Faculty Bibliography

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

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: In-flight pain emergencies are responsible for 17% of medical diversions on commercial airlines [1]. While the Federal Aviation Authority mandates that airlines carry aspirin in the emergency medical kit (EMK), some airlines carry opioids. This case highlights the risks associated with in-flight administration of opioid analgesics from an ill-equipped EMK. Case report: The poison center was consulted about a 38-yearold, opioid-naive woman who was brought to an emergency department directly from the airport following a transatlantic flight on a large European airliner. She had normal vital signs but was somnolent and nauseous with bilateral miosis. In her possession was a physician note attesting that she had complained of leg pain during the flight and was given buprenorphine (400 mug sublingual) and aspirin (300mg oral) from the emergency medical kit on board the flight. In the absence of hypoventilation, we recommended against naloxone administration. The patient was admitted to the intensive care unit for monitoring and discharged home 24 hours later without sequelae. We investigated the EMK contents of the patient's airline and were extremely concerned by our findings. The quantity of buprenorphine (30 x 200 mug tablets), its convenient location within the lid compartment (next to the stethoscope and face mask), and the relative scarcity of naloxone (2 x 0.4 mg ampules) were all striking. While buprenorphine has a ceiling effect on respiratory depression in healthy volunteers, its high mu-opioid receptor affinity makes it difficult to treat with standard doses of naloxone [2]. Many physicians are also unfamiliar with analgesic buprenorphine doses which are 10-fold lower than doses used for opioid medication assisted therapy. Lastly, sublingual buprenorphine has a peak therapeutic effect 1-4 hours following administration: too late and too long for pain on a plane for shorter flights.
Conclusion(s): The large quantity of easily-accessible buprenorphine in an airline's EMK directly contributed to this patient's overdose. While the patient did not suffer permanent injury, she was subjected to many medical tests and hospitalized for 24 hours in a costly ICU bed. We seriously question the role of buprenorphine in the management of in-flight pain crises. (Table Presented)

Objective: Digoxin toxicity is determined largely by physical examination and electrocardiogram (ECG) findings; concentrations serve for confirmation. Some reports suggest decreased digoxin sensitivity in younger patients. We report a case of an infant with a very elevated digoxin concentration successfully managed conservatively. Case report: A 2-month-old boy (3.1 kg) with a past medical history of congestive heart failure was admitted to the hospital for vomiting and failure to thrive. The patient was started on oral digoxin, ordered as 0.015 mg twice daily. Due to a medication error, he was instead given 0.15mg twice a day for four days. His only other medication was furosemide. He had no new symptoms or change in the frequency of his vomiting. During a new medication reconciliation, the error was discovered. At that time, his vital signs were blood pressure 88/43mmHg, heart rate 123 beats/minute, respiratory rate 52, temperature 36.9 degreeC, and oxygen saturations 100% (on supplemental oxygen). His electrocardiogram (ECG) showed a sinus rhythm at 122 beats/minute with normal intervals. There was no evidence of increased automaticity or any arrhythmias. A serum digoxin concentration drawn 5 hours after his last dose was 16 nmol/L. Other laboratory findings at that time were notable for a potassium of 5.2mmol/L with slight hemolysis and a creatinine of 3.5 mumol/g. Repeat laboratory tests 8 hours after his last dose revealed a digoxin concentration of 15 nmol/L, potassium 5.3mmol/L (hemolyzed), creatinine 2.7 mumol/g and magnesium 0.72 mmol/L. He remained hemodynamically stable despite occasional episodes of vomiting. No cardiac ectopy or other events were noted. Oral digoxin was withheld and Digifab was not given. Repeat digoxin concentrations on day 1, 2, 4 and 5 were 9.6, 4.9, 2.9 and 1.92 nmol/L, respectively.
Conclusion(s): Digoxin toxicity often manifests with cardiac and constitutional symptoms. While toxicity is usually expected with elevated digoxin concentrations, only 63% of infants with a digoxin concentration greater than 6.4 nmol/L developed toxicity [1]. In fact, some evidence suggests that infants have decreased sensitivity to digoxin [2]. In this case the significantly elevated post-distribution digoxin concentration with no clear signs or symptoms of toxicity supports this presumption

