Sanders T, Murphy C, Davis G
… +4 more, Aspinwall C, Theriot L, McVicker C, Arnold T
J Med Toxicol
· 2025 Oct · PMID 40892140
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INTRODUCTION: Copperheads and cottonmouths are responsible for most snake envenomations in Louisiana. While the United States Food and Drug Administration has approved both Crotalidae polyvalent immune Fab (FabAV) and Cr...INTRODUCTION: Copperheads and cottonmouths are responsible for most snake envenomations in Louisiana. While the United States Food and Drug Administration has approved both Crotalidae polyvalent immune Fab (FabAV) and Crotalidae immune F(ab') (Fab2AV) for Agkistrodon envenomations, data is limited comparing their efficacies for this indication. METHODS: This is a retrospective study comparing FabAV to Fab2AV in the treatment of suspected Agkistrodon envenomations in Louisiana between April 2017 and October 2024. Cases identifying rattlesnakes were excluded. The primary outcome was the need for additional antivenom doses to achieve control after the initial antivenom dose. RESULTS: One hundred fifty-eight patients received FabAV or Fab2AV, with 100 cases meeting inclusion criteria. Fifty-seven patients received FabAV and 43 received Fab2AV. The snake was identified as copperhead in 48 cases, cottonmouth in 23, and unidentified in 29. In the FabAV cohort, the initial number of vials ranged from four to 12 with a median dose of four vials. Nine FabAV cases (16%) required additional vials for initial control after the first dose. In the Fab2AV cohort, all patients received 10 vials initially, with 24 cases (56%) requiring additional vials for initial control after the first dose. There was a significant difference in the percentage of patients requiring additional control vials between FabAV and Fab2AV. CONCLUSION: In this cohort of suspected Agkistrodon envenomations, control with initial recommended dosing was more often achieved with FabAV compared to Fab2AV (84% vs. 44%). The results suggest potential benefit to hospitals stocking FabAV in Louisiana and possibly other Agkistrodon-predominant regions.
Murphy C, Runyon M, Gellar M
… +3 more, Rozario N, Patterson CG, Kerns Ii WP
J Med Toxicol
· 2025 Oct · PMID 40760267
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INTRODUCTION: Calcium channel antagonists contribute to many overdose related deaths each year and treatment options are limited. Hydroxocobalamin has shown promise in reversal of multiple shock states, and we evaluated...INTRODUCTION: Calcium channel antagonists contribute to many overdose related deaths each year and treatment options are limited. Hydroxocobalamin has shown promise in reversal of multiple shock states, and we evaluated its use in the treatment of nifedipine-induced shock in a swine model. METHODS: Twenty-two swine (39 to 50 kg) were anesthetized, instrumented, and acclimatized. Toxicity was induced by administering a nifedipine infusion at 0.0266 mg/kg/min. Once the toxic end point, defined as a 20% decrease from the initial mean arterial pressure, was reached, all animals received a 20 mL/kg bolus of saline and either 60 mL of saline (NP group) or 150 mg/kg of hydroxocobalamin dissolved in 60 mL of saline (NP + HX group). Hemodynamics were analyzed and compared between the NP and NP + HX groups over time using linear mixed models with Bonferroni correction. RESULTS: Modeling of the hemodynamic data demonstrated an increase in both systolic blood pressure and change in MAP from the nadir. Mean arterial pressure (MAP) and diastolic blood pressure were increased (p < 0.01) in the NP + HX group at multiple time points. There were no differences detected in the time-to-death between groups. CONCLUSION: Improvements in hemodynamics were noted in the group treated with hydroxocobalamin, but there was no evidence for improvement in mortality. Given this, hydroxocobalamin may serve a role in bridging patients to high dose insulin, vasopressors, extracorporeal membrane oxygenation, or transfer to a higher level of care.
