Serotonin Syndrome Associated With High-dose Diphenhydramine Use Complicating Abdominoplasty and Mastopexy

Serotonin syndrome is a condition associated with increased serotonergic transmission in the central nervous system. Although shortfalls with diagnostic criteria have led to misleading associations with multiple medications, a possible precipitant is diphenhydramine. Documentation of such an association would prove important for physician practice, as diphenhydramine remains one of the most popular antihistamines available. We present a case of a 43-year-old woman who developed serotonin syndrome after bilateral mastopexy, miniabdominoplasty, and liposuction. The patient was on multiple serotonergic medications, including duloxetine, asenapine, and trazodone, in addition to high-dose diphenhydramine. Postoperatively, she developed tachycardia, leukocytosis, respiratory distress, and elevated lactate, initially leading to concerns of sepsis; however, further evaluation revealed the likely diagnosis of serotonin syndrome, triggered by the combination of serotonergic agents and intraoperative fentanyl. Management included an intensive care unit admission with discontinuation of serotonergic medications, administration of benzodiazepines, intravenous fluids, and norepinephrine for shock. The patient's condition improved for 36 hours, and she was discharged with adjustments to her psychiatric medications. This case contributes to the growing body of literature highlighting the risks of serotonin syndrome in patients on serotonergic polytherapy, particularly in the postoperative period. The interaction between our patient's chronic diphenhydramine abuse and multiple other serotonergic medications likely precipitated this condition. Preoperative medication reconciliation, early recognition of triggers and signs, and prompt intervention are key to preventing adverse outcomes in serotonin syndrome.