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In patients undergoing coronary artery bypass grafting surgery, the cyclooxygenase 2 inhibitor combination, parecoxib/valdecoxib, was effective for postoperative analgesia. However, the 14-day treatment regimen also was associated with an increased incidence of serious adverse events overall and sternal wound infections in particular. Therefore our study raises important concerns requiring their comprehensive evaluation in a large-scale trial before these cyclooxygenase 2 inhibitors are used in patients undergoing coronary artery bypass grafting surgery.

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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 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. Therefore, we assessed the affect of aprotinin on both blood transfusion requirements and renal function in patients undergoing cardiovascular surgery and DHCA. Methods and Results-We reviewed the records of 853 patients who underwent aortic or thoracoabdominal surgery at Stanford University Medical Center between January 1992 and March 2000. Two hundred three of these patients were treated with DHCA, and 90% (183) survived for more than 24 hours. Preoperative patient characteristics and intraoperative and postoperative clinical and surgical variables were recorded, and creatinine clearance (CRCl) was calculated for the preoperative and postoperative periods; renal dysfunction was prospectively defined as a 25% reduction in CRCl. The association between perioperative variables, including aprotinin use, and renal dysfunction was assessed by ANOVA techniques. Total urine output was 1294Ϯ1024 mL and 3492Ϯ1613 mL during and after surgery, respectively. CRCl decreased significantly after DHCA from 86Ϯ8 mL/min (before surgery) to 67Ϯ4 mL/min (in the intensive care unit) (PϽ0.01). Thirty-eight percent of patients (70 of 183) had postoperative renal dysfunction. Multivariate regression analyses identified 5 factors independently associated with a Ͼ25% reduction in CRCl: requirement for Ն5 U of packed red blood cells (Pϭ0.0002; ORϭ2.1), Յ800 mL of urine collected in the operating room (Pϭ0.0011; ORϭ1.9), nonuse of dopamine (Pϭ0.0430; ORϭ1.6), hematocrit Յ21 mg% (Pϭ0.0343; ORϭ1.5), and Յ2100 mL of urine during the first 24 hours in the intensive care unit (Pϭ0.0039; ORϭ2.0). Aprotinin did not increase the likelihood of postoperative renal dysfunction (Pϭ0.951), nor did it significantly reduce packed red blood cell transfusion requirements in either primary (nϭ107) (Pϭ0.456) or reoperative cardiovascular (nϭ76) (Pϭ0.176) procedures. During the operative period, the aprotinin group received a greater number of units of platelets (10.0 versus 6.6 U, PϽ0.012), fresh frozen plasma (4.8 versus 3.1 U, PϽ0.03), and cryoprecipitate (9.9 versus 5.4 U, PϽ0.002) than patients not prescribed aprotinin. Similarly, patients given aprotinin received more cryoprecipitate in the intensive care unit (

Moderate to severe functional bowel disease results in debilitating abdominal pain, nausea, intermittent vomiting, early satiety, bloating, abdominal distension, and/or altered bowel habits. Because it occurs approximately 20-30 times more frequently in women than in men and its symptoms often coincide with the menstrual cycle, we hypothesized that reproductive steroids may antagonize diseased nerves of the gastrointestinal tract, enhancing the expression of symptoms. No effective or consistent therapy has existed for these patients. We prospectively investigated the effect of a gonadotropin-releasing hormone analog, leuprolide acetate, in 30 women with symptoms of moderate to severe functional bowel disease. The study was phase II, randomized, double blind, and placebo controlled. Lupron Depot 3.75 mg (which delivers a continuous low dose of drug for one month) or placebo were given intramuscularly monthly for three months. Symptom scores were assessed at each four-week visit. Follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone levels were assessed before and after therapy. Patients treated with low-dose leuprolide improved progressively and significantly in scores for nausea, vomiting, bloating, abdominal pain, and early satiety, and for overall symptoms (P < 0.01-0.05). All hormone levels decreased significantly (P < 0.05) except luteinizing hormone (P = 0.054).