Faculty Bibliography

CONTEXT/BACKGROUND:Anion gap metabolic acidosis (AGMA) is common in patients presenting for emergency care. While some disease processes and ingestions are easily excluded, diagnosing toxic alcohol (TA) ingestion can be challenging. This is especially true if drug concentrations are not readily available, which forces clinicians to rely on surrogate markers. Like TA ingestion, alcoholic ketoacidosis (AKA) produces an elevated osmol gap and an AGMA. The aim of this study was to identify risk factors suggestive of AKA when TA ingestion was the primary alternative differential diagnosis. We hypothesized that the odds of an AKA diagnosis would increase as ethanol concentration increased. METHODS:This was a retrospective analysis of data from 2000 through 2019 from a single US Poison Control Center. Records were reviewed to identify cases coded as "methanol" or "ethylene glycol"; or coded as "alcohol" or "ethanol with acidosis." The case definition for AKA required: (1) documented alcohol use disorder; (2) urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) anion gap ≥ 14 mmol/L. The inclusion criterion for TAs was a detectable methanol or ethylene glycol concentration. RESULTS: = .03). CONCLUSIONS:In this retrospective analysis, the odds of diagnosing AKA instead of TA ingestion increased as ethanol concentration increased. The limited ability of common clinical factors to differentiate these diagnoses highlights the need to obtain quantitative TA concentrations in real time. Until prospective validation, interpretation of ketone concentrations and toxic alcohol concentrations (when available) will continue to guide decision making.

OBJECTIVE:Although hemodialysis is recommended for patients with severe metformin-associated lactic acidosis (MALA), the amount of metformin removed by hemodialysis is poorly documented. We analyzed endogenous clearance and hemodialysis clearance in a patient with MALA. METHODS:A 62-year-old man with a history of type II diabetes mellitus presented after several days of vomiting and diarrhea and was found to have acute kidney injury (AKI) and severe acidemia. Initial serum metformin concentration was 315.34 μmol/L (40.73 μg/mL) (typical therapeutic concentrations 1-2 μg/mL). He underwent 6 h of hemodialysis. We collected hourly whole blood, serum, urine, and dialysate metformin concentrations. Blood, urine, and dialysate samples were analyzed, and clearances were determined using standard pharmacokinetic calculations. RESULTS:The total amount of metformin removed by 6 h of hemodialysis was 888 mg, approximately equivalent to one therapeutic dose. Approximately 142 mg of metformin was cleared in the urine during this time. His acid-base status and creatinine improved over the following days. No further hemodialysis was required. CONCLUSION/CONCLUSIONS:We report a case of MALA likely secondary to AKI and severe volume depletion. The patient improved with supportive care, sodium bicarbonate, and hemodialysis. Analysis of whole blood, serum, urine, and dialysate concentrations showed limited efficacy of hemodialysis in the removal of metformin from blood, contrary to previously published data. Despite evidence of acute kidney injury, a relatively large amount of metformin was eliminated in the urine while the patient was undergoing hemodialysis. These data suggest that clinical improvement is likely due to factors besides removal of metformin.

BACKGROUND:Illicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine. CASE REPORTS/METHODS:Over a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients denied prior illicit opioid use. All patients endorsed insufflating cocaine shortly prior to ED presentation. Soon after exposure, all developed lightheadedness and/or respiratory depression. Seven patients received naloxone en route to the hospital; all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients were discharged home after observation. Blood +/- urine samples were obtained from eight patients. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates. DISCUSSION/CONCLUSIONS:IMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. This confirmed outbreak demonstrates that providers should elevate their level of suspicion for concomitant unintentional IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses must prepare for future IMF-contamination outbreaks.

Objective: This study was designed to determine the fatality rate of suspected cyclopeptide-containing mushroom ingestions reported to the National Poison Data System (NPDS).Background: Although silibinin reportedly improves survival in suspected cyclopeptide-containing mushroom ingestions, the greater than 20% untreated fatality rate that is often cited is based on decades-old data. An ongoing open-label silibinin trial will likely use historical cases as comparators. A recent single poison control center (PCC) study showed a fatality rate of 8.3%. This study was designed to validate those findings in the NPDS.Methods: This study was an 11-year (1/1/2008-12/31/2018) retrospective review of suspected cyclopeptide-containing mushroom ingestions reported to NPDS. Inclusion and exclusion criteria were the same as the ongoing silibinin trial: Age >2-years-old; history of eating foraged mushrooms; gastrointestinal symptoms within 48 h of mushroom ingestion; and aminotransferases above the upper limit of normal within 48 h after ingestion. Each original participating PCC confirmed eligibility, diagnosis, treatment, and outcome on included cases.Results: During the study period, 8,953 mushroom exposures were reported to NPDS, of which 296 met inclusion criteria. The PCC survey response rate was 60% (28/47 PCCs), and the individual case response rate was 59% (174/296). Twenty-six cases were subsequently excluded leaving 148 included cases. The overall mortality rate was 8.8% (13/148). Mortality in silibinin/silymarin-treated vs untreated cases was 9.5% (4/42), vs 8.5% (9/106), respectively. A mycologist identified mushrooms in 16.9% of cases (25/148), of which 80% (20/25) were cyclopeptide-containing. Among these confirmed cases, the mortality rate was 10% (1/10) in both silibinin/silymarin-treated and untreated cases.Conclusions: The contemporary mortality rate of patients with presumed cyclopeptide-mushroom poisoning is only 8.8%. This likely represents improved supportive care for patients with acute liver injury and should be considered the current standard for historical controls in the United States.

Introduction: Suicide attempts by poisoning are increasing and suicide occurrence may be associated with seasonality. We performed a retrospective analysis of poisoning exposure data from a single Poison Control Center (PCC) to determine if suicide attempts were associated with season, day of the week, and/or US holidays.Methods: We analyzed exposure cases identified as "intentional overdose - suspected suicide attempt" over 2009-2012. We used singular spectrum analysis (SSA) to detect cyclic patterns in the data and then performed Poisson regression and t-tests to determine if the number of cases were associated with season, day of the week, and US holidays.Results: There were 42,578 cases of "intentional overdose - suspected suicide" during the study period. Singular Spectrum Analysis (SSA) showed that the number of cases associated with poisoning suicide attempts peaked in the Spring and dipped in the Fall. Regression analysis showed higher numbers of suspected suicide attempts from intentional overdose in spring compared with winter by 1.07 times (p = 0.003), and on Sunday (p < 0.001), Monday (p < 0.001), and Thursday (p = 0.02) compared with Saturday by at least 1.09 times. No significant difference was seen for most holidays except for lower numbers of cases around Christmas (3 days before and after; 22.0 vs. 32.3 on control dates, p < 0.001).Conclusions: Suicide attempts by poisoning are associated with season of the year and some days of the week. Further research is required determine reasons for these associations and implementation of public health interventions.