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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Change in heat pain tolerance from baseline (using QST Medoc)
Time frame: At intervals: 30, 60, 90, 120, 180, 240, 300, 360, 410 min following drug and 24 hours following drug.
Change in electrical pain tolerance from baseline
Time frame: At same time intervals as primary outcome
Plasma concentration of methadone, fentanyl, morphine (and metabolites)
Time frame: At each of the time intervals as for primary endpoint
Pupilometry
Time frame: At each of the time intervals as primary endpoint
Respiratory rate and arterial CO2 tension
Time frame: At each of the time intervals as primary endpoint
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