A Systematic Review of Alpha-2 Agonists for Sedation in Mechanically Ventilated Neurocritical Care Patients

The use of sedative medications is commonplace in intensive care units (ICUs) and an invaluable clinical tool for the intensive care physician. Sedation for critically ill, mechanically ventilated patients provides an opportunity to reduce anxiety, discomfort as well as ventilator intolerance and dyssynchrony. Alpha-2 agonists in particular have become increasingly popular for use in the neurocritical care population due to their proposed effectiveness in facilitating examinations and procedures as well as reducing the need for adjunctive agents. However, there is a paucity of literature to assess the safety of their use in the neurocritically ill patients, a population that presents unique sensitivities and considerations for management of global and cerebral hemodynamics, agitation and facilitation of neurological assessments. This review assesses the safety and efficacy of alpha-2 agonists for non-procedural sedation in critically ill brain-injured patients on mechanical ventilation. In June 2016, we searched the EMBASE, MEDLINE and CENTRAL Cochrane Databases for randomized controlled trials, prospective and retrospective cohort studies examining neurocritically ill adult patients aged 18 years and older who are on mechanical ventilation and receiving alpha-2 agonists for non-procedural sedation. Primary outcomes of interest include mean arterial pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). Secondary outcomes include adverse events, duration of mechanical ventilation, 30-day mortality, ICU length of stay, incidence of delirium, and quality of sedation. We identified 17 studies for inclusion, all reporting on dexmedetomidine use, only 7 of which reported on our primary outcomes of interest. We found mixed results with regard to statistically significant changes in ICP, CPP, and MAP but did not find evidence of severe hemodynamic disturbances. However, the studies are notably limited by lack of reporting on sedative and hemodynamic adjuncts. Based on the limited available data, dexmedetomidine does not appear to result in severe, uncompensated hemodynamic disturbances (cerebral or systemic). The validation of an effective and safe agent with reporting of dosing strategy, sedation protocol use, co-interventions administered, and a priori defined adverse events is recommended.