B48-20 Fentanyl-Induced Serotonin Syndrome Mediated by Methadone Use

Abstract Introduction Serotonin Syndrome is a potentially fatal condition caused by increased synaptic cleft concentrations of serotonin due to interactions between serotonergic drugs. Symptoms include hyperthermia, hyperreflexia, and clonus, which can progress to rhabdomyolysis and multiorgan failure. We describe a case of fentanyl overdose in a patient taking methadone for opiate use disorder (OUD) likely leading to the development of severe serotonin syndrome with multiorgan failure. Case Presentation A 29-year-old man with OUD on methadone was admitted to the ICU after being found down in his car with a temperature of 108 F, heart rate of 140, and blood pressure of 60/30. Exam was notable for minimally reactive pupils, hypertonia with myoclonic jerking, and withdrawing extremities to noxious stimuli only. Initial workup revealed rhabdomyolysis complicated by acute renal failure requiring urgent renal replacement therapy initiation and acute liver failure necessitating emergent transplant evaluation. His clinical presentation was consistent with serotonin syndrome; however, the initial point of care urine drug testing did not reveal any serotonergic agents. Fortunately, with aggressive supportive care he had rapid clinical improvement, and was extubated and transferred out of the ICU one week after initial presentation. Extended serum drug screening (obtained at initial presentation, prior to any fentanyl administration during the hospitalization) showed high levels of fentanyl and its metabolites (fentanyl 24 ng/mL, norfentanyl 46 ng/mL), which based on drug pharmacokinetics and his last known normal suggests an initial fentanyl concentration of 94 ng/mL. Interpretation of this value is complicated by lack of routine serum fentanyl concentration monitoring. However, based on a recent study showing an average level of 8.7 ng/mL in everyday fentanyl users presenting with overdose, our patient’s level was likely high enough to be fatal in most users. Ultimately, it was determined the combination of his methadone and fentanyl use causing serotonin syndrome was the most likely etiology of his presentation. Discussion While fentanyl has known serotonergic properties and has been implicated in serotonin syndrome in ICU patients on fentanyl drips, reports of serotonin syndrome from fentanyl overdose as an outpatient are rare. For many patients the amount of fentanyl needed to induce serotonin syndrome causes significant respiratory depression such that respiratory failure precedes the development of serotonin syndrome. This case highlights that for patients with OUD on methadone, the combination of high opiate tolerance and the presence of a baseline serotonergic medication, puts them at risk for serotonin syndrome from a fentanyl overdose. This abstract is funded by: None