2026 Eastern States Conference

Title: Evaluating the Safety and Efficacy of Clonidine versus Guanfacine for Transitioning Off Dexmedetomidine 

Authorship: Juliet Nowak, PharmD; Rachel Winner, PharmD, BCCCP; Skyler Starkel, PharmD, BCCCP; Lydia R. Ware, PharmD, BCCCP, BCPS; Jeremy R. DeGrado, PharmD, BCCCP; Kenneth Lupi, PharmD, BCCCP, BCPS; Kaitlin E. Crowley, PharmD, BCCCP, BCPS; Brigham and Women’s Hospital, Boston, MA 
 
Learning Objective: At the end of this presentation, participants will be able to evaluate the use of enteral agents to facilitate dexmedetomidine (DEX) discontinuation. 

Background: Clonidine and guanfacine, alpha-2 agonists, have been used to facilitate DEX discontinuation. This analysis compared the safety and efficacy of clonidine and guanfacine for dexmedetomidine weaning in intensive care unit (ICU) patients.

Methods: This single-center, retrospective cohort analysis at a tertiary medical center included adult ICU patients who received DEX infusion >24 hours and more than one dose of enteral clonidine or guanfacine concomitantly. Patients were excluded if they died while on DEX, received one of the enteral agents prior to admission, used both guanfacine and clonidine during DEX wean attempt, or received DEX for sleep. The major outcome was discontinuation of DEX within 48 hours of clonidine or guanfacine initiation. Discontinuation was defined as cessation of DEX without reinitiation for at least 12 hours. Minor outcomes included hypotension (MAP <65 mmHg, initiation of vasopressors, or ≥25% increase in vasopressor dose), bradycardia (HR <50 bpm or >20% decrease), ICU/hospital length of stay (LOS), and in-hospital mortality. For categorical data, Chi-Square or Fisher’s exact tests were used as appropriate. Wilcoxon rank sum tests were used for non-parametric continuous data.

Results: A total of 136 patients (102 receiving clonidine and 34 receiving guanfacine) were included in a 3:1 ratio. Patients were enrolled from September 2015-November 2025. There was no statistically significant difference between the two groups in discontinuation of DEX within 48 hours of enteral agent initiation (68% in clonidine group vs 56% in guanfacine group, p=0.21). Incidence of hypotension was higher in the guanfacine group (67%) compared to clonidine (43%) (p=0.01). Additionally, vasopressor use at the time of enteral agent initiation was greater in the guanfacine group than in the clonidine group, respectively (38% vs 21%; p=0.04). There was no difference in bradycardia, hospital LOS, ICU LOS, or in-hospital mortality between the two groups.

Conclusion: This is the first study to our knowledge that compared clonidine versus guanfacine for transitioning off DEX in the ICU. Although there was no associated difference in groups between discontinuation of DEX within 48 hours of clonidine or guanfacine initiation, rates of hypotension were more prevalent in the guanfacine group, through this may be confounded by higher vasopressor use in the guanfacine group. This analysis also gives guidance on feasibility for a future prospective randomized controlled trial.
 
 
Self- Assessment Question:  
Within the first 48 hours of dexmedetomidine weaning, which oral α₂-agonist was associated with a higher incidence of hypotension? 
A. Guanfacine
B. Clonidine
C. Both medications have similar rates of hypotension
D. Hypotension is uncommon with either medication