The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial.

BACKGROUND: Evidence confirms that perioperative ketamine administration decreases opioid usage. To reduce the risk for potential psychodysleptic side effects, however, ketamine dosing tends to be limited to low-dose regimens. We hypothesized that even lower doses of ketamine would be sufficient, with minimal side effects, when used as a component of multimodal perioperative pain management. METHODS: In this triple-blinded, randomized, active- and placebo-controlled clinical trial, patients undergoing elective major abdominal surgery were randomized to one of three treatment groups: low-dose S-ketamine (a 0.25 mg/kg bolus and 0.125 mg/kg/h infusion for 48 hours), minimal-dose S-ketamine (a 0.015 mg/kg/h infusion following a saline bolus), and placebo (saline bolus and infusion). Opioid consumption, pain levels, hyperalgesia at the incision site, and delirium scores were assessed 48 h postoperatively. RESULTS: Patients in the placebo group had the highest cumulative piritramide consumption and the largest normalized areas of hyperalgesia at the incisional site, while those in the low-dose group had the highest delirium scores. Postoperative pain levels did not differ significantly between the treatment groups. CONCLUSIONS: Our data demonstrate that minimal-dose S-ketamine was comparable to the conventional low-dose regimen in reducing postoperative opioid consumption and hyperalgesia. Postoperative delirium, however, was less frequent with the minimal-dose regimen. We therefore suggest that minimal-dose S-ketamine may be a useful low-risk component of balanced perioperative analgesia.