Accuracy of a Glycerol Dehydrogenase Assay for Ethylene Glycol Detection.

INTRODUCTION: Ethylene glycol (EG) is a frequently considered toxicant in poisoned patients. Definitive diagnosis relies on gas chromatography (GC), but this is unavailable at most hospitals. A glycerol dehydrogenase (GDH)-based assay rapidly detects EG. A rapid turnaround time and wide availability of necessary instrumentation suggest this method could facilitate the rapid detection of EG. METHODS: This is a prospective, observational analysis of banked, remnant serum samples submitted to the laboratory of a large, multi-hospital healthcare system. Samples were submitted over a 12-month period for the explicit purpose of testing for suspected EG ingestion. All samples underwent GC and the GDH-based assay. RESULTS: Of the 118 analyzed samples, 88 had no EG detected by GC, and 30 were "positive." At the manufacturer's threshold of 6 mg/dL EG, there was 100% (95%CI; 88.7-100) positive percent agreement (PPA) and 98% (92.1-99.6) negative percent agreement (NPA). Adjusted to a threshold of 9 mg/dL, both the PPA and NPA were 100%. Deming regression of the observed concentrations revealed a slope of 1.16 (1.01 to 1.32) and intercept of -5.3 (-8.9 to -1.7). CONCLUSIONS: The GDH assay provides a sensitive and specific method for the detection and quantification of EG that is comparable to a GC-based method. More widespread use of this rapid, inexpensive assay could improve the care of patients with suspected toxic alcohol exposure. Further study is needed to evaluate the test performance in real-time patient treatment decisions.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Fomepizole should be used more liberally in paracetamol overdose.

Growing clinical and basic science data support the use of fomepizole as an adjunct to N-acetylcysteine in paracetamol poisoning. This safe antidote may be helpful in severely poisoned patients.

61-year-old woman • nausea • paresthesia • cold allodynia • Dx?

► Nausea ►Paresthesia ► Cold allodynia.

Fomepizole as an adjunctive therapy for acetaminophen poisoning: cases reported to the toxicology investigators consortium (ToxIC) database 2015-2020.

INTRODUCTION: Fomepizole inhibits formation of toxic acetaminophen (APAP) metabolites and may prevent or reverse mitochondrial toxicity. Given these mechanisms, it may be beneficial in patients with severe APAP toxicity. Current patterns of use for this indication are not well-studied. METHODS: This is a secondary analysis of patients enrolled in the Toxicology Investigators Consortium (ToxIC) database from January 2015 to July 2020. We queried cases in which APAP was listed as an ingested agent and fomepizole was also administered. We excluded cases in which APAP was not the primary agent, N-acetylcysteine (NAC) was not administered, or fomepizole was explicitly administered for another indication. Additionally, we sent a survey to each ToxIC site that administered fomepizole for APAP toxicity to better understand when, why, and how they were using it for this indication. RESULTS: Twenty-five cases of fomepizole administration following an APAP ingestion met our inclusion criteria. There were one to four cases per year between 2015 and 2019 and eight cases in 2020. Seventeen of 25 (68%) cases were for a known acute ingestion. Eighteen of 25 (72%) patients developed hepatotoxicity (AST or ALT > 1000 IU/L) and 10 of 25 (40%) developed coagulopathy (PT > 15s). This was an ill patient population, with 18 of 25 (72%) developing metabolic acidosis (pH <7.20), 12 of 25 (48%) were intubated, 9 of 25 (36%) receiving vasopressors, and 6 of 25 (24%) receiving continuous renal replacement therapy. Overall, mortality was 24%. CONCLUSION: The use of fomepizole is increasing in frequency in a small subset of critically ill and acutely APAP-poisoned patients.

Antithrombotic and Antiplatelet Drug Toxicity.

