Clonidine Taper Shortens Dexmedetomidine Wean Without Increasing Withdrawal After Prolonged Infusion

Introduction: Prolonged dexmedetomidine infusions are associated with withdrawal symptoms upon discontinuation. Clonidine, an oral alpha-2 agonist, was previously shown to be a viable medication treatment to facilitate dexmedetomidine wean and mitigate withdrawal in a pilot study due to its longer half-life, ease of administration, and lower cost. We conducted a follow up study to evaluate the safety and efficacy of clonidine treatment to mitigate dexmedetomidine withdrawal symptoms after prolonged treatment.


Methods: This single-center, retrospective cohort study included adult patients admitted to medical, surgical, or cardiothoracic ICUs between December 1, 2016 to June 30, 2024. Eligible patients received a continuous dexmedetomidine infusion for ≥72 hours prior to weaning. Exclusion criteria included pre-admission clonidine use, chronic Alzheimer’s disease/dementia, active substance or alternate medication withdrawal, or acute neurologic injury. The primary outcome was the incidence of ≥2 withdrawal symptoms within 24 hours of dexmedetomidine discontinuation, defined as: new positive CAM-ICU score, RASS ≥+2, rebound hypertension, or rebound tachycardia. Secondary outcomes included dexmedetomidine infusion duration after wean initiation, hospital length of stay (LOS), and ICU LOS.


Results: A total of 709 patients met inclusion criteria: 196 received a clonidine taper and 513 were weaned without clonidine. Psychiatric history was more frequent in the clonidine group (4.6% vs. 1.8%, p = 0.032). Withdrawal symptoms occurred in 18% (n = 511) of clonidine patients vs. 15.3% (n = 172) of non-clonidine patients (p = 0.68). Post-wean dexmedetomidine infusion duration was significantly shorter with clonidine (29.5 ± 38.3 hours) compared to no clonidine (47.9 ± 60.5 hours; p < 0.001). Hospital LOS (45.1 ± 34.4 vs. 42.1 ± 37.6 days; p = 0.33) and ICU LOS (29.7 ± 28.1 vs. 25.3 ± 26.2 days; p = 0.05) did not differ significantly between groups.


Conclusions: In ICU patients receiving prolonged dexmedetomidine infusions, clonidine tapering shortened wean duration without increasing withdrawal symptoms. These findings support clonidine as a safe and efficient adjunct for discontinuation of prolonged dexmedetomidine therapy. Larger, prospective randomized controlled studies may be beneficial to confirm these results.