Manejo de hemorragia asociada a anticoagulantes orales directos: estado actual de las estrategias de reversión / Management of bleeding associated with direct oral anticoagulants: update on reversal strategies

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.

Metahemoglobinemia relacionada con ingesta de puré de acelgas / Methemoglobinemia due to ingestion of chard puree

La metahemoglobinemia es un síndrome clínico dado por la presencia de una forma aberrante de hemoglobina, ocasionada por diversos agentes oxidantes. Se describe un caso clínico de metahemoglobinemia severa asociada a la ingesta de puré de acelgas con alto contenido en nitratos y nitritos. Paciente de un año, con antecedentes de comunicación interauricular (CIA), que presentó un cambio en coloración de la piel 7 h antes, en forma progresiva, acompañado de vómitos. Ingresó al Departamento de Emergencia con cianosis generalizada que no mejoró con oxigenoterapia, taquicardia y tendencia a hipotensión arterial. En cuidados intensivos se realizó ecocardiograma que evidenció CIA sin repercusión hemodinámica. Metahemoglobinemia 37%. Se realizó dosis de azul de metileno al 1% por vía intravenosa, con franca mejoría clínica a la hora de la administración del antídoto y descenso de niveles de metahemoglobina. Alta médica a las 36 horas del ingreso. Existía una relación cronológica entre la exposición a nitratos por ingesta de un puré de acelgas y la aparición del cuadro. Los niveles de nitratos hallados en dicho alimento fueron muy elevados considerando estándares internacionales, lo que sumado a una inadecuada conservación del alimento cocido los días previos, permitió confirmar el planteo etiológico realizado. Resulta importante sospechar esta entidad patológica poco frecuente frente a cianosis que no mejora con oxígeno, y prevenir cuadros similares al descrito mediante una adecuada manipulación y conservación de las verduras con alto contenido en nitratos.

Methemoglobinemia is a clinical syndrome due to the presence of an aberrant form of hemoglobin, caused by various oxidizing agents. The study reports a case of severe methemoglobinemia associated with the ingestion of chard puree with high levels of nitrates and nitrites. A 1-year-old patient with a history of atrial septal defect (ASD), who progressively showed change of skin color 7 hours earlier, accompanied by vomiting. She was admitted to the Emergency Department with generalized cyanosis not improving with oxygen therapy, tachycardia and tendency to hypotension. In the intensive care unit, an echocardiogram showed ASD without hemodynamic complications. Methemoglobinemia 37%. A 1% methylene blue dose was administered intravenously, with clinical improvement one hour after antidote administration and decrease in methemoglobin levels. Medical discharge at 36 hours of admission. There was a chronological relationship between nitrates exposure by ingestion of chard puree and the clinical onset of methemoglobinemia. The toxic cause was confirmed after high nitrates levels were found in this vegetable considering international standards, and an inadequate preservation of the cooked chard on previous days. It is important to suspect this rare pathological entity when cyanosis fails to improve with oxygen, and to prevent poisonings similar to those described by an adequate manipulation and preservation of vegetables with high nitrate levels.

Plant-antivenom: database of anti-venom medicinal plants

Plant-antivenom is a computational Websystem about medicinal plants with anti-venom properties. The system consists of a database of these plants, including scientific publications on this subject and amino acid sequences of active principles from venomous animals. The system relates these data allowing their integration through different search applications. For the development of the system, the first surveys were conducted in scientific literature, allowing the creation of a publication database in a library for reading and user interaction. Then, classes of categories were created, allowing the use of tags and the organization of content. This database on medicinal plants has information such as family, species, isolated compounds, activity, inhibited animal venoms, among others. Provision is made for submission of new information by registered users, by the use of wiki tools. Content submitted is released in accordance to permission rules defined by the system. The database on biological venom protein amino acid sequences was structured from the essential information from National Center for Biotechnology Information (NCBI). Plant-antivenom's interface is simple, contributing to a fast and functional access to the system and the integration of different data registered on it. Plant-antivenom system is available on the Internet at http://gbi.fmrp.usp.br/plantantivenom.

A simplified acute physiology score in the prediction of acute aluminum phosphide poisoning outcome.

Background : Aluminum phosphide (AlP) is used as a fumigant. It produces phosphine gas, which is a mitochondrial poison. Unfortunately, there is no known antidote for AlP intoxication, and also, there are few data about its prognostic factors. AIMS: The aim of this study was to determine the impact of the Simplified Acute Physiology Score II (SAPS II ) in the prediction of outcome in patients with acute AlP poisoning requiring admission to the Intensive Care Unit (ICU). Materials and Methods : This was a prospective study in patients with acute AlP poisoning, admitted to the ICU over a period of 12 months. The demographic data were collected and SAPSII was recorded. The patients were divided into survival and non-survival groups due to outcome. Statistical Analysis : The data were expressed as mean ± SD for continuous or discrete variables and as frequency and percentage for categorical variables. The results were compared between the two groups using SPSS software. Results : During the study period, 39 subjects were admitted to the ICU with acute AlP poisoning. All 39 patients required endotracheal intubation and mechanical ventilation in addition to gastric decontamination with sodium bicarbonate, permanganate potassium, and activated charcoal, therapy with MgSO 4 and calcium gluconate and adequate hydration. Among these patients, 26 (66.7%) died. SAPSII was significantly higher in the non-survival group than in the survival group (11.88 ± 4.22 vs. 4.31 ± 2.06, respectively) (P < 0.001). Conclusion : SAPSII calculated within the first 24 hours was recognized as a good prognostic indicator among patients with acute AlP poisoning requiring ICU admission.

