Effects of mild to moderate sedation on saccadic eye movements

Sedatives alter the metrics of saccadic eye movements. If these effects are nonspecific consequences of sedation, like drowsiness and loss of attention to the task, or differ between sedatives is still unresolved. A placebo-controlled multi-step infusion of one of three sedatives, propofol or midazolam, both GABA-A agonists, or dexmedetedomidine, an α2-adrenergic agonist, was adopted to compare the effects of these three drugs in exactly the same experimental conditions. 60 healthy human volunteers, randomly divided in 4 groups, participated in the study. Each infusion step, delivered by a computer-controlled infusion pump, lasted 20min. During the last 10min of each step, the subject executed a saccadic task. Target concentration was doubled at each step. This block was repeated until the subject was too sedated to continue or for a maximum of 6 blocks. Subjects were unaware which infusion they were receiving. A video eye tracker was used to record the movements of the right eye. Saccadic parameters were modeled as a function of block number, estimated sedative plasma concentration, and subjective evaluation of sedation. Propofol and midazolam had strong effects on the dynamics and latency of the saccades. Midazolam, and to a less extent, propofol, caused saccades to become increasingly hypometric. Dexmedetedomidine had less impact on saccadic metrics and presented no changes in saccadic gain. Suppression of the sympathetic system associated with dexmedetomidine has different effects on eye movements from the increased activity of the inhibitory GABA-A receptors by propofol and midazolam even when the subjects reported similar sedation level.