Intoxicación por cianuro posterior a infusión prolongada de Nitroprusiato de sodio: a propósito de un caso / Cyanide poisoning following prolonged infusion of Sodium Nitroprusside: A case report / Intoxicação por cianeto após infusão prolongada de nitroprussiato de sódio: a propósito de um caso

El nitroprusiato de sodio fue aprobado desde 1974 como medicamento para las crisis hipertensivas. Desde entonces existe controversia sobre el potencial tóxico del mismo. La toxicidad por cianuro es una complicación poco común del nitroprusiato de sodio, que puede ser difícil de diagnosticar en pacientes críticamente enfermos. Dentro de los factores de riesgo está la utilización de infusiones prolongadas y dosis altas, por lo que se sugiere que la dosis no exceda 2 µg/kg/min. A continuación, se reporta el caso de un paciente de 49 años que ingresa a un servicio de urgencias después de un síndrome cerebrovascular y una emergencia hipertensiva que requirió infusión de nitroprusiato de sodio, seguida de signos y síntomas, los cuales sugirieron toxicidad. Entre dichos síntomas predominaban los cambios neurológicos, por lo cual fue manejado con hiposulfito de sodio y hubo una buena respuesta. El objetivo de este reporte de caso es sensibilizar al personal de salud sobre la necesidad de un uso adecuado del nitroprusiato y sobre la importancia de sospechar toxicidad en paciente con factores de riesgo.

Sodium Nitroprusside has been approved since 1974 as a medication for hypertensive crises. However, there has been ongoing controversy regarding its potential toxicity. Cyanide toxicity is a rare complication of Sodium Nitroprusside, which can be challenging to diagnose in critically ill patients. Risk factors include prolonged infusions and high doses; hence it is suggested that the dose should not exceed 2 µg/kg/min. Here, we present the case of a 49-year-old patient who entered the emergency department after a cerebrovascular event and a hypertensive emergency that required Sodium Nitroprusside infusion, followed by signs and symptoms suggestive of toxicity. Neurological changes were predominant among these symptoms, and the patient was managed with sodium thiosulfate, resulting in a good response. The objective of this case report is to raise awareness among healthcare professionals about the need for appropriate use of Sodium Nitroprusside and the importance of suspecting toxicity in patients with risk factors.

O nitroprussiato de sódio foi aprovado desde 1974 como medicamento para crises hipertensivas. Desde então tem havido controvérsia sobre o seu potencial tóxico. A toxicidade por cianeto é uma complicação rara do nitroprussiato de sódio, que pode ser difícil de diagnosticar em pacientes gravemente enfermos. Entre os fatores de risco está o uso de infusões prolongadas e altas doses, por isso sugere-se que a dose não ultrapasse 2 µg/kg/min. Relata-se a seguir o caso de uma paciente de 49 anos admitida em pronto-socorro após síndrome cerebrovascular e emergência hipertensiva com necessidade de infusão de nitroprussiato de sódio acompanhada de sinais e sintomas sugestivos de toxicidade. Dentre esses sintomas, predominaram as alterações neurológicas, para as quais foi tratado com hipossulfito de sódio e apresentou boa resposta. O objetivo deste relato de caso é sensibilizar os profissionais de saúde sobre a necessidade do uso adequado do nitroprussiato e sobre a importância de suspeitar de toxicidade em pacientes com fatores de risco.

Intoxicación por cianuro, perspectiva desde urgencias: reporte de dos casos y revisión de la literatura / Cyanide poisoning, perspective from the emergency room: report of two cases and literature review / Intoxicação por cianeto, perspectiva desde urgências: relato de dois casos e revisão da literatura

Aunque poco común, la intoxicación por cianuro acarrea una mortalidad alta, sobre todo, cuando no se administra el tratamiento oportuno. La exposición a este tóxico puede darse por inhalación o por ingestión oral. Lo que se ha descrito sobre el manejo de esta intoxicación está basado en reportes de casos y pequeñas series, dado que en la literatura no se encuentran estudios que den un sustento claro. Dentro de estos reportes, y según los aspectos fisiopatológicos, son especialmente relevantes: el nitrito de sodio, el nitrito de amilo, el tiosulfito de sodio y la hidroxicobalamina, como arsenal terapéutico de esta intoxicación.