Culbreth R, Mazer-Amirshahi M, Mycyk MB
… +4 more, Falise A, Brent J, Aldy K, Wax P
J Med Toxicol
· 2025 Oct · PMID 40751111
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In recent years, medical toxicology research has evolved from relying heavily on case reports and case series to more rigorous methodologies, including randomized controlled trials and high-quality systematic reviews. En...In recent years, medical toxicology research has evolved from relying heavily on case reports and case series to more rigorous methodologies, including randomized controlled trials and high-quality systematic reviews. Engaging patients as partners in research is increasingly recognized as a promising approach to generate evidence that is trusted, meaningful, and useful to clinicians, policymakers, as well as patients and community members. The American College of Medical Toxicology (ACMT) recently conducted a patient engagement project to promote meaningful research engagement with patients who have lived experiences with overdoses. This review intends to provide an overview of patient-centered outcomes research (PCOR) for the field of medical toxicology, which includes study design considerations, planning for recruitment of patients and stakeholders, and supporting sustainable partnerships.
D'Aloia M, Smith D, Boley R
… +4 more, Schamber E, Thorpe D, Thompson TM, Chhabra N
J Med Toxicol
· 2025 Oct · PMID 40745148
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BACKGROUND: Fomepizole has been suggested as adjunctive therapy for severe acetaminophen poisoning though clinical efficacy is unknown. We sought to determine trends in the use of fomepizole for acetaminophen poisoning....BACKGROUND: Fomepizole has been suggested as adjunctive therapy for severe acetaminophen poisoning though clinical efficacy is unknown. We sought to determine trends in the use of fomepizole for acetaminophen poisoning. METHODS: This is a cross-sectional analysis of hospitalized patients with acetaminophen poisoning from January 2013 through December 2024, using Epic Cosmos, a research database of 298 million patients nationally. We identified encounters involving acetaminophen poisoning by International Classification of Diseases, version 10 (ICD-10-CM) code. Data extracted included administration of N-acetylcysteine (NAC) and fomepizole, demographic data, and outcomes of death and liver transplantation. Data were analyzed using descriptive statistics to identify trends and multivariable logistic regression to determine associations with death. RESULTS: There were 114,111 hospital encounters involving acetaminophen poisoning with 64,957 (56.92%) receiving NAC, and 1,552 (1.36%) receiving fomepizole. In 2013, 0.44% of NAC-treated acetaminophen poisoning cases also received fomepizole. This rose to 6.27% in 2024. From 2013 to 2019, the proportion of NAC-treated acetaminophen cases receiving fomepizole was stable, but from 2019 to 2024, there was a 1029.64% increase in fomepizole use. Regression modeling indicated increased odds for death (OR = 5.88, aOR = 5.32 [95% CI: 4.52, 6.27]) among those who received fomepizole in addition to NAC, indicating increased fomepizole use in patients with severe toxicity. CONCLUSION: Fomepizole use in acetaminophen poisoning has risen dramatically since 2019, particularly among patients at highest risk for death and liver transplantation. It is of critical importance to determine the efficacy of fomepizole for acetaminophen poisoning.
