Howard A. Greller

Prolonged severe hypotension following combined amlodipine and valsartan ingestion

Introduction. Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipines prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan. Case Report. A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a “handful” of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance. Conclusion. Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects.

Thyroid Storm After Pediatric Levothyroxine Ingestion

A 2-year-old girl was found with an empty bottle of levothyroxine and blue coloring around her mouth. Forty tablets of 150-μg levothyroxine tablets were missing. Her 6-hour postingestion total thyroxine (T4) level was 68.1 μg/dL (normal range: 5–12 μg/dL), and her total triiodothyronine (T3) level was 472 ng/dL (normal range: 40–130 ng/dL). Serum levels of thyrotropin, T3, and T4 were then checked on days 3, 5, 7, and 10. On postingestion day 5, the child presented for follow-up with hyperthermia, vomiting, irritability, and increased lethargy. She was referred to the emergency department, where a heart rate of 220 beats per minute, a blood pressure of 130/80 mm Hg, and a temperature of 101°F were recorded. She also had multiple episodes of diarrhea. The patient was treated with oral propranolol (0.8 mg/kg) every 6 hours, intravenous normal saline, and ibuprofen; all her vital signs improved. Serial T3, T4, and thyrotropin serum levels were measured. Her total T3 levels were >800, 798, 445, 446, and 98 ng/dL on days 3, 5, 6, 9, and 13, respectively. Total T4 measurement was repeated on day 13, and the concentration was found to be 11.9 μg/dL. Her thyrotropin levels remained undetectable throughout the course of treatment. The patient was discharged from the hospital after a 4-day PICU stay, in good condition, on oral propranolol 0.8 mg/kg every 8 hours. Propranolol administration was discontinued 8 days after initiation with no further tachycardia, hypertension, or hyperthermia. The child tolerated the recommended regimen.

NAC: still the way to go

We would like to thank Yang and colleagues for their attempt to determine the possibility of delayed hepatic recovery with N-acetylcysteine (NAC) administration in acetaminophen-induced hepatotoxicity [1]. We are concerned, however, about the possible consequences that may arise from their conclusions. Owing to the wide availability of acetaminophen, intentional and unintentional overdoses are one of the leading causes of liver failure in the world [2]. NAC is currently a highly effective and safe antidote to treat acute acetaminophen overdose, and is most efficacious when administered within 8 hours of ingestion [3]. Furthermore, one landmark study showed that even in patients who presented with delayed acetaminophen-induced fulminant hepatic failure, intravenous NAC administration improved survival versus control individuals (48% vs. 20%) [4]. Another study found that the infusion of acetylcysteine in patients with acetaminophen-induced liver failure resulted in an increase in mean oxygen delivery and in an increased mean arterial pressure [5]. It is difficult to believe that the mouse model of Yang and colleagues has any correlation to humans, since the already established human data are so overwhelmingly positive. The amount of acetaminophen administered in their study caused hepatotoxicity but did not induce death, and therefore is not applicable to real-life situations where people may ingest potentially fatal doses of acetaminophen. It is not clear to us why the authors came to explore this study topic. The conclusions drawn from their article are potentially dangerous and should be viewed with caution and scepticism.

Profound Shock after Initiation of Clozapine Therapy

Clozapine, a tricyclic dibenzodiazepine, is an atypical antipsychotic with dopaminergic, muscarinic, histaminic and serotonergic activity that has been used in the treatment of schizophrenia [1]. Although prescribers commonly recognize the hematologic adverse effect agranulocytosis its cardiac side effects, such as myocarditits, are less often considered [2]. A retrospective analysis of an Australian reporting system of patients with recent initiation of clozapine found an incidence of myocarditis about 1 in 500 young adults [3]. Studies since this publication have demonstrated incidences ranging from 0.015% to 8.5%. This compares to an estimated incidence of clozapine-induced agranulocytosis of between 3.8% and 8% [4]. A case definition for clozapine-related myocarditis used by Ronaldson et al described the syndrome as “any new symptoms of myocarditis within 45 days of commencing clozapine with histologic or clinical signs of cardiac dysfunction with either laboratory or radiographic evidence of myocardial pathology or congestive heart failure in the absence of alternative plausible schizophrenia” [5].