Alpha2 Agonist Use in Critically Ill Adults: A Focus on Sedation and Withdrawal Prevention

The management of sedation in critically ill adults poses a unique challenge to clinicians. Dexmedetomidine, an α₂ agonist, has a unique mechanism and favorable pharmacokinetics, making it an attractive intravenous option for sedation and delirium in the intensive care unit. However, patients may be at risk for withdrawal with prolonged use, adding to the complexity of sedation and agitation management in this patient population. Enteral α₂ agents have the benefit of cost savings and ease of administration, thus playing a role in the ability to decrease intravenous sedative use and prevent dexmedetomidine withdrawal. Clonidine and guanfacine are the two most common enteral α₂ agents utilized for this purpose, however, there is a paucity of evidence regarding the comparative benefit between the two agents. The decision to use one vs the other agent should be determined based on their differing pharmacology, pharmacokinetics, and side effect profile. The most effective dosing strategy for these agents is also unknown. Ultimately, more robust literature is required to determine enteral α₂ agonists place in therapy. This narrative review evaluates the currently available literature on the use of α₂ agonists in critically ill adults with an emphasis on sedation, delirium, and withdrawal.