Using dexmedetomidine as adjunctive therapy for patients with severe alcohol withdrawal syndrome: another piece of the puzzle.

May 2014 • Volume 42 • Number 5 Managing patients presenting with withdrawal syndromes, specifically alcohol withdrawal syndrome, remain a great challenge for critical care practitioners—both for medical and surgical patients (1, 2). By the time patients with alcohol withdrawal syndrome are presenting to the ICU, they are often intubated, potentially requiring high doses of benzodiazepines and continuous infusions of propofol. These patients, more often than not, require significant resources no matter how one measures it: prolonged duration of mechanical ventilation, long stays in the ICU, and high levels of nursing care. The perfect drug for management of severe alcohol withdrawal syndrome (SAWS) would be one that would have both oral and IV forms, would be easily titratable, would be able to prevent intubation, would allow the patient to remain cognitively intact throughout the duration of their hospital stay, and, importantly, would have no side effects. Unfortunately, no such perfect pharmacotherapeutic intervention currently exists. Current standards of care include the use of benzodiazepines, and if the patient develops SAWS, the patient may require intubation and continuous infusions of benzodiazepines, propofol, or both. There are those who promulgate the use of ethanol infusions, though there are many concerns, and the data are limited and somewhat controversial (3). As there is no truly high-quality drug for managing SAWS, other adjunctive therapies have been explored. Specifically, dexmedetomidine (DEX), the S-enantiomer of medetomidine (a veterinary sedative and analgesic), whose primary action is as a central, presynaptic α-2 agonist, has been evaluated in this setting. Given DEX’s lack of activation of either the gamma-aminobutyric acid or opioid receptors, it can provide sedation without respiratory depression. There have been important recent trials and guidelines evaluating and recommending its use for critically ill patients who require pain and sedation management, though the current Food and Drug Administration–approved indication is still only for 24 hours (4, 5). The data, heretofore, regarding the value of DEX in patients with SAWS have been limited primarily to case series and retrospective analyses (6–13). It is in that context that we discuss the study by Mueller et al (14) published in this issue of Critical Care Medicine. This study focused on patients with SAWS; as such they randomized 24 patients with a CIWA (Clinical Institute Withdrawal Assessment) score of greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam (LOR) over a 4-hour period into one of three arms: high-dose DEX (1.2 μg/kg/hr), lowdose DEX (0.4 μg/kg/hr), or placebo in addition to standard therapy for patients with SAWS. The infusion could be continued for up to 5 days or until the clinicians judged that the patients were no longer in withdrawal. The patients were treated according to their institutional, symptom-driven, nurse-managed sliding-scale LOR regimen (2–4 mg of LOR could be given every 30 min for a CIWA score ≥ 15. If ≥ 8 mg of LOR was given in an hour, the clinician was to be notified, and further medications were prescribed as deemed appropriate.) There were two primary outcomes. The first was the change in total LOR requirements over the first 24-hour period after starting the study drug compared with the 24-hour period prior starting the study drug. The second was the cumulative total dose of LOR given over the first 7 days of the SAWS. Secondary outcomes included total and daily LOR requirements, need for endotracheal intubation, prevalence of seizures, occurrence of SAWS or severe agitation, and prevalence of moderate AWS or moderate agitation, comparing the placebo group with the DEX group. The study drug (DEX) was infused for a median of 61 hours (approximately 2.5 d) while the placebo was infused for 70 hours (approximately 3 d). With statistical significance, the total 24-hour LOR requirement after starting the DEX was approximately 56 mg lower in the DEX arm as opposed to being only 8 mg lower in the placebo arm. The authors found that this decrease happened quickly, with statistical significance noted as early as 12 hours. No dose response was noted between highdose and low-dose DEX. There was no statistical difference in the amount of LOR given over the first 7 days between the DEX and the placebo arms, nor were there any differences in total LOR given after starting the study drug. No other statistical differences were noted between the DEX and placebo arms. Twenty-five percent of the DEX *See also p. 1131.