Objective: Aggressive gastric emptying is often withheld in poisoning due to concerns over safety and efficacy. Despite this, endoscopy performed by emergency medicine physicians demonstrates significant retention of residual drug products many hours after ingestion [1]. Decedents may also demonstrate significant drug retention [2]. We developed a novel video technique in an attempt to improve the safety, efficacy, and completeness of orogastric lavage.
Method(s): Using SolidWorksTM (Dassault Systems, Waltham, MA, 2018), we designed and produced a special Y-adapter with a polylactic acid medium using a 3D Printer (Monoprice, Rancho Cucamonga, CA, 2018) to permit side hole insertion of a disposable AmbuR aScopeTM three intubating bronchoscope (Columbia, MD, 2018) into a standard 40 Fr orogastric lavage tube (OGT). This allowed bronchoscope placement into the orogastric tube (OGT) with an air-tight seal and the ability to visualize through a distal side port. To simulate overdose, 50 pills (acetaminophen 500 mg/diphenhydramine 25mg tablet) were placed into the mannequin stomach with 200 mL of tap water. The mannequin was positioned in the left lateral decubitus position; the apparatus was assembled; and gastric lavage was accomplished with 2 L of tap water.
Result(s): We were able to easily visualize tube passage and placement into the stomach to an appropriate depth, appreciating an initially cloudy solution with numerous pill fragments. The adapted system then permitted lavage under constant bronchoscope visualization. Gastric contents were easily ascertained through the distal ports, and the stomach could be evaluated to the pylorus to exclude bezoars or remaining pill fragments. After lavage, a clear solution with no remaining evidence of pill slurry was evident. After extensive lavage, using the bronchoscope, only a small amount of pill fragments were visualized in the fundus.
Conclusion(s): This study demonstrates a proof of concept, linking visualization with OGT placement and active lavage. If these findings can be confirmed in vivo, our novel device may help clarify the indications, improve the safety and efficacy, and define the endpoints of orogastric lavage

Objective: Diphenhydramine is a common over-the-counter antihistamine which rarely leads to severe toxicity. We report a patient with a diphenhydramine overdose manifested with seizure and cardiac arrest. Though her hemodynamics improved with VA-ECMO and hydroxocobalamin, the patient was ultimately declared brain dead and underwent organ procurement. Case report: A 34-year-old woman with a history of depression was found by emergency medical services with seven bottles of diphenhydramine, two of which were empty. The patient seized and moments afterwards went into cardiac arrest. Advanced cardiac life support (ACLS) was initiated, with chest compressions performed for 35 minutes, 2mg of epinephrine given intravenously, an epinephrine infusion and intubation. Additionally, the patient received intermittent boluses of sodium bicarbonate totaling 150 mEq, 25 g dextrose and 1 g calcium gluconate. Toxicology was consulted and recommended an additional 150 mEq IV bolus of sodium bicarbonate and, within 5 minutes, the patient regained a pulse. On physical exam, she had minimally reactive pupils and was unresponsive to painful stimuli. Initial laboratory findings were remarkable for a lactate of 9 mmol/L and a potassium of 2.5mmol/L. The electrocardiogram (ECG) demonstrated a QRS of 154 ms and a QTc of 463 ms and she was placed on a bicarbonate infusion. Decontamination was performed using gastric lavage and 50 g of activated charcoal. Four hours following presentation, her vasopressor requirements included: 20 mug/min epinephrine, 60 mug/min norepinephrine, 200 mug/min phenylephrine, and 0.04 U/min vasopressin. She developed acute respiratory distress syndrome (ARDS) so was placed on VA-ECMO. Given profound vasoplegic shock, she received 5 g of hydroxocobalamin and was quickly weaned off her vasopressor requirements to 5 mug/min epinephrine and 15 mug/min norepinephrine. Repeat ECG showed a QRS of 160 ms and QTc 565 ms. Her ECG normalized within 24 hours of arrival and bicarbonate infusion was discontinued. She was on VA-ECMO for seven days with stable hemodynamics, and never developed acute kidney or liver injury. She was declared brain dead on hospital day 7 and underwent organ procurement. The initial serum diphenhydramine concentration was 1,400 ng/mL (normal range 90-120 ng/mL).
Conclusion(s): We present a unique case of diphenhydramine overdose who obtained return of spontaneous circulation after ACLS and 150 mEq IV push of sodium bicarbonate, placed on VAECMO, and treated for vasoplegic shock with hydroxocobalamin. While there is increasing use of ECMO in poisoned patients, its use as a bridge to organ donation requires further ethical consideration

