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

BACKGROUND Dexmedetomidine (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). METHODS Eligible 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. RESULTS Median 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). CONCLUSIONS DEX 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.