Faculty Bibliography

BACKGROUND:We report a patient with a massive hydroxychloroquine overdose manifested by profound hypokalemia and ventricular dysrhythmias and describe hydroxychloroquine toxicokinetics. CASE REPORT/METHODS:A 20-year-old woman (60 kg) presented 1 h after ingesting 36 g of hydroxychloroquine. Vital signs were: BP, 66 mmHg/palpation; heart rate, 115/min; respirations 18/min; oxygen saturation, 100% on room air. She was immediately given intravenous fluids and intubated. Infusions of diazepam and epinephrine were started. Activated charcoal was administered. Her initial serum potassium of 5.3 mEq/L decreased to 2.1 mEq/L 1 h later. The presenting electrocardiogram (ECG) showed sinus tachycardia at 119 beats/min with a QRS duration of 146 ms, and a QT interval of 400 ms (Bazett's QTc 563 ms). She had four episodes of ventricular tachydysrhythmias requiring cardioversion, electrolyte repletion, and lidocaine infusion. Her blood hydroxychloroquine concentration peaked at 28,000 ng/mL (therapeutic range 500-2000 ng/mL). Serial concentrations demonstrated apparent first-order elimination with a half-life of 11.6 h. She was extubated on hospital day three and had a full recovery. CONCLUSION/CONCLUSIONS:We present a massive hydroxychloroquine overdose treated with early intubation, activated charcoal, epinephrine, high dose diazepam, aggressive electrolyte repletion, and lidocaine. The apparent 11.6 hour half-life of hydroxychloroquine was shorter than previously described.

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: 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

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: 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