Hendry-Hofer TB, Severance C, Haberkorn CJ
… +8 more, Wetmore N, West WG, Sultana S, Lippner DS, Rhoomes MO, Logue BA, Rockwood GA, Bebarta VS
J Med Toxicol
· 2025 Oct · PMID 40730696
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INTRODUCTION: Cyanide poisoning poses an ongoing threat to military personnel and civilian populations. FDA approved antidotes require intravenous administration which can be challenging to accomplish in austere environm...INTRODUCTION: Cyanide poisoning poses an ongoing threat to military personnel and civilian populations. FDA approved antidotes require intravenous administration which can be challenging to accomplish in austere environments. Intranasal (IN) delivery is an innovative approach to developing easy to administer medical countermeasures for field use. Rapid absorption through the nasal mucosa and passage of dimethyl trisulfide across the blood-brain barrier could enhance effectiveness in mitigating cyanide toxicity. METHODS: An acutely lethal swine model of cyanide poisoning was used to assess the efficacy of IN dimethyl trisulfide (DMTS) on survival, clinical outcomes, and cognitive function. Swine were anesthetized and instrumented for monitoring of vital signs and blood sampling prior to exposure to potassium cyanide. Cyanide exposure continued until 6 min after apnea occurred. Upon cessation of cyanide exposure IN DMTS (n = 12) or saline control (n = 6) was administered. Six animals from the DMTS treatment group were survived for 7 days post treatment to assess for cognitive deficits following rescue. RESULTS: Prior to experimentation physiological and laboratory characteristics were similar across both study groups. Following treatment, survival in the DMTS group was 75% compared to 0% in the control group (p = 0.0014). Blood lactate concentration in the DMTS group was significantly improved (i.e., lower) compared to controls (p < 0.0001; 6.78 ± 4.58 vs. 17.22 ± 2.56 mmol/L, respectively). Additionally, swine treated with IN DMTS demonstrated no long-term cognitive deficits 7 days post rescue. CONCLUSION: Treatment with IN DMTS improved survival and clinical outcomes in an acutely lethal porcine model of cyanide poisoning.
Jones S, Li I, Gale J
… +3 more, Fox E, Weisberg S, Carreiro S
J Med Toxicol
· 2025 Oct · PMID 40637791
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INTRODUCTION: C4 is a plastic explosive commonly used in military applications, and is predominantly composed of cyclonite or RDX (Royal Demolition Explosive). C4 toxicity is a documented but not commonly known cause of...INTRODUCTION: C4 is a plastic explosive commonly used in military applications, and is predominantly composed of cyclonite or RDX (Royal Demolition Explosive). C4 toxicity is a documented but not commonly known cause of altered mental status and recurrent seizures. CASE REPORTS: We describe two cases of military personnel who ingested C4 as part of a hazing ritual who presented to the emergency department with witnessed seizure, tremor and petechial rash. One of the patients had a second witnessed seizure within hours of ingestion. They were treated with intravenous benzodiazepines acutely, then with levetiracetam for 48 hours. Both patients were observed in the intensive care unit and discharged with no neurologic sequelae. DISCUSSION: C4 is a common military-grade explosive containing cyclonite which functions as a non-competitive, reversible GABAA antagonist and a rare but clinically significant cause of altered mental status and seizures when ingested. Management is primarily supportive with airway protection and treatment with GABAergic medication.
J Med Toxicol
· 2025 Jul · PMID 40536638
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Poisoning is a major public health issue and one of the leading causes of injury related death in the US. Poisonings result from intentional or unintentional use of prescription drugs or illicit overdose including opioid...Poisoning is a major public health issue and one of the leading causes of injury related death in the US. Poisonings result from intentional or unintentional use of prescription drugs or illicit overdose including opioids, inhalation of toxic fumes, ingestion of contaminated food or drinking water, and envenomations. The cost of poisonings to US health care is large, especially when considering the costs of addiction and illicit opioids. As specially trained physicians, medical toxicologists play a major role in the treatment and care of poisoned patients while improving patient care, population health, and health care systems related to chemical exposures and poisonings including prevention. They also play a major role in the opioid epidemic and in caring for patients with opioid use disorder and substance use disorders more broadly. Regardless of these important roles, the recognition and knowledge of the value that medical toxicologists provide to health and the health care system is limited. As reimbursement becomes linked to outcome in a value-based care (VBC) market, medical toxicologists must continue to demonstrate their value to stakeholders. The American College of Medical Toxicology (ACMT) has long recognized the need for medical toxicologists to articulate their value and to advocate for themselves, the profession, and for the patients they serve. To that end, modeling infectious disease (ID) efforts in establishing value for their specialty, this paper outlines the 'value' of medical toxicologists in improving patient outcomes, and their positive impact on population health and health care systems.
