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Alpha-2 Agonists for Long-Term Sedation During Mechanical Ventilation in Critically Ill Patients

Bolton, Nerys MSc (Renal), BSc (Hons), RN, PGCLT (HE), NMC

AJN, American Journal of Nursing: February 2016 - Volume 116 - Issue 2 - p 21
doi: 10.1097/01.NAJ.0000480489.10481.df
Cochrane Corner

Editor's note: This is a summary of a nursing care–related systematic review from the Cochrane Library.

Nerys Bolton is senior lecturer in the School of Nursing, pathway director of the IPL Adult Nursing Programme at Canterbury Christ Church University, Canterbury, UK, and a member of the Cochrane Nursing Care Field.

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Compared with traditional sedatives, are alpha-2 agonists effective and safe for long-term sedation in mechanically ventilated, critically ill patients?

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This is an intervention review of seven randomized controlled trials that compared the long-term efficacy and safety of the alpha-2 agonist dexmedetomidine with traditional sedatives in patients who are critically ill and mechanically ventilated.

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Patients who require mechanical ventilation typically need some form of sedation. However, some commonly used sedatives, such as propofol, midazolam, and lorazepam, also lower blood pressure, depress breathing, and delay awakening after a long-term infusion. They may also prolong breathing support time and hospital length of stay. Alpha-2 agonists, such as dexmedetomidine and clonidine, sedate patients but staff can still interact with them, ease pain but do not depress breathing, and enable patients to be easier to wake and more able to communicate their discomfort and pain. Therefore, these drugs may be a good alternative to the more traditional sedatives for use in long-term sedation.

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After searching several databases for studies on the efficacy and safety of the alpha-2 agonists dexmedetomidine and clonidine as compared with traditional sedatives for long-term sedation (more than 24 hours) in mechanically ventilated, critically ill patients, the authors found seven studies, with a total of 1, 624 participants, that met their criteria. These studies compared dexmedetomidine with traditional sedatives, such as propofol, midazolam, and lorazepam. The primary outcomes were duration of mechanical ventilation, risk of delirium, and risk of coma.

Compared with traditional sedatives, dexmedetomidine reduced the geometric mean duration of mechanical ventilation by 22% and the ICU length of stay by 14%. There was no evidence that dexmedetomidine decreased the risk of delirium. Only one study assessed the risk of coma, but lacked methodological reliability.

The most commonly reported adverse event was bradycardia. Meta-analysis provided no evidence that dexmedetomidine had any impact on mortality. The general quality of evidence ranged from very low to low owing to high risks of bias, serious inconsistency and imprecision, and strongly suspected publication bias.

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Although dexmedetomidine can help to reduce ventilation time and ICU length of stay in critically ill, mechanically ventilated adults, there was no evidence to support its use in reducing the risk of delirium, and inadequate evidence for its use in reducing the risk of coma. Although the most common adverse event of dexmedetomidine was bradycardia, in most cases the bradycardiac effect was harmless and did not need to be treated. Dexmedetomidine would be a poor choice to use for deep sedation; even for light sedation, its use might result in insufficient sedation in one of every eight to 10 patients.

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As none of the seven studies investigated clonidine, there is a need for a large prospective study to eval­uate the efficacy, safety, and cost-effectiveness of clonidine for long-term sedation. All of the studies were in adults; therefore, studies in children are also needed. Studies could also focus on specific populations, such as those with chronic obstructive pulmonary disease, adult respiratory distress syndrome, or brain injuries.

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Chen K, et al. Alpha-2 agonist for long-term sedation during mechanical ventilation in critically ill patients Cochrane Database Syst Rev. 2015;1:CD010269
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