S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial

Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative op...

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Bibliographic Details
Published in:PloS one 2021-06, Vol.16 (6), p.e0252626-e0252626
Main Authors: Brinck, Elina C. V, Virtanen, Taru, Mäkelä, Sanna, Soini, Venla, Hynninen, Ville-Veikko, Mulo, Jukka, Savolainen, Urmas, Rantakokko, Juho, Maisniemi, Kreu, Liukas, Antti, Olkkola, Klaus T, Kontinen, Vesa, Tarkkila, Pekka, Peltoniemi, Marko, Saari, Teijo I
Format: Article
Language:English
Subjects:
Alcoholism
Analgesia
Analgesics
Anesthesiology
Apnea
Bone surgery
Chemotherapy
Clinical trials
Cytochrome
Cytochrome P450
Cytochromes P450
Dosage and administration
Double-blind studies
Drafting software
Drug abuse
Drug dosages
Drug therapy
Editing
General anesthesia
Heterogeneity
Hospitals
Informed consent
Intensive care
Intolerance
Intravenous administration
Ketamine
Kidney diseases
Liver diseases
Management
Medicine
Medicine and Health Sciences
Methodology
Musculoskeletal system
Narcotics
Opioids
Orthopedics
Pain
Pain management
Pain perception
Patient satisfaction
Patients
Pharmacy
Placebos
Postoperative period
Registration
Research and Analysis Methods
Sleep
Sleep disorders
Spine
Surgery
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Summary:Spinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown. We randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml-1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery. Of the 100 patients analyzed, patients receiving 0.75 mg ml.sup.-1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml.sup.-1 (74.7 mg) or 0.25 mg ml.sup.-1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: -20.6 mg; 95% confidence interval [CI]: -41 to -0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml.sup.-1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013-0.32, P = 0.033). The occurrence of adverse events was similar among the groups. Oxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0252626