| Study Summary: |
|
After 6 h of fasting, each volunteer will have a 20G arterial-line placed in the radial
artery for early blood sampling and an 18 G peripheral intravenous catheter placed in the
contralateral forearm for drug administration and later blood sampling. Continuously
monitored vital signs will include ECG, invasive blood pressure, hemoglobin, O2 saturation,
end-tidal CO2, and respiratory rate (from the capnogram) recorded.
After baseline PD data acquisition, a bolus of 0.2 mg/kg hydromorphone will be administered
over 10 sec via the free-flowing peripheral IV (t=0) and 3 mL arterial blood samples will be
obtained at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, and 2 min using a stop-cock and manifold
system. Subsequent blood samples will be acquired at 3, 4, 5, 7.5, 10, 15, 20, 25, 30, and
45 min and 1, 1.25, 1.5, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 20, and
24 h. Although EEG will be acquired continuously, the remaining pharmacologic data will be
recorded at discrete times s in the initial 5 min: pupillometry at 1, 2, and 5 min;
ventilation at 2 min; temperature analgesia at 3 and 5 min, and sedation level at 4 min.
This will allow the ventilation and pupillometry to be acquired in a resting state, thereby
limiting distortion of these responses by stimulation. Subsequently, all data will be
acquired at all PK time points in the following sequence - ventilation and EEG
(simultaneously), pupillometry, modified OAA/S score, and temperature analgesia. After 2 h,
once a pharmacologic parameter has returned to baseline for 2 sequential measurements,
recording of that parameter will be stopped. During the study, if the volunteer is unable to
use the device trigger, due to opioid-induced sedation, the tolerance level for increased
temperature will be defined as the temperature at which the volunteer exhibits withdrawal
movement of the tested limb. Once all data acquisition has been completed, the volunteer
will be allowed to drink clear liquids. Subsequently, the diet will be advanced as
tolerated. The volunteer will be monitored hourly (vital signs) in the Clinical Research
Unit until all of the blood samples have been acquired.
|