Cyanide intoxication is a rare condition. Yet, it leads to a high mortality, especially when proper treatment is not available. The exposure to this substance may occur via inhalation or oral ingestion. The basis of this intoxication´s treatment is on little case series and reports; this is due to the fact that the literature to support it remains scant and unclear. Based on physiopathological aspects, within this evidence the following are particularly relevant: sodium nitrile, amile nitrile, sodium tiosulphite, and hidroxicobalamin, as part of this intoxication´s treatment.

Embora pouco comum, a intoxicação por cianeto provoca uma mortalidade alta, sobre tudo, quando não se administra o tratamento oportuno. A exposição a este tóxico pode dar-se por inalação ou por ingestão oral. O que se há descrito sobre o manejo desta intoxicação está baseado em reportes de casos e pequenas séries, dado que na literatura não se encontram estudos que deem um sustento claro. Dentro destes relatos, e segundo os aspectos fisiopatológicos, são especialmente relevantes: o nitrito de sódio, o nitrito de amilo, o tiossulfato de sódio e a hidroxicobalamina, como arsenal terapêutico desta intoxicação.

Antidotes Stocking and Delivery for Acute Poisoning Patients at 20 Emergency Departments in Korea 2015–2017

PURPOSE: The National Emergency Medical Center has been running a project for the storage and delivery of antidotes for acute poisoning patients of the Department of Health and Welfare, Korea. This study analyzed the results of this project over the past two years. METHODS: The requests received by the National Emergency Medical Center and the data on the delivery process were analyzed. RESULTS: This study analyzed a total of 121 patients with acute poisoning, who were requested to receive an antidote reserved at 20 key hospitals in 2015–2017, and whose age was 52.3±23.5 years; old; 54 were women. Intentional poisoning were 58.7%, and the home was the most common place of exposure (66.9%). The toxic substances were chemicals (32.2%), pesticides (27.3%), medicines (24.8%), and snake venom (4.1%). The patient's poison severity score was 2.4±0.7 (median 3) indicating moderate-to-severe toxicity. Antidote administration was the cases treated in key hospitals 67.8% (82/121), in which transferred patients accounted for 57.3% (47/82). After receiving an antidote request from a hospital other than the key hospitals, the median was 75.5 minutes (range 10 to 242 minutes) until the antidote reached the patient, and an average of 81.5 minutes was required. The results of emergency care were intensive care unit (70.3%), general wards (13.2%), death (10.7%), and discharge from emergency department (5.0%). CONCLUSION: This study showed that the characteristics of acute poisoning patients treated with an antidote were different from previous reports of poisoned patients in the emergency department, and basic data on the time required for delivery from key hospitals was different.

The Effect of Glehnia Littoralis on Alpha-amanitin Induced Hepatotoxicity in a Murine Model

PURPOSE: Glehnia littoralis has been reported to have several pharmacological properties but no in vivo reports describing the protective effects of this plant on α-amanitin-induced hepatotoxicity have been published. α-Amanitin is a peptide found in several mushroom species that accounts for the majority of severe mushroom poisonings leading to severe hepatonecrosis. In our previous in vitro study, we found that α-amanitin induced oxidative stress, which may contribute to its severe hepatotoxicity. The aim of this study was to investigate whether Glehnia littoralis acetate extract (GLEA) has protective antioxidant effects on α-amanitin-induced hepatotoxicity in a murine model. METHODS: Swiss mice (n=40 in all groups) were divided into four groups (n=10/group). Three hours after giving α-amanitin (0.6 mg/kg, i.p.) to the mice, they were administered silibinin (50 mg/kg/d, i.p.) or Glehnia littoralis ethyl acetate extract (100 mg/kg/d, oral) therapies once a day for 3 days. After 72 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurement, and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was assessed by a pathologist blinded to the treatment group and divided into 4 categories according to the grade of hepatonecrosis. RESULTS: GLEA significantly improved the beneficial functional parameters in α-amanitin-induced hepatotoxicity. In the histopathological evaluation, the toxicity that was generated with α-amanitin was significantly reduced by GLEA, showing a possible hepatoprotective effect. CONCLUSION: In this murine model, Glehnia littoralis was effective in limiting hepatic injury after α-amanitin poisoning. Increases of aminotransferases and degrees of hepatonecrosis were attenuated by this antidotal therapy.

