Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Original Investigation

Comparison between oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in autism spectrum disorder: double-blind randomized clinical trial

Heber de Moraes Penna, Andreia Portela Martins Paiva, Antônio José Marques Romano, Rodrigo Leal Alves, Paulo do Nascimento Junior, Norma Sueli Pinheiro Módolo

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Conventional dental care is often impossible in patients with Autism Spectrum Disorder (ASD). Non-collaborative behaviors, sometimes associated with aggressiveness, are usual justifications for premedication in this population. Thereby, this research focuses on the effects of oral midazolam versus oral ketamine plus midazolam as preanesthetic medication in ASD.

The sample included 64 persons with ASD, aged 2˗59 years, scheduled for dental care under general anesthesia. The primary objective of this study was to compare degrees of sedation between two parallel, double-blinded, equally proportional groups randomized to receive oral midazolam (0.5−1, maximum 15 mg) or oral midazolam (0.5−1) associated with oral S(+)-ketamine (3−1, maximum 300 mg). The secondary outcomes were the need of physical stabilization to obtain intravenous line, awakening time, and occurrence of adverse events.

According to the dichotomous analysis of sedation level (Ramsay score 1 and 2 versus Ramsay ≥ 3), oral association of S(+)-ketamine and midazolam improved sedation, with increased probability of Ramsay ≥ 3, Relative Risk (RR) = 3.2 (95% Confidence Interval [95% CI] = 1.32 to 7.76) compared to midazolam alone. Combined treatment also made it easier to obtain venous access without physical stabilization, RR = 2.05 (95% CI = 1.14 to 3.68). There were no differences between groups regarding awakening time and the occurrence of adverse events.

The association of oral S(+)-ketamine with midazolam provides better preanesthetic sedation rates than midazolam alone and facilitates intravenous line access in patients with autism.


Autism;  Autism spectrum disorder;  Dental care;  Ketamine;  Midazolam;  Preanesthetic medication


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