Anticoagulant and antiplatelet drugs target a specific portion of the coagulation cascade or the platelet activation and aggregation pathway. The primary toxicity associated with these agents is hemorrhage. Understanding the pharmacology of these drugs allows the treating clinician to choose the correct antidotal therapy. Reversal agents exist for some of these drugs; however, not all have proven patient-centered outcomes. The anticoagulants covered in this review are vitamin K antagonists, heparins, fondaparinux, hirudin derivatives, argatroban, oral factor Xa antagonists, and dabigatran. The antiplatelet agents reviewed are aspirin, adenosine diphosphate antagonists, dipyridamole, and glycoprotein IIb/IIIa antagonists. Additional notable toxicities are also reviewed.

Metabolic and mitochondrial treatments for severe paracetamol poisoning: a systematic review.

BACKGROUND: Paracetamol (acetaminophen) remains a leading cause of poisoning in Europe, North America, and Australia. For over four decades, acetylcysteine has been the antidote of choice. However, despite the use of acetylcysteine, some patients who ingest very large doses of paracetamol or who reach hospital late in the course of their poisoning, develop acute liver failure. Some will develop metabolic acidosis indicating mitochondrial toxicity. OBJECTIVE: We review the experimental and clinical data reported with the use of cimetidine, fomepizole, and calmangafodipir in the treatment of paracetamol toxicity to determine if these treatments alone or in combination with acetylcysteine might be of benefit. METHODS: We searched Ovid Medline 1946-2020, Embase 1947-2020, Scopus 2004-2020, Cochrane Databases of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov 1997-2020 for records including the concepts of paracetamol poisoning and cimetidine, fomepizole, calmangafodipir, and acetylcysteine. We included basic science studies in animals and all available study types in humans. We reviewed the reference lists of included articles to search for references missed in the original search. We registered the protocol in PROSPERO. RESULTS: We completed all search strategies on 20 August 2019, 27 January 2020, and 15 June 2020. These produced 6,826 citations. We identified and deleted 2,843 duplicate resulting in a total of 3,856 unique citations. After applying inclusion and exclusion criteria, 89 studies remained. The largest numbers of studies described the past use of cimetidine, and the more recent use of fomepizole.Cimetidine: There is good animal evidence that cimetidine blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. Early case reports were inconclusive regarding the benefit to humans in paracetamol poisoning. Two comparative trials found no benefit of cimetidine in paracetamol poisoning, but few patients had severe poisoning.Fomepizole: There is good animal evidence that fomepizole blocks CYP 2E1 with the potential to inhibit the toxic metabolism of paracetamol. There are no comparative trials of fomepizole for acute paracetamol poisoning. Case reports are inconclusive due to multiple other interventions including the use of acetylcysteine in all cases. The benefit of fomepizole as adjunct treatment has not been demonstrated.Calmangafodipir: Calmangafodipir, a drug mimicking superoxide dismutase, has emerged as a potential treatment for severe paracetamol toxicity because the formation of superoxide free radicals appears to explain part of the mitochondrial toxicity of extremely large paracetamol overdoses. Calmangafodipir has reached Phase I/II trial of safety in humans with acute paracetamol overdose. Planning for a Phase III study of efficacy is currently underway. CONCLUSIONS: The vast majority of patients with acute paracetamol overdose enjoy excellent outcomes with acetylcysteine alone. Although cimetidine and fomepizole inhibit CYP 2E1 in animals, there is insufficient evidence to recommend their use either as a primary treatment or adjunct therapy in paracetamol poisoning. Calmangafodipir remains investigational.

Antidotal use of lipid emulsion - the pendulum swings.

Intravenous lipid emulsion (ILE) is a widely accepted treatment for local anesthetic systemic toxicity (LAST), particularly resulting from bupivacaine. The past decade has seen interest in antidotal use of ILE for other poisonings wax and wane. Numerous anecdotes have raised enthusiasm while more rigorous reviews have cast skepticism. The truth may lie between these two poles.We illustrate the recent trends in published reports on ILE. We highlight the gaps in our knowledge and suggest sources of data that may clarify how useful ILE may be for poisonings other than LAST. We offer the example of bupropion, which is hazardous in overdose and which has a Log P (octanol-water partition coefficient) similar to that of bupivacaine.Current data sources including the AAPCC National Poison Data System (NPDS), the ACMT Toxic Investigators Consortium (ToxIC), and a voluntary online registry (www.lipidrescue.org) each give an incomplete view of the problem. We propose analysis of newer NPDS data, which will include ILE as a treatment field code beginning with the 2019 data, and a structured, prospective registry of antidotal use of ILE for poisonings other than LAST.

Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series.

BACKGROUND: Cannabinoid hyperemesis syndrome (CHS) is characterized by symptoms of cyclic abdominal pain, nausea, and vomiting in the setting of prolonged cannabis use. The transient receptor potential vanilloid 1 (TRPV1) receptor may be involved in this syndrome. Topical capsaicin is a proposed treatment for CHS; it binds TRPV1 with high specificity, impairing substance P signaling in the area postrema and nucleus tractus solitarius via overstimulation of TRPV1. This may explain its apparent antiemetic effect in this syndrome. PURPOSE: We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers. METHODS: A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management. RESULTS: All 13 patients experienced symptom relief after administration of capsaicin cream. CONCLUSION: Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed.

Can AST/ALT ratio indicate recovery after acute paracetamol poisoning?

CONTEXT: Paracetamol (acetaminophen or APAP) is the most common pharmaceutical exposure in the US. Elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels indicate hepatic toxicity. AST and ALT levels rise in similar proportions but later decline at different rates, with AST falling more rapidly than ALT. OBJECTIVE: To determine whether the AST/ALT ratio can indicate that a patient has passed the time of peak AST concentration. METHODS: We retrospectively identified cases of patients hospitalized for acute APAP poisoning by querying the pharmacy database of all patients treated with acetylcysteine (NAC) from January 1, 2001 to March 19, 2013. We included all patients with severe APAP poisoning, defined as AST or ALT greater than 1000 IU/L. Patients who were given NAC for other indications, those without APAP poisoning, and those receiving liver transplantation were excluded. We then recorded paired AST and ALT concentrations from each patient's hospital course. We classified each pair as clearly post-peak or not, and calculated the AST/ALT ratio for each pair of values. We compared different thresholds of AST/ALT ratio in increments of 0.1 to find the optimal value that reliably indicated resolving transaminases. RESULTS: We identified 1820 patients who received NAC during the study period. Of these, 333 received NAC for suspected poisoning by APAP. After excluding patients without severe APAP poisoning, other diagnoses explaining transaminase elevations, and patients who underwent liver transplantation, we had 37 evaluable patients with 343 evaluable pairs of AST and ALT concentrations. An AST/ALT ratio less than or equal to 0.4 was 99% sensitive for identifying patients with resolving transaminases. CONCLUSION: An AST/ALT ratio less than or equal to 0.4 following severe hepatoxicity from paracetamol poisoning appears to be highly predictive of recovery in patients treated with NAC. This has potential to be an indicator of safe discontinuation of NAC treatment.

Underdosing of common antibiotics for obese patients in the ED.

BACKGROUND: Obesity is a growing problem in the United States. Obesity alters the pharmacokinetic profiles of various drugs. Although there are guidelines for dose adjustments for many of the antibiotics commonly used in the emergency department (ED), they are seldom used. METHODS: This is an institutional review board-approved retrospective study at an American Society of Metabolic and Bariatric Surgery Center of Excellence and a level I trauma center with annual ED volumes of more than 80,000 visits. Data were retrospectively collected from ED pharmacy records during a 3-month period in 2008. Any first dose of cefepime, cefazolin, or ciprofloxacin administered in our ED to a patient recorded as both more than 100 kg and with a body mass index greater than 40 kg/m(2) was compared with our hospital guidelines and found to either adhere or not adhere to those guidelines. RESULTS: There were 1910 orders found to meet the study criteria: 775 orders for cefepime, 625 orders for cefazolin, and 510 orders for ciprofloxacin. Adherence rates for first dose of cefepime, cefazolin, and ciprofloxacin administered, respectively, were 8.0%, 3.0%, and 1.2%. CONCLUSION: Emergency physicians frequently underdose cefepime, cefazolin, and ciprofloxacin in obese patients. Underdosing antimicrobials presents risk of treatment failure and may promote antimicrobial resistance. Education is necessary to improve early antibiotic administration to obese patients.