S4601 From Sleep Aid to Sedation Saboteur: Melatonin’s Hidden Clinical Curveball

Introduction: Melatonin is increasingly used to manage sleep disturbances. Several studies explored its perioperative use for anxiolysis and its effects on intraoperative sedative requirements. Despite its benign side effect profile, the interaction between chronic melatonin usage and procedural sedation remains up for debate. We observed multiple cases where patients requiring higher-than-expected doses of sedatives were associated with a history of chronic melatonin use. Case Description/Methods: A 45-year-old woman with irritable bowel syndrome presented for elective esophagogastroduodenoscopy-colonoscopy due to persistent dyspepsia despite prior proton pump inhibitor therapy and unrevealing imaging. She had been taking 2.5 mg of melatonin nightly for 4 years. Her alcohol intake was minimal drinking 1 alcohol beverage per week. During the procedure, she received 150 mcg of intravenous (IV) fentanyl, 7 mg of IV midazolam, and 50 mg of IV diphenhydramine. Despite these high doses, she was awake and fully conversive throughout both procedures. This case mirrors multiple similar instances observed among various providers in the past 10 years. These patients required similarly elevated sedative doses in which all involved long-term melatonin use. In most cases, melatonin use was not captured during routine pre-procedure medication reconciliation. Discussion: This pattern raises concern that chronic melatonin usage even as low as 2.5 mg may blunt the efficacy of standard moderate sedation regimens. At our institution, typical sedation does not exceed 5 mg of midazolam and 100 mcg of fentanyl which is reflective of the American Gastroenterological Association review of sedation guidelines for endoscopic procedures. However, patients in this melatonin subgroup routinely required midazolam doses of 10 mg IV and fentanyl up to 200 mcg IV. One randomized intensive care unit trial showed acute melatonin use reduced sedation requirements which highlights how the effect of melatonin may vary by chronicity. While prior studies suggest melatonin may reduce sedative needs, our findings suggest chronic use may contribute to sedation resistance through possible overlapping medication tolerance. Given melatonin’s increasing use and potential to influence sedation efficacy, we recommend specific screening for its use during pre-procedure evaluation in addition to recommending alternative sedatives such as propofol when establishing moderate sedation. These preliminary observations warrant further prospective research to clarify melatonin’s role in procedural sedation.