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

Minerva Anestesiol. 2016 Oct;82(10):1069-1076. Epub 2016 Jun 21.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / surgery*
  • Analgesics / administration & dosage*
  • Analgesics / adverse effects
  • Analgesics, Opioid / administration & dosage*
  • Delirium / diagnosis
  • Double-Blind Method
  • Elective Surgical Procedures
  • Female
  • Humans
  • Hyperalgesia / drug therapy*
  • Ketamine / administration & dosage*
  • Ketamine / adverse effects
  • Male
  • Middle Aged
  • Pain, Postoperative / drug therapy*
  • Pirinitramide / administration & dosage*
  • Surgical Wound / complications

Substances

  • Analgesics
  • Analgesics, Opioid
  • Pirinitramide
  • Ketamine