α2-Receptor Agonists for Treatment and Prevention of Iatrogenic Opioid Abstinence Syndrome in Critically III Patients

OBJECTIVE: To review the literature regarding the use of alpha(2)-agonists in the treatment and prevention of iatrogenic opioid abstinence syndrome (IOAS) in critically ill patents. DATA SOURCES: Primary literature was identified through a search of MEDLINE (1950-June 2009), EMBASE (1988-June 2009), International Pharmaceutical Abstracts (1970-June 2009), and the Cochrane Library (1996-June 2009), using the names of individual (alpha(2)-agonists and the following key words: children, opioid withdrawal, opioid, and adult. Relevant abstracts from the Society of Critical Care Medicine, reference citations from selected articles, and manufacturers' product information were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data sources were evaluated. Three retrospective studies and 6 case reports/series representing 44 patients were included for analysis. DATA SYNTHESIS: Central alpha(2)-agonists are thought to minimize symptoms of IOAS by decreasing presynaptic outflow of catecholamines. Successful use of clonidine and dexmedetomidine for management of IOAS has been reported. Lofexidine, an alpha(2)-agonist not yet approved in the US, may offer similar withdrawal symptom relief but has yet to be studied in the intensive care setting. Although the quality of studies identified was limited, preliminary evidence does provide some support for the use of transdermal clonidine and injectable dexmedetomidine in the treatment and prevention of IOAS. These agents were shown to facilitate discontinuation of opioids and to minimize withdrawal symptoms with few reported adverse events. CONCLUSIONS: Central alpha(2)-agonists appear to be effective and safe second-line agents for treatment and prevention of IOAS. Further studies should be conducted to determine their role in the therapy of patients with IOAS.