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

Phase 4

Completed

Conditions: Chronic Postoperative Pain

Interventions: Drug: Ketamine

Registration Number: NCT01296347

Lead Sponsor: Imperial College Healthcare NHS Trust

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 77

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ketamine	Ketamine	Patients will receive intravenous ketamine, starting 10 minutes prior to surgery and will continue for 96 hours

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Incidence of Side Effect, Lightheaded	108 hours	The presence of lightheaded recorded at the above time points
Analgesic Consumption (Opioid)	6 weeks, 3 month, 6 month	Analgesia consumption will be measured post-operatively and at 6 weeks
Incidence of Side-effects, Nausea	108 hours	The presence of nausea recorded at the above time points
Incidence of Side Effect, Vomiting	108 hours	The presence of vomiting recorded at the above time points
Incidence of Side Effect, Vivid Dreams	108 hours	The presence of vivid dreams recorded at the above time points
Sensory Testing	6 weeks, 6 months, 12 months	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.