Factor IX complex for the treatment of severe bleeding after cardiac surgery.

BACKGROUND: Previous reports have been published on the use of recombinant Factor VIIa for intractable bleeding after cardiac surgery; however, there is limited information on the use of Factor IX Complex in this population. METHODS: A retrospective cohort study of adult patients who underwent cardiac surgery and experienced severe postoperative bleeding, defined as a mean chest tube output ≥300 mL/h. Primary outcomes were changes in chest tube output and blood product usage pre- and post-Factor IX Complex administration. RESULTS: Eleven patients received Factor IX Complex for severe postoperative bleeding. The mean dose of Factor IX Complex was 35 (13-52) units/kg. Chest tube output was significantly reduced after Factor IX Complex administration (mean pre-Factor IX Complex 381 ± 49 mL/h, mean post-Factor IX Complex 151 ± 38 mL/h; P = 0.003). Blood product usage decreased after Factor IX Complex but was not statistically significant (mean pre-Factor IX Complex 373 ± 81 mL/h, mean post-Factor IX Complex 212 ± 48 mL/h; P = 0.669). Adverse events included 1 pulmonary embolism (postoperative day 43) and 2 episodes of acute renal failure requiring dialysis (postoperative days 2 and 5). CONCLUSIONS: In this small group of patients, Factor IX Complex effectively controlled severe bleeding after cardiac surgery preventing the need for re-exploration.

Effect of a dexmedetomidine substitution during a nationwide propofol shortage in patients undergoing coronary artery bypass graft surgery.

STUDY OBJECTIVE: To assess the effect of substituting dexmedetomidine for propofol during a nationwide propofol shortage on postoperative time to extubation and opioid requirements in patients who underwent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective case-control study. SETTING: Single-center cardiothoracic intensive care unit (ICU) in a tertiary academic medical center. PATIENTS: Seventy adults undergoing isolated, primary, elective CABG who received dexmedetomidine between April 1 and June 30, 2010, during the propofol shortage (35 patients [cases]) or who received propofol between January 1 and March 31, 2010, or between July 1 and September 30, 2010 (35 patients [controls]) for postoperative sedation were included. Patients in the dexmedetomidine group were matched 1:1 to patients in the propofol group based on age, sex, weight, number of vessels bypassed, preoperative ejection fraction, cardiopulmonary bypass time, and aortic cross-clamp time. MEASUREMENTS AND MAIN RESULTS: The primary outcome consisted of opioid requirements in the first 12 hours after arrival to the ICU in the dexmedetomidine- and propofol-treated patients. Secondary outcomes included the time to extubation (from ICU admission until extubation) and opioid requirements in the first 24 hours. No significant demographic differences were noted between treatment groups. Median opioid requirements in the first 12 hours, as measured by morphine equivalents, were 8.0 mg in the propofol group and 7.0 mg in the dexmedetomidine group (p=0.1). Similarly, at 24 hours, opioid requirements were 16.7 and 17.3 mg in the propofol and dexmedetomidine groups, respectively (p=0.4). The time to extubation demonstrated that patients in the propofol group were extubated at a median of 300 minutes and patients in the dexmedetomidine group were extubated at a median of 318 minutes after ICU arrival (p=0.5). CONCLUSION: No statistically significant differences were noted between the propofol and dexmedetomidine groups when assessing the outcomes of opioid requirements and the time to extubation. A multicenter, prospective, randomized, blinded study is needed to determine the optimal sedative after CABG surgery.

Nosocomial pneumonia risk and stress ulcer prophylaxis: a comparison of pantoprazole vs ranitidine in cardiothoracic surgery patients.

