Preventing Pain After Heart Surgery

Study Overview
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Brief Summary
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The use of pre-emptive analgesia to prevent pain following sternotomy for cardiac surgery

Official Title
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Prospective, Double-blinded, Randomised, Placebo Controlled Trial of Pre-emptive Analgesia to Prevent Pain Following Sternotomy for Cardiac Surgery.

Conditions
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Pain, Hyperalgesia, Chronic Illness, Neuropathic Pain

Intervention / Treatment
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* Drug: Pregabalin
* Drug: Ketamine infusion
* Drug: Placebo capsules
* Drug: Placebo infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent First time sternotomy for all cardiac surgery Patient aged 18 - 80 years Exclusion Criteria: Emergency surgery (decision to operate taken on the day of surgery) Previous sternotomy Preoperative renal failure (eGFR <60 ml/min) History of chronic non-anginal pain Chronic pain medication other than paracetamol and non-steroidal anti-inflammatory drugs Concurrent use of oxycodone, lorazepam, or ethanol. Concurrent use of any drugs for neuropathic pain e.g. antiepileptics, antidepressants Allergy to pregabalin, gabapentin or ketamine Pregnancy Limited understanding of numerical scoring scales Previous participation in other trials investigating analgesic agents or any IMP in previous three months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control: Placebo + Placebo<br>Placebo capsules and Placebo infusion | Drug: Placebo capsules<br>* Single capsule (2hrs) pre operatively and twice daily post operatively for 10 days, followed by dose reduction to single capsule twice daily for 2 days and finally to single capsule twice daily for 2 days<br>Drug: Placebo infusion<br>* Normal saline placebo intravenous infusion for 48 hours<br>|
| Active Comparator: Pregabalin and Placebo infusion<br>Pregabalin capsules and Placebo infusion | Drug: Pregabalin<br>* 150mg (2hrs) pre operatively and twice daily post operatively for 10 days, followed by dose reduction to 75mg twice daily for 2 days and finally to 50 mg twice daily for 2 days<br>Drug: Placebo infusion<br>* Normal saline placebo intravenous infusion for 48 hours<br>|
| Active Comparator: Pregabalin + Ketamine infusion<br>Pregabalin capsules + Ketamine infusion | Drug: Pregabalin<br>* 150mg (2hrs) pre operatively and twice daily post operatively for 10 days, followed by dose reduction to 75mg twice daily for 2 days and finally to 50 mg twice daily for 2 days<br>Drug: Ketamine infusion<br>* 0.1mg/kg/hr for 48 hours post operatively<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Rating Scale (NRS) pain score (around sternotomy incision site) post surgery, at rest and following 3 maximal coughs. |  | 3 and 6 months post sternotomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total morphine consumption at 24 hours post surgery |  | 24 hours post surgery | 
| Visual Analogue Scale (VAS) scores at 24 hrs post surgery, at rest and following 3 maximal coughs |  | 24 hours post surgery | 
| Sedation (including pCO2) and nausea scores at 24 hours post surgery |  | 24 hours post surgery | 
| Side effect episodes (dizziness, confusion, blurred vision) |  | First 48 hours | 
| Time to extubation |  | Post op recovery period | 
| Length of stay in intensive care and hospital |  | Post operative - acute | 
| 28 day mortality |  | 28 days post surgery | 
| Neuropathic pain score | S-LANSS (Short form Leeds Assessment of Neuropathic Symptoms and Signs) | 3 and 6 months post surgery | 
| Quality of Life | EQ-5D validated scoring scale | 3 and 6 months | 
| Survival |  | 3 and 6 months | 
| QST measurements | Pain Pressure Thresholds (PPT) using algometry, both pre and post Diffuse Noxious Inhibitory Control (DNIC) Tactile and Pain Detection Thresholds with mechanical static stimulus using Von Frey hairs (VFH) Dynamic assessment of temporal summation and secondary hyeralgesia with VFH | Pre op and post op at 72hrs and 3 months |