Quantification of Pain and Distress Associated With Intranasal Midazolam Administration in Children and Evaluation of Validity of Four Observational Measures Daniel S. Tsze, MD, MPH, Maria Ieni, MD, Pamela L. Flores-Sanchez, MD, Sripriya T. Shen, MD, Joan S. Bregstein, MD, Nicole C. O'Connell, MD, and Peter S. Dayan, MD, MSc Objectives: The aims of this study were to quantify the pain and distress associated with the administration of intranasal (IN) midazolam in young children using 4 observational measures and to evaluate the degree of validity of these measures. Methods: We conducted a prospective observational pilot study. Children aged 1 to 7 years requiring IN midazolam were enrolled. Children were videotaped, and scores were assigned to baseline and administration phases using the Observational Scale of Behavioral Distress–Revised (OSBD-R), Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), and the Faces-Legs-Activity-Cry-Consolability (FLACC) scale. The cry duration following administration was assessed. Interrater reliability and con- vergent validity were determined for all 4 measures. Internal consis- tency and responsivity for the OSBD-R, CHEOPS, and FLACC scales were determined. Results: We enrolled 20 children. The mean OSBD-R, CHEOPS, and FLACC scores associated with administration of IN midazolam were 27.1 (SD, 13.5), 11.5 (SD, 1.2), and 8.9 (SD, 2.7), respectively. The mean cry duration was 105.5 (SD, 68.8)seconds. The intraclass correlation coef- ficients for all measures ranged from 0.82 to 0.99. The Cronbach α's for the OSBD-R, CHEOPS, and FLACC were between 0.71 and 0.97. Pearson correlation coefficients for comparisons between OSBD-R, CHEOPS, and FLACC were between 0.82 and 0.96 but were between 0.32 and 0.51 for comparisons involving cry duration. Conclusions: We have identified estimates of pain and distress associ- ated with administration of IN midazolam in young children that can be used to determine desired effect sizes for trials that study interventions to treat this pain and distress. The OSBD-R, CHEOPS, and FLACC scales are suitable choices for outcome measures. Key Words: distress, intranasal midazolam, midazolam, pain scales (Pediatr Emer Care 2018;00: 00–00) I ntranasal (IN) midazolam is a commonly used, safe, and effec- tive sedative for facilitating procedures in children. 1 However, administration of IN midazolam is associated with intense nasal burning that is painful and distressing. 2 Few studies have evalu- ated methods to decrease the pain associated with administration of IN midazolam in children, particularly in younger children. 3,4 Younger children require sedation more frequently and are more vulnerable to having their pain undertreated, partly because of their inability to use self-report measures of pain. To rigorously study methods of treating the nasal burning associated with IN midazolam administration in younger children, it is necessary to quantify the pain and distress that IN midazolam causes using common observational measures, rather than self-report mea- sures, and to ensure that these measures have strong validity in the context of a brief, painful medical procedure. Our primary aim was to quantify the amount of pain and distress associated with IN midazolam administration using observational measures. Our secondary aim was to evaluate the degree of validity of 4 common observational measures (Observa- tional Scale of Behavioral Distress–Revised [OSBD-R], Children's Hospital of Eastern Ontario Pain Scale [CHEOPS], Faces-Legs- Activity-Cry-Consolability [FLACC] scale, and cry duration) by determining their interrater reliability, internal consistency, and construct validity in this context. 5–8 METHODS Study Design We conducted a prospective, observational pilot study. Our institutional review board approved this study, and written informed consent was obtained. Study Setting and Population The study was conducted in an urban pediatric emergency department with 55,000 annual visits. We enrolled English- and Spanish-speaking children between 1 and 7 years of age, inclusive, for whom IN midazolam was being administered as part of their medical care. We excluded children for any of the following: known allergy to midazolam, developmental delay, autism/autism spec- trum disorder, abnormal baseline neurological status, history of chronic pain condition (eg, sickle cell disease), history of multiple prior painful procedures (eg, oncology patient), nasal obstruction that could not be easily cleared, or presenting with a fracture or abscess. Study Protocol All patients were videotaped during 2 phases: baseline and administration. For the baseline phase, we videotaped patients for 1 minute, prior to IN midazolam administration. For the administra- tion phase, patients were videotaped from just before IN midazolam administration until 30 seconds after the patient stopped crying. If the patient did not cry, we videotaped the patient until 1 minute after the IN midazolam was administered. All patients received 0.5 mg/kg of midazolam (5 mg/mL concentration) with a maximum total dose of 10 mg (maximum volume of 2 mL). The midazolam was divided into 2 equal aliquots and administered using an LMA Mucosal Atomization Device (MAD) Nasal (Teleflex, Morrisville, NC). The aliquots were either administered simultaneously into both nares or administered one immediately after the other into separate nares, From the Division of Pediatric Emergency Medicine, Columbia University College of Physicians and Surgeons, New York, NY. Disclosure: The authors declare no conflict of interest. Unlabeled medication disclosure: Administration by the intranasal route is an off-label use of midazolam. Reprints: Daniel S. Tsze, MD, MPH, Division of Pediatric Emergency Medicine, Columbia University College of Physicians and Surgeons, 3959 Broadway CHN-1-116, New York, NY (e‐mail: dst2141@columbia.edu). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0749-5161 ORIGINAL ARTICLE Pediatric Emergency Care • Volume 00, Number 00, Month 2018 www.pec-online.com 1 Copyright © 2018 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.