Effect of intravenous S-ketamine on the MAC of sevoflurane: a randomised, placebo-controlled, double-blinded clinical trial

Ketamine is routinely used in operating theatres, emergency departments, ICUs, and even outpatient units. Despite the widespread use of ketamine, only basic aspects of its interactions with inhalation anaesthetic agents are known, and formal testing of interactions in humans is lacking. The minimum alveolar concentration (MAC) of inhalation anaesthetics is used to guide the depth of anaesthesia, and several drugs are known to influence the MAC. The aim of this study was to investigate whether intravenous application of ketamine influences the MAC of sevoflurane in humans.Adult patients undergoing elective surgery were included in this randomised, double-blinded, placebo-controlled study. Patients were assigned to one of three groups, each of which received a bolus of placebo, 0.5 mg kg-1S-ketamine, or 1 mg kg-1S-ketamine followed by an infusion of the same amount per hour after inhalation induction with sevoflurane was performed. The response to skin incision (movement vs non-movement) was recorded. The MAC of sevoflurane was assessed using an up-and-down titration method.Sixty patients aged 30-65 yr were included. Each group consisted of 20 patients. The MAC of sevoflurane was higher in the placebo group (2.1 (sd 0.1) %) than in the low-dose ketamine group (0.9 (0.1)%, P<0.01) and the high-dose ketamine group (0.5 (0.1)%, P<0.01). In addition, the MAC of sevoflurane was higher in the low-dose ketamine group compared with the high-dose ketamine group (P<0.01).The administration of S-ketamine significantly and dose-dependently reduced the MAC of sevoflurane in humans.EudraCT ref. no. 2012-001908-38.