Faculty Bibliography

Objective: Clozapine-induced myocarditis has a high mortality rate secondary to cardiogenic shock. The Impella is a percutaneously inserted, microaxial flow, short-term ventricular support device. We describe a case of a patient with clozapine-induced fulminant myocarditis successfully bridged to recovery with placement of an Impella. Case report: A 26-year-old man with a history of schizoaffective disorder, epilepsy, and polysubstance use developed fever associated with malaise, nausea, and myalgias while admitted to inpatient psychiatry. His medications included: clozapine, valproic acid, lacosamide, lithium, trazodone, benztropine, and risperidone. Clozapine was started 18 days prior to onset of symptoms. Fever to 39.4 degreeC persisted for 2 days. On evaluation, his vital signs were: blood pressure 102/62 mmHg, heart rate 120/minute, respiratory rate 20/minute, oxygen saturations 90% (room air) and temperature 38.3 degreeC. On examination, he had tachycardia with no murmur, bibasilar rales, and jugulovenous distension. Laboratory testing was notable for a troponin of 45.6 ng/mL, brain natriuretic peptide (BNP) 696.8 pg/mL, lactate 5.6mmol/L, white blood cell count 11.0 x 10³ with 2.2% eosinophils, erythrocyte sedimentation rate (ESR) 6 mm/h, and C-reactive protein 194.3 mg/L. His electrocardiogram showed sinus tachycardia with a right bundle branch block (RBBB), ST depressions in V1 and V2, ST elevations in III, aVF, and aVR. Echocardiogram revealed left ventricle ejection fraction (LVEF) 35% with infero-lateral wall motion abnormalities. Clozapine was discontinued. The patient was transferred to the Cardiac Care Unit, where he became more tachypneic and was intubated. Cardiac catheterization found evidence of right heart failure with no coronary artery disease. An Impella CP device was placed via the right femoral artery for circulatory support. He was treated with vasopressors, inotropes, high-dose steroids and antibiotics. He developed worsening cardiogenic shock with an LVEF 10%. A left ventricular assist device (LVAD) and extracorporeal membrane oxygenation (ECMO) therapy were discussed, but he was not a candidate. Despite minimal pulsatile flow, the patient was supported by the Impella with flow up to 3.3 L/min. After 5 days, cardiac output improved, and the Impella was removed seven days after placement. He was extubated after 9 days. Prior to discharge, echocardiogram was repeated, and LVEF improved to 50%. Laboratory analysis for all rheumatologic and infectious studies were negative, and the onset of disease within 3 weeks of starting clozapine made clozapine- induced myocarditis the most likely diagnosis.
Conclusion(s): Circulatory support devices, such as the Impella should be considered a therapeutic option for management of cardiogenic shock in patients with clozapine-induced myocarditis

Objective: Clozapine is a second-generation antipsychotic medication used to treat refractory schizophrenia. There are limited reports of confirmed clozapine ingestions in young children. We report a case of two siblings who ingested clozapine due to a pharmacy dispensing error; both recovered with supportive care. Case report: A 5-year-old girl and her 19-month-old sister, both previously healthy, presented to the emergency department (ED) around 10 pm with lethargy and confusion soon after they both took their first evening dose of what was believed to be 200mg cimetidine, newly prescribed to treat molluscum contagiosum. In the ED, they were both tachycardic, but otherwise had ageappropriate vital signs. On physical examination, both children were noted to be lethargic and drooling with roving eye movements. The older sibling was also confused and agitated at times with abnormal arm movements. Both children were observed for four hours and discharged home. The 19-month-old remained somnolent, but returned to baseline the following afternoon. The 5-year-old was persistently lethargic and confused the following day, with some improvement 36 hours post-ingestion. Their mother was in close contact with their pediatrician during this time. Given the persistence of symptoms inconsistent with cimetidine, the mother examined the tablets in the prescribed bottle and through a pill identifier, identified the tablets as 200 mg clozapine. Both children were seen in the pediatrician's office on day two and day three post-ingestion with normal electrocardiograms and normal complete blood counts on day three. About 85 hours post-ingestion the older sibling's serum clozapine concentration was reported as 17 mug/L and norclozapine concentration as 55 mug/L (25-400 mug/L). The older sibling returned to her baseline 4 days post-ingestion. When the dispensing error was reported to the pharmacy, it was discovered that the bottles of cimetidine and clozapine had been placed next to one another on the shelf in the pharmacy. Further investigation into the error was undertaken and as a preliminary safety measure, clozapine was moved to a more secure location in the pharmacy. Three months post-exposure, both children were healthy with no sequelae noted on follow-up.
Conclusion(s): We describe two children who ingested clozapine and developed drooling and altered mental status. It took several days for the children to return to their baseline mental status, but complete recovery occurred with supportive care. Efforts should be taken to reduce pharmacy dispensing errors that can lead to serious toxicity in children

