Guía de actuación y abordaje frente a intoxicación por dióxido de cloro/clorito de sodio, a partir de la experiencia de los CIAT de América Latina / Guidelines for action and approach to chlorine dioxide/sodium chlorite poisoning based on the experience of the CIATs in Latin America

Resumen El 11 de marzo de 2020, la Organización Mundial de la Salud, declaró la pandemia a nivel mundial por la COVID-19. Ante este escenario, los centros de información y asesoramiento toxicológico (CIAT) de América Latina comenzaron a recibir consultas por exposición/intoxicación a dióxido de cloro/clorito de sodio y sus compuestos relacionados, por desvío de uso, destinado a la prevención y/o tratamiento de la COVID-19 sin aval científico alguno ni contar con registro sanitario para ese fin. A través de la Red de Toxicología de América Latina y el Caribe (RETOXLAC), se comprobó que no eran hechos aislados, sino que se estaba produ ciendo el mismo fenómeno en toda la región y que existían antecedentes de intoxicaciones con dichos productos y alertas desde hace más de una década, con indicaciones no aprobadas, para el tratamiento de distintas patologías como SIDA, cáncer, esclerosis lateral amiotrófica ELA, malaria, autismo, entre otras, sin evidencia. Ante esta realidad, los CIAT presentan una revisión de los signos y síntomas observados según la vía de ingreso, basados en la comunicación de riesgo en salud; proponiéndose pruebas de apoyo al diagnóstico, algoritmo de tratamiento para las intoxicaciones y modelo de ficha clínica para la vigilancia epidemiológica de los casos atendidos. Recomendamos a las autoridades y organismos responsables, reforzar las acciones tendientes a la vigilancia, control y prevención de este tipo de intoxicaciones, producto del mal uso de un desinfectante no autorizado para fines terapéuticos/médicos.

Abstract On March 11th, 2020, the World Health Organization declared a global pandemic due to COVID-19. Faced with this sce- nario, the Poison Control Centers (CIATs for its initials in spanish) in Latin America began to receive consultations for exposure/poi- soning to chlorine dioxide/sodium chlorite and its related compounds for their use aimed to prevent or treat COVID-19 without any scientific endorsement or having a sanitary registry for that purpose. It was found through the Toxicology Network of Latin America and the Caribbean (RETOXLAC) that they were not isolated events but rather that the same phenomenon was occurring throughout the region and that there has been a history of poisoning and alerts with these products for more than a decade with unapproved indications for the treatment of different pathologies such as AIDS, cancer, amyotrophic lateral sclerosis (ALS), malaria, autism, among others, without evidence. In the light of this situation, the CIATs present a review of the signs and symptoms observed ac- cording to the route of exposure based on health risk communication; proposing tests to support the diagnosis, an algorithm for poisoning treatment, and a model of a clinical record for the epidemiological surveillance of the assisted cases. We recommend to the authorities and responsible organisms reinforce the actions aimed at surveillance, control, and prevention of this type of poisoning due to the misuse of an unauthorized disinfectant for therapeutic or medical purposes.

Caracterización epidemiológica de las exposiciones a dióxido de cloro/clorito de sodio en el contexto de la pandemia COVID-19: Reporte de los centros toxicológicos de América Latina / Epidemiological characterization of exposures to chlorine dioxide/ sodium chlorite in the context of the COVID-19 pandemic: Report of Poison Control Centers in Latin America

