Tsze, DS, leni, M, Fenster, D. Annals of Emergency Medicine, Vol. 69, no. 5, 2017, pp. 600–609.
Intranasal medications have become both a popular and efficient method of delivering anxiolytic and pain medications. Notably for pediatric patients, intranasal medications often eliminate the need for distressing peripheral IV starts. Additionally, intranasal medications are known for bypassing first pass metabolism and coming into direct contact with the central nervous system. These two characteristics lead to more timely delivery of sedation medications. However, the optimal volume for delivery of sedation medications, most commonly midazolam, has not been well described in the literature.
In this randomized, outcome assessor-blinded superiority clinical trial, Tsze et al sought to determine the optimal volume of administration of intranasal midazolam during laceration repairs in the emergency department. The primary outcome studied was onset to minimal sedation. The secondary outcomes included procedural distress, time to procedure start, deepest level of sedation, adverse events and clinician satisfaction. A convenience sample of children ages 1-7 years were enrolled in the study from November 2013 to September 2015. Enrolled participants had facial lacerations requiring simple repair whose attending physician determined that intranasal midazolam was necessary to facilitate the procedure. All children received a midazolam dose of 0.5mg/kg. Participants were randomized to receive one of three volumes of administration: 0.2mL, 0.5mL and 1mL. The dose was administered in aliquots, alternating between nostrils, no sooner than 10 second intervals in the same nostril, until the appropriate volume was reached. The midazolam concentration was 5mg/mL and maximum dose was 10mg. Patients were video-taped during the procedure. Three trained assessors, blinded to assigned volume, independently scored each video recording. Each assessor evaluated the primary outcome (onset to minimal sedation) based on the Michigan Sedation Scale. Procedural distress was also measured using the Observational Scale of Behavioral Distress-Revised. Adverse events and inadequate sedations were also recorded.
The investigators enrolled 99 total patients. Ninety-six were evaluated for the primary outcome and 90 were evaluated for procedural distress. The median onset to time of minimal sedation was 4.7 minutes when a volume of 0.2mL was administered, 4.3 minutes when 0.5mL was administered and 5.2 minutes when 1mL was administered. While there was a shortest onset to sedation reached statistical significance with the 0.5mL volume, this difference was not felt to be clinically meaningful, given that it was less than one minute. There were no differences noted between the groups with regard to procedural distress, time to procedure start or deepest level of sedation. Thus, any of the three volumes would produce clinically similar results. There were no serious adverse events reported. The only adverse event noted was vomiting and inadequate sedation with no difference noted between the three groups. There are several limitations to this study. First, the observational nature of the study has the potential for bias. Second, the use of restraint for laceration repair was a decision made by the proceduralist and could not be standardized.
So, when using intranasal midazolam should we be worried if we use up to a volume of 1mL? Do we get better results with smaller volumes?
The authors briefly addressed concerns about “run-off” with larger volumes, which is often believed to lead to suboptimal sedation. The results showed that larger volumes of administration have efficacy similar to smaller volumes, i.e, there was no overall advantage to using smaller aliquots of administration, as long as the volume of administration was no more than 1mL. Additionally, the authors pointed out that the use of multiple, smaller doses was associated with lower provider satisfaction scores. This dissatisfaction was likely related to the overall time required to deliver the medication and the effect on patient compliance. Wolfe et al, in 2010, similarly studied delivery of intranasal midazolam and also emphasized maximizing drug concentration while minimizing drug volume. They suggested that administering volumes larger than 1mL may contribute to run-off, largely due to mucosal saturation. This issue of run-off appears to be greatest for adolescents and adults, due to weight based dosing.
The article abstract can be found via the link on our blog, http://www.pedzzzz.com.
References:
- Tsze, DS, leni, M, Fenster, D. “Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial.” Annals of Emergency Medicine, Vol. 69, no. 5, 2017, pp. 600–609.
- Wolfe, TR and Braude, DA. “Intranasal Medication Delivery for Children: A Brief Review and Update.” Pediatrics, vol. 126, no. 3, Sept. 2010, pp. 532–537.
Carmen D. Sulton, MD
Assistant Professor of Pediatrics and Emergency Medicine
Emory University School of Medicine
Atlanta, GA
Laurie Burton, MD
Assistant Professor of Pediatrics and Emergency Medicine
Emory University School of Medicine
Atlanta, GA
Pradip Kamat, MD, MBA, FCCM
Associate Professor of Pediatrics
Emory University School of Medicine
Director Children’s Sedation Services at Egleston
Atlanta, GA
Jason Reynolds, MD
Assistant Professor of Pediatrics
Section of Pediatric Sedation
Baylor College of Medicine
San Antonio, TX
Patricia Scherrer, MD
Associate Professor of Pediatrics
Section of Pediatric Sedation
Baylor College of Medicine
San Antonio, TX
