Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial

Abstract

BACKGROUND The current opioid epidemic highlights the urgent need for effective adjuvant therapies to complement postoperative opioid analgesia. Intra-operative ketamine infusion has been shown to reduce postoperative opioid consumption and improve pain control in opioid-tolerant patients after spinal fusion surgery. Its efficacy for opioid-naïve patients, however, remains controversial. OBJECTIVE We hypothesised that low-dose ketamine infusion after major spinal surgery reduces opioid requirements in opioid-tolerant patients, but not in opioid-naïve patients. DESIGN Randomised placebo-controlled study. SETTING Single-centre, tertiary care hospital, November 2012 until November 2014. PATIENTS A total of 129 patients were classified as either opioid-tolerant (daily use of opioid medications during 2 weeks preceding the surgery) or opioid-naïve group, then randomised to receive either ketamine or placebo; there were thus four groups of patients. All patients received intravenous hydromorphone patient-controlled analgesia postoperatively. INTERVENTION Patients in the ketamine groups received a ketamine infusion (bolus 0.2\u200amg\u200akg−1 over 30\u200amin followed by 0.12\u200amg\u200akg−1\u200ah−1 for 24\u200ah). Patients in the placebo groups received 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was opioid consumption during the first 24\u200ah postoperatively. The secondary outcome was numerical pain scores during the first 24\u200ah and central nervous system side effects. RESULTS Postoperative hydromorphone consumption was significantly reduced in the opioid-tolerant ketamine group, compared with the opioid-tolerant placebo group [0.007 (95% CI 0.006 to 0.008) versus 0.011 (95% CI 0.010 to 0.011)\u200amg\u200akg−1\u200ah−1, Bonferroni corrected P\u200a<\u200a0.001]. There was no difference in hydromorphone use between the opioid-naïve groups (0.004 and 0.005\u200amg\u200akg−1\u200ah−1 in the opioid-naïve ketamine and placebo group, respectively, P\u200a=\u200a0.118). Pain scores did not differ significantly between the opioid-tolerant ketamine group and the opioid-naïve groups. There was no significant difference in side effects among groups. CONCLUSION Postoperative low-dose ketamine infusion reduces opioid requirements for the first 24\u200ah following spinal fusion surgery in opioid-tolerant, but not in opioid-naïve patients. TRIAL REGISTRATION NCT03274453 with clinicaltrials.gov.