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

NCT02085577 | Completed Phase 4

• 2 other identifiers: SM3-RS-20142014-000839-16
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Pain; Chronic Pain; Analgesics

Keywords

Morphine consumption; Postoperative pain; Ketamine; Side effects; Spine surgery; Chronic pain

Outcome Measures

Primary Outcomes (1)

• Morphine consumption

  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)

  0-24 hours postoperatively

Secondary Outcomes (9)

• Pain during mobilization

  2, 6, 12, 18 and 24 hours postoperatively

• Pain at rest

  2, 6, 12, 18 & 24 hours postoperatively

• Nausea

  2, 6, 12, 18 & 24 hours postoperatively

• Vomiting

  0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively

• Ondansetron

  0-24 hours postoperatively

Study Arms (2)

Ketamine

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

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

Placebo

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

Drug: Isotonic sodium chloride 0.9 percent; Drug: Paracetamol 1 g; Drug: Morphine Sulphate 1 mg/ml; Drug: Ondansetron 2 mg/ml; Drug: Usual daily opioids; Drug: Sufentanil 5 microgram/ml

Interventions

(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.

Also known as: Ketamine

Ketamine

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.

Also known as: Isotonic saline

Placebo

Paracetamol 1 g DRUG

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

Also known as: Paracetamol

Ketamine; Placebo

Morphine Sulphate 1 mg/ml DRUG

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

Also known as: Morphine

Ketamine; Placebo

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

Also known as: Zofran

Ketamine; Placebo

Usual daily opioids DRUG

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

Also known as: Morphine

Ketamine; Placebo

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.

Also known as: Sufentanil

Ketamine; Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Glostrup University Hospital, Copenhagen: collaborator

Study Sites (1)

Department of Anaesthesiology, Glostrup Hospital

Glostrup Municipality, 2600, Denmark

Location

Related Publications (1)

• 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.

  PMID: 20693876 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Chronic Pain

Interventions

Ketamine; Sodium Chloride; Acetaminophen; Morphine; Ondansetron; Sufentanil

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, 3-Ring; Fentanyl; Piperidines

Study Officials

• Rikke V Nielsen, MD

  Glostrup University Hospital, Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 11, 2014
• First Posted: March 13, 2014
• Study Start: May 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2016
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

DK (1)