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

NCT ID: NCT02085577

Last Updated: 2017-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 147 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2016-11-01

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.

Detailed 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.

Conditions

Postoperative Pain; Chronic Pain; Analgesics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

• (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

Group Type: EXPERIMENTAL

Morphine Sulphate 1 mg/ml

Intervention Type: DRUG

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

Intervention Type: 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

Intervention Type: DRUG

The patients usual daily opioid consumption are administered during the study period

Morphine Sulphate 1 mg/ml

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.

Sufentanil 5 microgram/ml

Intervention Type: 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.

(S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml

Intervention Type: 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.

Paracetamol 1 g

Intervention Type: 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

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively

Placebo

• 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

Group Type: PLACEBO_COMPARATOR

Morphine Sulphate 1 mg/ml

Intervention Type: DRUG

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

Intervention Type: 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

Intervention Type: DRUG

The patients usual daily opioid consumption are administered during the study period

Morphine Sulphate 1 mg/ml

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.

Sufentanil 5 microgram/ml

Intervention Type: 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.

Isotonic sodium chloride 0.9 percent

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively

Interventions

Morphine Sulphate 1 mg/ml

Morphine Sulphate 1 mg/ml, bolus 2.5 mg administered by the PACU nurse on request of the patient for the first hour postoperatively.

Intervention Type: DRUG

Ondansetron 2 mg/ml

Ondansetron 2 mg/ml 4 mg iv in case of moderate to severe nausea, supplemented by Ondansetron 1 mg iv if needed

Intervention Type: DRUG

Usual daily opioids

The patients usual daily opioid consumption are administered during the study period

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml

Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.

Intervention Type: DRUG

Sufentanil 5 microgram/ml

Sufentanil 5 microgram/ml, bolus 5 micrograms administered by the anaesthetic nurse in the operating room if the patient is in pain upon awakening.

Intervention Type: DRUG

(S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml

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.

Intervention Type: DRUG

Isotonic sodium chloride 0.9 percent

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.

Intervention Type: DRUG

Paracetamol 1 g

Paracetamol 1 g orally 1 hour preoperatively and every 6 hours after extubation time during the first 24 hours.

Intervention Type: DRUG

Morphine Sulphate 1 mg/ml

Morphine Sulphate 1 mg/ml administered as patient-controlled analgesia (PCA, bolus 2.5 mg, lockout 5 minutes) 0-24 hours postoperatively

Intervention Type: DRUG

Other Intervention Names

Ketamine; Isotonic saline; Paracetamol; Morphine; Morphine; Zofran; Morphine; Morphine; Sufentanil

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Glostrup University Hospital, Copenhagen

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Rikke Vibeke Nielsen, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rikke V Nielsen, MD

Role: PRINCIPAL_INVESTIGATOR

Glostrup University Hospital, Copenhagen

Locations

Department of Anaesthesiology, Glostrup Hospital

Glostrup Municipality, , Denmark

Countries

Denmark

References

Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, Beach ML. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010 Sep;113(3):639-46. doi: 10.1097/ALN.0b013e3181e90914.

Reference Type: BACKGROUND

PMID: 20693876 (View on PubMed)

Other Identifiers

2014-000839-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SM3-RS-2014

Identifier Type: -

Identifier Source: org_study_id