title: Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial.
abstract: 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·h 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.
authors.affiliation: Department of Neuroanesthesiology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: Rikke Vibeke
authors.initials: RV
authors.lastname: Nielsen
authors.affiliation: Department of Neuroanesthesiology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: Jonna Storm
authors.initials: JS
authors.lastname: Fomsgaard
authors.affiliation: Department of Anesthesiology, Nykoebing Falster Hospital, Nykoebing Falster, Denmark, Copenhagen University Hospital.
authors.forename: Hanna
authors.initials: H
authors.lastname: Siegel
authors.affiliation: Department of Neuroanesthesiology, Rigshospitalet-Glostrup, Copenhagen University Hospital, Glostrup, Denmark.
authors.forename: Robertas
authors.initials: R
authors.lastname: Martusevicius
authors.affiliation: Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Nikolajsen
authors.affiliation: Department of Anesthesiology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jørgen Berg
authors.initials: JB
authors.lastname: Dahl
authors.affiliation: Department of Anesthesiology, Zealand University Hospital Koege, Copenhagen University Hospital, Koege, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mathiesen
mesh_terms: D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled; D000700:Analgesics / Q000008:administration & dosage*; D000701:Analgesics, Opioid; D059350:Chronic Pain / Q000188:drug therapy* / Q000601:surgery*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009020:Morphine; D009293:Opioid-Related Disorders / Q000209:etiology*; D010149:Postoperative Pain / Q000188:drug therapy*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D013123:Spinal Fusion; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D007649:Ketamine; D009020:Morphine