SAT-554 "The Silent Threat: Methadone-Induced Hypoglycemia Leading to Cardiac Arrest"

Abstract Disclosure: A.D. Patel: None. C.E. Guillen Lopez: None. S. Abou Khachfe: None. M.L. Ionescu: None. R.M. Patel: None. Methadone, a synthetic opioid with a prolonged half life (15-60 hours) is widely used in opioid dependence and pain management. While generally well-tolerated, it can rarely cause hypoglycemia. It enhances insulin sensitization in muscle and adipose tissue, increasing glucose uptake and inhibits gluconeogenesis via NMDA receptors. Chronic use also suppresses the sympathetic response, contributing to hypoglycemia. The risk of hypoglycemia is dose-dependent, with an average hypoglycemia rate of 6.9 % per day in doses >40 mg/day. It prolongs the QT interval, predisposing patients to arrhythmias. Severe hypoglycemia can lead to hyperkalemia and trigger a sympathetic surge, further increasing the risk of arrhythmias. Additionally it impairs the cardiovascular conduction, promoting conduction disturbances and reentrant arrhythmias. Our patient, a 53-year-old female, had a history of bipolar disorder managed with Valproate and polysubstance use disorder involving cocaine, opioids, and benzodiazepines. She presented with altered mental status, likely due to recurrent moderate to severe hypoglycemia episodes, which improved with dextrose. The patient also had acute kidney injury on CKD stage 3, which improved with intravenous fluid resuscitation. Additionally, she had chronic mild hyponatremia, hypotension, and low 8 AM cortisol (2.6 µg/dL with low albumin). A cosyntropin stimulation test indicated mild adrenal insufficiency (peak cortisol at 60 min: 16.7 µg/dL).Hypoglycemia workup was negative for a hypoglycemia medication panel, serum insulin level - 9 µU/mL with poc glucose of 37 mg/dl, and C-peptide level - 2.3 ng/mL, both considered abnormally normal. Despite the initiation of stress-dose steroids, her hypoglycemia didn’t improve, raising concern for an alternate etiology. Given her chronic methadone use (80 mg/day), medication-induced hypoglycemia was suspected. A slow taper of methadone was initiated to mitigate the risk of withdrawal, along with reduction in valproate dose. Few weeks later, she experienced persistent severe refractory hypoglycemia, eventually leading to cardiac arrest from PEA and Ventricular fibrillation (VF); and death. When presented with a case of hypoglycemia, it is crucial for physicians to consider methadone as a potential underlying cause. Understanding the dose-dependent risk of hypoglycemia associated with methadone is essential. Early de-escalation of the opioid dose can help mitigate potential harm, and in some cases, substituting with alternate treatment may be necessary. There is an urgent need for comprehensive guidelines addressing the management of hypoglycemia, particularly for rare causes such as methadone. Hypoglycemia, as a potentially life-threatening condition, should be considered more systematically in the differential diagnosis of cardiac arrest and integrated back into the list of 'H’s' for emergency care. Presentation: Saturday, July 12, 2025