Case Presentation: A 57-year-old male with past medical history of alcohol-induced chronic pancreatitis complicated by chronic pain, opioid use disorder (OUD) on methadone, and depression on sertraline presented to the emergency department with dizziness, dyspnea, and nausea. About six months prior to admission, he had been transitioned from buprenorphine to methadone for better pain control. An EKG obtained at his outpatient methadone clinic prior to starting methadone was notable for a QTc of 447 ms. He was subsequently titrated to a dose of 150 mg of methadone without obtaining a repeat EKG during this time period. Shortly prior to presentation, he complained of nausea and was prescribed ondansetron as needed. On arrival to the emergency department he was found to be mildly hypokalemic (K 3.2 mmol/L) with a prolonged QTc (669 ms). He experienced multiple runs of non-sustained ventricular tachycardia. He subsequently developed Torsades de Pointes leading to cardiac arrest for which ACLS was initiated with return of spontaneous circulation. Transthoracic echocardiogram did not demonstrate wall-motion abnormalities and ischemic evaluation was deferred. It was ultimately thought that the severely prolonged QTc was the result of electrolyte abnormalities and multiple QTc prolonging medications including methadone, ondansetron, and sertraline. As he had not experienced sufficient pain control previously with buprenorphine, he declined it as a substitute for methadone for treating his OUD and chronic pain. Shared decision making was undertaken with the patient seeking to balance his risk of QTc prolongation and arrhythmia with his risk of relapsed substance use in setting of inadequately treated chronic pain and substance use disorder. He was weaned to a lower dose of methadone, transitioned to a non-QTc prolonging anti-depressant, and recommended to avoid any additional QTc prolonging medications in the future. On day of discharge, his QTc normalized to 445 ms.
Discussion: Drug-induced Torsades de Pointes is a rare phenomenon with an incidence of approximately 3.2 per million person years (1). However, the opioid epidemic has led to increased need for medication assisted treatment including methadone. Compared to other QTc prolonging medications, methadone is more often implicated in cases of Torsades (2). QTc prolongation on methadone is commonly seen at higher doses, particularly those exceeding 120 mg/day (3). This case demonstrates the rare but potentially severe cardiovascular complications of methadone for patients on high doses often required for substance use disorder, as well as highlighting the importance of QTc monitoring in this population. It also emphasizes the need for attentiveness when prescribing and administering common QTc prolonging medications. This patient’s methadone was increased to high doses without serial EKGs, and this in addition to concurrent sertraline use, recent increased frequency of ondansetron administration, and electrolyte derangements likely created the perfect combination for severe QTc prolongation.
Conclusions: Providers caring for patients on methadone should be aware of its QTc prolonging effects. Attention when prescribing additional QTc prolonging medications and a framework for EKG monitoring when titrating doses of methadone can help protect patients from a potentially life-threatening arrhythmia.