BACKGROUND: Stress ulcer prophylaxis (SUP) using ranitidine, a histamine H2 receptor antagonist, has been associated with an increased risk of ventilator-associated pneumonia. The proton pump inhibitor (PPI) pantoprazole is also commonly used for SUP. PPI use has been linked to an increased risk of community-acquired pneumonia. The objective of this study was to determine whether SUP with pantoprazole increases pneumonia risk compared with ranitidine in critically ill patients. METHODS: The cardiothoracic surgery database at our institution was used to identify retrospectively all patients who had received SUP with pantoprazole or ranitidine, without crossover between agents. From January 1, 2004, to March 31, 2007, 887 patients were identified, with 53 patients excluded (pantoprazole, 30 patients; ranitidine, 23 patients). Our analysis compared the incidence of nosocomial pneumonia in 377 patients who received pantoprazole with 457 patients who received ranitidine. RESULTS: Nosocomial pneumonia developed in 35 of the 377 patients (9.3%) who received pantoprazole, compared with 7 of the 457 patients (1.5%) who received ranitidine (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.9 to 14.9). Twenty-three covariates were used to estimate the probability of receiving pantoprazole as measured by propensity score (C-index, 0.77). Using this score, pantoprazole and ranitidine patients were stratified according to their probability of receiving pantoprazole. After propensity adjusted, multivariable logistic regression, pantoprazole treatment was found to be an independent risk factor for nosocomial pneumonia (OR, 2.7; 95% CI, 1.1 to 6.7; p = 0.034). CONCLUSION: The use of pantoprazole for SUP was associated with a higher risk of nosocomial pneumonia compared with ranitidine. This relationship warrants further study in a randomized controlled trial.

Effects of a waiting period after clopidogrel treatment before performing coronary artery bypass grafting.

STUDY OBJECTIVE: To assess the effects of a waiting period after clopidogrel treatment before coronary artery bypass grafting (CABG). Design. Single-center, prospective, observational study. SETTING: Cardiothoracic surgery intensive care unit at a university-affiliated medical center. PATIENTS: One hundred consecutive patients who received clopidogrel and were scheduled to undergo primary CABG. In 64 of these patients, CABG was delayed at least 5 days after clopidogrel treatment (group A). The other 36 patients received clopidogrel treatment within 5 days of undergoing CABG (group B). MEASUREMENTS AND MAIN RESULTS: Data were collected on patient demographics, time of last clopidogrel dose, preoperative anticoagulant and/or antiplatelet agents administered, surgical characteristics, intraoperative transfusions, blood products transfused, and chest tube output for 24 hours after surgery. No significant differences in baseline characteristics or intraoperative variables (number of bypasses, aortic cross-clamp time, and cardiopulmonary bypass time) were noted between the two groups. Mean +/- SD number of packed red blood cell units/patient was 1.1 +/- 1.4 in group A versus 2.1 +/- 2.5 in group B (p=0.009). Mean +/- SD number of platelet units/patient transfused was 0.5 +/- 0.9 in group A versus 1.9 +/- 1.6 in group B (p<0.001). When comparing a subset of 21 patients who received clopidogrel within 72 hours of surgery with the 64 whose CABG was delayed at least 5 days after clopidogrel treatment, the transfusion rates were significantly higher (95% vs 52%, p<0.05). Specifically, the mean +/- SD number of transfused units/patient of red blood cells (3.1 +/- 2.8 vs 1.1 +/- 1.4, p<0.005) and platelets (2.6 +/- 1.5 vs 0.5 +/- 0.9, p<0.007) was greater in patients who received clopidogrel within 72 hours of surgery. CONCLUSION: A strategy to delay CABG after clopidogrel treatment led to reduced blood product administration. The optimal waiting period after clopidogrel treatment is not known but appears to be at least 5 days before CABG.

Does the combination of aprotinin and angiotensin-converting enzyme inhibitor cause renal failure after cardiac surgery?

