The Association Between Dexmedetomidine and Bradycardia: An Analysis of FDA Adverse Event Reporting System (FAERS) Data and Transcriptomic Profiles

Abstract

Background/objectives: Bradycardia, an uncharacteristically low heart rate below 60 bpm, is a commonly reported adverse drug event (ADE) in individuals administered dexmedetomidine for sedation. Dexmedetomidine is frequently used as a sedative and analgesic for both intubated and non-intubated patients due to its low risk of respiratory depression. The purpose of this study was to further characterize the safety profile of dexmedetomidine using safety reports collected from the FDA Adverse Event Reporting System (FAERS) and transcriptomic data.

Methods: Association rule mining was used to both identify additional ADEs that presented concurrently with bradycardia in patients sedated with dexmedetomidine, as well as to characterize potential drug-drug interactions (DDIs). Furthermore, public transcriptomic data were analyzed to identify differentially expressed genes that may elucidate the genetic drivers of elevated bradycardia risk in those administered dexmedetomidine.

Results: Bradycardia was the most frequently reported ADE for individuals administered dexmedetomidine. Other cardiovascular-related ADEs commonly associated with bradycardia included syncope (lift = 4.711), loss of consciousness (lift = 3.997), cardiac arrest (lift = 2.850), and hypotension (lift = 2.770). Several possible DDIs were identified, including Lactated Ringer's solution (lift = 5.441), bupivacaine (lift = 2.984), and risperidone (lift = 2.434), which may elevate bradycardia risk. Finally, eight genes related to cardiac muscle contraction were identified as possible regulators of dexmedetomidine-induced bradycardia, including COX5B, COX6A2, COX8B, MYH7, MYH6, MYL2, UQCRQ, and UQCR11 in mouse cardiac cells.

Conclusions: Key clinical takeaways include the co-presentation of multiple cardiovascular ADEs, including cardiac arrest, hypotension, and syncope, alongside dexmedetomidine-associated bradycardia. Furthermore, several possible DDIs with dexmedetomidine were also identified.

Keywords: DDI; FAERS; RNA-seq; association rules; bradycardia; dexmedetomidine; drug interactions; pharmacovigilance.

Figure 1

Volcano plot for differentially expressed genes between dexmedetomidine treatment and control at p ≤ 0.05.

Figure 2

Enriched pathways for downregulated genes at FDR ≤ 0.05.