They were randomized to either placebo or one of three doses of clonidine.Treatments consisted of a loading dose of placebo or clonidine, 1, 2 or 4 µg kg), and a nasal cannula for end‐tidal carbon dioxide monitoring.Subjects were asked to abstain from alcohol for 24 h and any oral intake for 6 h before the study.Each volunteer participated on four occasions separated by at least 7 days, but not more than 10 days. Response end‐points included sedation (bispectral index, visual analogue scale and observer assessment of sedation), analgesia to a cold pressor test, memory (recall of word lists), cognitive function (digit symbol substitution test (DSST)), respiratory function (respiratory rate, end‐tidal carbon dioxide, oxygen saturation) and haemodynamic stability (heart rate and mean arterial pressure).Clonidine infusions resulted in significant and progressive sedation, but all subjects were easily awoken to perform tests and evaluations.After all the baseline measurements and tests had been done, infusions were started with both investigators and subject blinded to the randomization code.
The MEM test consisted of listening to a series of 16 unrelated words and immediately reciting as many as possible.
The MEM test at the 90 min recovery point was different.
Subjects did not listen to a new series of words, but rather they were asked to recall as many of the words as possible from the three previous lists, which had been given at baseline, 60 min of infusion and 45 min of recovery.
Psychomotor (Digital Symbol Substitution Test, DSST), cold pressor and memory tests were performed only at the end of the 60 min infusion period.
After drug termination, all tests and assessments were repeated at 45 and 90 min of recovery. The first was objective and measured from the processed EEG signal, which indicated the state of hypnosis (BIS).