Evaluation of Dexmedetomidine Withdrawal and Management After Prolonged Infusion

Clin Ther. 2024 Oct 7:S0149-2918(24)00268-6. doi: 10.1016/j.clinthera.2024.09.006. Online ahead of print.

Abstract

Purpose: Dexmedetomidine is often used for longer than its labeled indication of 24 hours, raising concerns for potential withdrawal. Data are limited regarding this syndrome in adult patients. This study aimed to further characterize dexmedetomidine withdrawal in critically ill adult patients after prolonged use.

Methods: This was an institutional review board-approved, single-center, retrospective chart review conducted at a tertiary academic medical center. Adult intensive care unit (ICU) patients on dexmedetomidine for ≥72 hours in 2019 were screened for inclusion. Exclusion criteria were interruption of dexmedetomidine for >6 hours, indications for dexmedetomidine other than sedation, or patients with neurological or burn injury. The major end point was the incidence of dexmedetomidine withdrawal, defined as meeting ≥2 of the following criteria within 24 hours of discontinuation: newly positive Confusion Assessment Method for ICU, Richmond Agitation Sedation Scale score of ≥+2, hypertension, and tachycardia. Minor end points were incidence of individual withdrawal signs as previously described, additional sedatives or antipsychotics required, dose and duration of dexmedetomidine infusion, length of ventilation, ICU and hospital length of stay, and new onset of the following: fever, vomiting, loose stools/diarrhea, diaphoresis, or seizure.

Findings: Of the 152 patients included, dexmedetomidine withdrawal occurred in 54 patients (35.5%). Rebound hypertension was the most common withdrawal sign (47 patients [87.0%]). In the withdrawal group, significantly more patients required additional β-blockers (29 [53.7%] vs 10 [10.2%]; P < 0.01), were reinitiated on dexmedetomidine (16 [29.6%] vs 10 [10.2%]; P < 0.01), and required a start or increased dose of clonidine (6 [11.1%] vs 3 [3.1%]; P = 0.04). There was no significant difference in the cumulative dose or duration of dexmedetomidine between the groups. Length of ventilation was longer in the withdrawal group (171 hours [83.7-280.8 hours] vs 159 hours [149.0-335.7 hours]; P < 0.01), but there was no difference in ICU or hospital length of stay.

Implications: Prolonged use of dexmedetomidine was associated with withdrawal syndrome in 35.5% of patients in our study. Larger trials are needed to confirm the risk factors for dexmedetomidine withdrawal and identify measures to prevent withdrawal.

Keywords: Critical care; Dexmedetomidine; Mechanical ventilation; Pharmacokinetics; Sedation; Withdrawal.