Source:Kain ZN, Hofstadter MB, Mayes LC, et al. Midazolam: effects on amnesia and anxiety in children.

The authors undertook to determine the minimum time needed to cause anterograde amnesia in children following oral administration of midazolam. The study children involved were patients aged 5–10 years at Yale University Hospital’s outpatient surgery center scheduled to undergo surgical procedures lasting 2 hours or less. Eighty children received 0.5 mg/kg of midazolam, while 33 patients in the control group received a placebo. Memory tests after midazolam were given 5, 10 and 20 minutes after the dose. The control group was tested 15 minutes after the placebo was given. Memory was tested using a standard test involving picture cards.1 The groups did not differ in demographic or family characteristics. The authors found that recall of picture card content (no visual stimuli involved in testing) and recognition of the picture cards when mixed with other distractor cards were significantly worse in the groups that were tested 10 and 20 minutes after the administration of midazolam (P=.0001). Recall memory was evaluated 10 minutes after midazolam administration and went from 58% at baseline to 33% (P=.004), while recognition memory went from 100% correct to 83% correct (P=.0001). In the group tested 20 minutes after midazolam administration, the recall memory score went from 67% baseline to 16.7% (P=.0001) and recognition decreased from 100% correct to 58% (P=.0001) correct. There was no statistical difference in recall between the placebo and the 5-minute group but there was a statistical difference (P=.0008) in recognition between these 2 groups.

This paper nicely documents both the degree and timing of the effect of orally administered midazolam on memory. Although the amnesic effect of orally administered midazolam has been reported, the timing of this effect had not.2 Anxiolysis, another prominent effect of midazolam, appears to have similar timing and these clinical observations correlate with known pharmacokinetic data.3 Pediatricians may have occasion to use oral midazolam to allay anxiety and sedate children for various medical tests or may use it along with analgesics to perform minor, painful procedures such as suturing of lacerations. In these situations it may be in the child’s best interest that memory of such events be diminished. The package insert for oral midazolam recommends that when used as a preoperative medication, the drug be administered at least 20 minutes before the induction of anesthesia. This paper demonstrates that amnesia begins as early as 10 minutes following oral administration, suggesting that the drug may be administered closer to medical procedures than has been done previously.

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