Antidote availability in the municipality of Campinas, São Paulo, Brazil / Disponibilidade de antídotos no município de Campinas, São Paulo

ABSTRACT CONTEXT AND OBJECTIVE: The lack of availability of antidotes in emergency services is a worldwide concern. The aim of the present study was to evaluate the availability of antidotes used for treating poisoning in Campinas (SP). DESIGN AND SETTING: This was a cross-sectional study of emergency services in Campinas, conducted in 2010-2012. METHODS: The availability, amount in stock, place of storage and access time for 26 antidotal treatments was investigated. In the hospitals, the availability of at least one complete treatment for a 70 kg adult over the first 24 hours of admission was evaluated based on stock and access recommendations contained in two international guidelines. RESULTS: 14 out of 17 functioning emergency services participated in the study, comprising pre-hospital services such as the public emergency ambulance service (SAMU; n = 1) and public emergency rooms for admissions lasting ≤ 24 hours (UPAs; n = 3), and 10 hospitals with emergency services. Six antidotes (atropine, sodium bicarbonate, diazepam, Phytomenadione, flumazenil and calcium gluconate) were stocked in all the services, followed by 13 units that also stocked activated charcoal, naloxone and diphenhydramine or biperiden. No service stocked all of the recommended antidotes; only the regional Poison Control Center had stocks close to recommended (22/26 antidotal treatments). The 10 hospitals had almost half of the antidotes for starting treatments, but only one quarter of the antidotes was present with stocks sufficient for providing treatment for 24 hours. CONCLUSION: The stock of antidotes for attending poisoning emergencies in the municipality of Campinas is incomplete and needs to be improved.

RESUMO CONTEXTO E OBJETIVO: A carência de disponibilidade de antídotos nas salas de emergência é uma preocupação mundial. O objetivo foi avaliar a disponibilidade de antídotos usados no tratamento de pacientes intoxicados no município de Campinas (SP). TIPO DE ESTUDO E LOCAL: Trata-se de estudo transversal de serviços de emergência de Campinas, realizado de 2010-2012. MÉTODOS: A disponibilidade, quantidade estocada, local de armazenamento e tempo de acesso a 26 tratamentos antidotais foi investigada. Nos hospitais, foi avaliada também a disponibilidade de pelo menos um tratamento complete para um adulto de 70 kg nas primeiras 24 horas da admissão, com base em recomendações de estoques e acesso contidas em duas diretrizes internacionais. RESULTADOS: 14 dentre 17 serviços de emergência em funcionamento participaram do estudo, que incluiu serviços pré-hospitalares, como o Serviço de Atendimento Móvel de Urgência (SAMU, n = 1) e três Unidades de Pronto Atendimento (UPAs, internação limitada até 24 horas), além de 10 hospitais com emergência. Seis antídotos (atropina, bicarbonate de sódio, diazepam, fitomenadiona, flumazenil e gluconate de cálcio) estavam estocados em todos os serviços, seguidos de 13 que também estocavam carvão ativado, naloxona, difenidramina ou biperideno. Nenhum serviço tinha estoque de todos os antídotos recomendados; somente o Centro de Controle de Intoxicações regional tinha estoque próximo ao perfil recomendado (22/26 opções terapêuticas). Os 10 hospitais tinham quase metade dos antídotos necessários para iniciar tratamento, mas somente um quarto dos antídotos estava em estoques suficientes para oferecer tratamento por 24 horas. CONCLUSÃO: O estoque de antídotos para atendimento de emergências toxicológicas no município de Campinas é incompleto e deve ser melhorado.

Research Progress of Binding Targets of Saxitoxin / 中国生化药物杂志

Saxitoxin (STX) is one of the most toxic marine toxins.Scientists have been focusing on STX research due to the potentially pharmaceutical values and serious threat to human safety and health.. This review summarizes the structure, properties, binding targets and combination of structural basis of STX and its analogues in recent years reported. STX can bind Na+, K+, Ca2+channels to suppress the channel ion current, but also combine the bullfrog Saxiphilin protein and puffer fish STX/TTX binding protein (PSTBP) to protect the body from STX toxicity. STX also as a substrate for STX enzymes and affects the activity of nitric oxide synthase, antioxidant enzymes. Furthermore,this review has a comprehensive analysis of these targets of STX and a preliminary discussion of the medicinal value of anesthesia and analgesia and the development of antidotes to STX. It is expected to provide a reference for further study of the nature of STX and its application in various fields.

Caso clínico histórico. Mordedura de serpiente "rabo de ají" en el año de 1968. Viacrucis de un herpetólogo / Case history. "Coral snake" Micrurus mipartitus bite in 1968. A herpetologist's ordeal

Historical clinical case that presented back in 1968 at a time when respiratory support and intensive care techniques were just emerging, with many shortcomings in hospital care areas and monitoring devices. The case is of a 58 year-old patient, outstanding citizen, recent winner in a television contest on snakes, who was bitten accidentally by a coral snake Micrurus mipartitus. The poison of this snake is a macromolecule that induces complete depolarizing muscle blockade which, if not reverted, leads to death from respiratory failure. A group of social leaders in the region managed to obtain the specific anti-venom that was not produced in the country, as well as the mechanical ventilation equipment, a negative pressure "iron lung" and a Bird Mark 7 positive pressure device. Manual ventilation was initiated by the anaesthesia team with the support of the medical students. Then, with the Bird Mark 7, the patient survived under empirical "intensive" care after 17 days of respiratory depression and 33 days in the hospital. Voluntary contributions of the community in an effort to solve the clinical problem are narrated.

Se presenta un caso clínico de carácter histórico, sucedido en el año de 1968, época de un desarrollo incipiente de las técnicas de soporte respiratorio y cuidado intensivo, con deficiencias de los sitios de atención en el hospital y en equipos de monitoreo. Paciente de 58 años, líder cívico, ganador de un concurso de televisión sobre ofídicos, es mordido accidentalmente por una culebra "Rabo de Ají" Micrurus mApartitus cuyo veneno es una macro molécula que produce un bloqueo muscular completo tipo despolarizante que de no ser resuelto, el paciente muere por insuficiencia respiratoria. Un movimiento cívico de la región logra conseguir el antídoto específico que no se producía en el país y los equipos de ventilación mecánica, uno de presión negativa un "pulmón de acero" y otro de presión positiva un Bird Mark 7. Se inició ventilación manual con el equipo de anestesia y estudiantes de medicina, y luego con el Bird Mark 7 el paciente sobrevive a un cuidado empírico "intensivo" después de 17 días de depresión respiratoria y 33 días de hospitalización. Se narran aportes voluntarios de la comunidad en apoyo a la resolución del problema clínico.

A Case of Aconite Poisoning Successfully Recovered after Intravenous Fat Emulsion Therapy

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.

A Case of Aconite Poisoning Successfully Recovered after Intravenous Fat Emulsion Therapy

Aconitum is a genus of various species of flowering plants that belongs to the Family Ranunculaceae. Most Aconitum sp. have extremely toxic alkaloid substances such as aconitine, mesaconitine and hypaconitine. Among these substances, aconitine can cause fatal cardiotoxicity by activating sodium channels followed by calcium channels in myocardial cells. Even though there have been various therapeutic plans suggested comprising antidotes based on diverse case reports and studies, there is no confirmatory treatment protocol for aconite poisoning. Here, we report an aconite poisoning patient who had refractory ventricular tachyarrhythmia that did not respond to intravenous amiodarone therapies even though they were sustained for over 2 hours, but showed successful recovery following intravenous fat emulsions (IFE) therapy.

Medical countermeasures against chemical threats:a review of antidotes / 中国药理学与毒理学杂志

Chemical warfare agents and chemical terrorism agents have been identified as one of the major threats to human survival and national security currently. The key to dealing with these threats is the effective medical countermeasures of which specific antidotes take center stage. In the past decade,real or potential chemical threats which has sparked regional conflicts,terrorist activities or chemical accidents intentionally or unintentionally have increased the investment in antidotes research and development worldwide. Here,we introduced the research status on medical countermeasures against chemical threat by giving an overview of the United States ″Countermeasures Against Chemi?cal Threats(CounterACT)Program″,and then the recent research progress in antidotes against nerve agents,sulfur mustard and cyanide toxicities were reviewed.

A Clinical Analysis of Patients Who Visited Emergency Department due to Chemical Incident Occurred at Industrial Place: A Retrospective Study

PURPOSE: The purpose of this study is to understand what kinds of chemical substances have been used annually and to investigate incidents that occurred due to chemical hazard release and to analyze statistically clinically chemical injury patients who visited one regional emergency medical center in Gumi city with documented references review. METHODS: Annual chemical waste emission quantity (Kg/Year) (Cwep) was reproduced using national web site data governed by the Ministry of Environment and 5 years (from 1 .Jan. 2010 to 31. Dec. 2014) of medical records of chemical injury patients who visited our emergency department were reviewed retrospectively. By applying exclusion criteria, 446 patients of 460 patients were selected. RESULTS: Dichloromethane, Toluene, Trichloroethylene, and Xylene were always included within Top 5 of Cweq. Six cases of chemical incidents were reported and in 3 of 6 cases involving Hydrogen fluoride were included during the study period. Male gender and twenties were the most prevalent group. Injury evoking chemicals were Hydrogen fluoride, unknown, complex chemicals (over 2 substances) in sequence. The most frequent site of wounds and injuries was the respiratory tract. Gas among status, intoxication among diagnosis, and discharge among disposition was most numerous in each group. CONCLUSION: There have been no uniform clinical protocols for chemical wounds and injuries due to various kinds of chemicophysical properties and ignorance of antidotes. Therefore conduct of a multicenter cohort study and experiments for ruling out chemicals according to chemicophysical priority as well as development of antidotes and clinical protocols for chemical injury patients is needed.

Kind and Estimated Stocking Amount of Antidotes for Initial Treatment for Acute Poisoning at Emergency Medical Centers in Korea

Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide estimation of the antidotes stocking amount in Korea. This study tried to estimate the quantities of stocking antidotes at emergency department (ED). An expert panel of clinical toxicologists made a list of 18 emergency antidotes. The quantity was estimated by comparing the antidote utilization frequency in a multicenter epidemiological study and the nation-wide EDs' data of National Emergency Department Information System (NEDIS). In an epidemiological study of 11 nationwide EDs from January 2009 to December 2010, only 92 (1.9%) patients had been administered emergency antidotes except activated charcoal among 4,870 cases of acute adult poisoning patients. Comparing with NEDIS data, about 1,400,000 patients visited the 124 EDs nationwide due to acute poisoning and about 103,348 adult doses of the 18 emergency antidotes may be required considering poisoning severity score. Of these, 13,224 (1.9%) adult doses of emergency antidotes (575 of atropine, 144 of calcium gluconate or other calcium salts, 2,587 of flumazenil, 3,450 of N-acetylcysteine, 5,893 of pralidoxime, 287 of hydroxocobalamin, 144 of sodium nitrite, and 144 of sodium thiosulfate) would be needed for maintaining the present level of initial treatment with emergency antidotes at EDs in Korea.

Lipid Emulsion in the Successful Resuscitation of Local Anesthetic Toxicity after Ankle Block / 대한구급학회지

Unexpected occurrence of local anesthetic toxicity is not rare and can cause fatal complications that do not respond to any known drug of intervention. Recently, the successful use of lipid emulsion for local anesthetic toxicity has been reported and recommended as a rescue method for cardiac or neurologic complications. We report a case of seizure attack and respiratory arrest successfully recovered with the use of intravenous lipid emulsion. Clinicians must be aware of the beneficial role of lipid emulsion in cases of local anesthetic toxicity.

Antídotos e medicamentos utilizados para tratar intoxicações no Brasil: necessidades, disponibilidade e oportunidades / Antidotes and medicines used to treat poisoning in Brazil: needs, availability and opportunities / Antídotos y medicamentos utilizados para tratar intoxicaciones en Brasil: necesidades, disponibilidad y oportunidades

Antídotos e determinados medicamentos são essenciais ao tratamento de algumas intoxicações e não podem sofrer falhas no abastecimento, sob o risco de prejudicar a saúde e a segurança da população. O objetivo deste trabalho foi avaliar a disponibilidade de antídotos e medicamentos recomendados para o tratamento de intoxicações no Brasil. A partir de consensos internacionais, foram selecionados 41 antídotos para análise, todos sem patente em vigência. Desses, 27 são registrados, porém 11 estão disponíveis em formas inadequadas ao tratamento de intoxicações, restando 16 medicamentos comercialmente disponíveis. Somente um terço dos medicamentos necessários para o tratamento de intoxicações está incluído na relação de medicamentos essenciais do país. Em adição, é apresentada proposta de suprimento das demandas a um dos antídotos, anticorpo antidigoxina, considerando a capacidade de produção nacional de imunobiológicos. Os resultados demonstram limitação da assistência adequada aos pacientes intoxicados no país e reforçam a necessidade urgente de políticas públicas na área.

Antidotes and certain other drugs are essential for treating some types of poisoning. Failures in their supply can jeopardize the population's health and safety. The current study aimed to assess the availability of antidotes and other drugs used in the treatment of poisonings in Brazil. International guidelines were used as the basis for selecting 41 antidotes for analysis, none of which currently protected by patents. Of these, 27 are registered in Brazil, but 11 of these are available in inadequate forms for treating poisoning, leaving 16 commercially available antidotes. Only one-third of the drugs needed for treating poisoning are included in the country's list of essential drugs. The article also presents a proposal for supplying the demand for one of the antidotes, anti-digoxin antibody, considering Brazil's domestic capacity for manufacturing immunobiologicals. The study's results show the limitations to adequate treatment for poison victims in Brazil and reinforce the urgent need to strengthen public policies in this area.

Los antídotos y determinados medicamentos son esenciales para el tratamiento de algunas intoxicaciones, y su disponibilidad no puede fallar, o la salud y la seguridad de la población se ponen en peligro. Este estudio tuvo como objetivo evaluar la disponibilidad de antídotos y fármacos recomendados para el tratamiento por intoxicaciones en Brasil. Se seleccionaron para el análisis 41 antídotos de reconocido consenso internacional, todos ellos sin patentes en vigor. Veintisiete estaban registrados en Brasil, pero 11 se venden en preparados farmacéuticos, no apropiados para el tratamiento de intoxicaciones, lo que da como resultado 16 medicamentos disponibles en el mercado. Sólo se incluyen en la lista brasileña de medicamentos esenciales un tercio de los medicamentos necesarios para tratar intoxicaciones. Además, se presenta una propuesta para suplir uno de los antídotos, anticuerpo antidigoxina, considerando la capacidad de producción nacional. Los resultados muestran limitaciones en una atención adecuada a los pacientes intoxicados en Brasil y refuerzan la necesidad urgente de fortalecer las políticas públicas en este ámbito.

Antidote for acetaminophen poisoning: N-acetylcysteine

N-acetylcysteine (NAC) is widely recognized as the antidote of choice for acetaminophen overdose. Acetaminophen is a commonly used analgesic and antipyretic agent, and its use is one of the most common causes of poisoning worldwide. Acetaminophen toxicity may occur acutely when supratherapeutic amounts are ingested purposefully or unintentionally. Liver failure may occur in severe toxicity. However, if treated early, patients with acetaminophen poisoning generally recover uneventfully. Acetaminophen is metabolized to N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione. In overdose, hepatic stores of glutathione are depleted and NAPQI binding to hepatocytes induces cell death and hepatic necrosis. NAC replenishes hepatic glutathione and may also act as a glutathione substitute, combining directly with the toxic metabolite. Intravenous NAC is indicated in patients who present with a history of acetaminophen overdose within the previous 8 to 10 hours, patients unable to tolerate oral NAC, and patients who present with evidence of fulminant hepatic failure. However, caution should be used in patients who have experienced previous hypersensitivity or anaphylactoid reactions to intravenous NAC, as well as in patients with asthma. The most common anaphylactoid reactions include rash, flushing, and bronchospasm. Adults should receive 150 mg/kg administered for 45 minutes, followed by 50 mg/kg administered for 4 hours, followed by 100 mg/kg administered for 16 hours. The total dose is 300 mg/kg delivered over 21 hours. Additionally, caution should always be used when intravenous NAC is prescribed and the amount of diluent is calculated. Monitoring of patients with a should include repeated neurologic and hemodynamic assessment.

Antidote for acquired methemoglobinemia: methylene blue

Methylene blue (MB) is an effective antidote for methemoglobinemia. MB is a basic dye, yielding a blue solution. In the human body, hemoglobin is the oxygen-carrying protein including a ferrous atom. Hemoglobin is oxidized to methemoglobin (MetHb) with the ferric atom, which cannot bind to or carry oxygen. Equilibrium between hemoglobin and MetHb is approximately 99:1. Thus a healthy man can have about 1% of methemoglobinemia. The cytochrome b5 MetHb reductase pathway plays a major role in reducing MetHb to hemoglobin. The nicotin amide adenine dinucleotide phosphate (NADPH) MetHb reductase pathway is a minor reducing system of MetHb, and it needs NADPH as a cofactor. However, to the exceeding exogenous oxidative stress, the cytochrome b5 MetHb reductase pathway is soon exhausted, and the NADPH MetHb reductase pathway can be activated 4 to 5 times by the exogenous cofactor, MB. The decision to initiate MB therapy for methemoglobinemia depends on the MetHb level and the symptoms. The indication for MB therapy in a symptomatic patient is a MetHb level >20% and in an asymptomatic patient, a MetHb level >30%. Patients with comorbidities such as anemia, heart disease, pneumonia, chronic obstructive pulmonary disease, or liver cirrhosis can be candidates for MB therapy with an even lower MetHb level. The recommended initial dose of MB is 1 to 2 mg/kg. It can be repeated every 30 minutes to 1 hour. However, the dose should not exceed 7 mg/kg. A high dose of MB may induce methemoglobinemia paradoxically and also cause hemolytic anemia. Like other antidotes, MB has its own adverse effects.

