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

Rigshospitalet

Status and phase: Completed; Phase 4

Conditions: Analgesics; Postoperative Pain; Chronic Pain

Treatments: Drug: Ondansetron 2 mg/ml; Drug: Isotonic sodium chloride 0.9 percent; Drug: Morphine Sulphate 1 mg/ml; Drug: (S)-(+)-Ketamine Hydrochloride Solution 25 mg/ml; Drug: Usual daily opioids; Drug: Paracetamol 1 g; Drug: Sufentanil 5 microgram/ml

Study type: Interventional

Funder types: Other

Identifiers

NCT02085577

2014-000839-16 (EudraCT Number)

SM3-RS-2014

Details and patient eligibility

About

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.

Full 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.

Enrollment: 147 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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147 participants in 2 patient groups, including a placebo group

Ketamine

Experimental group

Description:

* (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

Treatment:

Drug: Sufentanil 5 microgram/ml

Drug: Usual daily opioids

Drug: Paracetamol 1 g

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

Drug: Morphine Sulphate 1 mg/ml

Drug: Morphine Sulphate 1 mg/ml

Drug: Morphine Sulphate 1 mg/ml

Drug: Ondansetron 2 mg/ml

Placebo

Placebo Comparator group

Description:

* 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

Treatment:

Drug: Sufentanil 5 microgram/ml

Drug: Usual daily opioids

Drug: Paracetamol 1 g

Drug: Morphine Sulphate 1 mg/ml

Drug: Morphine Sulphate 1 mg/ml

Drug: Isotonic sodium chloride 0.9 percent

Drug: Morphine Sulphate 1 mg/ml

Drug: Ondansetron 2 mg/ml