N-Acetyl Cysteine in Rodenticide Poisoning: A Systematic Review and Meta-Analysis.

BACKGROUND: Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning. METHODS: This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies. RESULTS: Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high. CONCLUSION: Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.

PREVALENCE OF ANTICOAGULANT RODENTICIDES IN FECES OF WILD RED FOXES (VULPES VULPES) IN NORWAY.

High occurrence of anticoagulant rodenticides (ARs) in wildlife is a rising concern, with numerous reports of secondary exposure through predation. Because of widespread distribution of the red fox (Vulpes vulpes), they may act as sentinels for small mammal-hunting predators in rural, suburban, and urban areas. No AR surveillance in wild mammals with analyses of residues in feces has been conducted throughout a single country. We collected 163 fecal samples from presumed healthy red foxes from 18 out of 19 counties in Norway. The foxes were shot during regular hunting between January and December 2016 and samples collected directly after death. Fecal samples were analyzed for six ARs: brodifacoum, bromadiolone, coumatetralyl, difenacoum, difethialone, and flocoumafen. We detected ARs in 54% (75/139) of the animals. Brodifacoum was most frequently detected (46%; 64/139), followed by coumatetralyl (17%; 23/139), bromadiolone (16%; 22/139), difenacoum (5%; 7/139), difethialone (1%; 2/139), and flocoumafen (1%; 2/139). More than one substance was detected in 40% (30/75) of the positive foxes, and 7% (5/75) of these animals were exposed to four different ARs. There were no statistically significant seasonal, age, or sex differences in foxes after exposure to one AR compound. We found a significant difference in occurrence of brodifacoum and coumatetralyl in foxes from different geographical areas. These findings demonstrate fecal analyses as a valuable method of detecting AR exposure in red foxes. We suggest using direct fecal sampling with analyses as a method to evaluate the occurrence of ARs in live endangered wildlife in connection with radio tagging or collaring operations.

Impact of Rodenticides on the Coagulation Properties of Milk.

In this study, we investigated the impact of the rodenticides (strychnine, bromadiolone, and brodifacoum) on milk pH, rennet coagulation time (RCT), and coagulum strength. Sub-lethal amounts of strychnine and bromadiolone produced an unnaturally large change in milk pH, compared to brodifacoum and brodifacoum on milk coagulation properties. All three studied rodenticides significantly affected RCT and coagulum strength. The presence of sub-lethal amounts of each individual rodenticide increased RCT by an overall mean of 17% (p < 0.001). Rodenticide contamination decreased coagulum strength by an overall mean of 26% (p < 0.05). Our results suggest that such changes could be noticeable at the farm, thus, potentially averting the mixture of contaminated milk with the tanker supply, and preventing downstream distribution to consumers.

Long-Acting Anticoagulant Rodenticide (Superwarfarin) Poisoning: A Review of Its Historical Development, Epidemiology, and Clinical Management.

Long-acting anticoagulant rodenticides (LAARs) inhibit vitamin K epoxide reductase (VKOR). Related bleeding may present a diagnostic challenge and require administration of blood component therapy, hemostatic agents, and vitamin K. This article intends to provide the reader a comprehensive understanding of LAAR poisoning. An exhaustive literature search of PubMed, Science Direct, US National Library of Medicine Toxicology Data Network, and Google Scholar yielded 174 reported cases of LAAR poisoning from which clinical data were extracted and reviewed. In addition, 25 years of epidemiologic data from the American Association of Poison Control Centers was reviewed. In the United States, on average, there were 10413 exposures reported with 2750 patients treated annually. For 25 years, there were 315951 exposures reported with nearly 90% among children and more than 100000 patients treated in a health care facility. Fortunately, only 2% of all exposures result in morbidity or mortality. Inhalational, transcutaneous, and oral routes of exposure have been documented. Most exposures are unintentional. The most frequently reported bleeding sites are mucocutaneous, with hematuria being the most common feature. Deaths were most commonly associated with intracranial hemorrhage. Long-acting anticoagulant rodenticide-induced paradoxical thrombosis and thrombotic complications accompanying hemostatic therapy have also been observed. Most patients present with coagulation assay values beyond measurable limits. Long-acting anticoagulant rodenticides have an extremely high affinity for VKOR compared with warfarin, characterized by rebound coagulopathy and bleeding after initial treatment and the need for high-dose, long-term therapy with vitamin K1. Treatment of acute hemorrhagic symptoms often required intravenous vitamin K1 in excess of 50 to 100 mg; chronic maintenance with 100 mg PO vitamin K1 daily was the most frequently used dose required to suppress coagulopathy. Treatment courses averaged 168 days. Adjunctive hemostatic therapy with recombinant factor VIIa and prothrombin complex concentrate has been reported, and phenobarbital has been used to expedite LAAR metabolism.

