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Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion

A randomised controlled trial

Boenigk, Kirsten; Echevarria, Ghislaine C.; Nisimov, Emmanuel; von Bergen Granell, Annelise E.; Cuff, Germaine E.; Wang, Jing; Atchabahian, Arthur

European Journal of Anaesthesiology (EJA): January 2019 - Volume 36 - Issue 1 - p 8–15
doi: 10.1097/EJA.0000000000000877
Postoperative pain

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 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 < 0.001]. There was no difference in hydromorphone use between the opioid-naïve groups (0.004 and 0.005 mg kg−1 h−1 in the opioid-naïve ketamine and placebo group, respectively, P = 0.118). 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 h following spinal fusion surgery in opioid-tolerant, but not in opioid-naïve patients.


From the Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University, New York, New York, USA (KB, GCE, EN, AEvBG, GEC, JW, AA)

Correspondence to Arthur Atchabahian, MD, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University School of Medicine, 301 East 17th Street – Room C2-222, New York, NY 10003, USA Tel: +1 212 598 6085; fax: +1 212 598 6163; e-mail:

Published online 14 August 2018

© 2019 European Society of Anaesthesiology