EXPLANATION

For a long time, chloral hydrate (CH) was the mainstay pharmacologic agent for children requiring sedation for transthoracic echocardiograms. However, it was voluntarily removed from the US markets by manufacturers in 2012 after reports of administration errors leading to oversedation, respiratory depression or death in various contexts. This removal left clinicians searching for safer alternatives that would provide adequate sedation and conditions for minimally- or non-painful procedures without IV access, such as transthoracic echocardiograms (TTE). Those options include, but are not limited to intranasal and oral midazolam, intranasal dexmedetomidine as well as oral and intranasal ketamine.

Dexmedetomidine is a highly selective centrally acting a2-agonist that inhibits the release of norepinephrine at the level of locus coeruleus in the brain, producing sedation. It also has mild analgesic properties from a2-receptor stimulation in the spinal cord. Intravenous (IV) dexmedetomidine has gained widespread use in both adult and pediatric cardiac populations as an adjunct for anesthesia and sedation due to its benzodiazepine and opioid-sparing properties in addition to the quasi-lack of respiratory depression, facilitating maintenance of spontaneous ventilation and early tracheal extubation. Common side-effects include bradycardia and hypotension or hypertension, which appear to be dose-dependent, but not age-dependent. Nevertheless, dexmedetomidine has been deemed to be a very safe medication, even in high-risk patients.^1-2

Intranasal dexmedetomidine (IN-Dex) was adopted in the 2010s by several centers across North America for its relative acceptability and safety profile. In the available literature, “acceptable sedation” with IN-Dex may be achieved with a doses ranging from 1 to 4 mcg/kg, with highly variable onsets and duration of action.² Rocha et al. published a systematic review on IN-Dex for a wide range of non-painful procedures, and reported “success rate” of ~ 84% with 2-3 mcg/kg, with an onset time of ~20 minutes and a duration of ~60 minutes. Side-effects included bradycardia, hypotension and minor desaturation, all of which were mostly mild, transient and self-resolving. The authors concluded IN-Dex was safe and effective, with heterogenous doses and success rates, which seems to stem from variable definitions of a “successful sedation” level and adverse events across studies.³ In a pharmacokinetic study, Uusalo et al. found that, for IN-Dex doses of 2-3 mcg/kg and similar sedation scores, school-aged children undergoing MRI scans achieved higher plasma concentrations than children < 2 years and pre-schoolers.⁴ A similar phenomenon was observed by Qiu et al. in children with non-cyanotic congenital heart disease (CHD), where infants, toddlers and pre-schoolers were found to have an ED₅₀ of 3.1, 3.3 and 2.4 mcg/kg respectively.⁵ Interestingly, Yang et al. found a difference in ED₅₀ and ED₉₅ in 55 children <18 months with either cyanotic or acyanotic CHD (ED₅₀= 3.3 vs 1.7 mcg/kg, ED₉₅= 3.7 vs 2.2 mcg/kg).⁶ This finding yet has to be reported by subsequent studies.

In the answer choices above, the patient most likely to require a higher IN-Dex dose is the 3-month-old with Tetralogy of Fallot (A) as IN-Dex effective dose seems to be higher in infants and toddlers, and perhaps with cyanotic CHD. The other two patients are older, nearing school-age, and therefore are likely to achieve adequate sedation level with a lower dose.

REFERENCES

1. Out CG, Andropoulos DB and Mossad EB, Chapter 10: Anesthesia Agents and their Cardiovascular Effects In: Andropoulos DB, Mossad EB, Gottlieb EA, eds. Anesthesia for Congenital Heart Disease. Fourth edition. John Wiley & Sons, Inc.; 2023: 190-210.

2. Grogan K, Thibault C, Moorthy G, Prodell J, Nicolson SC, Zuppa A. Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease. Anesth Analg. 2023;136(1):152-162. doi:10.1213/ANE.0000000000005988

3. Rocha KO, Santos ERFA, Pombeiro MM, Fidelis MNDSL, Kakehasi FM, Teixeira DC. Intranasal dexmedetomidine for procedural sedation in children: a systematic review and meta-analysis. Braz J Anesthesiol. 2026;76(1):844717. doi:10.1016/j.bjane.2025.844717

4. Uusalo P, Guillaume S, Siren S, et al. Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients. Anesth Analg. 2020;130(4):949-957. doi:10.1213/ANE.0000000000004264

5. Qiu L, Cao L, Lang Z, Li X, Lin H, Fan T. Preoperative sedation in children with congenital heart disease: 50% and 95% effective doses, hemodynamic effects, and safety of intranasal dexmedetomidine. J Clin Anesth. 2022;81:110908. doi:10.1016/j.jclinane.2022.110908

6. Yang F, Li S, Shi Y, et al. Fifty Percent Effective Dose of Intranasal Dexmedetomidine Sedation for Transthoracic Echocardiography in Children With Cyanotic and Acyanotic Congenital Heart Disease. J Cardiothorac Vasc Anesth. 2020;34(4):966-971. doi:10.1053/j.jvca.2019.11.037