Simultaneous Determination of Toxic Alkaloids and Rat Poisons in Toxic Samples by Dispersive Liquid-liquid Micro-extraction Combined with Gas Chromatography-Mass Spectrometry / 分析化学

A novel method for simultaneous determination of 3 rat poisons ( tetramine, bromadiolone, brodifacoum) and 5 toxic alkaloids ( hyoscyamine, scopolamine, gelsemine, strychnine, brucine ) in toxic samples by dispersive liquid-liquid micro-extraction ( DLLME ) coupled with gas chromatography-mass spectrometry was established. A mixture extractant containing 100 μL trichloromethane and 600 μL methanol was injected into the prepared sample to form an emulsion and the extraction process was accomplished. After centrifuged at 8000 r/min for 5 min, the settled drop of trichloromethane solvent was transferred to a conical insert within a GC autosampler vessel, and analyzed by GC-MS. Factors affecting extraction efficiency such as the type and volume of extractant, dispersive agent, extraction time, pH value and salt concentration of extraction system were studied. The limits of detection(LODs) were from 0. 003 to 1 μg/L in water sample, urine sample and rice wine sample. LODs were from 0. 002 to 0. 2 μg/kg in rice sample. The recoveries of toxic samples were in the range of 81. 0%-110%. The relative standard deviations( RSDs) were lower than 7%. The proposed method was sensitive, effective, and suitable for the simultaneous determination of toxic alkaloids and rat poisons in food poisoning sample.

Ingestão acidental de brodifacoum por um cão / Brodifacoum accidental ingestion by a dog

Produtos utilizados para controle de roedores ocupam a terceira posição entre as causas mais comuns de exposições a agentes tóxicos em cães. Cerca de 20% dessas exposições resultam em intoxicação (OSWEILER, 1998). A terapêutica adequada e o tempo decorrido entre a ingestão e os primeiros procedimentos são os principais fatores determinantes do sucesso do tratamento, o qual pode ocasionar distúrbios de coagulação e morte do paciente, se não for bem conduzido. Este trabalho relata um caso de ingestão acidental de brodifacoum por um cão e a subsequente abordagem terapêutica emergencial.

Intoxicação por agrotóxicos no Distrito Federal, Brasil, de 2004 a 2007 - análise da notificação ao Centro de Informação e Assistência Toxicológica / Intoxication due to pesticides in the Federal District of Brazil between 2004 and 2007 -analysis of notification to the Toxicological Information and Assistance Center

Exposure to toxic substances, including pesticides, can cause irreversible damage to humans, including death, and is therefore considered a serious public health problem worldwide. This is a retrospective study using data gathered by the Toxicological Information and Assistance Center of Brazil's Federal District (Ciat-DF) between 2004 and 2007. During this period, 709 intoxications with pesticide occurred in the DF and were analyzed in this study. Fifty-one percent of the intoxicated individuals were men; the events occurred mostly in the home (91 percent), in the urban area (86.3 percent) and by ingestion (84 percent). Children from 1 to 4 years of age and adults from 20 to 39 years were involved in 30 percent and 36 percent of the cases, respectively. Accidental intoxication corresponded to 47.1 percent of the cases, followed by attempted suicide (44.2 percent). The illegal rodenticide known as "chumbinho", the main ingredient of which is carbamate insecticide aldicarb, was involved in 35.1 percent of the cases, mostly in suicide attempts. In eighteen cases, the intoxicated individuals died after exposure to the pesticides, namely 15 suicides and 3 accidental poisonings. When compared with other data sources, this study identified a high level of underreporting to the Ciat-DF of intoxication by pesticide during the period under study.

A exposição humana a substâncias tóxicas, incluindo agrotóxicos, pode levar a danos irreversíveis no organismo e até ao óbito, sendo considera um grave problema de saúde pública. Este é um estudo retrospectivo, que utilizou dados reportados ao Centro de Informação e Assistência Toxicológica do Distrito Federal, Brasil (Ciat-DF) referentes a intoxicações por agrotóxicos ocorridas no DF de 2004 a 2007. Nesse período, 709 intoxicações foram notificadas e avaliadas neste estudo. A maioria dos indivíduos envolvidos nas intoxicações foi do sexo masculino (51,2 por cento), intoxicados no domicílio (91 por cento), em área urbana (86,3 por cento) e por via oral (84 por cento). Crianças de 1 a 4 anos e adultos de 20 a 39 anos estiveram envolvidos em 30 e 36 por cento das intoxicações, respectivamente. As intoxicações acidentais corresponderam a 47,1 por cento dos casos, seguidas pelas tentativas de suicídio (44,2 por cento). O raticida ilegal chumbinho, conhecido por conter, principalmente, o inseticida carbamato aldicarbe, esteve envolvido em 35,1 por cento dos casos, principalmente em tentativas de suicídio. Dezoito das intoxicações registradas evoluíram a óbito, 15 por suicídio e 3 por acidente individual. Quando comparado com outras fontes de dados, este estudo detectou uma alta taxa de subnotificação das intoxicações por agrotóxicos reportadas ao Ciat-DF no período do estudo.

Acute hepatic failure due to yellow phosphorus ingestion.

We report a case of three year old girl, who was brought to hospital for accidental consumption of rat-poison (3% phosphorus). The patient was asymptomatic for first 48 hours. Later on she developed the symptoms of hepatic failure. She was managed conservatively and was discharged after 14 days.