Addition of dexmedetomidine to benzodiazepines for patients with alcohol withdrawal syndrome in the intensive care unit: a randomized controlled study

Abstract

BackgroundDexmedetomidine (DEX) is a centrally acting alpha-2-adrenoceptor agonist that has potential in the management of alcohol withdrawal syndrome (AWS) owing to its ability to produce arousable sedation and to inhibit the adrenergic system without respiratory depression. The objective of this randomized controlled study was to evaluate whether addition of DEX to benzodiazepine (BZD) therapy is effective and safe for AWS patients in the intensive care unit (ICU).MethodsEligible participants were randomly assigned to intervention (Group D; n = 36) or control (Group C; n = 36). In Group D, DEX infusion was started at a dose of 0.2–1.4 μg/kg/h and titrated to achieve the target sedation level (–2 to 0 on the Richmond Agitation Sedation Scale (RASS)) with symptom-triggered BZD (10 mg diazepam bolus) was used as needed. Patients in Group C received only symptom-triggered 10 mg boluses of diazepam. The primary efficacy outcomes were 24-h diazepam consumption and cumulative diazepam dose required over the course of the ICU stay; secondary outcomes included length of ICU stay, sedation and communication quality and haloperidol requirements.ResultsMedian 24-h diazepam consumption during the study was significantly lower in Group D (20 vs. 40 mg, p < 0.001), as well as median cumulative diazepam dose during the ICU stay (60 vs. 90 mg, p < 0.001). The median percentage of time in the target sedation range was higher in Group D (median 90 % (90–95) vs. 64.5 % (60–72.5; p < 0.001). DEX infusion was also associated with better nurse-assessed patient communication (<0.001) and fewer patients requiring haloperidol treatment (2 vs. 10 p = 0.02). One patient in Group D and four in Group C were excluded owing to insufficient control of AWS symptoms and use of additional sedatives (p = 0.36). There were no severe adverse events in either group. Spontaneous breathing remained normal in all patients. Bradycardia was a common adverse event in Group D (10 vs. 2; p = 0.03).ConclusionsDEX significantly reduced diazepam requirements in ICU patients with AWS and decreased the number of patients who required haloperidol for severe agitation and hallucinations. DEX use was also associated with improvement in diverse aspects of sedation quality and the quality of patient communication.Trial registration: ClinicalTrials.gov: NCT02496650

Alcohol withdrawal syndrome: mechanisms, manifestations, and management

“…As ɑ‐2 agonists lack the GABAergic activity to prevent and treat DT or seizures, they can only be used as adjunctive therapy to reduce autonomic hyperactivity that cannot be controlled by BZD alone 3, 80, 86. Several studies demonstrated a BZD‐sparing effect with significant reduction in BZD requirement 87, 88, 89…”

Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients

“…Current evidence for the use of DEX for management of AWS is limited to several small observational studies and two single‐center randomized controlled trials . Most of these studies showed a decrease in BZD use with the addition of DEX but with a variable effect on intubation rates, ICU LOS, and hospital LOS.…”

Use of Propofol Plus Dexmedetomidine in Patients Experiencing Severe Alcohol Withdrawal in the Intensive Care Unit

“…In previous studies the use of either propofol or dexmedetomidine as adjunctive therapy to benzodiazepines has been associated with a significant decrease in benzodiazepine use . Both propofol and dexmedetomidine have been associated with hypotension, with 1 study reporting about 28.5% of patients in the propofol group experiencing it and 17.6% of patients in the dexmedetomidine group experiencing it .…”

“…Inclusion criteria were patients admitted to the adult medical/surgical ICU between September 1, 2015 and September 30, 2018 who had a diagnosis of alcohol withdrawal as indicated by the International Classification of Diseases, 10th edition , codes for alcohol dependence with withdrawal delirium (F10.231) and/or alcohol dependence with withdrawal—unspecified (F10.239), were receiving lorazepam as their primary treatment for alcohol withdrawal, received a continuous infusion of propofol, dexmedetomidine, or both propofol and dexmedetomidine as adjunctive therapy to lorazepam, and had at least 1 revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA‐Ar) score of ≥15 (indicating moderate to severe alcohol withdrawal) within the 24 hours preceding the initiation of their sedation medication. The CIWA‐Ar scale scores patients in 10 different areas based on symptoms associated with alcohol withdrawal: nausea/vomiting, tremor, diaphoresis, anxiety, agitation, tactile disturbances, auditory disturbances, visual disturbances, headache, and orientation . CIWA‐Ar scores range from 0 to 63 with higher scores for more severe symptoms.…”

“…Both propofol and dexmedetomidine individually have been used in the management of severe AWS in those patients resistant to high doses of benzodiazepines, but the published data are limited, especially with dexmedetomidine. Previous studies have demonstrated that dexmedetomidine has been associated with reduced need for lorazepam . Phenobarbital may also be used to manage AWS in patients who are refractory to benzodiazepines …”