Volume 15: Issue 1

Dexmedetomidine (Precedex, Hospira World-wide Inc, Lake Forest, IL) is a centrally acting, α₂-adrenergic agonist which exerts its physiologic effects by activation of specific receptors throughout the central nervous system thereby producing its sedation, anxiolysis and analgesia. Although both dexmedetomidine and clonidine are imidazole compounds, clonidine exhibits an α₂:α₁ specificity ratio of 200:1 while that of dexmedetomidine is 1600:1. The shorter half-life of dexmedetomidine (2–3 hours versus 12–24 hours for clonidine) allows titration by a continuous infusion. Additionally, dexmedetomidine is available in a preparation for intravenous administration compared to clonidine, where the epidural formulation is

OBJECTIVE

Dexmedetomidine was approved by the Food and Drug Administration in 1999 for the sedation of adults receiving mechanical ventilation in an intensive care setting. It provides sedation with minimal effects on respiratory function and may be used prior to, during, and following extubation. Based on its efficacy in adults, dexmedetomidine is now being explored as an alternative or adjunct to benzodiazepines and opioids in the pediatric intensive care setting. This review describes the studies evaluating the safety and efficacy dexmedetomidine in infants and children and provides recommendations on dosing and monitoring.

METHODS

The MEDLINE (1950–November 2009) database was searched for pertinent abstracts, using the key term dexmedetomidine. Additional references were obtained from the bibliographies of the articles reviewed and the manufacturer. All available English-language case reports, clinical trials, retrospective studies, and review articles were evaluated.

RESULTS

Over two dozen case series and clinical studies have documented the utility of dexmedetomidine as a sedative in children requiring mechanical ventilation or procedural sedation. In several papers, dexmedetomidine use resulted in a reduction in the dose or discontinuation of other sedative agents. It may be of particular benefit in children with neurologic impairment or in those who do not tolerate benzodiazepines. The most frequent adverse effects reported with dexmedetomidine have been hypotension and bradycardia, in 10% to 20% of patients. These effects typically resolve with dose reduction.

CONCLUSIONS

Dexmedetomidine offers an additional choice for the sedation of children receiving mechanical ventilation in the intensive care setting or requiring procedural sedation. While dexmedetomidine is well tolerated when used at recommended doses, it has the potential to cause hypotension and bradycardia and requires close monitoring. In addition to clinical trials currently underway, larger controlled studies are needed to further define the role of dexmedetomidine in pediatric intensive care.

OBJECTIVES

Dexmedetomidine is an α₂-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events.

METHODS

Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose.

RESULTS

Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1–204 months) and median PRISM III score was 2 (range, 0–18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2–193.7) and 0.5 (range, 0.2–0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3–263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events.

CONCLUSIONS

Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

Dexmedetomidine is a α₂-adrenergic agonist which possesses sedative, analgesic, and anxiolytic properties. It is approved for short-term use in adults to provide sedation while mechanically ventilated and for noninvasive procedural sedation. An increased number of anecdotal reports describe the use dexmedetomidine in children. Cardiovascular withdrawal symptoms have been reported in the literature. However, there have been few published reports of neurologic withdrawal symptoms following discontinuation of prolonged infusions of dexmedetomidine. We describe a 2 year-old child who received a prolonged continuous infusion (263 hours) of dexmedetomidine as an adjunctive sedative agent. Following abrupt discontinuation of dexmedetomidine, the patient presented with symptoms suggestive of neurological withdrawal. The symptoms gradually resolved over two days without further intervention, and the patient had full resolution of symptoms and was discharged home with no further neurologic sequelae.

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Dominique L. RoppPharmD,

Courtney RanalloMD,

Hala ChaabanMD,

Lucila Garcia-ContrerasPhD,

Stephen NeelyMPH, and

Jamie L. MillerPharmD

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Dexmedetomidine Use in Pediatric Intensive Care and Procedural Sedation

OBJECTIVE

METHODS

RESULTS

CONCLUSIONS

Evaluation of Adverse Events Noted in Children Receiving Continuous Infusions of Dexmedetomidine in the Intensive Care Unit

OBJECTIVES

METHODS

RESULTS

CONCLUSIONS

Neurologic Withdrawal Symptoms Following Abrupt Discontinuation of a Prolonged Dexmedetomidine Infusion in a Child

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