A 29-year-old female with history of heroin abuse and depression presented after being found altered and confused. At the time, the patient was known to be taking an estimated 300 tablets of loperamide daily for “chronic stomach issues” (1 tablet is 2 mg for an approximate total of 600 mg). Her husband reported that within the past year, he would witness her taking at least one entire bottle of loperamide with roughly 96 tablets up to 3 times per day. There were no other medications reported, including use of any antidepressants.\nOn presentation, she was tachycardic to 156 BPM (beats per minute) and hypotensive to 70/40 mm Hg. Initial electrocardiogram (ECG) showed polymorphic VT with prolonged QTc of 669 ms ( and ). Subsequently, she developed recurrent episodes of VT that degenerated into torsades de pointes, resulting in multiple cardioversions and her admission to the cardiac intensive care unit.\nPreliminary laboratory findings were unremarkable except for the following: leukocytosis 18 bil/L, anion gap 16, and lactate 2.2 mmol/L. Chemistries showed a sodium 136 mmol/L, potassium 4.3 mmol/L, calcium 2.2 mmol/L, and magnesium 1.6 mmol/L. Urine drug screen was positive for cannabinoids, and her chest X-ray was normal. A serum loperamide level was ordered but would not result until after her discharge.\nAfter cardioversion in the emergency room, the patient was stabilized. Repeat ECG shortly after demonstrated a QTc of 515 ms. Poison control was contacted immediately and recommended supportive management. Unfortunately that evening, she began having frequent episodes of nonsustained VT triggered by positional change and vomiting (). Additional intravenous magnesium sulfate was given but symptoms persisted. A sodium bicarbonate infusion at 150 mEq/h was initiated per the recommendations of the electrophysiologist on call.\nSeveral hours later, the patient further decompensated into sustained VT. Electrical cardioversion with 120 J was required to maintain hemodynamic stability. Given her tenuous status and recurrent VT storm, she was intubated and sedated to suppress sympathetic overstimulation. Subsequently, an isoproterenol infusion was started at 2 µg/min to reduce the number of subsequent VT episodes.\nAfter 8 hours without VT, isoproterenol was reduced to 1 µg/min and the bicarbonate infusion was discontinued. Her transthoracic echocardiogram was completed and shown to be normal. Isoproterenol was stopped on day 3, and the patient was extubated. By then, she was free of VT for more than 24 hours and her QTc improved to 500 ms. No additional anti-arrhythmics were started, and the patient was downgraded and later discharged from the hospital ().\nThe final results of her serum loperamide and desmethyl loperamide (the primary metabolite of loperamide) were elevated to 26 ng/mL (normal is <10 ng/mL) and 160 ng/dL (normal is <20 ng/dL), respectively.
46-year-old male was presented in the ER after cardiac arrest. Patient had two-hour flight before he started feeling light-headed and passed out at the airport. The airport emergency services found him in ventricular fibrillation and provided him with two shocks before he regained consciousness. Subsequent EKG showed normal sinus rhythm and prolonged QT (QTc-589 msec); EKG is not available. Upon arrival to ER, patient was alert and oriented but amnesic about past events. Patient was taken for cardiac catheterization which revealed nonobstructive coronaries and normal ejection fraction. Electrolytes were unremarkable except potassium of 3.1 which was replaced. Complete blood counts, renal function, serum troponin, and serum magnesium were within normal limits. MRI of brain revealed no significant abnormalities. Shortly after coronary angiogram, patient again went to cardiac arrest and resuscitated with one shock. Cardiac monitor showed torsades de pointes ventricular tachycardia () with hemodynamic instability. Patient was intubated for airway protection and received IV magnesium and IV amiodarone. Toxicology screen was unremarkable except benzodiazepine he received during intubation (midazolam) for sedation. EKG showed normal sinus rhythm, nonspecific ST-T wave abnormality, and prolonged QT (QTc-620 msec) (). Echocardiogram revealed structurally normal heart. Acute pulmonary embolism was also ruled out with computed tomography pulmonary angiogram. Patient's spouse reported that patient has been taking large amount of Loperamide for irritable bowel syndrome for more than 5 years. However, she was not able to quantify the amount of Loperamide. Patient persistently experienced multiple episodes of sustained ventricular tachycardia requiring multiple defibrillation in setting of significantly prolonged QTc (>600 msec) on multiple serial EKGs. Patient was treated with metoprolol, lidocaine, and magnesium infusion. Over the period of 7 days, patient stopped having sustained ventricular tachycardia. Frequency of nonsustained ventricular tachycardia was also reduced and patient was extubated after several days of CCU monitoring. Lidocaine and magnesium were discontinued and metoprolol was continued. Loperamide levels were not obtained. After extubation, patient denied having similar episode in the past, chest pain, palpitations, syncope, shortness of breath, and any family history of sudden cardiac death or cardiac diseases. However, patient admitted that he has been self-medicating with over-the-counter 2 mg Loperamide approximately 50 tablets a day for diarrhea predominant irritable bowel syndrome for more than 5 years. He also admitted having approximately 100 pills of Loperamide daily for the last 2 days before admission. Since patient was buying over-the-counter Loperamide from different pharmacy; we could not determine exact frequency of purchase. Patient denied using illicit drug use, herbal supplements, or concurrent p-glycoprotein inhibitors. Serial EKG monitoring showed gradual decrease in QTc. However, serial EKG monitoring off Loperamide for several days revealed normal sinus rhythm and QTc of 472 msec () and 456 msec (). Only one EKG revealed QTc of 432 msec (). Thus, patient's QTc interval did not completely normalize after several days off all QTc prolonging medications and subsequently he received dual chamber automated cardioverter defibrillator (AICD) before discharge for secondary prevention of cardiac arrhythmia related death. Since majority of patient's QTc interval was >440 msec even after a week of stopping all QT prolonging medications, at this time, we think that patient may have subclinical long QT syndrome which was unmasked by Loperamide. However, electrophysiological studies were not performed to verify the diagnosis. Patient was instructed not to use Loperamide again.