Prevention and therapy of alcohol withdrawal on intensive care units: systematic review of controlled trials

Background: Alcohol withdrawal syndrome (AWS) occurs in 16 to 31% of intensive care unit (ICU) patients after cessation of sedation. There exist many preventive and therapeutic strategies, but no systematic review (SR) has been published on this topic so far. We aimed to perform a synopsis of all controlled trials of AWS prevention and therapy in ICU published between 1971 and 30 March 2011 following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) statement.

Methods: We performed a MEDLINE search with the terms "alcohol" AND "ICU" as well as "alcohol withdrawal" AND "intensive care." All publications that matched our eligibility criteria were analyzed according to our predefined criteria.

Results: We identified 6 controlled trials about AWS prevention and 8 about AWS therapy in ICUs. For AWS prevention, benzodiazepines (BZO), ethanol (EtOH), and clonidine were evaluated as single agents, and BZO, clonidine, clomethiazol and haloperidol were studied in drug combinations. All evaluated single agents and combinations were found to be effective for AWS prevention. Clomethiazol was found to be associated with a higher tracheobronchitis rate and thus disadvised for critically ill patients. For AWS therapy, BZO, gamma-hydroxybutyric acid (GHB), and clomethiazol were evaluated in randomized controlled trials as single agents and phenobarbital, clonidine, and haloperidol as adjuncts. All evaluated regimens were found to be effective for AWS therapy. Overall, in the ICU, BZO were found to be superior to GHB and clomethiazol regarding safety and efficacy. Furthermore, 4 cohort trials with historical control groups evaluated the effect of the implementation of a standardized protocol of BZO therapy for AWS in ICUs. All of these 4 studies found better outcome for the intervention groups.

Conclusions: Based on the evidence of this SR, EtOH or BZO can be advised for AWS prevention on ICU patients with alcohol dependence, but EtOH is not allowed for therapy of AWS. AWS therapy should be standardized and based on symptom-triggered BZO administration. Alpha2-agonists and haloperidol should be added for autonomic and productive psychotic symptoms.