[Total i.v. anesthesia with S-(+)-ketamine in orthopedic geriatric surgery. Endocrine stress reaction, hemodynamics and recovery].

Unlabelled: Clinically-used ketamine is a racemic mixture of two isomers, S-(+)- and R-(-)-ketamine. Previous investigations showed the anaesthetic potency of S(+)-ketamine to be three times higher than that of R-(-)-ketamine. It was the aim of this study to compare the effects of S-(+)-ketamine and racemic ketamine on endocrine and cardiovascular parameters, recovery, and side effects in geriatric patients during total intravenous anaesthesia (TIVA) for orthopaedic surgery.
Methods: Forty patients over 60 years of age scheduled for elective hip or knee replacement were investigated in a double-blind, randomised design. For induction of TIVA, patients received 0.1 mg midazolam, 0.5 mg atropine, 1 mg/kg S(+)-ketamine or 2 mg/kg racemic ketamine, respectively, 2 mg vecuronium, and 1.5 mg/kg suxamethonium. After intubation and relaxation with a total dose of 0.1 mg/kg vecuronium, a continuous infusion of 2 mg/kg per hour S-(+)- or 4 mg/kg per hour racemic ketamine was administered throughout surgery. Blood samples were taken through a central venous catheter at seven time-points, before induction as well during and after surgery, until the 1st postoperative morning for analysis of adrenaline, noradrenaline (by high-pressure liquid chromatography with electrochemical detection), anti-diuretic hormone (ADH), adrenocorticotropic hormone (ACTH), cortisol (by radioimmunoassay), glucose, and lactate. In addition, systolic arterial pressure (SAP), heart rate (HR), and arterial oxygen saturation were measured, and the time intervals between the end of ketamine infusion and the return of consciousness and orientation were protocolled. The incidence and assessment of dreams and other side effects were reported by the patients.
Results: Biometric data of the groups were comparable, the mean age of both groups being 68 years. Plasma adrenaline, noradrenaline, ADH, ACTH, cortisol, and glucose as well as SAP and HR increased significantly (P < 0.05) during the course of anaesthesia. The influence on lactate levels was not significant. There were no differences between S(+)- and racemic ketamine with respect to these parameters. Three patients in the ketamine-racemate group showed severe arterial hypertension and were withdrawn from the study. Recovery clearly improved after administration of S(+)-ketamine compared to the racemate. Simple orders were followed after 2.0 +/- 3.4 versus 4.9 +/- 6.8 min (P = 0.07), orientation with respect to person returned after 5.7 +/- 4.0 versus 14.6 +/- 10.0 min (P < 0.001) and spatial orientation after 8.2 +/- 5.4 versus 17.4 +/- 9.7 min (P < 0.001). After racemic ketamine, 1 patient remembered a negative dream and 1 patient a positive dream. In the S(+)-group, 1 positive dream was reported. No intraoperative awareness was reported, and all patients would accept the same anaesthesia again.
Conclusions: Increases in cardiovascular parameters and insufficient reduction of the stress response with respect to ADH, ACTH, and cortisol seem to require a more potent hypnotic element during TIVA with ketamine. With regard to endocrine and cardiovascular parameters, the pharmacodynamic effects of racemic and S-(+)-ketamine were comparable. Because of the significant improvement in recovery and the reduced quantitative drug load, S-(+)-ketamine offers a clinical advantage compared with currently used racemic ketamine.