Unraveling the Delirious Knot: Cyclobenzaprine Versus Methocarbamol in Cardiac Surgery Patients

Introduction: Delirium is common after cardiac surgery and associated with increased costs, morbidity and mortality. Multimodal analgesia is preferred for effective pain control and reduced opioid requirements, with muscle relaxants like cyclobenzaprine and methocarbamol often utilized as a part of this strategy. Cyclobenzaprine alters neurotransmitter levels, theoretically increasing the delirium risk, while methocarbamol acts without this direct effect posing a lower risk. The purpose of this study was to compare the incidence of delirium in patients receiving cyclobenzaprine versus methocarbamol in post-operative cardiology patients.


Methods: This IRB approved, retrospective, cohort study included adult post-cardiac surgery patients admitted to the cardiovascular intensive care unit (ICU) between January 1, 2020, and August 31, 2024. Patients were separated into two cohorts based on post-operative receipt of methocarbamol or cyclobenzaprine and were followed for up to14 days post-surgery or ICU discharge, whichever occurred first. The primary outcome was the incidence of post-operative delirium, determined via Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Secondary outcomes included ICU length of stay, anti-psychotic, opioid or sedative medication administration, and incidence of new-onset atrial fibrillation. Data was analyzed via Chi-square, Mann-Whitney U, or multivariable logistic regression, as appropriate.


Results: A total of 272 patients were included (136 per cohort). Baseline characteristics were comparable across cohorts. Delirium incidence was similar (11.8% vs. 13.2%, p = 0.714), though median duration was shorter with cyclobenzaprine (1 ± 0.5 vs. 2 ± 1.0 days, p = 0.018). Both groups received study drugs for a median of 3 days (±2.3 vs. ±2.5, p=0.73). No significant difference was observed in any secondary outcomes except patients receiving cyclobenzaprine required cumulative lower doses of dexmedetomidine (p = 0.002) and propofol (p = 0.009).


Conclusions: There was no difference in the rate of delirium in post-cardiac surgery patients receiving methocarbamol or cyclobenzaprine. Patients receiving methocarbamol had a longer delirium duration and higher sedative needs. Both drugs remain viable options, but further prospective research is needed due to study limitations.