Post-Discharge Adverse Events following Pediatric Sedation with High Doses of Oral Medication Luciane Rezende Costa, PhD 1 , Paulo Sucasas Costa, PhD 2 , Sarah Vieira Brasileiro, BDS 3 , Cristiane Baccin Bendo, MSc 4 , Cl  audia Marina Viegas, MSc 4 , and Saul Martins Paiva, PhD 5 Objective To compare the occurrence of post-discharge adverse events in children having received a high dose of either chloral hydrate (CH) or midazolam (MZ) during outpatient dental treatment. Study design A repeated-measures study design was carried out with 42 children treated at a sedation center. The sample comprised 103 dental sedation sessions among 22 male and 20 female patients, 1-8 years old, receiv- ing either MZ (1.0-1.5 mg/kg) or CH (70.0-100.0 mg/kg). During treatment, a single observer recorded intraoperative adverse events. Twenty-four hours later, the observer called the child’s main caregiver seeking information on fur- ther adverse events. Data analysis involved descriptive and bivariate statistics and the general estimating equation for repeated measures. Results The most common intraoperative and post-discharge adverse events were hallucination (3.9%) and excessive sleep (41.9%), respectively. The chance of the occurrence of an adverse event following oral pediatric se- dation was lesser among the children who received MZ than those who received CH (OR: 0.09; 95% CI: 0.01-0.88). Conclusions High doses of CH were associated with post-discharge adverse events in children having under- gone pediatric dental sedation, whereas high doses of MZ were not associated with these events in pediatric patients. (J Pediatr 2012;160:807-13). A dverse events with different degrees of severity have been reported for outpatient sedation. Serious adverse events, such as neurologic damage and death, during pediatric sedation have been associated with drug regimens (drug interactions, overdose, administration pathways) and all classes of sedatives, especially when medications are administered ‘‘outside the safety net of medical supervision.’’ 1 These kinds of events, however, are rarely observed at well-organized services that are able to control minor occurrences. 2-4 Data from the Pediatric Sedation Research Consortium reveal that among 30 037 seda- tion/anesthesia sessions carried out in 2004 and 2005, the most frequent adverse event was desaturation (157 times per 10 000 sedations); serious adverse events were rare and no deaths were reported. 2 Oral drug administration has sometimes been used as the sole pathway for pediatric sedation in different fields, such as ra- diology, 5 dentistry, 6,7 and premedication for surgery. 8,9 Among the different pharmacologic agents available for oral adminis- tration, chloral hydrate (CH) and midazolam (MZ) are reported to enhance the cooperation of pediatric patients. 6,7,9-15 Pediatric doses for MZ as a sole oral agent for pediatric sedation have varied from 0.5 mg/kg to 1.0 mg/kg, 6,9,11,14-17 but it was reported as being successful when administered as a preanesthetic medication for infants and children who underwent sur- gery at a dose of 1.5 mg/kg. 18 CH is commonly prescribed in doses varying from 25 to 50 mg/kg, 7,9,19 but it can reach 80 to 100 mg/kg without toxicity. 5,19,20 However, taking the dental setting as an example, today’s sedative regimens are not 100% effective and there is no scientific evidence regarding the most favorable pediatric sedation technique that ensures both effectiveness and patient safety 21 ; studies with different sedatives and dosages are still required. In the past 10 years, studies of moderate sedation have demonstrated that CH and MZ may be associated with minor or major adverse events (Table I). Moreover, there is a lack of longitudinal data on adverse events following procedural sedation, as most studies in this field consist of retrospective analysis or data collection during or soon after the sedative procedure; post- discharge complications are rarely documented formally. 13 The aim of the present study was to compare the occurrence of post-discharge adverse events in children who received high doses of either CH or MZ during outpatient dental treatment. The hypothesis was that high doses of both types of medication are associated with minor complications even when the procedural sedation protocol follows well-established guidelines regarding preparedness of personnel, monitoring, and rescue availability. From the 1 Faculty of Dentistry, 2 Department of Pediatrics, Faculty of Medicine, and 3 Medical School, Universidade Federal de Goi as, Goi^ ania; and the 4 Dental School and 5 Department of Pediatric Dentistry and Orthodontics, Faculty of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Supported by the Brazilian Coordination of Higher Edu- cation (CAPES), Ministry of Education, National Council of Technological and Scientific Development (CNPq), Ministry of Science and Technology, and State of Minas Gerais Research Foundation (FAPEMIG), Brazil. The au- thors declare no conflicts of interest. 0022-3476/$ - see front matter. Copyright ª 2012 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2011.10.025 CH Chloral hydrate GEE Generalized estimating equation MZ Midazolam NESO Center for Studies in Dental Sedation 807