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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methadone | Active Comparator | Epidural methadone bolus 4mg |
|
| Morphine | Active Comparator | Epidural morphine 4mg bolus |
|
| Fentanyl | Active Comparator | Epidural fentanyl 200 microgram bolus |
|
| Saline | Placebo Comparator | Epidural saline bolus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epidural administration of bolus | Drug |
|
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| ID | Term |
|---|---|
| D010146 | Pain |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010468 | Perceptual Disorders |
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| 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 |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |