Intoxicación con rodenticidas anticoagulantes: serie de casos y revisión de literatura / Intoxication with anticoagulant rodenticides: Case series and review of the literature

Introducción. Los superwarfarinicos (SWF) son una de las herramientas utilizadas por el ser humano para el control de roedores y a la vez son tóxicos para el hombre y pueden conducir a la muerte sin los debidos cuidados en su uso.Casos clinicos. Tres pacientes masculinos, que consultaron por sangrados (gingivorragia, epistaxis, hematuria, hemartrosis y hematomas cutaneos) asociados a alteraciones del coagulograma (Tiempo de protrombina (TP) y tiempo de tromboplastina parcial (KPTT) prolongados). Todos tuvieron exposición a superwarfarinicos. Nuestro servicio no dispone del análisis de SWF en suero. Se administró vitamina K1 en los tres pacientes y plasma fresco congelado (PFC) en uno solo (sangrado mayor: hematuria). El seguimiento se realizó mediante controles seriados de coagulograma y su evolución fue favorable. Discusión. En todos los casos, el diagnóstico de intoxicación por SWF fue clínico, basado en caracteristicas clínicas de pacientes y alteraciones en sus parámetros de coagulación, y debido a imposibilidad de derivación de análisis a otro laboratorio. Se realizo tratamiento especifico (vitamina K1 y PFC) segun recomendación de expertos, ya que no hay hasta la fecha, estudios clinicos que evaluen las diferentes opciones terapéuticas. Conclusión. La intoxicación por SWF aunque no es frecuente, debe sospecharse en casos de paciente con coagulopatia sin otras causas que puedan justificarlo. El manejo del cuadro tóxico es la reposición de vitamina k y de plasma fresco congelado, en casos donde se necesite una rápida corrección de la alteración hemostática, como los sangrados mayores. Es imprescindible la oportuna consulta con médicos hematólogos y/o la consulta con un centro regional de control de intoxicaciones para todas las exposiciones sospechosas por SWF.

Introduction. Superwarfarinics (SWF) are one of the tools used by humans for rodent control. They are toxic to humans and can lead to death without due care in its use. Clinical cases. Three male patients, who consulted due to bleeding (gingivorragia, epistaxis, hematuria, hamartrosis and skin hematomas) associated with coagulogram alterations (prolonged protombine time (PT) and partial thromboplastin time (KPTT)). All them exposure to superwarfarinics. SWF serum analysis was not available in our hospital. Vitamin K1 was administered in all three patients and fresh frozen plasma (PFC) in only one (major bleeding: hematuria). The followup was performed by serial coagulogram controls and the evolution was. Discussion. In all cases, the diagnosis of SWF intoxication was clinical, based on clinical characteristics of patients and alterations in their coagulation parameters, due to the impossibility of deriving the analysis of SWF in serum to another laboratory. Specific treatment was carried out (vitamin k and PFC) according to experts' recommendation, since there are no clinical studies to evaluate the different therapeutic options to date. Conclusion. SWF poisoning, although not frequent, should be suspected in patients with coagulopathy without other causes that may justify it. The management of toxic symptoms is the administration of vitamin K1 and fresh frozen plasma, in cases where a rapid correction of the haemostatic alteration is required, such as major bleedings. It is essential to consult with hematologists and / or consult a regional poison control center for all suspicious exposures by superwarfarins.

Simultaneous determination of 12 rodenticides in whole blood and urine samples by high performance liquid chromatography-tandemmass spectrometry / 中华劳动卫生职业病杂志

Objective@#To develop a method for Simultaneous and rapid determination of 12 rodenticides including pindone, vacor, coumatetralyl, warfarin, diphacinone, coumachlor, chlorphacinon, difenacoum, brodifacoum, bromadiolone, difethialone and flocoumafen in whole blood and urine samples by high performance liquid chromatography-tandem mass (LC-MS-MS) .@*Methods@#The whole blood samples were precipitated with acetonitrile, purified by OstroTM 96-well plate, The urine samples were extracted by acetonitrile, and then separated on a ODS column, analyzed with high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) . The external standard calibration were tested.@*Results@#A good linearity was observed in their respective concentration ranges of 12 rodenticides. The related coefficients were 0.993 0~0.999 8. The limit of detections were 0.05 μg/L~1.4 μg/L. The rates of recovery were 92.5%~118.0%. The relative standard deviations were between 0.8%~17.3%.@*Conclusion@#The method was simple, rapid, sensitive, accurate and suitable for simultaneous detection of the 12 rodenticides in whole blood and urine samples of intoxicated patients.

Rodenticide poisoning in a Toxicological Assistance Center / Intoxicação por raticida em um Centro de Assistência Toxicológica

Objective: to characterize rodenticide poisoning sold illegally under the name Chumbinho. Methods: this is a descriptive and cross-sectional study by retrospective analysis of epidemiological forms of Toxicological Occurrence of a Toxicological Assistance Center, from 2006 to 2013. Results: 115 forms were analyzed, with an annual average of 14.4 ± 4.8 cases and 35.6% of the records in the fourth biennial. Most poisonings occurred in males (57.3%), aged between 15 and 49 years (78.3%) and suicide attempted (90.4%). It was found clinical severity of cases because 92.1% intoxicated required hospitalization and occurred four deaths (3.5%). Conclusion: the cases of poisoning by Chumbinho increased gradually over the studied years, in males, in an economically active age, and by intentional poisoning. There is a need for greater sanitary inspection in the region, aiming to reduce supply and improvement of guidance to consumers.

Objetivo: caracterizar as intoxicações por raticida comercializado clandestinamente sob a denominação de chumbinho. Métodos: estudo descritivo e transversal, por análise retrospectiva de fichas epidemiológicas de Ocorrência Toxicológica de um Centro de Assistência Toxicológica, dos anos de 2006 a 2013. Resultados: foram analisadas 115 fichas, com média anual de 14,4 ± 4,8 casos e 35,6% dos registros no quarto biênio. A maioria das intoxicações ocorreu no sexo masculino (57,3%), na faixa etária entre 15 e 49 anos (78,3%) e pela circunstância tentativa de suicídio (90,4%). Constatou-se gravidade clínica dos casos, pois 92,1% intoxicados necessitaram de internação hospitalar e aconteceram quatro óbitos (3,5%). Conclusão: os casos de intoxicação por chumbinhoaumentaram gradualmente nos anos estudados, em indivíduos do sexo masculino, em idade economicamente ativa e por intoxicação intencional. Há necessidade de maior fiscalização sanitária na região, visando diminuição da oferta e aprimoramento das orientações aos consumidores.

Determination of five anticoagulant rodenticides in whole blood by high-performance liquid chromatography / 中国职业医学

OBJECTIVE: To establish a method for simultaneous detection of 5 anticoagulant rodenticides including brodifacoum, bromadiolone, flocoumafen, warfarin and difenacoum in whole blood by high-performance liquid chromatogarphy. METHODS: The 0. 5 m L of blood sample was extracted by 2. 0 m L ethyl acetate,then separated by Diamonsil C18 column( 250. 0 mm × 4. 6 mm × 5. 0 μm) using acid-ammonium acetate( 20. 0 mmol / L,p H = 5. 5) /methyl alcohol( 2∶ 8,V / V) as a mobile phase and detected by diode-array detector under the ultraviolet spectrum of 310 nm through high-performance liquid chromatogarphy. RESULTS: The good linear range of the 5 anticoagulant rodenticides was0. 50-10. 00 mg / L,and the correlation coefficients were > 0. 999 00. The detection limits of brodifacoum,bromadiolone,flocoumafen,warfarin and difenacoum were 0. 08,0. 06,0. 09,0. 04 and 0. 10 mg / L and the lower limits of quantitation were 0. 79,0. 58,0. 92,0. 45 and 0. 96 mg / L,respectively. The recovery rate was 98. 40%-104. 00%. The within-run relative standard deviation( RSD) was 0. 61%-7. 84%,and the between-run RSD was 1. 10%-9. 62%. The samples can be stored for 14 days in the refrigerator at 4 ℃. CONCLUSION: The method has advantages of simple operation,good separating effect,high sensitivity,precision and accuracy,which is suitable for detection of whole blood samples in rodenticide poisoning patients.

Intoxicaciones con rodenticidas superwarfarínicos / Superwarfarin rodenticide poisoning

Introducción: en la actualidad existe utilización masiva de rodenticidas y su venta no está restringida al público. Las etiologías de intoxicación por estos agentes son variadas pudiendo ser de tipo intencional o accidental. Objetivo: analizar estudios realizados en torno a intoxicaciones con rodenticidas superwarfarínicos en humanos con el propósito de reunir información que oriente a un adecuado tratamiento. Metodología: se realizó una revisión integradora en las bases de datos electrónicas PubMed, TripDataBase, Cochrane, además de Google Scholar y SciELO, libros de divulgación científica, documentos de convenciones, páginas web de instituciones públicas, privadas y artículos vinculados a efectos, cuadro clínico y tratamiento de exposiciones a rodenticidas en seres humanos. Se analizaron los documentos y la información se organizó en tres temáticas: toxicidad de los rodenticidas superwarfarínicos, cuadro clínico y tratamiento médico, y rodenticidas no anticoagulantes disponibles en Chile. Resultados: la dosis tóxica mínima reportada en adultos es de 1 mg de principio activo; en pacientes pediátricos ingestas accidentales rara vez producen síntomas. Los síntomas se observan de forma tardía y su toxicidad es variable. El examen de elección es el International Normalized Ratio (INR) y se realiza en todo paciente con factores de riesgo presentes. El antídoto no se administra de forma profiláctica y la dosis se ajusta individualmente. Conclusión: en niños las ingestas accidentales no son riesgosas por lo que pueden ser observados en el hogar. Pacientes con ingestas masivas requieren controles de INR por meses por lo que es importante que posterior al alta médica exista una óptima coordinación con nivel primario de atención.

Introduction: Currently there is a widespread use of rodenticides, unrestricted to the public. The exposure to these agents may varied being intentional or accidental. Objective: To analyze studies about superwarfarin poisoning in humans, with the purpose of gathering information to guide proper treatment. Methodology: It was conducted an integrative review in the electronic databases PubMed, TripDataBase, Cochrane, Google Scholar and SciELO, science books (reference textbooks), convention documents, websites from public and private institutions and articles about the effects, clinical manifestations and treatment of human exposures to rodenticides. Documents were analyzed and the information organized into three themes: superwarfarin toxicity, clinical features and medical treatment, and non-anticoagulant rodenticides available in Chile. Results: In adults, the minimum dose reported to cause toxicity is 1 mg of active ingredient. In pediatric patients, accidental intakes rarely produce symptoms. The symptoms of poisoning are usually delayed and its toxicity is variable. The test of choice is International Normalized Ratio (INR) and it is performed in all patients with risk factors. The antidote must not be administered prophylactically and the dose is adjusted individually. Conclusions: Accidental intakes in children are not risky and they can be observed at home. Patients with massive intakes require INR monitoring for months so, it is important that an optimal coordination with primary care facilities still exists after medical discharge.

Manejo terapéutcco de la intoxicación con fluorcetato de sodio (guayaquil®) enn caninos: reporte de cinco casos -201--2013- / Therpeutic managgement of canine poioning with sodium fluoroacetatee (guayaquil®): report of 5 cases -201--2013-

El presente reporte relata el manejo terapéutico de la intoxicación con fluoracetato de sodio dispensado a cinco caninos en la Clínica Veterinaria de Antioquia, Medellín (Colombia), entre los años 2012 y 2013. Cinco pacientes caninos llegaron a consulta con cuadro neurológico, disforia y convulsiones, con una hora de evolución. Los animales entraron en contacto con el fluoracetato de sodio (rodenticida Guayaquil®) por vía oral. Los pacientes fueron sometidos a un protocolo de manejo que incluyó canalización de vena cefálica externa a solución lactato de Ringer, así como control de las convulsiones con pentobarbital (10 mg/kg) endovenoso como dosis inicial, después de lo cual fueron intubados. Recibieron además etanol (28%, 10 ml/kg diluidos en solución de Hartmann), gluconato de calcio (1 mg/kg en infusión) y guayacolato de glicerilo (110 mg/kg, endovenoso lento). Los pacientes fueron evaluados respecto de sus constantes fisiológicas y estado neurológico según la escala Glasgow. Se mantuvo el protocolo citado hasta obtener ausencia de signos convulsivos, disforia y delirio. Los cinco pacientes sobrevivieron a la intoxicación y el promedio de recuperación fue de tres días. Aunque no se pudo determinar ocurrencia de secuelas neurológicas posteriores a la intoxicación, los pacientes recibieron control médico durante 15 días. El manejo oportuno del cuadro tóxico, con anticonvulsivantes, soluciones alcalinizantes, gluconato de calcio, guayacolato de glicerilo y etanol, demostraron ser efectivas como estrategias para el manejo de la intoxicación por fluoracetato de sodio.

This paper aims to report on therapeutic management of poisoning with sodium fluoroacetate in five dogs, who were attended at the Veterinary Clinic of Antioquia, Medellin (Colombia), between 2012 and 2013. Five canine patients arrive to consult with neurological, dysphoria, and upheaval states, with an hour of evolution time; all animals came into oral contact with sodium fluoroacetate (Guayaquil™ rodent killer). The five canines underwent a management protocol with channeling external cephalic vein, Ringer lactate solution (Hartmann), seizure control with Pentobarbital (10 mg/kg IV initial dose), then intubated, and received: ethanol (28%, 10 ml/kg diluted in Hartmann), calcium gluconate (1 mg/kg infusion) and glyceryl guaiacolate (110 mg/kg, intravenous slow). All patients were evaluated in their constant physiological and neurological status following the Glasgow scale. The protocol was maintained until no signs seizure, dysphoria and delirium remained. The five patients survived the poisoning with an average recovery of three days. Neurological consequences could not be determined after intoxication. The patients received medical control 15 days later. The timely handling of the toxic substance with anticonvulsant, alkalizing solutions, calcium gluconate, and ethanol glyceryl guaiacolate proved to be effective strategies for the management of sodium fluoroacetate poisoning.

Impact on Morbidity & Mortality by Rodenticidal Poisoning.

Background : Rodenticidal poisoning is a very common clinical entity regularly encountered in outdoor & emergency department in various parts of India. This is the commonest type of poisoning. We present the prospective study of clinical profile, course, complication & outcome of various rodenticidal poisoning in 170 patients. Objectives : To determine the clinical symptoms, morbidity and mortality in various rodenticidal poisoning. To study the clinical profile & laboratory investigations. To study the course, complications & outcome. Methods : Study period was from 01 May 2011 to 30 April 2012. Historically and documented evidence of 170 patients of various rodenticidal poisoning admitted in the emergency, medical wards & I.C.U. under department of medicine, undergone for various laboratory investigations and imaging study. Statistical analysis was done in mean, range, standard deviation and percentage. Results : A total of 170 cases of various rodenticidal poisoning admitted in MBS hospital, Govt. Medical College, Kota were studied. The age of patients ranged from 10 to 65 years. Age groups were divided in four group, 10-18, 19-30, 31-45 & 45-65. Most common age group was ranged from 18-30 year. Most common gender was female (females 92 males 78). Mode of poisoning were suicidal, accidental & homicidal. Commonest mode of poisoning was suicidal uptake of poison. Route of poisoning was ingestion. Common presenting signs & symptoms were nausea & vomiting seen in 157(92.35%), Tachycardia in 156(91.7%), Tachypnoea in 137(80.62%), & Abdominal pain 129(75.8%). Few patients presented with Headache, Palpitation & Sweating. Deranged laboratory findings on day third of admission include Anemia in 21.76%, Leucocytosis in 20.59%, prolonged Prothrombin time (PT) in 16.47% & increased serum Bilirubin in 11.18%. Morbidity developed in 8 cases(4.71%), Of which four have Hemorrhagic complication ( e.g. Bleeding gums, Purpura Melena & Hematuria) by Dicoumarol , Bromadiolone and Brodifacoum. Three patients of Zinc phosphide poisoning produced cardiac insult and one patient of Barium carbonate poisoning developed cardiac arrhythmia. Transient arrhythmias and respiratory failure developed in other rodenticidal poisoning. All patients treated symptomatically and according to complications. Six cases of our study remained asymptomatic for two to three days then they developed delayed hemorrhagic complication ( Bleeding gums, Purpura, Melena & Hematuria). These patients had deranged liver function test (LFT) & prolonged Prothrombin time (PT). Mortality was seen in 1.76%( 3 cases). By Zinc phosphide in 2 patient and Barium carbonate in 1 patient. Conclusion : We concluded that bleeding, bruising & other hemorrhagic complications should be treated and monitored according to Prothrombin time (PT) & INR. Awareness should be increased especially for Zinc phosphide and arrhythmia produced by Barium carbonate.

Clinical analysis of 45 patients with acquired deficiencies of vitamin K-dependent coagulation factors / 中国综合临床

Objective To explore the acquired deficiencies of vitamin K-dependent coagulation factors in etiology, clinical characteristics and treatment. Methods Retrospective analysis was performed on the data of etiology, clinical manifestations of 45 patients with acquired deficiencies of vitamin K-dependent coagulation factor. All patients were treated with Vitamin K1 10 -40 mg/d, i. v. , for three months. Some patients with severe blooding were additionally treated with fresh freezing plasma or prothromibin complex. Prothrombin time(PT) and activated partial thromboplastic time(APTT) were measured using Stago automatic blood coagulation analyzer before and after treatment. Ⅱ , Ⅶ, Ⅸ and Ⅹ were measured in some patients. Results Among the 45 cases, no certain cause was found in 19 cases (42.2%), anticoagulant rodenticides poison was a common cause ( 11 cases,42.3% ). The main presentations was hemorrhage, the most common bleeding sites were mucosa (77.8%) (35/45)and hematuria (46.7%) ( 21/45 ). After vitamin K1 treatment, PT and APTT had shortened remarkably from ( 110.35 ± 35.36 ) s,(98.91 ±48.98)s to (13.48 ±2. 17)s,(33.25 ±6.95)s,respectively(t=19.10 and 6.19,Ps ＜0.01)and the activities of factor Ⅱ、Ⅶ、Ⅸ、Ⅹ had rapidly increased from ( 17.48 ± 10.93 ) %, ( 10.23 ± 5.68 )%, ( 11.98 ±4.69)%,(12.93±7.48)% to (70. 12 ±21.31)%,(92.76 ±29. 15)%,(88.64 ±40. 21)%,(63.97 ±20.11)%(t=12.13,14.43,13.27and9. 74,respectively,Ps＜0. 01).Conclusions The histories of patients with acquired deficiencies of vitamin K-dependent coagulation factors are usually hiding, therefore it is easily misdiagnosed. It is worth of detecting PT and APTT in diagnosis and monitoring. Using vitamin K1 10 -40 mg/d is effective and safety.

Korean Patients with Superwarfarin Intoxication and Their Outcome

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

A Successful Treatment of Patient with Fatal Complications after beta-fluoroethyl acetate Ingestion

The highly toxic sodium monofluoroacetate (SMFA) was banned as a rodenticide in this country in the 1980s. The fluoroacetate metabolite, fluorocitric acid blocks cellular metabolism by inhibiting the Klebs cycle, producing wide spread clinical effects including respiratory, neurologic, cardiologic, and fluid-electrolyte abnormalities. We report the survival case by continuous renal replacement therapy from fatal complications after beta-fluoroethyl acetate ingestion. 61-year old male was brought to our emergency center with chief complaint of beta-fluoroethyl acetate ingestion. Soon after 80 minutes of hospital admission, he developed the symptoms of mild metabolic acidosis, respiratory failure, coma, transient tachycardia, and refractory hypotension. On the second hospital day, we guessed that drug induced severe rhabdomyolysis and renal failure were in progress. At 28 hours after hospital admission, we started the continuous renal replacement therapy (CRRT) with the informed consent. Dramatically, at 24 hour after beginning the CRRT, the patient were completely recovered from coma, respiratory failure, and refractory shock, although severe rhabdomyolysis and renal failure still existed. Additionally, four times of hemodialysis were performed. On 25th hospital admission, he discharged with non oliguric renal failure state, arranging to return to out patient department.

Caracterização química dos raticidas granulados comercializados na cidade de Belém-Pará / Chemical identification of granulated rodenticides market in Belém-Pará

Objetivo: caracterizar a composição química dos raticidas granulados comercializados na região metropolitana de Belém - Pará. Método: triagem por cromatografia em camada delgada de 120 amostras de raticidas emfeiras livres e outros estabelecimentos comerciais na região metropolitana de Relém. Resultado; amostras analisadas foram positivas para carbamatos, 25% para organofosforados e 5% para cum encontradas 15% da associação carbamato e organofosforado. Conclusão: os carbamatos foram os mais encontrados (55%).

Objective: this work aimed the chemical identification of granulated rodenticides market in Belem-Para, for help in the diagnosis and treatment of the intoxicated patients. Method: screening by thin layer chromatography of 120 samples of granulated rodenticides acquired commercial establishments located in the metropolitan region of Belem-Para. Results: 55% of the analyzed samples were positive for carbamate, 25% for organophosphates and, 5% for coumarins. Were founds 15% of carbamate and organophosphate associations. Conclusion: the treatmen and laboratorial evaluation of poisoning for those compounds require differentiated procedures.