Effect of midazolam on the auditory event-related potential: measures of selective attention

To elucidate the delayed effects of midazolam, we assessed electrophysiologic and motor responses by measuring auditory event-related potentials and a button-press reaction time response in 10 normal volunteers (aged 25-36 yr). Fifty minutes after intravenous infusion of 0.07 mg/kg of midazolam, subjects were mildly sedated, oriented, and readily responsive to verbal commands. To obtain ERPs, frequent tones (85%: 1000 Hz) and rare tones (15%: 2500 Hz) were presented at intervals of 1.5 s. Electroencephalographic signals were collected from FZ, CZ, and PZ for 1000 ms after stimulus presentation until 40 artifact-free rare-tone responses were obtained (average time, 6 min). Peak-to-peak amplitudes and latencies for N2, P3, and the subsequent negative slow wave (N3) were averaged within condition and were analyzed by repeated measures analysis of variance. After midazolam infusion, there was a 50% decrease in amplitude of P3 in response to target tones (P less than 0.006), whereas N3 latency increased by 40 ms (P less than 0.05). Event-related potential amplitudes were still significantly larger to rare (target) stimuli (P less than 0.003) after midazolam infusion. Although reaction time increased by 70 ms (P = 0.031), performance accuracy remained unchanged. Self-ratings of sleepiness and concentration show that a significant sedation effect was still present 50 min after infusion. Although routine clinical examination may be normal, full recovery from the effects of a typical intravenous dose of midazolam requires more than 50 min. The potential for adverse drug interaction, particularly with narcotics, is still present at this time.