# Prevalence of Serotonergic Drug Use in Patients Exposed to Perioperative Methylene Blue: A Cross-Sectional Study

## TL;DR

This study finds that over 10% of patients receiving methylene blue during surgery are also on serotonergic drugs, highlighting a risk for serotonin syndrome.

## Contribution

The study quantifies the real-world prevalence of serotonergic drug use in patients exposed to methylene blue.

## Key findings

- 10.14% of patients receiving methylene blue were also on serotonergic medications.
- SSRIs had the highest concomitant use at 63.04 per 1000 cases.
- MAO inhibitors had the lowest concomitant use at 0.26 per 1000 cases.

## Abstract

Background: Methylene blue is a widely used medication in various medical procedures, particularly in cardiovascular operations where it serves as a diagnostic dye and a treatment for conditions like methemoglobinemia and vasoplegic syndrome. While its clinical applications are well-documented, methylene blue's pharmacological properties as a monoamine oxidase (MAO) inhibitor present a potential risk of serotonin syndrome when administered to patients taking serotonergic medications. This study examines the prevalence of serotonergic medications, including lithium, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs), in patients who were administered methylene blue.

Methods: This cross-sectional study used de-identified electronic health records (EHRs) from the TriNetX database, which pools data from 97 healthcare organizations. The analysis focused on isolating patients who were administered methylene blue perioperatively and calculating the prevalence of concomitant serotonergic drug use by drug class.

Results: The large database analysis revealed that among the 249,131 patients who received perioperative methylene blue, 25,282 (10.14%) were concomitantly given serotonergic drugs. By drug class, SSRIs had the highest concomitant use with 15,705 cases and a prevalence of 63.04/1000 cases. Next were SNRIs, with 6,341 cases and a prevalence of 25.45/1000 cases; TCAs, with 2,979 cases and a prevalence of 11.96/1000 cases; lithium, with 292 cases and a prevalence of 1.17/1000 cases; and MAO inhibitors, which had the lowest concomitant use at 65 cases and a prevalence of 0.26/1000 cases.

Conclusion: The prevalence of serotonergic agent use in patients administered methylene blue is relatively high exceeding 10%, with the highest prevalence observed in those on SSRIs, followed by SNRIs and TCAs. This underscores the importance of a thorough preoperative evaluation by an anesthesiologist to minimize the risk of intraoperative complications such as serotonin syndrome.