Objective: Isopropyl alcohol ingestion is reported to cause ketosis without acidosis. We report a case of confirmed isopropyl alcohol ingestion associated with an anion gap metabolic acidosis with no preceding hypotension. Case report: A 15-year-old female with a past medical history of depression presented to the emergency department after being found somnolent at home. Thirty minutes prior to arrival, she drank 300mL of 70% isopropyl alcohol. She had one episode of vomiting and was intubated for airway protection. Initial vital signs were blood pressure 115/66mmHg, heart rate 86 beats/minutes, respiratory rate 20/minute, temperature 36.3 degreeC, and oxygen saturations 100% (on supplemental oxygen). Electrocardiogram (ECG) showed sinus rhythm (92 beats/minute) with normal intervals. Venous blood gas analysis showed pH 7.2, PCO2 50.4 mmHg, and lactate 0.34 mmol/L. Basic metabolic profile showed sodium 137mmol/L, potassium 2.9mmol/L, chloride 105mmol/L, bicarbonate 24mmol/L, blood urea nitrogen 11mmol/L, creatinine 244 mumol/L, glucose 9 mmol/L, and anion gap 8mmol/L. Measured serum osmoles were 353 mOsm/L with a calculated osmolar gap of 65. Ethanol, acetaminophen and salicylate were undetectable. Urine ketones were undetectable but serum acetone was 21 mg/dL. Repeat laboratory tests seven hours after admission were arterial blood gases pH 7.21, PCO2 27 mmHg, lactate 1.1mmol/L, with sodium 141mmol/L, potassium 3.5mmol/L, chloride 102mmol/L, bicarbonate 15mmol/ L, blood urea nitrogen 10mmol/L, creatinine 244 mumol/L, glucose 8 mmol/L and anion gap 23. Given the rising anion gap and elevated lactate, a loading dose of fomepizole 15mg/kg in addition to thiamine and folate were administered. She was started on continuous veno-venous hemofiltration (CVVH) 15 hours post-admission for 2 hours and was later switched to hemodialysis. Toxic alcohol concentrations sent after 2 hours of CVVH were isopropyl alcohol 69 mg/dL and acetone 82mg/dL. Ethylene glycol and methanol were undetectable. She completed 4 hours of hemodialysis, with resolution of acidosis. Following extubation, she admitted to ingesting only isopropyl alcohol.
Conclusion(s): Isopropyl alcohol is either eliminated unchanged via kidneys or lungs or is metabolized by alcohol dehydrogenase to acetone, the latter eliminated by the liver or lungs. However, rodent studies show that acetone may be further metabolized to lactate, generating formate, which can contribute to an anion gap metabolic acidosis. While this pathway may explain the acidosis and hyperlactemia in our patient, it has not been demonstrated in humans. The development of acidosis in this patient is puzzling and unexpected

Background: Alcoholic ketoacidosis (AKA) is a metabolic derangement caused by poor nutritional status and an altered oxidation-reduction state in patients with alcohol use disorder (AUD). During starvation, fatty acids undergo beta-oxidation, with resulting ketone and ketone-like byproducts causing both an elevated osmolar gap and an elevated anion gap metabolic acidosis. Ingestion of toxic alcohols (TAs), such as methanol or ethylene glycol, also produces an elevated osmolar gap, and subsequently an elevated anion gap metabolic acidosis. It is difficult to distinguish AKA from TA ingestion clinically, many hospitals do not provide timely serum TA concentrations, and the cost of unnecessary fomepizole and/or hemodialysis is significant. The aim of this study is to identify risk factors suggestive of AKA when TA ingestion is the primary alternative differential diagnosis. We hypothesize that a positive ethanol concentration will be predictive of the diagnosis of AKA.
Method(s): This is a retrospective analysis of data from a single Poison Control Center (PCC) from 2000 to 2019. A structured query language search (SQL) of Toxicall