Organophosphorus poisoning.

Acute poisoning by organophosphorus (OP) compounds is a major global clinical problem, with thousands of deaths occurring every year. Most of these pesticide poisoning and subsequent deaths occur in developing countries following a deliberate self ingestion of the poison. Metacid (Methyl parathion) and Nuvan (Dichlorovos) are commonly ingested OP pesticides; Dimethoate, Profenofos, and Chlorpyrifos are other less frequently ingested compounds in Nepal. The toxicity of these OP pesticides is due to the irreversible inhibition of acetylcholinesterase (AChE) enzyme leading to accumulation of acetylcholine and subsequent over-activation of cholinergic receptors in various parts of the body. Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning. The diagnosis depends on the history of exposure to these pesticides, characteristic manifestations of toxicity and improvements of the signs and symptoms after administration of atropine. The supportive treatment of OP poisoning includes the same basic principles of management of any acutely poisoned patient i.e., rapid initial management of airways, breathing, and circulation. Gastric lavage and activated charcoal are routinely used decontamination procedures, but their value has not been conclusively proven in this poisoning. Atropine is the mainstay of therapy, and can reverse the life threatening features of this acute poisoning. However, there are no clear cut guidelines on the dose and duration of atropine therapy in OP poisoning. Cholinesterase reactivators, by regenerating AChE, can reverse both the nicotinic and muscarinic effects; however, this benefit has not been translated well in clinical trials. All these facts highlight that there are many unanswered questions and controversies in the management of OP poisoning and there is an urgent need for research on this aspect of this common and deadly poisoning.

Extracorporeal methods in the treatment of poisoning.

Among the various ways of managing poisoning, haemodialysis may help in enhancing excretion of the toxic substance. We report a case, a Russian male, 35 years old, who was rushed to the Gleneagles Hospital Medan from the airport after being evacuated from Banda Aceh together with another older Russian who died as they arrived at the admission and Emergency Department. From the result of intensive allo anamnesis and the high anion gap metabolic acidosis, in the absence of disturbed renal and liver function, we presumed this patient was suffering from methanol intoxication. The time of exposure was approximately 70 hours before. The exact length of dialysis time to excrete the noxious substance from the blood without plasma methanol determination was difficult. Moreover the time elapsed from exposure to treatment had been approximately 70 hours, which means the optic nerve had been so long exposed to formic acid, the toxic metabolite of methanol, that the damage should have been very severe. Ethanol is also known to be an antidote of methanol, which can be given orally by nasogastric tube, or i.v. It should be given early, and plasma ethanol level should be closely monitored to make it effective and safe. This was also unavailable. Another antidote is fomepizole which is also as yet unavailable in Medan. Folic acid, thiamin, and i.v. folinic acid are also recommended by the literature, as well as oral steroid.

The antidotal effects of high-dosage gamma-aminobutyric acid on acute tetramine poisoning as compared with sodium dimercaptopropane sulfonate / 华中科技大学学报（医学）（英德文版）

To investigate the therapeutic effect of high-dosage gamma-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice. Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.

Intoxicación por clobutinol y oxolamina / Poisoning for clobutinol and oxolamine

El objetivo de este artículo es revisar los efectos y rasgos tóxicos descritos en la literatura y establecer un manejo clínico adecuado y específico para la intoxicación con estos medicamentos.

Hyperinsulinemic-euglycemic therapy for intoxication with calcium channel blockers

Conventional therapy for intoxication with calcium channel blockers consists of crystalloid solutions, calcium gluconate, glucagon and vasopressor agents. These therapies often fail to improve hemodynamic function in intoxicated patients. The pathophysologic mechanism proposed for intoxication with these agents, suggest hypoinsulinemia as the determinant factor. We will describe the case of a 77 years old man treated for an overdose of nifedipine and atenolol who arrived at our institution with hypotension and bradycardia. After conventional therapy failed to improve the patient's hemodynamic status, hyperinsulinemia and euglycemia contributed to the improvement of the patient's neurologic and hemodynamic condition. Thus, hyperinsulinemic-euglycemic therapy was of benefit in this patient with hemodynamic compromise secondary to intoxication with calcium channel blocker not responding to conventional therapy. We will review the mechanism of action of calcium channel blocker drugs as well as the clinical presentation and treatment options for calcium channel blocker intoxication.

