Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation

Abstract

Dexmedetomidine (Precedex™) may be used as an alternative sedative in children, maintaining spontaneous breathing, and avoiding tracheal intubation in a non-intubated moderate or deep sedation (NI-MDS) approach. This open-label, single-arm, multicenter study evaluated the safety of dexmedetomidine in a pediatric population receiving NI-MDS in an operating room or a procedure room, with an intensivist or anesthesiologist in attendance, for elective diagnostic or therapeutic procedures expected to take at least 30 min. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Patients received one of two doses dependent on age: patients aged ≥28 weeks' gestational age to <1 month postnatal received dose level 1 (0.1 μg/kg load; 0.05–0.2 μg/kg/h infusion); those aged 1 month to <17 years received dose level 2 (1 μg/kg load; 0.2–2.0 μg/kg/h infusion). Sedation efficacy was assessed and defined as adequate sedation for at least 80% of the time and successful completion of the procedure without the need for rescue medication. In all, 91 patients were enrolled (dose level 1, n = 1; dose level 2, n = 90); of these, 90 received treatment and 82 completed the study. Eight patients in dose level 2 discontinued treatment for the following reasons: early completion of diagnostic or therapeutic procedure (n = 3); change in medical condition (need for intubation) requiring deeper level of sedation (n = 2); adverse event (AE; hives and emesis), lack of efficacy, and physician decision (patient not sedated enough to complete procedure; n = 1 each). Sixty-seven patients experienced 147 TEAEs. The two most commonly reported AEs were respiratory depression (bradypnea; reported per protocol-defined criteria, based on absolute respiratory rate values for age or relative decrease of 30% from baseline) and hypotension. Four patients received glycopyrrolate for bradycardia and seven patients received intravenous fluids for hypotension. SpO2 dropped by 10% in two patients, but resolved without need for manual ventilation. All other reported AEs were consistent with the known safety profile of dexmedetomidine. Two of the 78 patients in the efficacy-evaluable population met all sedation efficacy criteria. Dexmedetomidine was well-tolerated in pediatric patients undergoing procedure-type sedation.

Dexmedetomidine Versus Lidocaine for Postoperative Analgesia in Pediatric Patients Undergoing Craniotomy: a Protocol for a Prospective, Randomized, Double-blinded, Placebo-controlled Trial

“…Such settings could help us understand whether the intervention medicines (dexmedetomidine and lidocaine) are effective and which is the preferred adjuvant choice to reduce postoperative pain. Second, previous studies have proved that the administration of lidocaine and dexmedetomidine in this protocol is clinically safe and common for children undergoing craniotomy [30,[48][49][50]. Thus, this study will not increase the risk for children administered these two adjuvant analgesics.…”

A randomized, double‐blind, dose‐controlled study of the use of dexmedetomidine alone for procedural sedation of children and adolescents undergoing MRI scans

“…At the time of this study, no pediatric pharmacokinetic/pharmacodynamic (PK/PD) model relating plasma concentration of dexmedetomidine to target sedation for children undergoing procedural sedation was available. Therefore, selection of the dosing regimen was based on: (1) recommended doses for procedural sedation in adults 2 ; (2) dosing experience and results of a previous open‐label pediatric procedural sedation safety study 4 ; (3) PK data from adult and pediatric ICU patients; and (4) simulated PK profiles at the projected doses for the current study based on a population PK model developed from pediatric ICU patients (Pfizer data on file).…”

The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural Sedation and Postoperative Behaviors in Pediatric Populations: A Systematic Review and Meta-analysis

“…13 Dexmedetomidine, a highly specific and effective α2 adrenergic receptor agonist, has not only greater receptor affinity than clonidine, but also sedative, analgesic, and antianxiety effects. 3,6,8,[14][15][16] Dexmedetomidine does not change the seizure threshold or affect the spike activity. It can directly bind to the α2 adrenergic receptor in the locus coeruleus to trigger the endogenous sleep production pathway.…”

“…22 Meanwhile, dexmedetomidine alone is not associated with respiratory depression, even during periods of deep sedation. 14,16 However, in terms of hemodynamics, bradycardia, hypotension, and transient hypertension are the most frequently reported hemodynamic adverse reactions of dexmedetomidine because of its peripheral vasoconstriction and sympathetic properties. 3,12 Pediatric sedation has always been one of the difficult problems in diagnosis and surgical procedures.…”