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This placebo-controlled, randomized study evaluated, on separate days, the dose–response relationship for 1 h infusions of clonidine 1, 2 and 4 µg kg–1 h–1, in eight healthy volunteers aged 22–30 yr. 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. Statistically significant analgesia, memory impairment and reduced performance on the DSST occurred during 4 µg kg–1 h–1 infusions (resulting in a plasma concentration of 2 ng ml–1. There were no statistically significant changes in cardiorespiratory variables throughout the study.