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Aprotinin, Blood Loss, and Renal Dysfunction in Deep Hypothermic Circulatory Arrest Mora Mangano CT, Neville MJ, Hsu PH,
Mignea I, King J, Miller C. Circulation 2001; 104 (suppl I):
I-276-I-281.
Abstract Excerpt: The technique of deep hypothermic circulatory arrest (DHCA) for cadiothoracic surgery is associated with increased risk for perioperative blood loss and renal dysfunction. Although aprotinin, a serine protease inhibitor, reduces blood loss in patients undergoing cardiopulmonary bypass, its use has been limited in the setting of DHCA because of concerns regarding aprotinin-induced renal dysfunction. These investigators assessed the affect of aprotinin on both blood transfusion requirements and renal function in patients undergoing cardiovascular surgery and DHCA. They retrospectively reviewed the records of 853 patients who underwent aortic or thoracoabdominal surgery at their institution between 1992 and 2000. 203 of these were subjected to DHCA and 183 survived for more than 24 hours. Preoperative patient characteristics and intraoperative and postoperative clinical and surgical variables were recorded in these 183 patients (44 received aprotinin, 139 did not receive aprotinin). Creatinine clearance was calculated for the preoperative and postoperative periods and renal dysfunction was prospectively defined as a 25% reduction in creatinine clearance. The association between perioperative variables, including aprotinin use, and renal dysfunction was assessed via ANOVA techniques. Regarding all patients, creatinine clearance decreased significantly after DHCA from 86 m1/min (before surgery) to 67 ml/min (after surgery) (p<0.0l). 70 of 183 (38%) patients developed postoperative renal dysfunction. Multivariate regression analysis identified five factors independently associated with a greater than 25% reduction in creatinine clearance: requirement for > 5 units of packed red blood cells (p=0.0002), < 800 ml of urine collected in the operating room (p=0.0011), nonuse of dopamine (p=0.043), hematocrit < 21% (p=0.0343), and < 2100 ml of urine during the first 24 postoperative hours (p=0.0039). Aprotinin did not increase the likelihood of postoperative renal dysfunction (p=0.951) nor did it significantly decrease packed red blood cell transfusion requirements in either primary (n=107, p=0.456) or reoperative (n=76, p=0.176) procedures. During the operative period, the aprotinin group received a greater number of units of platelets (10.0 vs 6.6 units, p < 0.012), fresh frozen plasma (4.8 vs 3.1 units, p< 0.03), and cryoprecipitate (9.9 vs 5.4 units, p<0.002) than patients not receiving aprotinin. The investigators conclude that the data suggest that administration of aprotinin to patients treated with DHCA does not increase the risk of renal dysfunction, that aprotinin may not ameliorate the problem of perioperative blood loss in DHCA, that patients with greater requirements for packed red blood cell transfusions or reduced urine production are more likely to have postoperative renal dysfunction, and that dopamine may provide renal protection in the setting of DHCA. Comments: While DHCA has proven to be life-saving for many children and adults, control of the adverse sequelae associated with the technique remains a formidable challenge. Coagulopathy remains a substantial problem accompanying DHCA and the introduction of aprotinin in the early 1990s was an important addition to the armamentarium available to decrease postoperative bleeding in patients when using the technique. However, use of the drug in this setting has been associated with reports of thromboembolic events, renal dysfunction, and other end-organ damage, making use of the drug in this fashion somewhat controversial. The present investigation suggests that use of aprotinin is not associated with renal dysfunction in patients subjected to DHCA. Somewhat surprisingly, aprotinin did not decrease perioperative blood loss, as quantified by a number of measures (blood products transfused, hematocrit values, chest tube drainage). Importantly, aprotinin did not reduce blood transfusion requirements in either patients at increased risk (reoperations) or patients undergoing a primary procedure with DHCA. Lastly, patients administered dopamine, either alone or in combination with one or more inotropic/vasoactive drugs were less likely to exhibit renal dysfunction. Despite decades of ubiquitous use of dopamine for prevention of renal dysfunction, this investigation is the first to indicate, through multivariate analysis, that dopamine may provide renal protection in the setting of DHCA. The retrospective nature of this investigation most certainly limits the conclusions that can be generated from the data. Despite this fact, the investigation does provide some additional information on the somewhat controversial use of aprotinin in patients subjected to DHCA. The investigation also emphasizes the need for well-controlled (prospective, randomized, blinded, placebo-controlled) studies regarding the effects of aprotinin on the coagulopathy and renal dysfunction in patients subjected to DHCA and the potential clinical benefits of perioperative use of dopamine in this scenario as well. Table of Contents
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