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 prospective 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 mg kg−1 over 30 min followed by 0.12 mg kg−1 h−1 for 24 h). Patients in the placebo groups received 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was opioid consumption during the first 24 h postoperatively. The secondary outcome was numerical pain scores during the first 24 h 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) mg kg−1 h−1, Bonferroni corrected P
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