Anticholinergic Adverse Effects Associated With Skeletal Muscle Relaxants in the Intensive Care Unit

Background: Pain is prevalent among critically ill patients and is frequently underrecognized due to sedation and mechanical ventilation. Opioids remain the primary analgesic therapy in the intensive care unit (ICU); however, opioid-related adverse effects have prompted increased adoption of multimodal analgesia strategies. Centrally acting skeletal muscle relaxants, including cyclobenzaprine and methocarbamol, are commonly used as adjuncts, yet data evaluating their anticholinergic adverse effects in critically ill populations are limited. Methods: The primary objective of this study is to determine the prevalence of anticholinergic adverse drug events (ADEs) associated with cyclobenzaprine and methocarbamol among ICU patients. Purpose: This retrospective cohort study evaluated adult patients (≥18 years) admitted to any ICU at a single academic medical center between January 1, 2023 and January 31, 2025, who received at least 1 dose of cyclobenzaprine or methocarbamol during ICU admission. The primary outcome was the prevalence of anticholinergic ADEs, identified through provider documentation and International Classification of Diseases, Tenth Revision (ICD-10) codes. Secondary outcomes included types of ADEs, dosing of the study drugs, and medication discontinuation rates. Results: Of 367 eligible patients, 260 were included in the final analysis. Cyclobenzaprine was administered to 112 patients (43%) and methocarbamol to 148 patients (57%). Potential anticholinergic ADEs were identified in 29 patients (14.4%) receiving cyclobenzaprine and 17 patients (10.8%) receiving methocarbamol. Among the 69 total ADEs, 55 (79%) prompted an intervention, most commonly pharmacologic therapy adjustments. Medication discontinuation due to ADEs was infrequent. Conclusions: Cyclobenzaprine and methocarbamol were associated with anticholinergic adverse effects in critically ill ICU patients, though this did not translate to medication discontinuation. These findings support the cautious use of centrally acting muscle relaxants as part of multimodal analgesia strategies. Pharmacists are uniquely positioned to evaluate and mitigate adverse drug effects in the critically ill.