Faculty Bibliography

CONTEXT: Manganese-associated parkinsonism is well described in occupational settings, in chronic methcathinone users, and in patients receiving long-term total parenteral nutrition. We present a unique case of acute intravenous manganese poisoning with a systematic evaluation of hemodialysis efficacy. CASE DETAILS: A 52-year-old woman was inadvertently administered a single intravenous dose of 800 mg compounded manganese chloride at an outpatient chelation center. In an attempt to minimize central nervous system (CNS) manganese deposition, she underwent urgent hemodialysis followed by five days of therapy with calcium disodium EDTA (1 g/m2 over eight hours daily). Her initial whole blood manganese concentration, obtained six hours after exposure and prior to treatment, was 120 mcg/L (2.19 micromol/L); normal <5 mcg/L (< 0.09 micromol/L). Following the first four-hour hemodialysis session her blood manganese concentration decreased to 20 mcg/L (0.36 micromol/L). Despite the fall in her blood manganese concentration, analysis of dialysate revealed a total elimination of only 604 mcg (11 micromol) manganese ( approximately 1.4% of manganese burden). Although she remained asymptomatic, an MRI on hospital day two revealed T1 hyperintensities within the bilateral globus pallidi, consistent with manganese exposure. DISCUSSION: Manganese poisoning is associated with irreversible neurologic toxicity. Hemodialysis did not appear to significantly enhance elimination in this case of acute intravenous manganese toxicity, beyond supportive care and calcium disodium EDTA chelation.

OBJECTIVE: Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration. CASE DETAILS: A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1-2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 degrees C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms. DISCUSSION: Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.

INTRODUCTION: Invasive meningococcal disease can be difficult to detect early in its course when patients may appear well and the severity of their illness is obscured by non-specific complaints. CASE PRESENTATION: We report five cases of meningococcal sepsis in adult patients who presented to an emergency department early in the course of their disease, but whose severity of illness was not recognized. CONCLUSION: Suspicion of meningococcal sepsis should be heightened in the setting of hypotension, tachycardia, elevated shock index, leukopaenia with left shift, thrombocytopaenia and hypokalaemia, prompting early sepsis care.

Caustics are common in household and industrial products, and, when ingested, they can pose a significant public health risk. Caustic exposures in adults typically present in the setting of occupational exposure or suicide attempt; exposures in children occur most often by unintentional ingestion. Caustics cause local damage upon contact with tissue surfaces and can lead to systemic toxicity. Endoscopy is recommended in all intentional ingestions (and many unintentional ingestions) to grade injury severity, determine treatment options, and assess prognosis; however, it is generally best performed within 24 hours post ingestion to avoid risk of perforation. Radiography and computed tomography may also be used to visualize injury in certain cases. This review examines the pathophysiology of caustic exposures, their clinical presentations, and the most current evidence on recommendations for decontamination, surgical consult, treatment, and disposition.

Background: Adverse cardiovascular events (ACVE) complicate up to 16.9% of hospitalizations for acute drug overdose. We previously derived a risk prediction rule for ACVE in these patients with 97.1% negative predictive value. Objectives: Our aim was to internally validate the ACVE rule test characteristics. Methods: This prospective cohort study was conducted over 17 months (2012-14) at 2 urban teaching hospitals. Patients were adults with suspected acute drug overdose enrolled from the ED. The study outcome, ACVE, was defined as any of the following: myocardial injury (elevated troponin I), shock (requiring vasopressors), ventricular dysrhythmia (VT/VF/TdP), or cardiac arrest (pulseless requiring CPR). The rule included any of these 3 factors: (1) prior cardiac disease (CAD or CHF); (2) QTc > 500ms; (3) initial serum bicarbonate < 20 mmol/L. Sample size was predetermined in order to produce test characteristics with 95% CI widths <5%; we calculated the need to analyze 900 patients. Results: There were 1,457 patients screened, of whom 552 were excluded (185 non-drug overdose, 145 pediatrics, 111 missing data, 110 alternate diagnosis, 1 chronic), leaving 905 for analysis (mean age, 41 years; female, 44%; suicidal, 40%). ACVE occurred in 65 (7.2%, CI 5.6- 9.1) patients (myocardial injury, 44; shock, 31; dysrhythmia, 16; cardiac arrests, 17) and there were 16 (1.8%, CI 0.9-2.6) deaths. The multivariable model adjusting for the previously derived risk factors, controlling for age, confirmed the following independent predictors of ACVE: QTc >500 msec (OR 5.5, CI 2.8-10.9), bicarbonate <20 mmol/L (OR 2.7, CI 1.5-4.9), and prior cardiac disease (OR 39.5, CI 17.9-87). The validated prediction rule had 75.4% (CI 63.1-85.2) sensitivity, 82.3% specificity (CI 79.9-85.1), and 97.8% negative predictive value (CI 96.4- 98.7). The presence of 2 or more risk factors had 51.5% positive predictive value (CI 34.5-68.6). Conclusion: The risk prediction rule for ACVE in patients with acute drug overdose performed with slightly improved sensitivity and negative predictive value in the validation cohort. External validation in distinct patient populations and clinical settings remains warranted

Background: ASA poisoning remains a significant public health threat with upwards of 20,000 exposures annually in the US and morbidity/mortality rates of up to 25%. Objectives: In order to facilitate targeted treatment to lower these rates, we aimed to establish early predictors of severe in-hospital outcomes in ED patients presenting with ASA poisoning. Methods: This was a secondary data analysis of ASA overdoses from a prospective cohort study of suspected acute drug overdoses at two urban university teaching hospitals from 2009-2013. Patients were enrolled consecutively and were considered eligible for inclusion based on clinical suspicion of ASA ingestion. Children (<18) and alternate diagnoses were excluded. Demographics, clinical parameters, serum ASA concentrations, treatment modalities and death/admission rate were collected from the medical record. Severe outcome was defined as a composite occurrence of any of the following: acidemia (pH<7.3 or bicarbonate<16mEq/L), hemodialysis, or death. Results: 48 patients met inclusion criteria, with 43.8% male, median age 32, mean initial ASA concentration 28.1, and 10 (21%) classified as severe outcome. There were two deaths, neither of whom received hemodialysis. Patients were treated with sodium bicarbonate in onethird of cases, while 54.2% received activated charcoal and 64.6% were admitted. Univariate analysis indicated that age, respiratory rate (RR), creatinine, lactate, coma, and presence of co-ingestions were significantly associated with severe outcome, while ASA alone had no association. However, when adjusted for serum ASA concentration, only age (OR 1.02 per additional year, 95%CI 1.0-1.1), RR (1.09 per additional breath/min, 95%CI 1.03-1.15), creatinine (2.8 per additional mg/dL 95%CI 1.1-7.1), and co-ingestions (OR 6.4, 95%CI 2.3-17.8) were independent predictors of severe outcome. Conclusion: Age, RR, creatinine, and co-ingestions are predictive of severe outcome in ED patients with acute ASA poisoning, while serum ASA concentration alone is not. Despite the severity of these cases, only one-third received sodium bicarbonate, suggesting potential barriers to administration which require further study