INTRODUCTION:Crotalidae polyvalent immune Fab (ovine) is indicated for the treatment of Agkistrodon contortrix (copperhead) envenomation. Medical toxicologists have used lower Crotalidae polyvalent immune Fab (ovine) antivenom doses than those recommended in the prescribing information for the treatment of copperhead envenomation. METHODS:We conducted a single-center retrospective chart review of patients with copperhead envenomation seen by our medical toxicology consult service between January 2001 and June 2023. Patients with dry bites, envenomation by other snakes, no antivenom treatment, treatment with non-Fab antivenom, or inaccessible data were excluded. Trained investigators abstracted data on antivenom dosing, demographics, examination findings, laboratory results, processes of care, and opioid administration from the medical record. The primary aim was to describe antivenom dosing. The secondary aim was to assess the relationship between initial antivenom dose (less than four vials versus four or more vials) and clinical outcomes. RESULTS:We included 143 patients. The median (IQR) initial and total antivenom doses were four vials (two-four vials) and four vials (four-six vials), respectively. Antivenom redosing occurred in 41 cases (29%). Lower initial doses of antivenom were not associated with increases in the Snakebite Severity Score, extent of soft tissue injury, total opioid dose, length of stay, or occurrence of redosing. DISCUSSION:Patients seen by our consult service frequently received lower doses of antivenom than those recommended in the prescribing information, without association with poor in-hospital clinical outcomes. These results are consistent with previous observational studies and, if confirmed by prospective research, may support a change in antivenom dosing strategies for copperhead envenomation that could result in substantial cost savings. CONCLUSION:Our consult service frequently used lower doses of antivenom for copperhead envenomation than recommended in the prescribing information. This practice did not appear to be associated with frequent antivenom redosing, progression of soft tissue injury, higher opioid doses, or increased length of stay.

INTRODUCTION:Arsenic is a metalloid that is highly toxic in its inorganic and organic forms. Ingestion of elemental arsenic is rare. CASE REPORTS:A 33-year-old woman ingested elemental arsenic 10 g purchased online. She experienced brief gastrointestinal upset but was otherwise asymptomatic. She underwent chelation with succimer until it became apparent that she had no toxicologic consequences. She remained asymptomatic at 19-day follow-up. Her spot urine inorganic arsenic concentrations were >5,000 µg/L, 109 µg/L, and 87 µg/L at 12 days, 36 days, and 19 days post-ingestion, respectively. A 20-year-old woman similarly ingested elemental arsenic 10 g purchased online. She presented to care 30 min post-ingestion. Abdominal radiography confirmed the presence of multiple radiodensities. She underwent gastrointestinal decontamination without chelation. She developed no apparent signs or symptoms of arsenic poisoning. Her 24 h urine inorganic arsenic concentration (from hospital day 2) was 253 µg/L. DISCUSSION:The poor water solubility and bioavailability of elemental arsenic may limit its toxicity in acute ingestion. CONCLUSIONS:Elemental arsenic ingestion resulted in no apparent toxicity, despite elevated arsenic concentrations in blood and urine. Elemental arsenic ingestion may not warrant emergent decontamination or chelation.

INTRODUCTION:Consensus guidelines for out-of-hospital assessment and triage of paracetamol (acetaminophen) exposure were published in 2006. Changes in the healthcare system, paracetamol ingestion trends, and availability of paracetamol-containing products necessitate an update to these guidelines. Updated guidelines were created for out-of-hospital management of paracetamol exposure in the United States and Canada. METHODS:A modified Delphi consensus methodology was used to create a decision framework to evaluate clinical aspects of care related to paracetamol overdose in the out-of-hospital setting. Twenty-one panelists were selected by four clinical toxicology societies (America's Poison Centers®, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association for Poison Centres and Clinical Toxicology) to participate as panelists. Guidelines were collected from most poison centers in the United States and Canada, and systematic collection and review of medical literature was conducted. RESULTS:The panel developed a guideline for out-of-hospital management of paracetamol exposure that encompasses acute and repeated supratherapeutic ingestion patterns. Acute ingestion is defined as any ingestion presenting within 24 h of initial ingestion, regardless of ingestion pattern. Repeated supratherapeutic ingestion is defined as an exposure that occurs over a period of 24 h or more. This guideline emphasizes the importance of obtaining accurate history. When ingestion history is determined as accurate, dosage and ingestion pattern are used to decide treatment referral. It is recommended that patients be referred to the emergency department if their ingestion amount is: (1) ≥200 mg/kg or 10 g (whichever is less) within 24 h; (2) ≥150 mg/kg/24 h or 6 g/day (whichever is less) within 48 h; (3) ≥100 mg/kg/24 h or 4 g/day (whichever is less) for more than 48 h. DISCUSSION:The need for standardizing the out-of-hospital assessment and triage of paracetamol exposure is pressing. Despite the availability of acetylcysteine, some patients develop fatal liver failure due to missed diagnoses and delays in treatment. Failure to recognize cases requiring acetylcysteine is associated with significant morbidity and mortality. CONCLUSION:This consensus statement provides evidence-based guidance for out-of-hospital management of paracetamol ingestion to standardize healthcare facility referral criteria for paracetamol exposed patients.

