Brazilian Journal of Anesthesiology
Brazilian Journal of Anesthesiology
Systematic Review

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

Getúlio Rodrigues de Oliveira Filho; Carlos Maestri Castilhos; Jean Philippe Kriegl; Giulia Nonticuri Bianchi

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Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication.

The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child’s behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria.

Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94–1.52);p =  0.15; I2 = 80%; GRADE = very low); satisfactory sedation (1.2 ( 1.10–1.31); p < 0.001; I2 = 71%; GRADE = very low); behavior during parental separation (1.2 (1.06–1.36); p = 0.003; I2 = 88%; GRADE = very low); facial mask acceptance (1.13 (1.04–1.24); p = 0.007; I2 = 49%; GRADE = very low); behavior during venipuncture (1.32 (1.11–1.57); p = 0.002; I2 = 66%; GRADE = very low).

While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child’s separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.


Medication, preanesthetic;  Child;  Pediatrics, surgery;  Cyclohexanes, ketamine;  Benzodiazepines, midazolam


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