The Experiences of the Emergency Antidote Stock and Delivery Service by the Korean Poison Information Center

PURPOSE: Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide stocking and delivery system for emergency antidotes in Korea. We report on a two-year experience of a nationwide stocking and delivery trial for emergency antidotes at emergency departments in Korea. METHODS: An expert panel of clinical toxicologists reviewed and made a list of 15 stocked antidote. These antidotes were purchased or imported from other countries and delivered from 14 antidote stocking hospitals nationwide 24 hours per day, seven days per week. RESULTS: From August 1, 2011 to April 30, 2013, 177 patients with acute poisoning, with a median age of 48.5 years, were administered emergency antidotes. The causes of poisoning were intentional in 52.0% and 88.0% were intentional as a suicide attempt. Regarding clinical severity, using the poisoning severity score, 40.7% of patients had severe to fatal poisoning and 39.0% had moderate poisoning according to clinical severity. The most frequent presenting symptom was neurologic deficit, such as altered mentality (62.7%). alerted mentality (62.7%). Emergency antidotes were administered as follows: methylene blue (49 cases), flumazenil (31), N-acetylcysteine (25), glucagon (17), 100% ethanol (15), cyanide antidote kit (12), anti-venin immunoglobulin (5), pyridoxine (4), hydroxocobalamine (2), and deferoxamine (1). The median time interval from antidote request to delivery at the patient's bedside was 95 minutes (interquartile range 58.8-125.8). CONCLUSION: Findings of this study demonstrated the possibility of successful operation of the nationwide system of emergency antidotes stocking and delivery in Korea.

Relato de uma exposição coletiva a superwarfarin e revisão da literatura / Report of a collective exposure to superwarfarin and literature review

Objetivos: Descrever um episódio de exposição coletiva a raticida do grupo superwarfarin e revisar a literatura a respeito do tema.Descrição dos casos: Cerca de 40 pessoas, incluindo crianças, ingeriram alimento contaminado por raticida em escola pública de ensino fundamental de Porto Alegre, Rio Grande do Sul. Foram registrados 34 casos individuais de ingestão acidental no Centro de Informação Toxicológica do Rio Grande do Sul. O caso foi amplamente divulgado na imprensa local. Após avaliação médica inicial, 19 pacientes apresentaram sintomas inespecíficos (como náuseas, dor abdominal e xerostomia), enquanto os outros permaneceram assintomáticos. Todos os pacientes foram acompanhados laboratorialmente, mediante controle do tempo de protrombina. Três deles apresentaram prolongamento do tempo de protrombina, tendo recebido vitamina K para reverter a coagulopatia. Dados locais e a revisão da literatura indicam que as exposições a raticidas da família dos superwarfarins são bastante frequentes. A ação desses agentes tóxicos ocorre principalmente sobre os fatores de coagulação produzidos pelo fígado e dependentes de vitamina K.Conclusões: Os pacientes expostos ao superwarfarin evoluíram bem, concordando com a literatura publicada, que indica que casos graves são incomuns. O seu acompanhamento e tratamento seguiu a indicação de utilizar a vitamina K como antídoto apenas nos casos em que se detecta efeito clínico ou laboratorial do agente tóxico.

Aims: To describe an episode of collective exposure to rodenticide of the superwarfarin group and to review the literatureon the subject.Cases description: About 40 people, including children, ate food contaminated with rodenticide in a public elementary school in Porto Alegre, Rio Grande do Sul. Thirty-four individual cases of accidental ingestion were reported to theToxicology Information Center of Rio Grande do Sul. The case was widely publicized in the local press. After initial medical evaluation, 19 patients had nonspecific symptoms (like nausea, abdominal pain and dry mouth), while the other remained asymptomatic. All patients were monitored by controlling the prothrombin time. Three of them showed prolongation ofprothrombin time and received vitamin K to reverse the coagulopathy. Local data and the literature review indicate thatexposures to rodenticides of the family of superwarfarins are frequent. The toxic action of these agents occurs mainly onclotting factors produced by the liver and vitamin K-dependent.Conclusions: The patients exposed to superwarfarin had a good outcome, in accordance with published literature, which indicates that severe cases are rare. The monitoring and treatment followed the indication of vitamin K as antidote onlyin cases where clinical or laboratorial effect of the toxic agent is detected.

