Best Evidence-Based Dosing Recommendations for Dexmedetomidine for Premedication and Procedural Sedation in Pediatrics: Outcome of a Risk-Benefit Analysis By the Dutch Pediatric Formulary

Abstract

Background Dexmedetomidine is currently off-label for use in pediatric clinical care worldwide. Nevertheless, it is frequently prescribed to pediatric patients as premedication prior to induction of anesthesia or for procedural sedation. There is ample literature on the pharmacokinetics, efficacy and safety of dexmedetomidine in this vulnerable patient population, but there is a general lack of consensus on dosing. In this project, we aimed to use the standardized workflow of the Dutch Pediatric Formulary to establish best evidence-based pediatric dosing guidelines for dexmedetomidine as premedication and for procedural sedation. Method The available literature on dexmedetomidine in pediatrics was reviewed in order to address the following three questions: (1) What is the right dose? (2) What is known about efficacy? (3) What is known about safety? Relevant literature was compiled into a risk-benefit analysis document. A team of clinical experts critically appraised the analysis and the proposed dosing recommendations. Results Dexmedetomidine is most commonly administered via the intravenous or intranasal route. Clearance is age dependent, warranting higher doses in infants to reach similar exposure as in adults. Dexmedetomidine use results in satisfactory sedation at parent separation, adequate sedation and a favorable recovery profile. The safety profile is good and comparable to adults, with dose-related hemodynamic effects. Conclusion Following the structured approach of the Dutch Pediatric Formulary, best evidence-based dosing recommendations were proposed for dexmedetomidine, used as premedication prior to induction of anesthesia (intranasal dose) and for procedural sedation (intranasal and intravenous dose) in pediatric patients.

Delayed Sequence Intubation in Children, Why Not?

“…It mimics the non-rapid eye movement phase of physiological sleep, preserving spontaneous ventilation and airway tone/reflexes, and causing minimal hemodynamic depression. [ 32 33 34 ]…”

Dexmedetomidine: An Alternative to Pain Treatment in Neonatology

“…Specific studies in the neonatal population are scarce [ 39 , 47 , 48 ]. We can find an interesting phase II/III, open-label multicenter trial study about its safety, efficacy, and PK in preterm and term neonates published by Constantinos et al in 2014.…”

Safety and quality in paediatric procedural sedation: what really matters?

“…Cardiovascular adverse effects such as bradycardia and hypotension are described and occur in 0–22 and 0.6–3.2% of cases, respectively, depending on dosage and rate of injection. Bradycardia is often self-limiting and does not need pharmacological intervention [35 ▪▪ ,38,40,41]. Dexmedetomidine can be applied safely particularly in children with cardiac comorbidities [37 ▪ ,42,43] and it is also suitable for all age groups including neonate and preterm infants [39 ▪ ,44].…”

“…Dexmedetomidine is the latest sedative of the three and it is not officially approved for use in paediatric procedural sedation in the EU, but it is widely used off-label. There is plenty of literature on the dosing, efficacy and safety of dexmedetomidine for paediatric procedural sedation [35 ▪▪ ,36,37 ▪ ]. Although induction of sedation with dexmedetomidine and recovery after the procedure take longer, it has an advantage that airway and spontaneous breathing are not impaired [36,38,39 ▪ ].…”