An ICD for Harm Reduction: Methadone-Associated Torsades de Pointes in a Patient With Opioid Use Disorder

Michelle Williamson, MD, Albert Einstein College of Medicine and Montefiore Medical Center

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A 45-year-old male with opioid use disorder (OUD) on methadone 160 mg daily, active intravenous fentanyl and cocaine use, active synthetic cannabis use, and untreated hypothyroidism presented to the emergency department in opioid withdrawal. Shortly after arrival, he received multiple QT-prolonging medications, including methadone and droperidol (for agitation). He was also found to have hypokalemia. He subsequently developed torsades de pointes (TdP) with cardiac arrest requiring defibrillation and resuscitation. TdP was attributed to multiple factors including droperidol and methadone administration, hypokalemia, chronic synthetic cannabis use, untreated hypothyroidism, and opioid withdrawal. After return of spontaneous circulation, he was intubated and admitted to the cardiac intensive care unit, where he remained for several days before successful extubation.

Following extubation, addiction psychiatry was consulted for agitation and withdrawal management in the setting of persistently prolonged QTc. Given recent TdP arrest and ongoing QTc concerns, methadone was withheld. Oxycodone was initiated for withdrawal management but proved insufficient to control symptoms at first. Given the level of withdrawal and agitation, a continuous intravenous fentanyl infusion was started in the alert, non-intubated patient, which effectively controlled agitation and withdrawal symptoms. He was eventually transitioned off the fentanyl infusion and cross titrated onto oral oxycodone, now effectively managing his withdrawal. Additionally, the patient was administered Valproate and Clonazepam for agitation and mood regulation throughout admission.

Given the cardiac risks associated with methadone, buprenorphine was recommended as an alternative; however, the patient declined, citing a history of inadequate craving control on prior buprenorphine trials, which had previously led to diversion of his buprenorphine and continued fentanyl use. The patient also stated he intended to obtain methadone independently if not prescribed, necessitating a supervised, harm-reduction approach.

Over several days, QTc normalized and a cautious methadone retitration was started at 40 mg daily with 20 mg increments every 24 hours. At methadone 100 mg, QTc prolongation (>500 ms) recurred, prompting dose reduction back to 40 mg. The QTc remained prolonged for approximately 6 days before normalizing. During this period, supplemental oxycodone was used to meet the patient's remaining opioid requirement, with the daily combined regimen approximating a morphine milligram equivalent of 564.

Given the patient's demonstrated susceptibility to methadone-associated TdP with cardiac arrest, clinical necessity for ongoing methadone therapy for OUD, stated intention to obtain methadone independently if not prescribed, risk of future exposure to additional QT-prolonging medications and substances in the future, and risk of future undertreated hypothyroidism as an additional risk factor for QTc prolongation, a multidisciplinary decision was made, involving the addiction psychiatry team, cardiac electrophysiology team, and the primary medical team to pursue subcutaneous ICD (Implantable Cardioverter-Defibrillator) implantation for secondary prevention of sudden cardiac death. The decision to use a subcutaneous rather than a transvenous device was deliberate given the patient's history of active intravenous drug use and the risk of returning to injection drug use after discharge. A transvenous lead would carry a substantially elevated risk of endovascular infection and endocarditis. This decision was framed as a harm reduction intervention.

A subcutaneous ICD was implanted without complication. Following ICD implantation, methadone was retitrated to 100 mg daily with close QTc monitoring, and supplemental oxycodone was gradually weaned. The patient was offered further dose escalation given his extensive history of high potency opioid use and prior requirement for higher methadone doses; however, he declined to increase above methadone 100 mg. He was counseled to discuss further dose titration with his outpatient treatment program if methadone 100 mg proved insufficient for craving control.

The patient was discharged to a single-room occupancy (SRO) housing placement with on site medication dispensing capability. He was scheduled to present to his outpatient methadone program for continuation of methadone 100 mg daily. He was also scheduled for outpatient cardiology follow up. Extensive counseling was provided regarding the risk of opioid overdose given his prolonged hospitalization and resultant decreased opioid tolerance.

Learning Objectives: 

• After a torsades arrest with multiple contributing factors, how do you decide whether methadone can ever be safely resumed?
• When a patient with prolonged QT declines buprenorphine, how do you weigh autonomy and the importance of treatment retention against the known risk of sudden cardiac death?
• When does continued methadone therapy after a torsades event justify ICD implantation for secondary prevention, and what factors (i.e. available hospital resources, specific patient characteristics) should drive that decision?