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PEDIATRIC ANESTHESIA

The Use of Dexmedetomidine to Facilitate Opioid and Benzodiazepine Detoxification in an Infant

Department of Anesthesiology, Children’s National Medical Center and George Washington University, Washington, DC

Address correspondence and reprint requests to Julia C. Finkel, MD, Department of Anesthesiology, Children’s National Medical Center, 111 Michigan Ave., N.W., Washington, DC 20010. Address e-mail to jfinkel{at}cnmc.org

	Abstract

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Prolonged use of opioids and benzodiazepines for the care of critically ill infants and children can generate physical dependence. We present a case of an 8-mo-old infant with Hunter’s syndrome who was maintained on very large doses of fentanyl and midazolam and who could not be weaned from these drugs by conventional taper. We used dexmedetomidine, an ₂-adrenergic agonist, to facilitate opioid and benzodiazepine withdrawal. A processed electroencephalogram (Bispectral Index) was used to guide the titration of dexmedetomidine in this neurologically impaired infant. This is the first report of this drug being used in an infant to manage chemical dependence withdrawal.

IMPLICATIONS: Dexmedetomidine was used to facilitate opioid and benzodiazepine withdrawal in an 8-mo-old infant. A processed electroencephalogram (Bispectral Index) was used to guide the titration of dexmedetomidine in this neurologically impaired infant. This is the first report of dexmedetomidine use in an infant to manage chemical dependence withdrawal.

	Introduction

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The use of opioids and benzodiazepines for sedation is a mainstay of intensive care unit (ICU) patient care. The dependence that develops with long-term use of these drugs creates new problems for the patients and the ICU team directing their care. We present a case of an 8-mo-old infant with Hunter’s syndrome who was maintained on very large doses of fentanyl and midazolam. He could not be weaned from these drugs by a conventional withdrawal taper technique, and dexmedetomidine was used.

	Case Report

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A 13.3-kg boy with Hunter’s syndrome developed respiratory failure of unknown etiology that required mechanical ventilation from birth. In the neonatal ICU (NICU), he was intubated and mechanically ventilated over the next 6 mo while the cause for his respiratory failure was investigated. At age 7 mo, the diagnosis of Hunter’s syndrome was verified, and the patient underwent a tracheostomy. Fentanyl 3370 µg/d and midazolam 270 mg/d were used to achieve adequate sedation. Attempts to slowly wean the sedatives by 5% yielded unacceptable agitation, tachycardia, and hypertension. To transfer the patient from the NICU, IV sedatives needed to be discontinued.

The Anesthesia Pain Service was consulted for evaluation of alternative methods for weaning the infant from opioid and benzodiazepine dependence. Methadone was not considered because of the infant’s severely limited enteral intake. An acute detoxification was therefore attempted with dexmedetomidine to prevent an acute abstinence syndrome.

The baseline neurological impairment of the infant made it difficult to evaluate the depth of sedation. The infant was both blind and deaf and manifested 10–20 beats of clonus when touched. Because typical sedation scales implement auditory and tactile stimuli, a Bispectral Index score (BIS) (Aspect Systems, Newton, MA) was used to help guide the titration of the dexmedetomidine. The BIS monitor was placed 6 h before the midazolam and fentanyl infusions were stopped, to determine the baseline values occurring with adequately sedated behavior. On the basis of the observations made during this period, a target BIS value of 60–80 was used.

Immediately after the fentanyl and midazolam infusions were discontinued, the dexmedetomidine infusion was initiated with an initial loading dose of 1 µg/kg given over 10 min followed by a continuous rate of 0.2 to 0.7 µg · kg^–1 · h^–1 to keep the BIS within the targeted range. If the maximum rate of 0.7 µg · kg^–1 · h^–1 was reached and the BIS score was more than 80 or the arterial blood pressure was >20% of baseline, the initial dose could be repeated every 6 h. (This was needed on Days 2, 3, and 4 at least once a day.) The infusion was tapered off on Day 7. No rebound effects were noted hemodynamically or behaviorally during the taper. The patient manifested no agitation for the ensuing 2 wk and was transferred to a chronic care facility.

	Discussion

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Dexmedetomidine, an ₂-adrenergic agonist with an affinity for the ₂ receptor 8 times more than that of clonidine, was used to facilitate acute benzodiazepine and opioid withdrawal in an infant (1). This was administered as a seven-day infusion to mitigate the hyperadrenergic state produced by acute benzodiazepine and opioid withdrawal. The advantage of dexmedetomidine in this setting is that it provides sedation, analgesia, and blunted sympathetic activity without significant respiratory depression (2–4).

There are limited reports of the use of dexmedetomidine in infants and children (5). We used the BIS monitor to guide the adequacy of sedation and the dose range of dexmedetomidine. The BIS monitor correlates with sedation scores and, thus, may be an effective sedation monitor for prolonged periods in sedated, mechanically ventilated NICU patients as well as in adult ICU patients (6–8). However, algorithms used in the BIS have been established in adult patients, and interpretation in neonates and infants should be made with caution. The BIS monitor was helpful in providing titration of the dexmedetomidine in this neurologically impaired patient.

The dexmedetomidine dose range implemented did not result in a decrease in heart rate or hypotension, as might be expected with the sympatholytic effect of the drug. The lack of anticipated hemodynamic effect in general may have been due to increased sympathetic tone secondary to the catecholamines present during the withdrawal process (9–11). An additional potential advantage of rapid detoxification in infants is the possibility of reducing the amount of developmental delay that is seen with chronic opioid administration in this population (12).

Whereas the use of ₂ agonists for the amelioration of opioid withdrawal symptoms has been described (13), their use in mitigating benzodiazepine withdrawal symptoms is not established. Two recent reports (14,15) detail the use of dexmedetomidine in the successful management of adult patients with multiple substance dependencies, including opioids, benzodiazepines, and cocaine. Dexmedetomidine has the theoretical advantage of blunting the adrenergic response to benzodiazepine withdrawal, as well as a sedative and analgesic effect, which may serve to ameliorate the anxiety component of benzodiazepine withdrawal. It is unclear, however, whether dexmedetomidine has an effect on the convulsions precipitated by benzodiazepine withdrawal. Central -adrenoreceptors mediate drug- and electroshock-induced seizure activity (16). Additionally, there is evidence that the cocaine seizure threshold is increased by dexmedetomidine, possibly via attenuation of the extracellular dopaminergic response to cocaine (17). The effect of dexmedetomidine on the seizure threshold during withdrawal from benzodiazepines has yet to be determined.

In summary, the use of dexmedetomidine for facilitating withdrawal from opioid and benzodiazepine dependence in critically ill infants and children needs to be further evaluated. The role of BIS monitoring in the management of acute detoxification should also be investigated.

	References

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