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

Chronic Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02085577
• Other study ID #: SM3-RS-2014
• Secondary ID: 2014-000839-16
• Status: Completed
• Phase: Phase 4
• First received: March 11, 2014
• Last updated: April 27, 2017
• Start date: May 2014
• Est. completion date: November 1, 2016

Study information

• Verified date: April 2017
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: November 1, 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Analgesics
• Chronic Pain
• Pain, Postoperative
• Postoperative Pain

Intervention

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.
• 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.
• Paracetamol 1 g
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 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 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
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
The patients usual daily opioid consumption are administered during the study period
• Morphine Sulphate 1 mg/ml
Morphine Sulphate 1 mg/ml, bolus 0.4 mg/kg administered 45 minutes before expected awakening.
• 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.

Locations

Country	Name	City	State
Denmark	Department of Anaesthesiology, Glostrup Hospital	Glostrup

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Glostrup University Hospital, Copenhagen

Country where clinical trial is conducted

Denmark, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Pain during mobilization	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.	2, 6, 12, 18 and 24 hours postoperatively
Secondary	Pain at rest	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.	2, 6, 12, 18 & 24 hours postoperatively
Secondary	Nausea	Level of nausea (none, mild, moderate, severe) (0-24h), measured at 2, 6, 12, 18 and 24 hours postoperatively.	2, 6, 12, 18 & 24 hours postoperatively
Secondary	Vomiting	Number of vomiting episodes (0-24 hours), registered in the periods 0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively.	0-2, 2-6, 6-12, 12-18, 18-24 hours postoperatively
Secondary	Ondansetron	Consumption of ondansetron (mg) during 0-24 hours postoperatively.	0-24 hours postoperatively
Secondary	Sedation	Level of sedation (none, mild, moderate, severe) (0-24 h) registered at time 2, 6, 12, 18 and 24 hours postoperatively.	2, 6, 12, 18 & 24 hours postoperatively
Secondary	Hallucinations and nightmares	Episodes of hallucinations and nightmares (yes/no) in the period 0-24 hours postoperatively.	0-24 hours postoperatively
Secondary	Chronic pain	Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 6 months postoperatively.	6 months postoperatively
Secondary	Chronic pain	Level of chronic pain and daily use of opioids assessed by the validated questionnaires EQ50, OWESTRY and DN4 at 12 months postoperatively.	12 months postoperatively