Journal of Medical Toxicology最新文献

Background: Evidence regarding acute hypersensitivity reactions (AHRs) to the snakebite antivenoms Crotalidae Polyvalent Immune Fab (ovine) (Fab) and Crotalidae Immune F(ab')₂ (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.

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 -80^oC 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.

Introduction: Although dihydropyridine calcium channel blockers (DHP CCBs) are considered to have less direct myocardial toxicity than non-dihydropyridines, DHPs remain a common cause of morbidity and mortality. We sought to examine various indices of critical illness and describe the clinical course of a population of DHP CCB-poisoned patients with special attention to vasopressor dosing and ischemic complications.

Methods: This is a retrospective chart review of DHP CCB exposures admitted to a single center. The study site was a single tertiary referral center with an in-house medical toxicology consultation/admitting service. Inclusion criteria included age ≥ 14 years and DHP ingestion noted on departmental patient log. Patients were excluded if DHP exposure was not documented in the medical record. The study period ranged from July 1, 2010 through December 31, 2022. Data on clinical presentation, management, and outcomes were reported.

Results: Sixty-eight cases of DHP exposure were analyzed; 87% were intentional ingestions. Amlodipine represented 88% of cases. 85% included cases involved co-ingestions. Vasopressors were administered in 42 cases (62%), with a median of three agents (IQR 1-4). Norepinephrine was most common (N = 41; 98%), followed by epinephrine (N = 23; 55%); median maximal rates were 45.0 (IQR 13.5-70.0) and 25.0 (IQR 12.0-30.0) mcg/min, respectively. 15% (N = 10) received high dose insulin-euglycemic therapy (HIE); all had > 2 vasopressors administered before administration of HIE. Twelve (18%) patients had ischemic complications; five (7%) experienced ischemic complications not evident before vasopressor administration. There were five deaths (7%).

Conclusions: Multiple vasopressor use was common in this population of patients with DHP CCB toxicity. Despite the high doses of vasopressors used, temporally related ischemic complications were uncommon.

Envenomation is a global health issue, with over 9,000 encounters managed in the United States yearly. The introduction of immunoglobulin fragment antivenom has reduced the risk of hypersensitivity. This study compares treatment costs of crotaline envenomation using the Fab and F(ab')₂ antivenoms as reported to the North American Snakebite Registry (NASBR), a nationwide surveillance tool.

Methods: This was a retrospective analysis of NASBR data between 2018 and 2020. The following data points were assessed: patient demographics (age, gender, race), snake species, type of antivenom used, and treatment costs. Unit costs were estimated based on United States Centers for Medicare and Medicaid Services data. Average (mean) per patient costs from the payer perspective were calculated by multiplying resources by the unit costs. Sensitivity analyses were performed regarding cost variance and snake species. All costs reported in this study are in U.S. dollars.

Results: The average total cost of treatment was $31,343 per person, with medications contributing 72% of the total. Average total cost among patients who received Fab treatments was $33,347 per person compared to $19,747 among patients who received F(ab')₂. Antivenom costs accounted for 75% of the total cost in the Fab group and 42% in the F(ab')₂ group. F(ab')₂ required more vials than Fab (median 18 versus 10). Non-antivenom costs such as hospitalizations were higher in the F(ab')₂ group. Using average sale prices increased average total cost to $52,572; Fab remained more expensive.

Conclusion: Antivenom is the primary cost driver in snakebite treatment in North America. Treatment with F(ab')₂ resulted in lower overall costs, driven by lower cost of antivenom. F(ab')₂ did not significantly lower overall resource use except for blood product administration.

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.

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.