Dexmedetomidine Infusion as Adjunctive Therapy to Benzodiazepines for Acute Alcohol Withdrawal

Pulmonary and Critical Care Medicine Division, Cooper University Hospital, Camden, NJ, USA.
Annals of Pharmacotherapy (Impact Factor: 2.06). 10/2008; 42(11):1703-5. DOI: 10.1345/aph.1K678
Source: PubMed


To report a case of alcohol withdrawal and delirium tremens successfully treated with adjunctive dexmedetomidine.
A 30-year-old man with a history of alcohol abuse was admitted to the general medical unit because of altered mental status and agitation. He was initially treated for alcohol withdrawal with benzodiazepines; his condition then deteriorated and he was transferred to the intensive care unit. Because of the patient's poor response to benzodiazepines (oxazepam and lorazepam, with midazolam the last one used), intravenous dexmedetomidine was started at an initial dose of 0.2 microg/kg/h and titrated to 0.7 microg/kg/h to the patient's comfort. Midazolam was subsequently tapered to discontinuation due to excessive sedation. In the intensive care unit, the patient's symptoms remained controlled with use of dexmedetomidine alone. He remained in the intensive care unit for 40 hours; dexmedetomidine was then tapered to discontinuation and the patient was transferred back to the general medical unit on oral oxazepam and thiamine, which had been started in the emergency department. He was discharged after 5 days.
A review of the PubMed database (1989-2007) failed to identify any other instances of dexmedetomidine having been used as the principal agent to treat alcohol withdrawal. The use of sedative to treat delirium tremens is well documented, with benzodiazepines being the agents of choice. The clinical utility of benzodiazepines is limited by their stimulation of the gamma-aminobutyric acid receptors, an effect not shared by dexmedetomidine, a central alpha(2)-receptor agonist that induces a state of cooperative sedation and does not suppress respiratory drive.
In patients with delirium tremens, dexmedetomidine should be considered as an option for primary treatment. This case illustrates the need for further studies to investigate other potential uses for dexmedetomidine.

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    • "Existing evidence suggests that dexmedetomidine may reduce benzodiazepine requirements and improve both hemodynamics and alcohol withdrawal severity. However, these findings have been limited to case reports and case series of heterogenous populations [10] [11] [12] [13] [14] [15]. The purposes of the present study were to investigate the benzodiazepinesparing properties of dexmedetomidine in AWS and to evaluate its influence on the hemodynamics of critically ill patients admitted for primary AWS. "
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    ABSTRACT: Although benzodiazepines are first-line drugs for alcohol withdrawal syndrome (AWS), rapidly escalating doses may offer little additional benefit and increase complications. The purpose of this study was to evaluate dexmedetomidine's impact on benzodiazepine requirements and hemodynamics in AWS. This retrospective case series evaluated 33 critically ill adults with a primary diagnosis of AWS from 2006 to 2012 at an academic medical center. Dexmedetomidine began a median (interquartile range) of 11 (2, 32) hours into intensive care unit admission and was titrated to an infusion rate of 0.7 (0.4, 0.7) μg kg(-1) h(-1) to achieve the desired depth of sedation. In the 12 hours after dexmedetomidine began, patients experienced a 20-mg reduction in median cumulative benzodiazepine dose used (P < .001), a 14-mm Hg lower mean arterial pressure (P = .03), and a 17-beats/min reduction in median heart rate (P < .001). Four (12%) patients experienced hypotension (systolic blood pressure <80 mm Hg) during therapy, and there were no cases of bradycardia (heart rate <40 beats/min). Dexmedetomidine decreased benzodiazepine requirements and improved the overall hemodynamic profile of patients with severe AWS. These results provide promising evidence about the potential benefit of dexmedetomidine for AWS.
    Full-text · Article · Nov 2013 · Journal of critical care
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    • "While the majority of the literature with alpha 2 agonists in alcohol withdrawal involves the use of clonidine, the use of dexmedetomidine as an adjunctive has been described in the literature [134] [138] [139] [140] [141] [142] [143]. When used adjunctively, alpha 2 agonists have demonstrated a reduction in the consumption of benzodiazepines in patients experiencing withdrawal [135] [136] [137]. "
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    ABSTRACT: Management of pain, agitation, and delirium is a complex process requiring a multimodal approach to optimize patient outcomes. Dexmedetomidine is a centrally acting alpha-2 agonist with sedative and analgesic properties that has demonstrated efficacy in managing pain, agitation, and delirium in a variety of critically ill patient populations. Dexmedetomidine has demonstrated the ability to provide a mild to moderate level of sedation in diverse ICU populations compared to conventional sedative regimens. Recent literature has demonstrated improved outcomes with dexmedetomidine based vs. benzodiazepine based sedation therapy in select mechanically ventilated ICU patients. However, dexmedetomidine therapy has also been associated with adverse cardiovascular events including hypotension, bradycardia, and asystole. The clinical pharmacology, therapeutic efficacy, safety considerations, controversies, and future directions of dexmedetomidine therapy in the ICU setting will be discussed.
    Full-text · Article · Dec 2012 · Current pharmaceutical design
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    • "Studies performed in mice found that dexmedetomidine reduced rigidity, tremor, and irritability during ethanol withdrawal, while exhibiting neuroprotective effects and potential antiepileptic activity [22,23,30]. Two case reports support the use of dexmedetomidine in benzodiazepine-refractory AWS [24,25]. Dexmedetomidine also was applied successfully in patients undergoing sedative/analgesic or polysubstance withdrawal in two case series consisting of two and three patients, respectively [26,27]. "
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    ABSTRACT: Patients undergoing alcohol withdrawal in the intensive care unit (ICU) often require escalating doses of benzodiazepines and not uncommonly require intubation and mechanical ventilation for airway protection. This may lead to complications and prolonged ICU stays. Experimental studies and single case reports suggest the α2-agonist dexmedetomidine is effective in managing the autonomic symptoms seen with alcohol withdrawal. We report a retrospective analysis of 20 ICU patients treated with dexmedetomidine for benzodiazepine-refractory alcohol withdrawal. Records from a 23-bed mixed medical-surgical ICU were abstracted from November 2008 to November 2010 for patients who received dexmedetomidine for alcohol withdrawal. The main analysis compared alcohol withdrawal severity scores and medication doses for 24 h before dexmedetomidine therapy with values during the first 24 h of dexmedetomidine therapy. There was a 61.5% reduction in benzodiazepine dosing after initiation of dexmedetomidine (n = 17; p < 0.001) and a 21.1% reduction in alcohol withdrawal severity score (n = 11; p = .015). Patients experienced less tachycardia and systolic hypertension following dexmedetomidine initiation. One patient out of 20 required intubation. A serious adverse effect occurred in one patient, in whom dexmedetomidine was discontinued for two 9-second asystolic pauses noted on telemetry. This observational study suggests that dexmedetomidine therapy for severe alcohol withdrawal is associated with substantially reduced benzodiazepine dosing, a decrease in alcohol withdrawal scoring and blunted hyperadrenergic cardiovascular response to ethanol abstinence. In this series, there was a low rate of mechanical ventilation associated with the above strategy. One of 20 patients suffered two 9-second asystolic pauses, which did not recur after dexmedetomidine discontinuation. Prospective trials are warranted to compare adjunct treatment with dexmedetomidine versus standard benzodiazepine therapy.
    Full-text · Article · May 2012 · Annals of Intensive Care
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