INOTROPIC EFFECTS OF PROPOFOL, THIOPENTAL, MIDAZOLAM, ETOMIDATE, AND KETAMINE ON ISOLATE HUMAN ATRIAL MUSCLE

Background: Cardiovascular instability after intravenous induction of anesthesia may be explained partly by direct negative inotropic effect s. The direct inotropic influence of etomidate, ketamine, midazolam, p ropofol, and thiopental on the contractility of isolated human atrial tissue was determined. Effective concentrations were compared with tho se reported clinically. Methods: Atrial tissue was obtained from 16 pa tients undergoing coronary bypass surgery. Each fragment was divided i nto three strips, and one anesthetic was tested per strip in increasin g concentrations (10(-6) to 10(-2) M). Strips were stimulated at 0.5 H z, and maximum isometric force was measured. Induction agents were stu died in two groups, group 1 (n = 7) containing thiopental midazolam, a nd propofol, and group 2 (n = 9) consisting of etomidate, ketamine, an d propofol. Results: The tested anesthetics caused a concentration-dep endent depression of contractility resulting in complete cessation of contractions at the highest concentrations. The IC(50)s (mean +/- SEMI mu M) for inhibition of the contractility were: thiopental 43 +/- 7.6 , propofol 235 +/- 48 (group 1), and 246 +/- 42 (group 2), midazolam 1 45 +/- 54, etomidate 133 +/- 13, and ketamine 303 +/- 54. Conclusions: This is the first study demonstrating a concentration-dependent negat ive inotropic effect of intravenous anesthetics in isolated human atri al muscle. No inhibition of myocardial contractility was found in the clinical concentration ranges of propofol, midazolam, and etomidate. I n contrast, thiopental showed strong and ketamine showed slight negati ve inotropic properties. Thus, negative inotropic effects may explain in part the cardiovascular depression on induction of anesthesia with thiopental but not with propofol midazolam, and etomidate. Improvement of hemodynamics after induction of anesthesia with ketamine cannot be explained by intrinsic cardiac stimulation.