Because salicylism is a clinical diagnosis, the serum concentration should be interpreted in conjunction with the clinical presentation. A 26-year-old man presented to the Emergency Department with abdominal painand had extremely elevated serum triglycerides (>7000 mg/dL). Ethanol, acetaminophen, and salicylate concentrations were checked because of concern of self-injurious behavior, which returned at 13.1 mg/dL, undetectable, and >100 mg/dL, respectively. His basic metabolic panel revealed a bicarbonate of 23 mEq/L and an anion gap of 11. An arterial blood gas showed a pH 7.39 and a PCO2 of 36.6 mmHg. On physical examination, he was awake and alert, and had a respiratory rate of 12–14/min. The possible effect of hyperlipidemia to falsely elevate the salicylate concentration was recognized. He was treated for severe hypertriglyceridemia and as his triglyceride level dropped, his repeat salicylate concentration was <1 mg/dL. Since dfferent sized lipoproteins contribute variably to serum sample turbiditythey have the potential to interfere with the absorption of light thereby producing erroneous laboratory results . Clinicians need to be aware of the implications of severe hyperlipidemia and interference to prevent clinical errors based on false positive laboratory results

Background: Aluminum phosphide (AlP) is a highly toxic fumigant that is restricted in the USA. When exposed to humidity or water, AlP generates phosphine gas, a mitochondrial toxin that can produce cardiovascular collapse, respiratory failure, metabolic acidosis, and death. Hypothesis: The use of extracorporeal life support (ECLS) in patients with severe AlP toxicity increases chances of survival. Methods: Single-patient chart review. Case: A 3-year-old girl with no significant past medical history presented to the emergency department with 10 h of cough and vomiting. Symptoms started after her father placed AlP pellets throughout the house for rodent control. Of note, her 47-year-old mother, 16-year-old brother, and 21-year-old sister all presented at the same time with minor gastrointestinal and upper respiratory symptoms that resolved quickly. The patient's vital signs were BP 60/40 mmHg, HR 150 beats/min, RR 25 breaths/min, T 99.5 degreeF, O2 Sat 100%. She was noted to be somnolent and had dry mucous membranes with delayed capillary refill. Venous blood gas showed pH 7.32; PCO2 28 mmHg, calculated HCO3 14 mEq/L, and a lactate 4.2 mmol/L. Anion gap was 29 mmol/L. ECG showed diffuse ST segment depressions. She remained hypotensive despite intravenous fluids and was started on IV dopamine. She was transferred to an ECLS center 2 h after presentation. Shortly after transfer, the patient had a ventricular tachycardia arrest and was connected to veno-arterial ECLS after 90 min of resuscitation. She was started on IV N-acetylcysteine and oral vitamin E as well as intravenous L-carnitine. Her hospital course was complicated by ventricular dysrhyth-mias, seizures and bacteremia, hepatic injury, pulmonary edema and acute kidney failure requiring dialysis. Cardiac function slowly improved, and the patient was weaned off ECLS on day 15 of admission with an intact mental status and no reported neurologic sequelae. Discussion: Phosphine poisoning is challenging for the provider since it is often lethal, has no specific antidotes and rarely occurs in the USA. Conclusion: Early transfer to an ECLS-capable center and aggressive treatment in aluminum phosphide toxicity may be associated with better outcomes