Faculty Bibliography

Background: Severe baclofen toxicity (BT) can result in respiratory failure, hypotension or hypertension, bradycardia, hypothermia, seizures, coma and death. While hemodialysis (HD) is well-described in the treatment of BT in patients with end-stage renal disease (ESRD), the utility of HD in the treatment of acute BT in patients with normal renal function is less clear. Implementing HD to speed recovery after a large acute baclofen exposure is tempting, considering: a) the potential for prolonged coma and ventilator-associated morbidity, and b) baclofen's low protein binding (31%), small size (213 Da), and moderate volume of distribution (Vd =2.4 L/kg). We report the lack of efficacy of HD in a patient with an intentional baclofen overdose and normal kidney function. Case report: A 51-kg 14-year-old girl with no past medical history presented to the emergency department with hypotension, obtundation, and status epilepticus after an intentional ingestion of 1200 mg of baclofen. Her post-intubation neurologic exam was concerning for coma without any need for sedation. A 14-hour post-ingestion baclofen level was 882 ng/ml (therapeutic range 80-400 ng/ml). Urgent hemodialysis was performed due to her concerning neurologic status, with the goal of reducing her time on the ventilator. A Revaclear 300 dialyzer was used with an ultimate blood flow rate (Qb) of 300 ml/min and a dialysis fluid flow rate (Qd) of 400 ml/min. A total of three HD sessions were performed, with serum concentrations collected accordingly (Figure 1), and slow but progressive improvement in mental status. Baclofen concentrations were also systematically obtained in urine and dialysate during her hospital course. The total baclofen removed in the first three-hour HD session was 3.05 mg. The total amount of baclofen removed from urine over 24 hours on hospital day one was 42 mg, hospital day 2 was 9.2 mg, and hospital day 3 was 27.8 mg. A follow-up magnetic resonance imaging of the brain showed no evidence of anoxic brain injury. She was discharged without neurologic deficits to inpatient psychiatry on day 14. Case Discussion: There are few reports on the use of HD for acute BT in patients with normal renal function, and limited data on HD efficacy. Given the 12-fold increased quantity of baclofen recovered in urine during hospital day one in comparison to HD, the use of HD appears largely ineffective in enhancing elimination for patients with normal kidney function. Furthermore, baclofen was below the limit of detection in the dialysate on days 2 and 3. Post-HD rebound was consistent with redistribution given baclofen's larger volume of distribution. It is possible that the drug had already been distributed to tissue at the time HD was started, about 30 hours post-presentation, rendering elimination by HD ineffective.
Conclusion(s): The amount of baclofen recovered during hemodialysis is negligible in comparison to normal renal elimination in this patient with normal renal function

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

Introduction: Amygdalin, marketed misleadingly as supplement "Vitamin B17," is a cyanogenic glycoside. When swallowed, it is hydrolyzed into cyanide in the small intestine, which causes histotoxic hypoxia via inhibition of cytochrome c oxidase. It remains available for purchase online despite a ban from the US Food and Drug Administration. We report a case of massive intentional amygdalin overdose resulting in recurrent cyanide toxicity after initial successful antidotal therapy. Case summary: A 33-year-old woman intentionally ingested 20 g of "apricot POWER B17 Amygdalin" supplements. She presented five hours post-ingestion with vital signs: P 127 bpm, BP 112/65 mmHg, RR 25/min, temperature 98.1 °F, and SpO2 98% RA. She was in agitated delirium, diaphoretic, and mydriatic. Her VBG was notable for a pH of 7.27 (rr 7.32-7.42) and lactate 14.1 mmol/L (rr 0.5-2.2), with ECG demonstrating QTc 538 ms (normal <440 ms). She was empirically treated with hydroxocobalamin and supportive care, but worsened clinically, requiring intubation and additional hydroxocobalamin and sodium thiosulfate, which resolved her toxicity. Twelve hours later, she developed recurrent hypotension, acidemia, and QTc prolongation that resolved with repeat hydroxocobalamin and sodium thiosulfate dosing. Discussion: Our case demonstrates rebound metabolic acidosis after massive amygdalin overdose. Toxicity was associated with prolonged QTc, which warrants further investigation into clinical significance. Redosing of combination antidotal therapy suggested efficacy without adverse effects.

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: 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: 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

BACKGROUND:The assessment and management of patients with QT interval prolongation in poisoning requires an appropriate method of measuring and adjusting the QT interval for the heart rate (HR) in order to decide if the patient is at risk of life-threatening dysrhythmias, notably torsade de pointes (TdP). As the Clinical Toxicology Collaborative (CTC) workgroup reviewed the published literature on drug-induced QT interval prolongation in poisoning, it became obvious that many publications were missing essential data that were necessary to thoroughly assess and compare the evidence. The aim of this guidance document is to identify essential and ideal criteria required when reporting a case of drug-induced QT interval prolongation and/or TdP in poisoning. METHODS:We employed a mixed methods approach as follows. Initially, we reviewed 188 cases of available published case reports and series in the literature regarding drug-induced QT interval prolongation and/or TdP in poisoning as the first step to another project. Common features and deficiencies were identified. Given the large gaps in reporting quality, we conducted an iterative consultative process involving all 23 members of the CTC to identify essential and ideal criteria to analyse publications of QT interval prolongation in poisoning. A priori standards were developed for acceptance or rejection of individual criteria. RESULTS:Survey response was 100%. A minimum set of essential criteria for reporting cases of QT interval prolongation and drug-induced TdP in overdose setting are provided and a 35-item checklist is presented. CONCLUSIONS:We report a QT reporting checklist to ensure published case reports and series describing drug-induced QT interval prolongation in poisoning can contribute to the fund of knowledge of QT interval prolongation, TdP and other malignant dysrhythmias.