Actualizaciones sobre el manejo del loxoscelismo / Update on loxoscelilsm management

Loxoscelismo es el cuadro tóxico provocado por el veneno que arañas del género Loxosceles inyectan en el momento de la mordedura, siendo la especie laeta su única representante en Chile. El cuadro clínico puede presentarse en dos formas: loxoscelismo cutáneo y cutáneo-visceral, cada una de ellas con características distintivas. El objetivo del trabajo es actualizar la información existente sobre el manejo de este cuadro para lo cual se revisa la literatura chilena e internacional publicada (Medline, Cochrane y otras bases de dato). Se puede concluir que la alta frecuencia de consultas debido a mordedura de arañas obliga al médico a saber prevenirlas, diagnosticarlas y tratarlas. Aún no existen estudios que demuestren la efectividad de los tratamientos usados en nuestros días. Se sugiere que sería importante establecer un protocolo de manejo en nuestro hospital.

Los antídotos en la lucha contra las intoxicaciones / The antidotes in the fight against poisonings

Como resultado del notable aumento de la industria química en los últimos años, la posibilidad de que ocurra una intoxicación aguda ya sea accidental o voluntaria, crece de forma vertiginosa en nuestros días. Este trabajo pretende aportar de forma sencilla aspectos relacionados con el tratamiento de las intoxicaciones agudas, tratando inclusive aspectos farmacológicos y básicos que tienen este tipo de sustancias tóxicas que deben dominar tanto el personal que labora en los centros de urgencia y la atención primaria, como la población en general y en especial aquellos lugares donde se hallan niños y donde se manipulan sustancias químicas peligrosas

Near-fatal amlodipine poisoning.

Amlodipine poisoning is very rare and only few cases have been reported in English literature. We report here a case of severe amlodipine poisoning with non-cardiogenic pulmonary edema.

Intoxicações exógenas em clínica médica / Exogenous intoxications in clinical medicine

Na primeira parte desta revisão, são discutidas as medidas gerais de tratamento das intoxicações exógenas (indução de vômitos, lavagem gástrica, administração de carvão ativado e de laxativos) e as medidas específicas de eliminação dos agentes tóxicos (diurese forçada e alcalinização da urina, hemodiálise e hemoperfusão e a utilização de antídotos e antagonistas). Na segunda parte, são discutidos os princípios do tratamento das mais freqüentes intoxicações exógenas em nosso meio (pesticidas agrícolas, depressores do sistema nervoso central e raticidas

Alacranismo en Colima: aspectos epidemiológicos / Scorpion sting in the state of Colima, Mexico: epidemiological aspects

Objetivo: describir el comportamiento epidemiológico de los casos con picadura de alacrán, informados en la Delegación Regional del Instituto Mexicano del Seguro Social (IMSS) en Colima, considerada zona epidémica.Material y métodos: se realizó estudio descriptivo de 4502 casos registrados durante 1998 en el Sistema de Información Médico-Operativo y el Sistema de Vigilancia Epidemiológica del IMSS. Se determinaron tasas y frecuencias absolutas y relativas. Resultados: la tasa de incidencia de picadura de alacrán fue de 218.3 por cada 10 mil usuarios derechohabientes; 26 por ciento de los casos ocurrió en menores de 15 años de edad, 68 por ciento en el grupo, de 15 a 64, y 6 por ciento en mayores de 64. En 40 por ciento de los casos (n = 1858) se administró suero antialacránico. La incidencia fue similar durante el año [febrero, 302 casos (6 por ciento); septiembre, 483 (10 por ciento); octubre, 440 (10 por ciento), respectivamente]. No se indicaron muertes. Conclusiones: La picadura de alacrán es un problema de salud en Colima, con una incidencia similar a lo largo del año, por lo cual se justifican acciones para prevenir, controlar y tratar dicha entidad clínica.

Quemaduras por agentes químicos / Chemical burns

Se realiza una revisión de la literatura nacional e internacional sobre quemaduras químicas. En primer término se describen las causas, la fisiopatología de las quemaduras y se presenta una clasificación de los compuestos químicos corrosivos que al ponerse en contacto con la piel general quemaduras químicas. Se destacan los ácidos inorgánicos, ácidos orgánicos, compuestos alcalinos y compuestos específicos que, por la naturaleza y gravedad de las lesiones que producen, requieren de una presentación individual, tales como el fósforo y el tetracloruro de titanio. A continuación se describen las medidas generales iniciales de tratamiento para toda quemadura química y algunas medidas especiales para corrosivos específicos de alta peligrosidad. Luego se definen las medidas de tratamiento local secundario. Por último, se incluye un párrafo especial para el manejo de las quemaduras oculares por agentes corrosivos. Al cierre, se destaca la necesidad de desarrollar una política educativa de prevención en el manejo de productos corrosivos como el mejor método par reducir la incidencia de lesiones graves