Use of DEX has been proposed in several pediatric clinical and surgical conditions, such as: to facilitate the weaning process after long period of mechanical ventilation, to prevent and treat delirium and abstinence syndrome, in the post-surgery period (cardiac, upper airway and neurosurgery surgery), and to facilitate non-invasive ventilation [3-8]. DEX is metabolized in the liver with 95% of the inactive metabolites excreted in urine [3,6].

We evaluated the main indications, initial and maximal doses, length of infusion and side effects related to prolonged DEX infusion in children and adolescent treated in a pediatric intensive care unit (PICU).

Observational and retrospective study involving children (age 2 months to 18 years) who received DEX infusion (>6 hours) in a referral Brazilian Pediatric Intensive Care Unit (PICU) between November 2011 and June 2014. The local Ethical and Research Committee approved the study.

We used DEX infusion starting at 0.3 µg/kg/hr and increasing up to 0.7 µg/kg/hr, at the discretion of the medical assistant, depending on clinical goals and child response. Two researchers collected the data in the medical chart. Demographic data, the main indications, the initial and maximal dose, length of use, the side effects related to DEX infusion, as well as the Heart Rate, systolic, diastolic and the mean arterial pressure (MAP) were evaluated at onset, 6 and 24 hours of continuous DEX infusion.

Prolonged DEX infusion was administered to 77 children with median (IQR) age of 15 [4, 84] months, weight of 10 [5.7, 20] kg and length of PICU stay of 8 [5,14] days (Table I). The median (IQR) PIM score was 0.82 [0.3, 4], with a mortality rate of 9% (7 children).

TABLE I	Characteristics of Children Receiving Dexmedetomidine Infusion in the Pediatric Intensive Care Unit (N=77)

Five groups were identified as the main indications for prolonged DEX infusion: mechanical ventilation weaning (32.5%), postoperative period of neurosurgery and upper airway surgery (24.7%), non-invasive mechanical ventilation (13%), refractory tachycardia (6.5%) and others (23.3%). There were no differences between the five groups (P=0.443) regarding the mean initial dose of DEX infusion, maximal dose, and mean length of DEX infusion (Table II).

TABLE II Characteristics of Dexmedetomidine Infusion as per Indication for Use 

The heart rate and the MAP decreased significantly (P=0.01) after 6 hours of DEX infusion when compared to the pre-infusion levels. However, when comparing the means values of heart rate and MAP over the 3 time periods (pre-infusion, 6 h and 24 h of infusion), there were no differences (P=0.80 and 0.38, respectively).

Opioids, midazolam and/or ketamine were concomitantly administered with DEX in 28 children (36.3%). In six children (8%), DEX was withdrawn in view of possible side effects: hypotension (4), bradycardia (1) and somnolence (1).

We demonstrated that DEX can be used in different circumstances in the PICU (e.g, facilitating non-invasive mechanical ventilation, to treat/prevent abstinence syndrome, as sedative in the post-operative period, adjunct treatment of symptomatic tachycardia). The average of initial and maximal dose of DEX infusion in our study was in the low range, demonstrating that even at a lower dose, the desired effects are achieved with only occasional side effects.

Bradycardia and hypotension induced by DEX are related to brain and spinal medulla receptor’s inhibition of norepinephrine release [2,9,10]. Reduction on HR and MAP 6 hours after DEX onset, without difference in the following 24 hours, has also been observed with conventional sedatives and analgesics [3,6]. Hypotension induced by DEX has been more frequently associated with intravenous bolus than with constant infusion [3]. This could be the reason for the low number of patients in our study presenting relevant hypotension demanding DEX withdrawal.

Originally, DEX infusion was recommend for short periods. Several pediatric studies support its use over prolonged periods [11-13]. Walker, et al. [12] reported an average of DEX infusion of 11 (2 to 50) days, with a median dose of 0.5 µg/kg/h, without major side effects. Reiter, et al. [4] demonstrated prolonged DEX use in children (110 ± 83h) with initial dose of 0.36 (0.16) µg/kg/h and maximal dose of 0.65 (0.34) µg/kg/h, without significant side effects [4]. Even considering the possible limitations of our study (retrospective analysis of the medical chart), our findings are consistent with other similar studies, highlighting the potential, safety, and spectrum of DEX infusion in critically ill children.

Contributors: All authors participated in study design, data collection, data analysis, manuscript writing, and its final approval.

Funding: None; Competing interest: None stated.