S-(+)-Ketamine and circulation

Abstract

The S-(+) isomer of ketamine has about twice the analgesic potency of the clinically used racemic mixture. Therefore, the known side effects may be reduced when one-half of the usual dose is administered. Several prospective, randomised, and double-blinded studies have been performed to assess whether the S-(+) isomer of ketamine is superior to the racemic mixture with respect to circulatory side effects. Studies in young, healthy volunteers showed that heart rate (HR) and arterial blood pressure (ABP) rise significantly after injection of 2 mg/kg ketamine racemate and 1 mg/kg S-(+) isomer without any significant difference between groups. In the study of Doenicke et al. plasma levels of adrenaline (A) were higher in the racemate group, whereas no difference was found in elevated plasma levels of noradrenaline (NA). Premedication with midazolam blunted major haemodynamic changes. The investigation of Adams et al. confirmed that HR and ABP rise significantly after injection of 2 mg/kg ketamine racemate and 1 mg/kg S-(+) isomer without any significant difference between groups. In this study, no differences were found between groups concerning elevated plasma levels of A and NA. A further study in healthy volunteers also showed comparable haemodynamic changes following i.m.injection of 1.0 mg/kg ketamine racemate or 0.5 mg/kg S-(+) isomer without any significant difference between groups. In a previous clinical study including 40 elderly patients undergoing elective orthopaedic surgery, total intravenous anaesthesia (TIVA) was performed with S-(+)-ketamine or ketamine racemate as an analgesic compound. For induction of TIVA, patients received 0.1 mg/kg midazolam and 1 mg/kg S-(+)-ketamine or 2 mg/kg racemic ketamine, respectively. Throughout surgery, a continuous infusion of 2 mg/kg per hour S-(+)-ketamine or 4 mg/kg racemic ketamine was administered. Three patients in the racemate group showed severe arterial hypertension after induction of anaesthesia and were withdrawn from the study. In both groups plasma A and NA levels as well as HR and ABP increased significantly. In our own randomised, double-blinded study, haemodynamic effects of 2 mg/kg S-(+)-ketamine and 4 mg/kg ketamine racemate, respectively, were investigated in 14 patients undergoing elective aorto-coronary bypass surgery. In both groups HR and ABP significantly increased in 3 patients, each although all patients were deeply sedated with midazolam. One patient in the S-(+)-ketamine group showed severe arterial hypertension and tachycardia after induction of anaesthesia and was withdrawn from the study. With respect to haemodynamic changes, the pharmacodynamic effects of ketamine racemate and S-(+)-ketamine are comparable. Therefore, it can be concluded that neither ketamine nor S-(+)-ketamine should be used in patients who suffer, e.g., from arterial hypertension and coronary artery disease.