Aprotinin in cardiac surgery.
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Aprotinin↗
Biomedical subjects
James G Ramsay
Publications and source records attributed to James G Ramsay.
An unusual case of endocarditis.
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Echocardiography, Transesophageal↗
A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery.
BACKGROUND: Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. STUDY DESIGN: One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. RESULTS: Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). CONCLUSIONS: Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery.
Adult↗
Off-pump coronary surgery: how do the anesthetic considerations differ?
In recent years, there has been much interest in performing coronary artery bypass graft (CABG) surgery without the aid of cardiopulmonary bypass (CPB). Initial efforts focused on "minimally invasive" direct coronary artery bypass, wherein the left anterior descending artery is bypassed with an in situ left internal mammary artery graft through a small left anterior thoracotomy. A more widely adopted approach however, is off-pump CABG (OPCAB), in which CABG surgery is performed on one or more vessels through the usual median sternotomy approach without the aid of CPB. This article reviews the differences in the anesthetic considerations of OPCAB compared to conventional CABG using CPB.
Anesthesia↗
Reliability of pharmacodynamic analysis by logistic regression: mixed-effects modeling.
BACKGROUND: Many pharmacologic studies record data as binary, yes-or-no, variables with analysis using logistic regression. In a previous study, it was shown that estimates of C50, the drug concentration associated with a 50% probability of drug effect, were unbiased, whereas estimates of gamma, the term describing the steepness of the concentration-effect relationship, were biased when sparse data were naively pooled for analysis. In this study, it was determined whether mixed-effects analysis improved the accuracy of parameter estimation. METHODS: Pharmacodynamic studies with binary, yes-or-no, responses were simulated and analyzed with NONMEM. The bias and coefficient of variation of C50 and gamma estimates were determined as a function of numbers of patients in the simulated study, the number of simulated data points per patient, and the "true" value of gamma. In addition, 100 sparse binary human data sets were generated from an evaluation of midazolam for postoperative sedation of adult patients undergoing cardiac surgery by random selection of a single data point (sedation score vs. midazolam plasma concentration) from each of the 30 patients in the study. C50 and gamma were estimated for each of these data sets by using NONMEM and were compared with the estimates from the complete data set of 656 observations. RESULTS: Estimates of C50 were unbiased, even for sparse data (one data point per patient) with coefficients of variation of 30-50%. Estimates of gamma were highly biased for sparse data for all values of gamma greater than 1, and the value of gamma was overestimated. Unbiased estimation of gamma required 10 data points per patient. The coefficient of variation of gamma estimates was greater than that of the C50 estimates. Clinical data for sedation with midazolam confirmed the simulation results, showing an overestimate of gamma with sparse data. CONCLUSION: Although accurate estimations of C50 from sparse binary data are possible, estimates of gamma are biased. Data with 10 or more observations per patient is necessary for accurate estimations of gamma.
Cardiac Surgical Procedures↗
Clevidipine in adult cardiac surgical patients: a dose-finding study.
BACKGROUND: Treatment of elevated blood pressure is frequently necessary after cardiac surgery to minimize postoperative bleeding and to attenuate afterload changes associated with hypertension. The purpose of this study was to investigate the pharmacodynamics and pharmacokinetics of a short-acting calcium channel antagonist, clevidipine, in the treatment of hypertension in postoperative cardiac surgical patients. METHODS: Postoperative cardiac surgical patients were randomized to receive placebo or one of six doses of clevidipine. Hemodynamic parameters were recorded and blood samples were drawn for determination of clevidipine plasma concentrations during infusion and after discontinuation of clevidipine. The concentration-response relation was analyzed using logistic regression, and pharmacokinetic models were applied to the data using population analysis. RESULTS: There were significant decreases in mean arterial blood pressure and systemic vascular resistance at doses greater than or equal to 1.37 microg. kg-1. min-1. There were no changes in heart rate, central venous pressure, pulmonary artery occlusion pressure, or cardiac index with increasing doses of clevidipine. The clevidipine C50 value for a 10% or greater decrease in mean arterial pressure was 9.7 microg/l and for a 20% or greater decrease in mean arterial pressure was 26.3 microg/l. The pharmacokinetics of clevidipine were best described with a three-compartment model with a volume of distribution of 32.4 l and clearance of 4.3 l/min. The early phase of drug disposition had a half-life of 0.6 min. The context-sensitive half-time is less than 2 min for up to 12 h of administration. CONCLUSION: Clevidipine is a calcium channel antagonist with a very short duration of action that effectively decreases systemic vascular resistance and mean arterial pressure without changing heart rate, cardiac index, or cardiac filling pressures.
Algorithms↗