Oral preanesthetic medication in children ... comparison between midazolam alone and in combination with ketamine: a systematic review and meta-analysis

Is the combination of oral midazolam and ketamine as preanesthetic medication a safe and effective practice?

“…The results are consistent with those observed in the systematic review and meta-analysis by Oliveira Filho et al, 11 in which the level of sedation achieved by the oral association of S-ketamine and midazolam promoted better sedation, with an increase in the probability of Ramsay ≥ 3, compared to midazolam alone. The association was also useful from an analgesic point of view, facilitating venous access without requiring physical restraint.…”

“…The rationale for the coadministration of these two drugs as premedication is the assumption that midazolam anxiolysis is added to the sedative and analgesic properties of ketamine, not increasing side effects. 11 Ketamine is a dissociative general anesthetic that, when used and in a lower dose, can be an analgesic. It is a racemic mixture, although more recently S-ketamine is commercially available.…”

“…Oral midazolam associated to ketamine was administered in 834 subjects, while 706 received only midazolam. 11 …”

“…According to Oliveira Filho et al, there is a great variation in the doses used for both drugs, from 0.2 to 0.75 mg.kg −1 for midazolam, and from 1 to 6 mg.kg −1 for ketamine, as well as the use of different pharmaceutical formulations. 11 The oral midazolam solution has adequate bioavailability for administration by this route, but when the parenteral presentation is used orally, changes in the solution's pH may occur, causing medication bioavailability and absorption changes interfering in the effectiveness of midazolam. 13 …”

“…The authors of the study concluded that, due to the small effect sizes, high within-study risk of bias, high methodological and statistical heterogeneity, and high risk of publication bias found in meta-analyses, a weak level of recommendation is provided for replacing oral midazolam alone with oral combinations of midazolam and ketamine for the preanesthetic medication of pediatric surgical patients. 11 …”