Resumen Los centros de información y asesoramiento toxicológico CIATs de América Latina, en el contexto de la pandemia de COVID-19, recibieron una serie de llamadas para consultas y asesoramientos relacionados con el uso de dióxido de cloro/clorito de sodio, que se estaban empleando en el tratamiento o prevención de dicha enfermedad. Dentro de la legislación vigente en los países de América Latina, no se contemplan productos farmacéuticos registrados para uso en humanos, ni se tiene evidencia de registros sanitarios en Europa, Canadá o Estados Unidos para tal fin, que contengan dióxido de cloro o clorito de sodio. Esta publicación, compila la información registrada como parte de la estadística del trabajo de ocho CIATs correspondientes a igual número de países de América Latina. Se identificó sexo, edad, sintomatología, circunstancia y grado de severidad de los 56 casos de pacientes intoxicados con dióxido de cloro/clorito de sodio registrados en el período del 15 de marzo al 30 de septiembre de 2020 en estos ocho países. Los resultados obtenidos confirman que la causa más común fue por mal uso, y el lugar de ocurrencia fue el hogar o sus alrededores, siendo el mayor porcentaje adultos jóvenes comprendidos entre 30 y 49 años. Los síntomas de intoxicación más frecuentemente encontrados fueron gastrointestinales, seguidos de cardiovasculares y respiratorios. La vía de ingreso al organismo en la mayoría de los casos fue por vía oral, reportándose algunos casos por vía inhalatoria, y en el 50% de los casos se constituyeron casos de severidad moderada, severa o fatal (3 fallecimientos). Este estudio contribuye a generar información relevante para las diferentes autoridades sanitarias, los ministerios de salud, las entidades encargadas de inspección, vigilancia y control de los países en los que se comercializan estos productos de manera ilegal por medio de redes sociales y promoviéndolos para uso en humanos para prevenir o curar COVID-19.

Abstract The Poison Control Centers in Latin America, in the context of COVID-19 pandemic, received a series of calls for consultations and recommendations related to the use of chlorine dioxide/sodium chlorite, in the treatment or prevention of CO-VID-19. Under current legislation in Latin America, no pharmaceutical products are registered for use in humans that contain chlorine dioxide or sodium chlorite, nor is there evidence of sanitary registries in Europe, Canada, or the United States for this purpose. This publication compiles the information registered by eight Poison Control Centers that correspond to the same number of Latin American countries. Sex, age, symptoms, circumstance, and degree of severity of the 56 cases of patients poisoned with chlorine dioxide/ sodium chlorite registered in the period from March 15th to September 30th, 2020 were identified. The results obtained confirm that the most common cause of poisoning was unintentional misuse, all of which occurred at home or its surroundings, with the highest percentage of registered cases being young adults between 30 and 49 years old. The most frequent symptoms of intoxication were gastrointestinal, followed by cardiovascular and respiratory. The route of exposure in most cases was oral, with some cases reported by inhalation; 48.2% of the cases were of moderate, severe, or fatal (3 deaths). This study contributes to the generation of relevant information for different health authorities, ministries of health, entities in charge of inspection, surveillance, and control in countries where these products are illegally marketed through social networks and promoted for use in humans to prevent or cure COVID-19.

[Acute hepatitis associated with Colpachi intake. Apropros of 5 cases]. / Hepatitis aguda asociada al consumo de Copalchi. A propósito de 5 casos.

The use of herbal medicines believed to have therapeutic properties is becoming increasingly widespread. These medicines are usually taken by patients on their own initiative and physicians are often unaware of which patients are taking these substances. Herbal medicines can be taken in the form of teas, powders, and liquid extracts. In the last few years, it has come to light that these natural remedies are not free of risks, especially the risk of interaction with other drugs or hepatotoxicity, ranging from asymptomatic forms to massive hepatic necrosis. We describe a series of 5 patients notified to the Spanish Pharmacovigilance System of medicinal products for human use. All the patients developed acute hepatitis during Colpachi treatment lasting several months, which resolved after discontinuing intake of this substance. Systematic examination of the literature revealed the existence of 6 other reported cases of suspected Colpachi-induced hepatotoxicity.

Antidepressants and risk of upper gastrointestinal bleeding.

Selective serotonin reuptake inhibitors (SSRIs) are nowadays the most widely used antidepressants in the world, mainly because they have a better adverse reaction profile and a higher safety margin in overdoses, when compared to other antidepressants. These drugs recently have been the target of important debates concerning safety issues, among them the possibility that they may increase the risk of bleeding. Over the 1990s, an increasing number of individual cases of bleeding disorders were reported in the literature and to the pharmacovigilance programmes which prompted several epidemiological and pharmacological studies. In this review we have examined all available data. The whole evidence supports the hypothesis that antidepressants with a relevant blockade action on serotonin reuptake mechanism increase the risk of bleeding. Such disorders may have different degrees of severity and may be located anywhere in the body. The epidemiological evidence is, however, more robust for upper gastrointestinal bleeding. It has been estimated that upper gastrointestinal bleeding may occur at a frequency ranging from 1 in 100 to 1 in 1,000 patient-years of exposure to high-affinity drugs (the SSRIs), with the very old patients being in the highest part of the range. The increased risk may be of particular relevance when the SSRIs are associated with NSAIDs as well as low-dose aspirin.