Distonia aguda relacionada ao uso de bromoprida em pacientes pediátricos / Acute dystonia after use of bromopride in pediatric patients

OBJETIVO: Descrever dois casos de distonia aguda após uso de bromoprida em crianças e realizar revisão da literatura em relação aos mecanismos fisiopatológicos de indução de liberação extrapiramidal, sua sintomatologia e tratamento. DESCRIÇÃO DO CASO: Caso 1: adolescente de 13 anos com quadro de dor e hipertonia cervical associados a febre, náuseas e vômitos, com hipótese inicial de meningite. A investigação subsequente revelou que o quadro iniciou-se após ingestão de uma única dose de bromoprida. O paciente apresentou boa resposta ao tratamento com difenidramina, sem necessidade de coleta de líquor. Caso 2: Lactente de seis meses que desenvolveu sintomas graves de liberação extrapiramidal relacionados à superdosagem de bromoprida, com reversão rápida dos sintomas após administração de biperideno. COMETÁRIOS: Este é o primeiro relato de distonia aguda após uso de bromoprida em crianças. Embora muito utilizada no Brasil como agente pró-cinético e antiemético, nenhum estudo clínico até o momento demonstrou melhor perfil de segurança da bromoprida em relação aos demais antieméticos antagonistas da dopamina. Até que tais estudos sejam realizados, sugere-se cautela na prescrição de bromoprida. Medidas não-farmacológicas devem ser recomendadas no tratamento de vômitos e da doença do refluxo gastresofágico. Quando o tratamento farmacológico for indispensável, deve-se dar preferência a drogas com perfil de segurança mais bem estabelecido.

OBJECTIVE: To report the case of two patients with acute dystonia induced by bromopride in children, followed by a review of the mechanisms of induction of movement disorders by antidopaminergic anti-emetic drugs, its clinical symptoms and treatment. CASE DESCRIPTION: Case 1: a 13 years old teenager who developed acute hypertonia and neck pain associated to fever and vomiting, suggestive of meningitis. Further investigation revealed that symptoms were associated with the ingestion of a single dose of bromopride. The symptoms stopped after administration of diphenidramine, preventing a spinal tap. Case 2: six months old infant who developed extrapyramidal movement disorder related to bromopride overdose, with prompt resolution of symptoms after treatment with biperiden. COMMENTS: This seems to be the first report of acute dystonia after the use of bromopride in children. Although frequently used in Brazil as an anti-emetic and prokynetic agent, no clinical study has showed that bromopride has a better safety profile than other antidopaminergic anti-emetic drugs. While such studies are not available, caution is needed in the context of pediatric prescription of bromopride. Non pharmacological measures should be adopted in the management of vomiting and gastroesophageal reflux. If medical treatment cannot be avoided, one would rather use medications with a better established safety profile.

Flumazenil Use in the Emergency Department: Benefit or Risk

PURPOSE: Flumazenil is frequently administered to poisoned and benzodiazepine-induced sedated patients. However, seizure, resedation, dysrhythmia, and death may occur in patients who awaken following flumazenil administration. Thus, this study investigated the benefit and the risk of the clinical use of flumazenil in emergency situations because the taking of an accurate history was often impossible METHODS: We included 177 patients given flumazenil in the emergency department. They were divided into four groups: Group I (n=51) was poisoned patients who were treated with flumazenil as an antidote, Group II (n=14) was patients in comas of unknown origin who were treated with flumazenil as a universal antidote, Group III (n=69) was patients who were treated with flumazenil for reversal from conscious, procedural sedation, and Group IV (n=43) was patients who were treated with flumazenil for recovery from unexpected oversedation. The benefits of flumazenil were analyzed based on a decreased need for procedures such as endotracheal intubation and mechanical ventilation. Then, the risks were evaluated based on the incidence of serious complications during flumazenil administration. RESULTS: In group I, removals of ventilators and endotracheal intubation were possible in 7/12 and 6/13 cases. However, more serious complications occurred in group I than in the other groups. In group II, a no-awakening response to flumazenil occurred in 71.4% of the patients. Group III had the lowest risk ratio among the groups. In group IV, removals of ventilator and endotracheal intubation were possible in 18/26 and 10/27 cases. However, in 16/43 (37.2%) cases, risk factors for seizures existed; thus, the use of flumazenil was considered inappropriate. CONCLUSION: Flumazenil may be safer and more effective for reversal action; but its clinical utility as an antidote in the emergency department is questionable.