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Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial

Nielsen, Rikke Vibeke; Fomsgaard, Jonna Storm; Siegel, Hanna; Martusevicius, Robertas; Nikolajsen, Lone; Dahl, Jørgen Berg; Mathiesen, Ole

doi: 10.1097/j.pain.0000000000000782
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Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. Primary outcome was morphine consumption 0 to 24 hours postoperatively. Secondary outcomes were acute pain at rest and during mobilization 2 to 24 hours postoperatively (visual analogue scale), adverse events, and persistent pain 6 months postoperatively. One hundred fifty patients were randomly assigned to intraoperative S-ketamine bolus 0.5 mg/kg and infusion 0.25 mg·kg−1·h−1 or placebo. Postoperatively, patients received their usual opioids, paracetamol and IV patient-controlled analgesia with morphine. In the final analyses, 147 patients were included. Patient-controlled analgesia IV morphine consumption 0 to 24 hours postoperatively was significantly reduced in the ketamine group compared with the placebo group: 79 (47) vs 121 (53) mg IV, mean difference 42 mg (95% confidence interval −59 to −25), P < 0.001. Sedation was significantly reduced in the ketamine group 6 and 24 hours postoperatively. There were no significant differences regarding acute pain, nausea, vomiting, hallucinations, or nightmares. Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.

Intraoperative ketamine significantly reduced opioid consumption and sedation after lumbar fusion surgery. Possible effects on persistent pain 6 months postoperatively.

aDepartment of Neuroanesthesiology, Rigshospitalet—Glostrup, Copenhagen University Hospital, Glostrup, Denmark

bDepartment of Anesthesiology, Nykoebing Falster Hospital, Nykoebing Falster, Denmark, Copenhagen University Hospital

cDepartment of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark

dDepartment of Anesthesiology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark

eDepartment of Anesthesiology, Zealand University Hospital Koege, Copenhagen University Hospital, Koege, Denmark

Corresponding author. Address: Department of Neuroanesthesiology, Rigshospitalet—Glostrup, Copenhagen University Hospital, Nordre Ringvej 57, 2600 Glostrup, Denmark. Tel.: 0045 60926839. E-mail address: rikkevibeke@gmail.com (R.V. Nielsen).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Received July 27, 2016

Received in revised form October 07, 2016

Accepted November 28, 2016

© 2017 International Association for the Study of Pain
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