J Med Toxicol
· 2025 Jul · PMID 40471523
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INTRODUCTION: Subcutaneous elemental mercury injection is typically not associated with systemic toxicity. This case report describes a man who developed persistent membranous nephropathy temporally associated with inten...INTRODUCTION: Subcutaneous elemental mercury injection is typically not associated with systemic toxicity. This case report describes a man who developed persistent membranous nephropathy temporally associated with intentional subcutaneous elemental mercury injection. CASE REPORT: A 21-year-old man injected elemental mercury into his left forearm after experiencing worsening depression during the COVID-19 pandemic. Several months later, he sought dermatology evaluation due to nodularity at the injection site. He underwent attempted excision of what was presumed to be a left forearm lipoma, but he did not report the history of mercury injection. He subsequently developed proteinuria and was diagnosed with membranous nephropathy. Treatment with rituximab did not improve his condition, and he eventually divulged the history of mercury injection three years after the initial exposure. He underwent surgical excision of the mercury deposits, left forearm flap reconstruction, and chelation with oral succimer. Despite these interventions, his proteinuria and urine protein to creatinine ratio remained persistently elevated, consistent with ongoing membranous nephropathy. DISCUSSION: Renal pathology is associated with mercury toxicity after dermal or inhalational exposure but is rarely reported to occur after subcutaneous injection of elemental mercury. The pathophysiology of mercury-induced membranous nephropathy may involve formation of autoantibodies and cytokines after direct renal tubular injury. Surgical excision is the primary treatment for subcutaneous mercury exposure. Chelation may be considered for patients with evidence of systemic toxicity or ongoing mercury exposure, although the optimal timing of perioperative chelation has not been defined. CONCLUSION: Significant systemic toxicity, including membranous nephropathy, may occur after subcutaneous mercury injection.
Gilbert BW, Wilson CS, Kim N
… +2 more, Cox TR, Ortiz MV
J Med Toxicol
· 2025 Jul · PMID 40445505
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Amlodipine and quetiapine are widely utilized medications that are generally well-tolerated at therapeutic doses. However, overdoses can lead to severe, life-threatening cardiovascular effects, leading to refractory vaso...Amlodipine and quetiapine are widely utilized medications that are generally well-tolerated at therapeutic doses. However, overdoses can lead to severe, life-threatening cardiovascular effects, leading to refractory vasoplegia. The management of poly-ingestion overdoses is challenging and often requires aggressive, multimodal treatment strategies especially when the causative agent is unknown. In this case report, a 38-year-old male intentionally ingested a large amount of amlodipine and quetiapine resulting in refractory shock despite high doses of vasopressors, calcium, and insulin therapy. After conventional therapies failed, the administration of exogenous angiotensin II (Ang II), a vasoconstrictor traditionally used for septic shock, led to a marked improvement in the patient's blood pressure and stabilization of hemodynamics. Sixty minutes after initiation of Ang II, the patient's mean arterial pressure (MAP) improved, allowing for the weaning of other vasopressors and a gradual reduction in insulin therapy. This case highlights the potential role of Ang II as a salvage therapy in polysubstance ingestions when other therapies fail.
