The safety of enteral guanfacine as an adjunct sedative and treatment for iatrogenic α2 withdrawal in an ICU cohort

Document Type

Conference Proceeding

Publication Date

9-4-2025

Publication Title

Clin Toxicol

Abstract

Background: Iatrogenic dependence and subsequent withdrawal associated with opioids and sedative-hypnotics is well characterized; however, withdrawal from centrally acting α2-agonists is less well described. This syndrome can occur after cessation of dexmedetomidine and can include tachycardia, hypertension, agitation and diaphoresis. Most published reports describe the utilization of clonidine for symptom management. Guanfacine, a selective α2-agonist with greater degree of specificity for the α2 receptor and less activity at imidazoline receptors in medulla, may pose a lower risk of bradycardia and hypotension due to reduced sympatholytic effects. This study investigates the effect of guanfacine on heart rate (HR) in critically ill patients, utilized for suspected α2-agonist withdrawal or as an adjunctive sedative.Methods: This was a single-center, retrospective chart review of patients admitted from 1 January 2024 to 1 April 2025. Patients aged ≤18 years admitted to an intensive care unit (ICU) at an urban academic hospital and initiated on guanfacine during their ICU course were included. Patients receiving guanfacine as a home medication prior to arrival were excluded. Data abstracted included patient demographics, initial and peak guanfacine doses, HR on the day before and after guanfacine initiation, HR at steady state on guanfacine dose, episodes of significant bradycardia (defined as HR ≤50) following guanfacine initiation, co-administration of dexmedetomidine and guanfacine, and HR before and after dexmedetomidine initiation. The primary outcome was the difference in HR before and after guanfacine initiation. Secondary outcomes included comparison of the change in HR (δHR) exacted by guanfacine vs dexmedetomidine, the relationship of guanfacine and heart rate response, and the incidence of bradycardia-related adverse events during guanfacine therapy.Results: Fifty-eight patients met inclusion criteria. The average age was 52.97 years old (range 20-78), and 69% were male (n = 40). Thirty-three patients (19.6%) were on venovenous extracorporeal membrane oxygenation (ECMO). Forty-six patients (27.4%) received dexmedetomidine during their ICU course, with co-administration of dexmedetomidine and guanfacine for more than 24 hours in 40 patients (23.8%). The mean starting daily dose of guanfacine was 2.42 mg (range 0.5-7 mg), and the mean peak dose was 3.85 mg (range 1-10 mg). Mean HR increased from 84.4 bpm on the day prior to guanfacine initiation to 88.8 bpm on the day after initiation (P < 0.001) and further increased to 93.7 bpm at steady state (P < 0.001). In contrast, dexmedetomidine initiation was associated with a significant reduction in HR, from 94.8 bpm on the day prior to 80.8 bpm on the day following dexmedetomidine initiation (P < 0.001). Three patients (5.2%) experienced episodes of significant bradycardia following guanfacine initiation. Two of these episodes were self-limited;one resulted in guanfacine discontinuation (n = 1, 1.7%). Linear regression analysis revealed no statistically significant relationship between either starting or peak guanfacine dose with HR (R2=0.034, P = 0.168).Conclusions: In this retrospective cohort of ICU patients, guanfacine demonstrated a favorable safety profile with respect to HR at doses up to 10 mg. Significant bradydysrhythmias were infrequent (n = 3, 5.2%) and guanfacine was associated with a lower propensity to reduce HR compared to dexmedetomidine. Further investigation is warranted to determine efficacy in preventing and/or treating iatrogenic α2-withdrawal.

Volume

63

First Page

78

Last Page

79

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