Journal of Medical Toxicology最新文献

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.

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.

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.

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.

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.