Glaser T, Culbreth R, Liebelt EL
… +5 more, Ruha AM, Greene S, Campleman S, Spyres MB, ToxIC Snakebite Study Group
J Med Toxicol
· 2025 Jul · PMID 40360965
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BACKGROUND: Evidence regarding acute hypersensitivity reactions (AHRs) to the snakebite antivenoms Crotalidae Polyvalent Immune Fab (ovine) (Fab) and Crotalidae Immune F(ab') (equine) (Fab2) supports no differences. Howe...BACKGROUND: Evidence regarding acute hypersensitivity reactions (AHRs) to the snakebite antivenoms Crotalidae Polyvalent Immune Fab (ovine) (Fab) and Crotalidae Immune F(ab') (equine) (Fab2) supports no differences. However, larger studies may not account for geographic differences. Recent data suggest a correlation with alpha-gal syndrome (AGS). This study investigates the incidence of AHRs in patients receiving Fab2, Fab, or both, with a focus on U.S. states with higher AGS prevalence. METHODS: This is an analysis of native pit viper envenomations reported to the Toxicology Investigators Consortium (ToxIC) North American Snakebite Registry (NASBR) between January 1, 2018, and December 31, 2023. Patients administered Fab2 or Fab on index hospitalization were included. High-AGS and low-AGS regions were defined according to epidemiologic data. The primary outcome was incidence of AHRs after administration of antivenom overall and in high-AGS vs. low-AGS states. Bivariate statistical tests and 95% confidence intervals (CI) for proportions were computed. RESULTS: A total of 1051 patients were identified. Fab2 was administered in 439 cases, and Fab was administered in 722 cases for a total of 1161 cases. Fifty AHRs were analyzed. AHRs were more common with Fab2 (6.6%; 95% CI: 4.6%, 9.3%) compared to Fab (2.9%; 95% CI: 1.9%, 4.4%) in the overall NASBR population (p = 0.004). In low-AGS states, there were 25/421 (5.9%; 95% CI: 4.1%, 8.6%) Fab2 AHRs vs. 16/569 (2.8%; 95% CI: 1.7%, 4.5%) Fab AHRs (p = 0.02). In high-AGS states, the Fab2 group had 4/18 (22.2%; 95% CI: 9.0%, 45.2%) AHRs vs. 5/153 (3.3%; 95% CI: 1.4%, 7.4%) in the Fab group (p = 0.008). CONCLUSION: In this ToxIC NASBR study, administration of Fab2 was associated with a higher incidence of AHRs compared to Fab. The difference was especially notable in states with a higher prevalence of AGS.
Bungatavula D, Greenwood JC, Shofer FS
… +7 more, Buehler G, Kao SH, Kelly M, Shin SS, Ehinger JK, Kilbaugh TJ, Jang DH
J Med Toxicol
· 2025 Jul · PMID 40295447
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INTRODUCTION: Carbon monoxide (CO) is a leading cause of environmental poisoning in the United States with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation,...INTRODUCTION: Carbon monoxide (CO) is a leading cause of environmental poisoning in the United States with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and mitochondrial dysfunction. Currently both biomarkers and therapies for CO poisoning are limited and require new approaches. METHODS: Rats (~ 300 g) were divided into four groups of ten rodents per group (exposure): Control (room air), CO-400 (400 ppm), CO-1000 (1000 ppm) and CO-2000 (2000 ppm). Rodents received the assigned exposure through a secured tracheotomy tube over 120 min followed by 30 min of re-oxygenation at room air for a total of 150 min. Five additional rodents in each group were administered a succinate prodrug (NV354) at the start of exposure for the duration of the experiment until the reoxygenation period as separate experiments. Cortical brain tissue and whole blood were obtained for mitochondrial respiration. Stored plasma and snap frozen tissue stored at -80C were used to obtain protein quantification with Western Blotting. RESULTS: All animals in the Sham, CO-400, and CO-1000 groups survived until the end of the exposure period; no animals in the CO-2000 groups survived the exposure and were counted as attrition. We observed a dose-dependent decrease in key respiratory states in both isolated brain mitochondria and peripheral blood mononuclear cells (PBMCs), and, PBMCs respiration more positively correlated with isolated brain mitochondria when compared to carboxyhemoglobin (COHb). There was no significant difference in mitochondrial respiratory states in animals treated with NV354 compared to the untreated group. CONCLUSIONS: The primary findings from this study include: (1) A dose-dependent decrease with key respiration states with higher concentrations of CO; (2) PBMCs had a higher correlation to isolated brain mitochondria respiration when compared to COHb; and (3) there was no treatment effect with the use of NV354.