Optimal Volume of Administration of Intranasal Midazolam in Children: A Randomized Clinical Trial

Abstract

Objectives The optimal intranasal volume of administration (VOA) for achieving timely and effective sedation in children is unclear. We aimed to compare clinical outcomes relevant to procedural sedation associated with using escalating VOA to administer intranasal midazolam. Methods We conducted a randomized, single-blinded, three-arm, superiority clinical trial. Children 1 to 7 years old undergoing laceration repair requiring 0.5 mg/kg intranasal midazolam (5 mg/mL) were block-randomized to receive midazolam using one of three VOA: 0.2mL, 0.5mL, or 1mL. Procedures were videotaped, with outcome assessors blinded to VOA. Primary outcome was time to onset of minimal sedation (i.e. score of 1 on the University of Michigan Sedation Scale). Secondary outcomes included procedural distress; time to procedure start; deepest level of sedation achieved; adverse events; and clinician and caregiver satisfaction. Results Ninety-nine children were enrolled; 96 were analyzed for the primary outcome and secondary outcomes, except for the outcome of procedural distress, for which only 90 were analyzed. Time to onset of minimal sedation for each escalating VOA was 4.7 (95% CI 3.8, 5.4), 4.3 (95% CI 3.9, 4.9) and 5.2 (95% CI 4.6, 7) minutes, respectively. There were no differences in secondary outcomes except for clinician satisfaction with ease of administration: fewer clinicians were satisfied when using a VOA of 0.2mL. Conclusions There was a slightly shorter time to onset of minimal sedation when using a VOA of 0.5mL compared to 1mL, but all three VOA produced comparable clinical outcomes. Fewer clinicians were satisfied with ease of administration using a VOA of 0.2mL.

Efficacy and Safety of Intranasal Midazolam Versus Chloral Hydrate as Sedation for Quality Computed Tomography Imaging in Children

“…Several clinical trials report satisfactory sedation with either of these dosages (5,21,29). Tsze et al (18), determined the optimal volume of administration of INM sedation with escalating volumes of administration (0.2, 0.5, and 1 mL) during laceration repair in children in an ED. A volume of administration of 0.5 mL was associated with a statistically shorter time to onset of minimal sedation compared with a volume of administration of 1 mL or 0.2 mL, but all 3 volumes of administration produced comparable clinical outcomes.…”

“…INM can be rapidly absorbed through the highly vascularized nasal mucosa, resulting in a rapid and reliable onset of action. The shorter half-life, ease of administration, predictability and increased bioavailability by circumventing first-pass metabolism makes it a useful drug in the ED setting (17)(18)(19)(20)(21).…”

“…The dose of INM used in different studies range between 0.2 mg/kg and 0.5 mg/kg. The most common adverse effects reported following INM are burning or irritation in the nose and a bitter taste in the mouth (17)(18)(19)(20)(21)(22)(23). Aerosolized administration of midazolam on mucosal surfaces may enhance drug delivery.…”

BAND-Statement zur intranasalen Medikamentenapplikation in der prähospitalen Notfallmedizin

“…Dosistabellen aus der klinischen Pädiatrie geben Gesamtvolumina (2 Nasenlöcher) von 0,3 ml (< 1 Jahr) bis 2 ml (Jugendliche > 50 kg) proportional zum Körpergewicht an. Auch höhere Dosen und Volumina (als Bolus und fraktioniert) wurden in einer randomisierten Studie zur effektiven Sedierung von Kleinkindern für kleinere Wundbehandlungen untersucht [3].…”

Leserbrief zum Artikel: M. Müller, R. Löb: Medikamentenapplikation im akuten epileptischen Anfall des Kindes. Notarzt 2019; 35: 119 – 121

“…Im Gegenteil erreicht ein höheres Volumen eine größere Schleimhautfläche und erhöht die Bioverfügbarkeit. Dabei wird von Klinikern ein ideales Volumen von 0,5 ml/Nasenloch angegeben, welches u. U. auf bis zu 1,0 ml/Nasenloch gesteigert werden kann [2]. Damit ist die Applikation ausreichender Absolutdosierungen möglich.…”