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.
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.



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.



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.



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.
Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria - helmar.bornemann@medunigraz.at.
Helmar
H
Bornemann-Cimenti
Mischa
M
Wejbora
Kristina
K
Michaeli
Alexander
A
Edler
Andreas
A
Sandner-Kiesling
D000005:Abdomen / Q000601:surgery*; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D003693:Delirium / Q000175:diagnosis; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy*; D007649:Ketamine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D010892:Pirinitramide / Q000008:administration & dosage*; D000072836:Surgical Wound / Q000150:complications
D000700:Analgesics; D000701:Analgesics, Opioid; D010892:Pirinitramide; D007649:Ketamine