Faculty Bibliography

BACKGROUND:histamine receptor antagonist, is a commonly used nonprescription medication that is used for the treatment of allergy, as a sleep aid, or combined with cough and cold remedies. Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is used commonly for analgesia. Although most cases of diphenhydramine or naproxen overdose require excellent supportive care only, meticulous attention should be given to cardiovascular and neurologic status. CASE REPORT/METHODS:A 22-year-old woman presented with altered mental status secondary to intentional ingestion of 240 combination caplets of naproxen sodium 220 mg and diphenhydramine hydrochloride 25 mg. While in the emergency department, she manifested a wide-complex tachycardia in the setting of hypotension that required repeated administration of sodium bicarbonate to overcome the sodium channel blockade caused by diphenhydramine. Aggressive potassium repletion was performed simultaneously. Her clinical course was complicated by status-epilepticus that required intubation. Orogastric lavage was performed, which returned blue pill slurry consistent with the ingested caplets. The patient was extubated on hospital day 2 and transferred to psychiatry thereafter. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In light of recent social media trends, such as the "Benadryl challenge" and its widespread availability, emergency providers should be familiar with diphenhydramine toxicity, especially the life-threatening neurologic consequences and risk of cardiovascular collapse. NSAIDs, such as naproxen, and other nonprescription analgesics are becoming more and more important in light of the current opioid crisis. There should be an emphasis on understanding these medications and their potential implications when taken in overdose.

INTRODUCTION/BACKGROUND:Acetaminophen is a commonly used analgesic and antipyretic, with the potential to cause significant injury when ingested in toxic amounts. Although the antidote n-acetylcysteine (NAC) is available, evidence supporting dose recommendations for patients weighing over 100 kg are lacking. We performed a retrospective, multi-center analysis to determine if a capped NAC dosing scheme is similar to a non-capped dosing scheme in patients weighing over 100 kg. METHODS:Between January 2009 and January 2016, we identified patients presenting to 12 different centers who were evaluated for acetaminophen poisoning treatment. Patients must have weighed greater than 100 kg and were evaluated and identified as needing treatment for acetaminophen-related poisoning with NAC. The primary outcome was occurrence of hepatic injury, defined as an AST or ALT ≥ 100 IU/L. Secondary endpoints included number of drug-related adverse events, occurrence of hepatotoxicity, cumulative NAC dose, regimen cost, length of hospital and intensive care unit stays, and in-hospital mortality. RESULTS:There were 83 patients identified as meeting the pre-specified inclusion and exclusion criteria. A capped NAC dosing scheme resulted in no difference in hepatic injury when compared to a non-capped regimen (49.4% vs 50%, p = 1.000). The capped dosage regimen was associated with a lower cumulative dose (285.2 mg/kg vs 304.6 mg/kg, p < 0.001) and cost. No other statistically significant differences were identified among the secondary endpoints. CONCLUSION/CONCLUSIONS:A capped NAC dosing scheme was not associated with higher rates of hepatic injury or hepatotoxicity in obese patients in the setting of acetaminophen poisoning when compared to a non-capped regimen. Further research is needed to verify these results.

AIMS/OBJECTIVE:Two guidelines for haemodialysis in lithium poisoning, one from the Extracorporeal TReatments in Poisoning (EXTRIP) workgroup and a single centre retrospective one (Paris) differ. We compared outcomes in lithium poisoning based on these criteria with a primary outcome of worsening neurological symptoms in patients for whom EXTRIP and Paris criteria were discordant. METHODS:Poison centre data were queried for lithium poisoned patients for whom haemodialysis was either recommended or performed. Patients were categorized according to EXTRIP and Paris criteria and excluded if the peak lithium concentration was <1.2 mmol/L or if neurological follow-up was unavailable. Comparative analyses were only performed when both criteria could be assessed. RESULTS:In total, 219 patients were analysed. Paris criteria were met in 70 and EXTRIP criteria in 178. Forty two patients were excluded because Paris criteria could not be evaluated. When Paris and EXTRIP both supported haemodialysis, 50/57 (88%) of patients who received haemodialysis improved, as did all 3 who did not receive haemodialysis. When Paris and EXTRIP did not support haemodialysis, all nondialysed patients did well. Among the 86 patients for whom EXTRIP supported haemodialysis but Paris did not, 4/19 (21%) patients not dialysed deteriorated (P = .02; odds ratio = 8.7, 95% confidence interval = 1.5-51.8), 1 of whom died. All 8 patients for whom Paris criteria supported haemodialysis but EXTRIP did not were dialysed and improved. CONCLUSIONS:When the EXTRIP and Paris criteria are discordant, EXTRIP criteria outperforms the Paris criteria at identifying potentially ill patients who might benefit from haemodialysis.

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: The "Pollyanna Phenomenon," an optimism for useful interventions appearing as efficacious as useless ones, was first described in 1992[1]. An editorial written in 1997 highlighted this phenomenon regarding passive data collection from Poison Control Centers (PCCs) and its limitations related to minimally symptomatic or asymptomatic patients[2]. PCCs continue to collect data passively with an immense data pool. Despite these "big data," limitations to PCC research persist. The term toxicovigilance was borne from this editorial and suggestions were made to improve PCC data fidelity and to overcome the "Pollyanna Phenomenon." We investigated PCC research over the past 40+ years to determine the impact of this editorial on toxicovigilance[2].
Method(s): We searched PubMed and EMBASE for PCC research from 1978 to 2020 using these search terms: "Poison Center", "Poison Control Center", "Poison Centre", "Poison Control Centre." Research articles before 1997 established a baseline for research quality[2]. Research articles from 1997 to April 2020, served as the intervention group assessing for changes in the quality of research and were examined for evidence of toxicovigilance. Articles were included in this study based on the following criteria: written in English; classified as original research; performed in a PCC setting, and the study objective was focused on an identifiable xenobiotic or xenobiotics. Each article was assessed for toxicovigilance based on the following criteria: confirmation of said xenobiotic(s) either qualitatively or quantitatively, study methodology (retrospective or prospective), and clinical recommendations made "beyond the scope of study methodology." If a study did not confirm xenobiotics' presence analytically, the study was considered to make recommendations beyond the scope of the study methodology.
Result(s): Our search initially identified 1614 articles. A random sample of 400 articles was chosen for review. From 1978-1997, 88 articles were initially identified. Twenty-five studies met inclusion criteria. Fifteen were retrospective and ten were prospective. Two studies confirmed exposure confirmation analytically in each group. Ten retrospective studies made clinical recommendations based on their conclusions, none of which confirmed the analytical presence of xenobiotic(s). Ten prospective studies made clinical recommendations with only two analytically confirming the presence of the xenobiotic. From 1998-2020, 138 research studies met inclusion criteria of which 117 were retrospective and 19 were prospective. Of these two groups, 19 and 7 had analytically confirmed xenobiotic presence in the retrospective and prospective studies, respectively. Sixty-eight retrospective studies and ten prospective studies made clinical recommendations without analytically confirming xenobiotic exposures. Comparing the baseline and intervention groups, we observed an increase in the frequency of retrospective studies with a similar proportion making clinical recommendations while lacking confirmation of exposures. There was an increase in rates of xenobiotic confirmation by 2% in the intervention period.
Conclusion(s): Toxicovigilance appears to be lacking in many PCC studies. Despite vast advancements in analytical techniques and the ability to gather and record data, the "Pollyanna Phenomenon" remains vibrant in PCC research. Efforts towards improving the frequency of analytical testing and confirmation of xenobiotic exposure are essential to improve PCC data collection and research and must be considered prerequisites for journal publication. (Table Presented)