The Effect of Intraoperative Ketamine on Opioid Consumption and Pain After Spine Surgery in Opioid-dependent Patients

Ketamine

Brief Summary

Patients with a daily use of opioids may develop higher postoperative pain levels, often need high doses of morphine and therefore their pain may be difficult to treat. A low dose of an old anesthetic drug, ketamine, administered during surgery can possibly reduce pain and morphine consumption in these patients. Our purpose is to investigate the effect of low dose ketamine on morphine consumption and pain after spine surgery in patients with a daily use of opioids. Our hypothesis is that low dose ketamine can reduce morphine consumption, pain and side-effects after spine surgery.

Intervention / Treatment

  • (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml (DRUG)
    Ketamine (25 mg/ml) bolus 0.5 mg/kg administered immediately after induction of anesthesia, followed by infusion ketamine 0,25 mg/kg/hour that is terminated when the last suture to the skin has been performed.
  • Isotonic sodium chloride 0.9 percent (DRUG)
    Isotonic sodium chloride 0.9 percent 0.02 ml/kg administered immediately after induction of anesthesia, followed by infusion isotonic sodium chloride 0.01 ml/kg/hour that is terminated when the last suture to the skin has been performed.
  • Paracetamol 1 g (DRUG)
    Paracetamol 1 g orally 1 hour preoperatively and every 6 hours after extubation time during the first 24 hours.
  • Morphine Sulphate 1 mg/ml (DRUG)
    Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.
  • Ondansetron 2 mg/ml (DRUG)
    Ondansetron 2 mg/ml 4 mg iv in case of moderate to severe nausea, supplemented by Ondansetron 1 mg iv if needed
  • Usual daily opioids (DRUG)
    The patients usual daily opioid consumption are administered during the study period
  • Sufentanil 5 microgram/ml (DRUG)
    Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening.

Condition or Disease

  • Postoperative Pain
  • Chronic Pain
  • Analgesics

Phase

  • Phase 4

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 85 Years
    Enrollment: 147 (ACTUAL)
    Funded by: Other
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: May 01, 2014
    Primary Completion: Oct 01, 2015 ACTUAL
    Completion Date: Nov 01, 2016 ACTUAL
    Study First Posted: Mar 13, 2014 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Apr 27, 2017

    Sponsors / Collaborators

    Lead Sponsor: Rigshospitalet, Denmark
    Responsible Party: N/A

    Location

    Glostrup, Denmark

    Opioid-dependent patients can develop hyperalgesia and often have a high opioid consumption postoperatively due to opioid tolerance. Intraoperative ketamine in subanesthetic doses can possibly reduce hyperalgesia and reduce opioid-tolerance in these patients. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that works by blocking the NMDA receptors in the central and peripheral nerve system. It can be used for general anesthesia but the drug also has other properties including lowering of central excitability and reducing postoperative opioid tolerance by modeling the opioid receptors. Further more it can possibly reduce chronic pain by blocking wind-up effect when blocking the NMDA receptors.

    Our purpose is to investigate the effect of intraoperative ketamine on opioid consumption and pain after spine surgery in opioid-dependent patients. Our hypothesis is that ketamine can reduce opioid consumption and reduce postoperative pain and side effects compared to placebo.

    Participant Groups

    • * (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml bolus 0.5 mg/kg administered immediately after induction of anesthesia, followed by infusion ketamine 0,25 mg/kg/h terminated at last suture to the skin. * Morphine. Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 min before expected awakening. * Escape sufentanil. Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening. * Morphine. PCA-morphine, bolus 2.5 mg, lock-out-time 5 min. Concentration : Morphine sulphate 1 mg/ml. * Escape morphine. Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively. * Ondansetron 2 mg/ml, 4 mg iv in case of moderate to severe nausea, supplemented by 1 mg iv if needed * Paracetamol 1 g orally 1 h preoperatively and every 6 h after extubation time during the first 24 h. * The patients usual daily opioids

    • * Isotonic sodium chloride 0.9 percent 0.02 ml/kg administered immediately after induction of anesthesia, followed by infusion isotonic sodium chloride 0.01 ml/kg/h terminated at last suture to the skin. * Morphine. Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 min before expected awakening. * Escape sufentanil. Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening. * Morphine. PCA-morphine, bolus 2.5 mg, lock-out-time 5 min. Concentration : Morphine sulphate 1 mg/ml. * Escape morphine. Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively. * Ondansetron 2 mg/ml, 4 mg iv in case of moderate to severe nausea, supplemented by 1 mg iv if needed * Paracetamol 1 g orally 1 h preoperatively and every 6 h after extubation time during the first 24 h. * The patients usual daily opioids

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 85
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Patients undergoing lumbar spinal fusion surgery in general anesthesia.
    * Daily use of opioids for a minimum of 6 weeks preoperatively (morphine, ketobemidone, oxycodone, fentanyl, tramadol and/or buprenorphine).
    * Back pain for a minimum of 3 months preoperatively.
    * Age \> 18 years and \< 85 years.
    * ASA 1-3.
    * BMI \> 18 and \< 40.
    * Fertile women need to have a negative urine HCG pregnancy test.
    * Patients who have given their written informed consent to participate in the study after understanding the content and limitations of the study

    Exclusion Criteria:

    * Participation in another concomitant drug trial.
    * Patients who do not understand or speak Danish.
    * Allergy to the drugs used in the trial.
    * Abuse of drugs - as assessed by the investigator.
    * Daily methadone use.
    * Increased intraocular pressure - assessed from the patients chart.
    * Uncontrolled hypertension - assessed from the patients chart.
    * Previous and current psychotic episodes - assessed from the patients chart

    Primary Outcomes

    • Total intravenous morphine consumption, other than the patients usual opioid use, 0- 24 hours postoperatively, administered as patient-controlled analgesia ((PCA), bolus 2.5 mg, lockout 5 minutes)

    Secondary Outcomes

    • Pain score during active mobilization, measured on a visual analogue scale (VAS) (0-100 mm), defined as a standardized movement from recumbent position to sitting on the bedside at 2, 6, 12, 18 and 24 hours postoperatively, the worst pain from the movement is registered. The endpoint, VAS-mobilization, will be calculated as area under the curve (AUC) (2-24h) from these measurements.

    • Pain score at rest, measured on a visual analogue scale (VAS) (0-100 mm), at 2, 6, 12, 18 and 24 hours postoperatively. The endpoint, VAS-rest, will be calculated as area under the curve (AUC) (2-24h) from these measurements.

    • Level of nausea (none, mild, moderate, severe) (0-24h), measured at 2, 6, 12, 18 and 24 hours postoperatively.

    • Number of vomiting episodes (0-24 hours), registered in the periods 0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively.

    • Consumption of ondansetron (mg) during 0-24 hours postoperatively.

    • Level of sedation (none, mild, moderate, severe) (0-24 h) registered at time 2, 6, 12, 18 and 24 hours postoperatively.

    • Episodes of hallucinations and nightmares (yes/no) in the period 0-24 hours postoperatively.

    • Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 6 months postoperatively.

    • Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 12 months postoperatively.

    More Details

    NCT Number: NCT02085577
    Other IDs: SM3-RS-2014
    Study URL: https://clinicaltrials.gov/study/NCT02085577
    Last updated: Sep 29, 2023