Remifentanil vs Fentanyl During Cardiac Surgery and Chronic Thoracic Pain

Study Overview
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Brief Summary
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This study will investigate the influence of intra-operative use of remifentanil versus fentanyl on the percentage of patients with chronic thoracic after cardiac surgery via sternotomy. Secondary quantitative sensory testing is performed to determine thermal and electrical detection and pain threshold and the difference in pain variability scoring. Postoperative pain scores, analgesic use, genetic variances and costs are measured.

Official Title
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A Randomised Clinical Trial Evaluating the Effect of Remifentanil vs Fentanyl During Cardiac Surgery on the Incidence of Chronic Thoracic Pain

Conditions
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Chronic Pain, Sternotomy, Remifentanil, Fentanyl

Intervention / Treatment
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* Drug: Fentanyl
* Drug: Remifentanil
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing cardiac surgery via sternotomy (Coronary artery bypass graft (CABG) and/or valve replacement) Patients admitted to the ICU or PACU in the St. Antonius hospital Patients between 18 and 85 years old Patients weighing between 45 and 140 kg Written informed consent Exclusion Criteria: Pregnancy/ breastfeeding Language barrier History of drug abuse Neurologic condition such as peripheral neuropathy Known remifentanil, fentanyl, morphine or paracetamol allergy Body Mass Index (BMI) > 35 kg/m2 Prior cardiac surgery (re-operations); Patients with chronic pain conditions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fentanyl<br>fentanyl bolus injections on an as needed base, next to the fentanyl bolus injections on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium. | Drug: Fentanyl<br>* fentanyl bolus injections on an as needed base, NEXT TO the fentanyl bolus injections on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium.<br>* Other names: Sublimaze;Drug: Fentanyl<br>* fentanyl bolus injections on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium.<br>* Other names: Sublimaze;|
| Active Comparator: Remifentanil<br>remifentanil, starting with 0.15 ug/Ideal Body Weight(IBW)(kg)/min, next to fentanyl bolus injections (200-500 ug) on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium. | Drug: Remifentanil<br>* starting with 0.15 ug/IBW(kg)/min, next to fentanyl bolus injections (200-500 ug) on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium.<br>* Other names: Ultiva;Drug: Fentanyl<br>* fentanyl bolus injections on predetermined times; before incision, at sternotomy, at aorta canulation and at opening of the pericardium.<br>* Other names: Sublimaze;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic thoracic pain | The percentage of patients reporting chronic thoracic pain one year after cardiac surgery. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic thoracic pain | The percentage of patients reporting chronic thoracic pain three months and six months after cardiac surgery | 3 and 6 months | 
| Mean Numerical Rating Scale (NRS) score | The mean NRS score of patients with chronic thoracic pain three months and six months after cardiac surgery. | 3, 6 and 12 months | 
| Quality of life | The quality of life (QoL) three months, six months and one year after surgery. | 3, 6 and 12 months | 
| Thermal detection and pain thresholds | The difference in postoperative pain thresholds three days and one year after cardiac surgery compared to the preoperative pain threshold (baseline) | preoperative, 3 days postoperative and 1 year after surgery | 
| Pain variability | Pain variability measured with a paradigm with electrical stimuli in only a part of the participants. The difference in pain variability preoperative, three days postoperative and one year after cardiac surgery. | preoperative, 3 days and 1 year postoperative | 
| Use of analgesics during and after hospitalization | The required amounts of analgesics (morphine/paracetamol) during hospital stay; The use of analgesics three months, six months and one year after cardiac surgery, measured with questionnaires; | 3 days during hospitalization and 3,6,12 months post surgery | 
| Genetic variances | Genetic variances involved in pain sensitivity (e.g. GTP-cyclohydrolase 1 (GCH-1), WDFY4, Zinc Finger gene Family (ZNF), Melanocortin 1 Receptor (MC1R)) and pharmacokinetics and pharmacodynamics of opiates (e.g. glucuronosyl transferase (UGT), Multidrug Resistance-associated Protein (MRP), mu-opioid receptor gene 1 (OPRM1), Catechol-O-methyltransferase (COMT)) | Blood sample at time of surgery | 
| Total medical costs and productivity costs during one year, including costs of hospitalization days (ICU and non-ICU) and costs of medications |  | 1 year after surgery | 
| Mean pain NRS (Numerical Rating Scale) | Mean NRS score during intensive care unit (ICU) stay and hospitalization. | 3-5 days during hospitalization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic thoracic pain, Remifentanil, Fentanyl, sternotomy