BACKGROUND: Aprotinin use in cardiac surgery has been associated with mild elevations in serum creatinine but generally has not been associated with an increase in the risk of acute renal failure. In the presence of angiotensin-converting enzyme (ACE) inhibitors, however, aprotinin may contribute to significant reductions in glomerular perfusion pressure. The purpose of this study was to test the hypothesis that the combination of ACE inhibitors and aprotinin cause renal failure after cardiac surgery. METHODS: The study consisted of a retrospective investigation of all adult patients undergoing coronary artery bypass graft, valve, or combined procedures during the years 2000 to 2002 at a single institution. Aprotinin was administered selectively for reoperations, combined procedures, and other operations deemed to be at higher risk for bleeding. Excluded from analysis were patients with preoperative serum creatinine greater than 1.5 mg/dL, a history of renal failure, emergent or salvage procedures, preoperative use of intraaortic balloon pump, and off-pump procedures. Perioperative renal failure was defined as creatinine greater than 2.0 mg/dL within 72 hours of surgery. Preoperative demographic and intraoperative variables were analyzed with univariate and logistic regression analysis with odds ratio (OR) and bootstrap validation. RESULTS: A total of 1,209 patients were included. The incidence of perioperative renal failure was 3.5%, and mortality in this group was 48%. Controlling for other demographic and intraoperative variables that may affect renal function (age, sex, diabetes mellitus, hypertension, New York Heart Association class, prior cardiac surgery, valve procedures, cardiopulmonary bypass time, aortic cross-clamp time, lowest hematocrit during cardiopulmonary bypass, transfusions) the preoperative use of ACE inhibitors along with intraoperative use of aprotinin was significantly associated with acute renal failure (OR 2.9, 95% confidence interval [CI]: 1.4 to 5.8, p < 0.0001). The effect of either drug alone was not significant. Other identified risk factors included age (OR 1.2 per year, CI: 1.01 to 1.5, p = 0.035), valve procedure (OR 2.7, CI: 1.3 to 5.7, p = 0.016), lowest hematocrit on cardiopulmonary bypass (OR 2.2, CI: 1.6 to 3.2, p < 0.0001), and transfusions of red blood cells (OR 1.04 per unit, CI: 1.02 to 1.06, p < 0.0001) and platelets (OR 1.7 per unit, CI: 1.2 to 2.4, p = 0.001). CONCLUSIONS: The combination of preoperative use of ACE inhibitors and intraoperative use of aprotinin should be avoided in cardiac surgery.

Effects of preoperative enoxaparin versus unfractionated heparin on bleeding indices in patients undergoing coronary artery bypass grafting.

BACKGROUND: We examined the effects of preoperative administration of enoxaparin (ENOX), a low-molecular-weight heparin, on bleeding indices and transfusion rates in patients undergoing coronary artery bypass grafting (CABG). METHODS: Patients undergoing isolated CABG between 1997 and 2002 who received preoperative ENOX or a continuous infusion of unfractionated heparin (UFH) were randomly divided into three groups: continuous UFH, ENOX last administered more than 12 hours before surgery (ENOX > 12), and ENOX administered less than 12 hours before surgery (ENOX < 12). Perioperative hemoglobin values, transfusion rates, and bleeding complications were compared. RESULTS: A total of 69, 58, and 34 patients comprised the UFH, ENOX > 12, and ENOX < 12 groups, respectively. Preoperative demographics and hematologic data were similar among the groups. Compared with the UFH group, the ENOX < 12 group had significantly lower postoperative hemoglobin values (9.6 +/- 1.3 g/dL versus 10.4 +/- 1.2 g/dL, p < 0.05), higher transfusion rates (73.5% versus 50.7%, p < 0.05), and required more total packed red cells per patient (882 +/- 809 mL versus 472 +/- 626 mL, p < 0.05). A nonsignificant increase was noted in the risk of returning to the operating room for bleeding in patients who had received ENOX compared with patients receiving UFH (6.5% versus 2.9%). CONCLUSIONS: The preoperative use of ENOX less than 12 hours before CABG is associated with lower postoperative hemoglobin values and higher rates of transfusion than continuous UFH.

Excessive argatroban anticoagulation for heparin-induced thrombocytopenia.

OBJECTIVE: To report 4 patients who became excessively anticoagulated with the recommended or lower starting doses of argatroban during treatment for heparin-induced thrombocytopenia type II (HIT-II) in a cardiothoracic intensive care unit. CASE SUMMARY: Four patients were treated with argatroban after confirmation of HIT-II after cardiac surgery. In 3 patients, argatroban was initiated at the recommended starting dose of 2 micro g/kg/min; in 1 patient, therapy was initiated at 1 micro g/kg/min. All patients had relatively normal hepatic function. In all cases, the resulting activated partial thromboplastin time was supertherapeutic and exceeded 100 seconds in 3 patients. Additionally, argatroban clearance appeared to be prolonged upon discontinuation. DISCUSSION: Argatroban pharmacokinetics in critically ill patients have not been investigated. Our case series demonstrates the potential over-anticoagulation that can occur in this patient population despite relatively normal hepatic function. An objective causality assessment revealed that the adverse drug event in these patients was probably caused by administration of argatroban. CONCLUSIONS: Formal pharmacokinetic studies of argatroban are needed in critically ill patients in order to optimize therapy.