of patien ts (70 of 183) had postoperative renal dysfunction. Multivariate regression analyses identified 5 factors independently associated with a > 25% reduct ion in CRCl: requirement for greater than or equal to5 U of packed red bloo d cells (P=0.0002; OR=2.1), less than or equal to 800 mL of urine collected in the operating room (P=0.0011; OR=1.9), nonuse of dopamine (P=0.0430; OR =1.6), hematocrit less than or equal to 21 mg% (P=0.0343; OR=1.5), and less than or equal to 2100 mL of urine during the first 24 hours in the intensi ve care unit (P=0.0039. OR=2.0). Aprotinin did not increase the likelihood of postoperative renal dysfunction (P=0.951), nor did it significantly redu ce packed red blood cell transfusion requirements in either primary (n=107) (P=0.456) or reoperative cardiovascular (n=76) (P=0.176) procedures. Durin g the operative period, the aprotinin group received a greater number of un its of platelets (10.0 versus 6.6 U, P <0.012), fresh frozen plasma (4.8 ve rsus 3.1 U, P <0.03). and cryoprecipitate (9.9 versus 5.4 U, P <0.002) than patients not prescribed aprotinin. Similarly, patients given aprotinin rec eived more cryoprecipitate in the intensive care unit (7.3 versus 3.0 U, P <0.024). Conclusions-These data suggest that the administration of aprotinin to pati ents treated with DHCA does not increase the risk of renal dysfunction. How ever., aprotinin may not ameliorate the problem of perioperative blood loss in DHCA. Patients with greater requirements for packed red blood cell tran sfusions or reduced urine production are more likely to have postoperative renal dysfunction. Dopamine may provide renal protection in the setting of DHCA.