Low Dose Peri-operative IV Ketamine for Chronic Post-surgery Pain Prevention

A Double-blind, Randomised Placebo-controlled Trial to Determine Whether Low-dose Intravenous Ketamine Peri-operatively Can Prevent Chronic Post-surgical Pain, in Patients Undergoing Thoracotomy or Video Assisted Thoracic Surgery (VATS)

This study will test the null hypothesis that low-dose ketamine given peri-operatively will have no effect on the development of chronic post-surgical pain, in patients undergoing thoracotomy or video assisted thoracic surgery (VATS) procedures

A double-blind, randomised placebo-controlled trial will be used to test the null hypothesis. Potential participants due to undergo either thoracotomy or video assisted thoracic surgery (VATS) will be identified by the collaborating thoracic surgeons in the out-patient department. Patients will be sent information about the study by post, prior to admission for surgery. If they are willing to participate, written consent will be sought on the ward preoperatively, where they will complete baseline measures of pain.

Patients will be randomised to receive an intravenous infusion of placebo (saline) or ketamine running at 0.1mg/kg/hour, starting 10 minutes prior to the surgical incision and continuing for the first three postoperative days (96 hours in total). Prior to starting the infusion a loading dose of ketamine (0.1 mg per kg) will be administered.

Study Overview

• Status: Completed
• Conditions: Chronic Postoperative Pain
• Intervention / Treatment: Drug: Ketamine

Detailed Description

This study will test the null hypothesis that low-dose ketamine given peri-operatively will have no effect on the development of chronic post-surgical pain, in patients undergoing thoracotomy or video assisted thoracic surgery (VATS) procedures

A double-blind, randomised placebo-controlled trial will be used to test the null hypothesis. Potential participants due to undergo either thoracotomy or video assisted thoracic surgery (VATS) will be identified by the collaborating thoracic surgeons in the out-patient department. Patients will be sent information about the study by post, prior to admission for surgery. If they are willing to participate, written consent will be sought on the ward preoperatively, where they will complete baseline measures of pain.

Patients will be randomised to receive an intravenous infusion of placebo (saline) or ketamine running at 0.1mg/kg/hour, starting 10 minutes prior to the surgical incision and continuing for the first three postoperative days (96 hours in total). Prior to starting the infusion a loading dose of ketamine (0.1 mg per kg) will be administered. All staff, including the anaesthetist, surgical team, ward nurses and the principal investigator will be blind to the treatment given throughout the study. The key to the randomisation will be revealed at the end of the study.

Patients will be asked to complete a numeric pain score (NPS) and standard pain questionnaires which includes the Brief Pain Inventory [BPI], short form Leeds Assessment of Neuropathic Symptoms and Signs [S-LANSS]) prior to surgery, then at 6 weeks, 3, 6 and 12 months after surgery. The surgical area will also be examined at 6 weeks, 6 and 12 months for signs of neuropathic or nerve pain. Whilst in hospital patients will be asked to score their pain daily, on a numeric pain scale of 0 to 10. Consumption of morphine and side-effects will be recorded.

Patients will receive standard post-operative analgesia.

A sample size calculation based on a previous study, to detect a reduction in pain of 2 points the 10 point numeric pain scale at the 6 week assessment, with α = 5%, 1 - β = 90% and a bilateral hypothesis, would require a sample size of 36 per group, 72 patients in total. This will require a total study population of 144 patients, as both video assisted thoracic surgery (VATS) and thoracotomy patients will be studied.

A two samples t-test will be used to compare the numeric pain scores between the ketamine and placebo groups at each time point. If these data are not normally distributed then the Mann Whitney test will be used. The scores from the Brief Pain Inventory (BPI) and short form Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) will be analysed in the same manner. The Chi Squared test will be used to compare dichotomous data, such as the incidence of side-effects.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All adult patients (18 years and above) who are undergoing either thoracotomy or video assisted thoracic surgery (VATS).
• Participants must be able to understand English.

Exclusion Criteria:

• Patient refusal
• History of previous chronic thoracic pain
• Neuropathic pain (whatever the site), existing at time of recruitment
• Pre-operative analgesic treatments which include the following medications: strong opioids (step 3 analgesics), tricyclic antidepressants, venlafaxine, gabapentin, pregabalin, duloxetine, clonazepam or carbamazepine.
• Allergy to bupivacaine, morphine, paracetamol, tramadol, dihydrocodeine or ketamine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Saline; Patients will receive a placebo infusion of 0.9% sodium chloride, which will start 10 minutes prior to the start of the operation and continue for 96 hours.
Experimental: ketamine; Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours	Drug: Ketamine; Intravenous infusion of ketamine starting 10 minutes prior to surgery and running for 96 hours, which will be administered at a rate of 0.1mg/kg/hour. A loading dose of 0.1mg/kg will be administered prior to the start of the infusion; Other Names: Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Score on Moving at 6 Weeks	Measures in pain include: Numeric pain score of 0 to 10. Zero denotes 'no pain'; 10 denotes 'pain as bad as you can imagine'	6 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analgesic Consumption (Opioid)	Analgesia consumption will be measured post-operatively and at 6 weeks	6 weeks, 3 month, 6 month
Sensory Testing	Hypoaesthesia: light touch of the blunt end of a paintbrush was felt less precisely, than in healthy tissue. Hyperalgesia: the pain induced by a sterile neurotip, applied perpendicular to the skin is felt abnormally strongly, in comparison to the contralateral side. Static allodynia: the application of a Von Frey hair number 14. (8g) was unpleasant, in comparison to the contralateral side. Dynamic allodynia: three successive gentle strokes of an 8 mm-wide paintbrush over a 40 mm distance, is unpleasant, in comparison to the contralateral side.	6 weeks, 6 months, 12 months
Incidence of Side-effects, Nausea	The presence of nausea recorded at the above time points	108 hours
Incidence of Side Effect, Vomiting	The presence of vomiting recorded at the above time points	108 hours
Incidence of Side Effect, Lightheaded	The presence of lightheaded recorded at the above time points	108 hours
Incidence of Side Effect, Vivid Dreams	The presence of vivid dreams recorded at the above time points	108 hours

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Collaborators: National Institute for Health Research, United Kingdom
• Investigators: Principal Investigator: Gillian M Chumbley, BSc, PhD, Imperial Healthcare NHS Trust

Publications and helpful links

General Publications

• Chumbley GM, Thompson L, Swatman JE, Urch C. Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain. Eur J Pain. 2019 May;23(5):985-993. doi: 10.1002/ejp.1366. Epub 2019 Feb 4.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: January 31, 2011
• First Submitted That Met QC Criteria: February 14, 2011
• First Posted (Estimate): February 15, 2011

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Pain; Ketamine; Thoracotomy; VATS
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: Chumbley1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO