Prolonged Dexmedetomidine Use in Critically Ill Children
Prolonged Dexmedetomidine Use in Critically Ill Children
Objectives: To evaluate the safety and efficacy of prolonged dexmedetomidine administration (≥96 hrs) in critically ill children with heart disease.
Design: Retrospective observational study.
Setting: Cardiovascular intensive care unit in a single, tertiary care, academic children's hospital.
Interventions: None.
Subjects: We conducted a retrospective review of the charts of all critically ill infants and children (up to 18 yrs of age) with congenital or acquired heart disease who received dexmedetomidine for ≥96 hrs in our pediatric cardiovascular intensive care unit between January 2009 and March 2010. Patients were divided into two groups for study purposes: the dexmedetomidine group (n = 52) included patients who received a dexmedetomidine infusion along with other conventional sedation agents, and the control group (n = 42) included patients who received conventional sedation agents without the use of dexmedetomidine. Clinical outcomes evaluated in our study included days of mechanical ventilation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. To evaluate the safety of dexmedetomidine, we collected physiologic data, including heart rate, mean arterial pressure, respiratory rate, systemic oxygen saturation by pulse oximetry, and inotrope score. To assess the efficacy of dexmedetomidine, we examined the amount and duration of concomitant sedation and analgesic infusions over a period of 24 hrs in both dexmedetomidine and control groups. We also examined the number of rescue boluses for each category prior to the initiation of sedative infusion, during the sedative infusion, and after the termination of the sedative infusion. The potential side effects evaluated in our study included nausea, vomiting, abdominal distension, dysrhythmias, neurological abnormalities, seizures, and signs and symptoms of withdrawal.
Measurements and Main Results: Patients' baseline characteristics were similar in the two groups. Patient complexity as measured by Risk-Adjusted Classification for Congenital Heart Surgery-1 score, ventricular ejection fraction, and proportion of patients receiving mechanical ventilatory support at the time of initiation of sedative infusion was also similar. The duration and amount of continuous midazolam and morphine infusions were significantly lower in the dexmedetomidine group when compared to the control group. During dexmedetomidine infusion, there was no statistical difference in the heart rate and blood pressure between the two groups. Inotrope score was significantly lower in the dexmedetomidine group as compared to the control group in the last 6 hrs prior to termination of dexmedetomidine infusion (p < .001), and at 1 hr (p < .001) and 6 hrs (p < .001) after termination of dexmedetomidine infusion. There was no difference in duration of mechanical ventilation (p = .77), cardiovascular intensive care unit length of stay (p = .29), or hospital length of stay (p = .43) in the two groups. One patient experienced junctional rhythm at 130 beats/min requiring temporary pacing. No other significant side effects were noted. A higher proportion of patients in the dexmedetomidine group were administered clonidine when compared to the control group after termination of dexmedetomidine (31% vs. 7%, p = .005).
Conclusions: Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support.
Providing adequate sedation for critically ill children with heart disease is a challenging clinical problem. These patients often have labile cardiovascular function and may require several days to weeks of sedation as a component of their intensive care unit management. The challenge remains to find an ideal pharmacologic agent(s) that is not only effective but also safe without altering a patient's hemodynamic status. Although it has been proposed by some that dexmedetomidine (DEX) is a useful addition to the sedation armamentarium of pediatric cardiac intensive care physicians, the safety and efficacy of this agent for prolonged administration in children is unknown. DEX (Precedex, Hospira Worldwide, Lake Forest, IL) is an α2-adrenergic agonist with sedative, anxiolytic, and analgesic properties. It contains an imidazole ring and has a similar structure to clonidine, but with α2:α1 specificity of nearly 1600 to 1. The shorter half-life of DEX (2–3 hrs vs. 12–24 hrs for clonidine) allows titration by a continuous infusion. DEX has limited effects on respiratory function; thus, interference with weaning from mechanical ventilation is less likely. In fact, it has been used both as a bridge to tracheal extubation as well as for sedation in non-intubated patients. The enthusiasm for this newer agent stems from several factors, including the lack of an ideal agent for sedation during mechanical ventilation, adverse effects associated with existing agents, and recognition over the past 10 yrs of the potential deleterious physiologic effects of untreated pain in the acute caresetting.
The Food and Drug Administration has approved DEX for the provision of sedation for up to 24 hrs in adults during mechanical ventilation and sedation of non-intubated patients prior to and/or during surgical and other procedures. These trials were designed to evaluate its use for only 24 hrs; thus, only limited data were generated to guide its use for more prolonged periods of time. To date, there continues to be little data regarding DEX use extending beyond 4–5 days. In this study, we evaluated safety and efficacy of prolonged DEX administration (≥96 hrs) in critically ill children with heart disease.
