Introduction: Dexmedetomidine use greater than 72 hours has been associated with withdrawal upon discontinuation including tachycardia, agitation, delirium, and hypertension, with an incidence as high as 64%. Gradual weaning may help decrease withdrawal symptoms but lengthens ICU stay and increases overall healthcare resources. Two enteral alpha-2 agonists: clonidine and guanfacine have been used to facilitate weaning and reduce withdrawal symptoms. Clonidine’s side effects of hypotension and bradycardia can limit its use in the ICU. Guanfacine’s higher selectivity for alpha-2a receptors potentially minimizes cardiovascular side effects, making its use more favorable. Moreover, we found no studies comparing the 2 agents against dexmedetomidine and aimed to compare all 3 agents regarding withdrawal mitigation and safety. Methods: This is a single-center retrospective chart review of adult patients receiving continuous dexmedetomidine drips for 72 hours or greater between January 1, 2021, and January 1, 2023. The primary outcome was the incidence of 2 or more withdrawal symptoms between the three groups (clonidine, guanfacine and dexmedetomidine alone) with dexmedetomidine weaning. Withdrawal symptoms were defined using the Withdrawal Assessment Tool-1 criteria: new incidence of agitation (RASS≥1), positive confusion assessment method assessment, incidence of tachycardia (HR > 90 beats/min), hypertension (SBP >140 mm Hg; DBP >90 mm Hg), loose stools, or a fever (>37.8° C). Results: Eighty-three patients met criteria for analysis with 33 receiving dexmedetomidine alone, 33 receiving clonidine and 17 guanfacine. There was no statistically significant difference in withdrawal symptoms for the clonidine and guanfacine groups compared to monotherapy (54.5% vs 41.2% vs 63.2%; p=0.315), but a trend toward reduction in withdrawal with guanfacine. There was a lower incidence of re-initiating dexmedetomidine within 72 hours (11.8% vs 21.2%) and bradycardia (26.4% vs 22.2%) with guanfacine compared to clonidine, however, this did not reach statistical significance. Conclusions: This study demonstrates similar incidence of dexmedetomidine withdrawal with enteral clonidine, guanfacine, or dexmedetomidine monotherapy. A larger study would be needed to further assess the differences in cardiovascular side effects.
Carrington et al. (Sun,) studied this question.