S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial

Abstract

Background: Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.

Methods: We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.

Results: Of the 100 patients analyzed, patients receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml-1 (74.7 mg) or 0.25 mg ml-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013-0.32, P = 0.033). The occurrence of adverse events was similar among the groups.

Conclusions: Oxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. DoseRespKeta trial structure and CONSORT 2009 flow diagram.

CONSORT indicates Consolidated Standards of Reporting Trials.

Fig 2. Postoperative cumulative oxycodone (top row) and S-ketamine (bottom row) consumption during the first 24 h in four patient-controlled analgesia (PCA) treatment groups (G1¬–G4).

PCA, patient-controlled analgesia. Box plots show the median and 25–75th percentiles, and the whiskers indicate the minimum and maximum. Blue diamonds show the mean oxycodone consumption in each plot.

Fig 3

A) Patient-reported numerical rating scale (NRS) values at rest during the first 24 h in four patient-controlled analgesia (PCA) treatment groups G1-G4. Box plots show the median and 25–75th percentiles, and the whiskers indicate the minimum and maximum. (B) Risk ratios (95% CI) for reporting NRS value 4 or higher. PACU, postoperative care unit; CI, confidence interval.