Overview

This trial is active, not recruiting.

Conditions postoperative pain, chronic pain, analgesics
Treatments (s)-(+)-ketamine hydrochloride solution 25 mg/ml, isotonic sodium chloride 0.9 percent, paracetamol 1 g, morphine sulphate 1 mg/ml, ondansetron 2 mg/ml, usual daily opioids, sufentanil 5 microgram/ml
Phase phase 4
Sponsor Rigshospitalet, Denmark
Collaborator Glostrup University Hospital, Copenhagen
Start date May 2014
End date October 2015
Trial size 150 participants
Trial identifier NCT02085577, 2014-000839-16, SM3-RS-2014

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
(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
(s)-(+)-ketamine hydrochloride solution 25 mg/ml Ketamine
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.
paracetamol 1 g Paracetamol
Paracetamol 1 g orally 1 hour preoperatively and every 6 hours after extubation time during the first 24 hours.
morphine sulphate 1 mg/ml Morphine
Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively
morphine sulphate 1 mg/ml 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 Zofran
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 Morphine
The patients usual daily opioid consumption are administered during the study period
morphine sulphate 1 mg/ml Morphine
Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.
sufentanil 5 microgram/ml 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.
(Placebo Comparator)
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
isotonic sodium chloride 0.9 percent Isotonic saline
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 Paracetamol
Paracetamol 1 g orally 1 hour preoperatively and every 6 hours after extubation time during the first 24 hours.
morphine sulphate 1 mg/ml Morphine
Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively
morphine sulphate 1 mg/ml 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 Zofran
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 Morphine
The patients usual daily opioid consumption are administered during the study period
morphine sulphate 1 mg/ml Morphine
Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.
sufentanil 5 microgram/ml 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.

Primary Outcomes

Measure
Morphine consumption
time frame: 0-24 hours postoperatively

Secondary Outcomes

Measure
Pain during mobilization
time frame: 2, 6, 12, 18 and 24 hours postoperatively
Pain at rest
time frame: 2, 6, 12, 18 & 24 hours postoperatively
Nausea
time frame: 2, 6, 12, 18 & 24 hours postoperatively
Vomiting
time frame: 0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively
Ondansetron
time frame: 0-24 hours postoperatively
Sedation
time frame: 2, 6, 12, 18 & 24 hours postoperatively
Hallucinations and nightmares
time frame: 0-24 hours postoperatively
Chronic pain
time frame: 6 months postoperatively
Chronic pain
time frame: 12 months postoperatively

Eligibility Criteria

Male or female participants from 18 years up to 85 years old.

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

Additional Information

Official title The Effect of Intraoperative Ketamine on Opioid Consumption and Pain After Spine Surgery in Opioid-dependent Patients
Principal investigator Rikke V Nielsen, MD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Rigshospitalet, Denmark.