Intranasal dexmedetomidine with and without buccal midazolam for procedural sedation in autistic children: a double-blind randomised controlled trial

Abstract Background Children with autism are often difficult to manage in the hospital setting, and they often require sedation for diagnostic procedures. Intranasal dexmedetomidine has been used increasingly in children for procedural sedation. This study was designed to compare the successful sedation rate of intranasal dexmedetomidine with and without buccal midazolam on children with autism. Methods This single-centre, double-blind randomised controlled trial was approved and conducted in the Guangzhou Women and Children's Medical Centre, China. Children aged 1–12 years with a diagnosis of autism who required sedation for a CT study or an auditory brainstem response test (ABR), or both, were recruited. Exclusion criteria included known allergy or hypersensitivity to dexmedetomidine or midazolam, renal or hepatic dysfunction, nasal discharge, or rhinorrhea. Children were randomly assigned to receive either dexmedetomidine with placebo (group D) or dexmedetomidine with midazolam (group DM). Randomisation lists with block of 6 and age stratification (1–4, 5–8, and 9–12 years) were produced by an independent statistician. All participants and investigators were masked to group allocation. Children assigned to group D received 3 μg/kg of intranasal dexmedetomidine by atomiser and buccal placebo in the form of syrup, children assigned to group DM received 3 μg/kg of intranasal dexmedetomidine with 0·2 mg/kg of buccal midazolam (5 mg/mL) mixed with simple syrup. The primary outcome was the proportion of participants with sedation success allowing completion of CT, ABR, or concurrent CT and ABR test without restrain. We analysed the success rate using the χ 2 test. This study was approval by the Institutional Review Board of Guangzhou Women and Children Medical Centre (approval number 2013053110) and registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-14004761). Informed consent was obtained from parents or legal guardians. Findings Between June 9, 2014, and Nov 9, 2015, 192 children completed the study, 97 were assigned to group D and 95 to group DM. 82 children from group D and 91 from group DM had CT studies. 51 children from group D and 55 children from group DM had ABR. Among these children, 38 children from group D and 49 from group DM had concurrent CT and ABR test. The success rate was significantly higher in the group DM than in the group D for CT (86/91 [94·5%] vs 67/82 [81·7%]; p=0·009), ABR (38/55 [69·1%] vs 25/51 [49·0%]; p=0·035], and for concurrent CT and ABR (32/49 [65·3%] vs 16/38 [42·1%]; p=0·031). No children had respiratory depression or haemodynamic disturbances that required medical intervention. Of the 95 children who received dexmedetomidine, two had hypotension and six had bradycardia. Of the children who received dexmedetomidine/midazolam, five had hypotension and nine had bradycardia. No children had concurrent hypotension and bradycardia. Interpretation When buccal midazolam was added to intranasal dexmedetomidine, 95% of children with autism were successfully sedated for CT, and over 65% for ABR. Since the administration of intranasal and buccal sedatives required little cooperation, this technique could be especially useful for sedation in children with autism. Funding Department of Anaesthesiology, Guangzhou Women and Children's Medical Centre.