Acute and clinically relevant drug-induced liver injury: a population based case-control study.

AIMS: To provide quantitative information about the absolute and relative risks of acute and clinically relevant drug-induced liver injury. METHODS: We performed a population-based case-control study using the UK-based General Practice Research Database as the source of information. A total of 1,636,792 persons subjects aged 5-75 years old registered in the database from 1 January, 1994 to 31 December, 1999 were followed-up for a total of 5,404,705 person-years. Cases were identified by an exhaustive computer search, then reviewed manually and finally validated against the clinical records. Only idiopathic cases serious enough to be referred to hospital or a consultant were selected. A total of 5000 controls were randomly sampled from the person-time of study cohort. Current users were defined if a prescription ended within 15 days of the index date, and nonusers if there was no prescription before the index date. RESULTS: One hundred and twenty-eight patients were considered as valid cases, being the crude incidence rate of 2.4 (95% confidence interval: 2.0, 2.8) per 100 000 person-years. The strongest associations were found with chlorpromazine (adjusted odds ratio (AOR); 95% CI = 416; 45, 3840), amoxicillin/clavulanic acid (AOR = 94.8; 27.8, 323), flucloxacillin (AOR = 17.7; 4.4, 71.0), macrolides (AOR = 6.9; 2.3, 21.0), tetracyclines (AOR = 6.2; 2.4, 15.8); metoclopramide (AOR = 6.2; 1.8, 21.3); chlorpheniramine (AOR = 9.6; 1.9, 49.7); betahistine (AOR = 15.3; 2.9, 80.7); sulphasalazine (AOR = 25.5; 6.0, 109); azathioprine (AOR = 10.5; 1.4, 76.4), diclofenac (AOR = 4.1; 1.9, 8.8) and antiepileptics (AOR = 5.1; 1.9, 13.7). A dose-effect was apparent for diclofenac, amoxicillin/clavulanic acid and flucloxacillin. The combination of two or more hepatotoxic drugs increased the risk by a factor of 6. The highest crude incidence rates were found for chlorpromazine, azathioprine, and sulfasalazine (about 1 per 1000 users). CONCLUSIONS: Idiopathic, acute and clinically relevant liver injury, which has the use of drugs as the most probable aetiology, is a rare event in the general population. The relative risks of 40 drugs/therapeutic classes are provided, along with the crude incidence rates for 15 of them where a statistical association was found.

Use of antipsychotic agents in Spain through 1985-2000.

OBJECTIVE: To analyze the trend of antipsychotic drug consumption in Spain from 1985 to 2000, and the impact of atypical antipsychotics on the overall consumption and on clozapine use. METHODS: Data on antipsychotic consumption were drawn from the ECOM database of the Spanish Ministry of Health, which contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System. Data are presented as defined daily doses (DDDs) per 1000 inhabitants per day, for each year. To evaluate the impact of atypical antipsychotics on clozapine use, data from the Spanish "Clozapine Monitoring Program" were analyzed. Consumption data from Nordic countries were obtained from national statistics. RESULTS: The use of antipsychotics in Spain increased progressively from 1.51 DDD/1000 inhabitants/d in 1985 to 5.73 DDD/1000 inhabitants/d in 2000. The pattern of use of individual drugs changed greatly over the study period. In 1985, haloperidol, fluphenazine and thioridazine, all typical antipsychotics, were the drugs most widely used, whereas in 2000, the three drugs most frequently used were risperidone, olanzapine and haloperidol. The introduction of olanzapine in December 1996 reduced the number of new treatments with clozapine to half. Antipsychotic use is still lower in Spain than in Nordic countries, despite the prevalence of schizophrenia being similar worldwide. CONCLUSIONS: Antipsychotic agent use in Spain has increased progressively since 1985, reducing the differences between Spain and other European countries (Nordic countries). Substantial differences in the pattern of drug use from 1985 to 2000 have been observed.