A Prospective Comparison of Methadone, Fentanyl, and Morphine for Post-laparotomy Epidural Analgesia

Study Overview
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Brief Summary
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The current study aim is to compare between the opioids morphine, fentanyl and methadone in terms of efficacy and side effects profile when administered epidurally for pain management after laparotomies. Intravenous morphine will also be used. The outcomes of that method will be compared to those obtained using epidurally administered opioids, as this is another commonly used postoperative pain relief method.

Official Title
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A Prospective Double Blind Randomized Comparison of Methadone, Fentanyl, and Morphine for Post-laparotomy Epidural Analgesia.

Conditions
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Post Laparotomy Pain Treatment

Intervention / Treatment
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* Drug: epidural morphine via PCEA
* Drug: epidural fentanyl via PCEA
* Drug: epidural methadone via PCEA
* Drug: intravenous morphine via PCA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: * Elective laparotomy Exclusion Criteria: Subjects with diabetes mellitus, other neurological or systemic disease associated with altered sensory perception Illicit drug abusers Chronic use of pain medication Inability to understand consent form Age < 18 Renal failure (Clcr<50 ml/min) Chronic use of drugs that can alter plasma levels and\or effect of the study drugs Corrected Q-T interval(QTc)=450msc and above Contra-indication for epidural catheter insertion Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: morphine, epidural<br>Epidurally administrated morphine | Drug: epidural morphine via PCEA<br> <br> |
| Active Comparator: fentanyl, epidural<br>epidurally administrated fentanyl | Drug: epidural fentanyl via PCEA<br> <br> |
| Active Comparator: methadone, epidural<br>epidurally administrated methadone | Drug: epidural methadone via PCEA<br> <br> |
| Active Comparator: morphine, intervenous<br>intravenously administrated morphine | Drug: intravenous morphine via PCA<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variable stimuli, fixed response: measurement of pain tolerance by gradual increase of temperature (quantitative sensory testing (QST))as compared to baseline |  | 72 hours post operatively | 
| Fixed stimuli, variable response: measurement of reaction to fixed temperature by visual analog scale (VAS) as well as Variable stimuli, variable response (electrical stimuli)as compared to baseline. |  | 72 hours post operatively | 
| patient controlled epidural analgesia (PCEI)/patient controlled analgesia (PCA)dose frequency as compared to baseline |  | 72 hours post operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of opioid concentration in plasma as compared to baseline |  | Baseline, 4 hours post surgery and twice daily for 72 hours starting 18-24 hours post surgery | 
| Pupillometry as compared to baseline |  | Baseline and twice daily for 72 hours starting 18-24 hours post surgery | 
| Respiratory rate as compared to baseline |  | Baseline, 4 hours post surgery and twice daily for 72 hours starting 18-24 hours post surgery | 
| Nasal capnography at rest as compared to baseline |  | Baseline and twice daily for 72 hours starting 18-24 hours post surgery | 
| Report of adverse effects' severity as compared to baseline |  | Baseline, 4 hours post surgery and twice daily for 72 hours starting 18-24 hours post surgery | 
| Report of pain severity- at rest, cough and deep breathing as compared to baseline |  | Baseline, 4 hours post surgery and twice daily for 72 hours starting 18-24 hours post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fentanyl, methadone, epidural, intravenous, pain, analgesia, morphine