A Prospective Randomized Comparison of Fentanyl, Methadone and Morphine for Epidural Analgesia in an Experimental Pain Model

Study Overview
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Brief Summary
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The aims of this study are to provide pharmacokinetic-pharmacodynamic data to quantify the analgesic and side effect profiles of epidural methadone, fentanyl and morphine. The investigators will compare the analgesic effect at three dermatomes to assess the rostral spread of drug, the investigators will assess plasma levels to assess the systemic redistribution of drug and the investigators will assess surrogate markers of central opiate effects (nasal capnography and pupilometry). The investigators hypothesize that due to the long-duration of action of methadone, and its intermediate lipophilicity, that methadone will provide a predominantly segmental analgesia of long duration of action, with low rostral spread and low direct central depressant effects (including respiratory depression).

Official Title
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A Prospective Randomized Comparison of Fentanyl, Methadone and Morphine for Epidural Analgesia in an Experimental Pain Model

Conditions
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Pain

Intervention / Treatment
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* Drug: Epidural administration of bolus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (men and women) scheduled for extracorporeal shock wave lithotrypsy (for nephrolithiasis) under regional anesthesia. Exclusion Criteria: Inability to understand consent form; poor communication Refusal to sign consent form Contraindication to regional anesthesia Chronic opioid administration ASA classification 3 or greater Age < 18 or > 70

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methadone<br>Epidural methadone bolus 4mg | Drug: Epidural administration of bolus<br> <br> |
| Active Comparator: Morphine<br>Epidural morphine 4mg bolus | Drug: Epidural administration of bolus<br> <br> |
| Active Comparator: Fentanyl<br>Epidural fentanyl 200 microgram bolus | Drug: Epidural administration of bolus<br> <br> |
| Placebo Comparator: Saline<br>Epidural saline bolus | Drug: Epidural administration of bolus<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in heat pain tolerance from baseline (using QST Medoc) |  | At intervals: 30, 60, 90, 120, 180, 240, 300, 360, 410 min following drug and 24 hours following drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in electrical pain tolerance from baseline |  | At same time intervals as primary outcome | 
| Plasma concentration of methadone, fentanyl, morphine (and metabolites) |  | At each of the time intervals as for primary endpoint | 
| Pupilometry |  | At each of the time intervals as primary endpoint | 
| Respiratory rate and arterial CO2 tension |  | At each of the time intervals as primary endpoint | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epidural, Analgesia, Methadone, Morphine, Pharmacokinetic-pharmacodynamic, Experimental pain - analgesic response