Objective Acute isoniazid toxicity causes refractory seizures due to pyridoxine deficiency-mediated gamma-aminobutyric acid depletion. While pyridoxine is the established antidote, its limited availability in emergency settings necessitates alternative treatments. This study aimed to evaluate the anticonvulsant efficacy of propofol, a GABA A receptor agonist and N-methyl-D-aspartate receptor antagonist, compared to pyridoxine and diazepam in isoniazid-induced seizures in mice. Methods Thirty-two Swiss albino mice were pretreated with: (1) normal saline (10 mL/kg), (2) pyridoxine (300 mg/kg), (3) propofol (50 mg/kg), or (4) diazepam (2.5 mg/kg), followed by isoniazid (300 mg/kg) after 30 minutes. All drugs were administered intraperitoneally. Seizure latency, duration, time to death, and survival were monitored for 120 minutes. Outcomes were analyzed using Kaplan-Meier/log-rank tests and ANOVA with Tukey’s post-hoc test. Results Isoniazid induced seizures and 100% mortality in the control group. Pyridoxine did not prevent seizures or improve survival (8/8 seizures and deaths). Propofol failed to improve seizure frequency, latency, duration, mortality, or time to death (8/8 seizures and deaths). Diazepam significantly reduced seizure frequency and mortality to 1 of 8 mice (p < 0.001), and delayed seizure onset. Conclusion Pretreatment with either propofol or pyridoxine failed to protect against isoniazid-induced seizures and death in mice. In contrast, diazepam was effective in preventing both seizures and death. Further studies are needed to investigate different propofol administration protocols and alternative animal models. ### Competing Interest Statement The authors have declared no competing interest.

The epidemic of illicit fentanyl use continues in the United States. Xylazine, a veterinary tranquilizer closely related to clonidine, is now a widespread adulterant in illicit fentanyl. More recently medetomidine (racemic version of dexmedetomidine) has appeared with increasing frequency in the fentanyl supply. Specific reversal agents for xylazine and medetomidine such as atipamezole and tolazoline have decades of approved use in animals and favorable experimental use in humans. However, an expert panel in 2024 opined that research into human use of alpha-adrenergic agonist was neither "necessary nor worthwhile". We disagree. We outline the unmet need for reversal agents for xylazine and medetomidine, discuss their human evidence of effectiveness, and suggest the path forward as the fentanyl epidemic continues to evolve.

Dear Editor, We read with interest the case report by Downey et al1 However, the authors fail to corroborate their speculation that propylene glycol (1,2-propanediol; PG) was the cause of her elevated lactate at the second hospital. We believe that the history of chronic cornstarch ingestion (amylophagia) is a "red herring." PG toxicity includes high anion gap metabolic acidosis, hyperosmolality, acute kidney injury, and elevated lactate without other explanation.2-4 However, other conditions—such as diabetic ketoacidosis and shock—have similar features. The diagnosis requires a verified PG exposure and, ideally, laboratory detection of PG. This case has neither of these. The authors assert without any reference that "cornstarch contains PG." The authors cite another case report mentioning a call to an unidentified cornstarch manufacturing company stating they do "not have specific data regarding PG content in our corn starch."5 The two leading brands of cornstarch in the US are Argo® (ACH Food Companies, Inc., Oakbrook Terrace, IL) and Clabber Girl® (Clabber Girl Corp., Terre Haute, IN). Both display "100% pure" and list cornstarch as the only ingredient. These do not contain PG. Her apparent rise in lactate concentration has an alternate explanation. Between the first lactate of 63.96 mg/dL (7.1 mmol/L) and the second lactate concentration of 173.69 mg/dL (19.3 mmol/L), she received 1 L of intravenous lactated Ringer's solution (LR). Lactated Ringer's solution contains 28 mmol/L of lactate.6 If the second blood draw came from the line used to infuse the LR, this would artificially increase the apparent lactate concentration.7 The reported serum osmolality from the referring hospital laboratory might be unreliable. Pires et al8 found that some hospitals could not easily measure osmolality on site. At least three hospital laboratories (among 38 respondents) acknowledged calculating osmolality but reporting it as "measured" osmolality. If the referring hospital used this practice, it would explain the reportedly normal osmolal gap at the referring emergency department (ED) followed by an increased osmolal gap at the children's hospital without speculating about PG exposure. Shock, which became manifest in this case, can also elevate osmolality.9 The patient reported daily ingestion of "one box" of cornstarch for 6 months. There is no clear mechanism to explain how amylophagia abruptly caused her acute illness. The patient had acute chest pain, shock requiring norepinephrine infusion, and a sharp rise in troponin concentrations. The authors offer no explanation for the troponin concentration peaking at 4832.90 ng/L—nearly 350 times the upper limit of normal (<14 ng/L). An acute viral illness with viral myocarditis would explain all the clinical and laboratory features of this case. The present case has no measurement of PG and no evidence of PG in the cornstarch. Neither PG ingestion nor amylophagia caused her acute illness. In the words of the fictional sleuth Sherlock Holmes, "It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts."10 The authors declare no conflict of interest. The authors have not received any grants or other financial support for this study. There was no prior presentations by the authors on this topic.