Abstract and Introduction
Abstract
Objectives: To evaluate the safety and efficacy of prolonged dexmedetomidine administration (≥96 hrs) in critically ill children with heart disease.
Design: Retrospective observational study.
Setting: Cardiovascular intensive care unit in a single, tertiary care, academic children's hospital.
Interventions: None.
Subjects: We conducted a retrospective review of the charts of all critically ill infants and children (up to 18 yrs of age) with congenital or acquired heart disease who received dexmedetomidine for ≥96 hrs in our pediatric cardiovascular intensive care unit between January 2009 and March 2010. Patients were divided into two groups for study purposes: the dexmedetomidine group (n = 52) included patients who received a dexmedetomidine infusion along with other conventional sedation agents, and the control group (n = 42) included patients who received conventional sedation agents without the use of dexmedetomidine. Clinical outcomes evaluated in our study included days of mechanical ventilation, cardiovascular intensive care unit length of stay, hospital length of stay, and mortality. To evaluate the safety of dexmedetomidine, we collected physiologic data, including heart rate, mean arterial pressure, respiratory rate, systemic oxygen saturation by pulse oximetry, and inotrope score. To assess the efficacy of dexmedetomidine, we examined the amount and duration of concomitant sedation and analgesic infusions over a period of 24 hrs in both dexmedetomidine and control groups. We also examined the number of rescue boluses for each category prior to the initiation of sedative infusion, during the sedative infusion, and after the termination of the sedative infusion. The potential side effects evaluated in our study included nausea, vomiting, abdominal distension, dysrhythmias, neurological abnormalities, seizures, and signs and symptoms of withdrawal.
Measurements and Main Results: Patients' baseline characteristics were similar in the two groups. Patient complexity as measured by Risk-Adjusted Classification for Congenital Heart Surgery-1 score, ventricular ejection fraction, and proportion of patients receiving mechanical ventilatory support at the time of initiation of sedative infusion was also similar. The duration and amount of continuous midazolam and morphine infusions were significantly lower in the dexmedetomidine group when compared to the control group. During dexmedetomidine infusion, there was no statistical difference in the heart rate and blood pressure between the two groups. Inotrope score was significantly lower in the dexmedetomidine group as compared to the control group in the last 6 hrs prior to termination of dexmedetomidine infusion (p < .001), and at 1 hr (p < .001) and 6 hrs (p < .001) after termination of dexmedetomidine infusion. There was no difference in duration of mechanical ventilation (p = .77), cardiovascular intensive care unit length of stay (p = .29), or hospital length of stay (p = .43) in the two groups. One patient experienced junctional rhythm at 130 beats/min requiring temporary pacing. No other significant side effects were noted. A higher proportion of patients in the dexmedetomidine group were administered clonidine when compared to the control group after termination of dexmedetomidine (31% vs. 7%, p = .005).
Conclusions: Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support.
Introduction
Providing adequate sedation for critically ill children with heart disease is a challenging clinical problem. These patients often have labile cardiovascular function and may require several days to weeks of sedation as a component of their intensive care unit management. The challenge remains to find an ideal pharmacologic agent(s) that is not only effective but also safe without altering a patient's hemodynamic status. Although it has been proposed by some that dexmedetomidine (DEX) is a useful addition to the sedation armamentarium of pediatric cardiac intensive care physicians, the safety and efficacy of this agent for prolonged administration in children is unknown. DEX (Precedex, Hospira Worldwide, Lake Forest, IL) is an α2-adrenergic agonist with sedative, anxiolytic, and analgesic properties. It contains an imidazole ring and has a similar structure to clonidine, but with α2:α1 specificity of nearly 1600 to 1. The shorter half-life of DEX (2–3 hrs vs. 12–24 hrs for clonidine) allows titration by a continuous infusion. DEX has limited effects on respiratory function; thus, interference with weaning from mechanical ventilation is less likely. In fact, it has been used both as a bridge to tracheal extubation as well as for sedation in non-intubated patients. The enthusiasm for this newer agent stems from several factors, including the lack of an ideal agent for sedation during mechanical ventilation, adverse effects associated with existing agents, and recognition over the past 10 yrs of the potential deleterious physiologic effects of untreated pain in the acute caresetting.
The Food and Drug Administration has approved DEX for the provision of sedation for up to 24 hrs in adults during mechanical ventilation and sedation of non-intubated patients prior to and/or during surgical and other procedures. These trials were designed to evaluate its use for only 24 hrs; thus, only limited data were generated to guide its use for more prolonged periods of time. To date, there continues to be little data regarding DEX use extending beyond 4–5 days. In this study, we evaluated safety and efficacy of prolonged DEX administration (≥96 hrs) in critically ill children with heart disease.
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