Seven- and thirty-day mortality in digoxin poisoning: Results from the DIGITOX study.

BACKGROUND: Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances. OBJECTIVE: To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning. DESIGN, SETTINGS AND PARTICIPANTS: A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic. OUTCOMES MEASURE AND ANALYSIS: To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis. MAIN FINDINGS: A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006). CONCLUSIONS: The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.

The Clinical Toxicology Recommendations Collaborative: purpose, organization, and methodology.

INTRODUCTION: Scientific societies aim to provide a collective voice and unified stance on important issues. The Clinical Toxicology Recommendations Collaborative was formed in 2016 to develop evidence- and consensus-based recommendations for the management of patients exposed to common and/or serious poisonings for which the management is unclear or controversial. ORGANIZATION: The Clinical Toxicology Recommendations Collaborative is led jointly by the American Academy of Clinical Toxicology, the Asia Pacific Association of Medical Toxicology, and the European Association of Poison Centres and Clinical Toxicologists. The Governance Committee is chaired by a Past-President of one of these Societies and comprised of the six Presidents and Immediate Past-Presidents of the three Societies. A Steering Committee oversees the process of each project workgroup. METHODOLOGY: The overall process is guided by standards set forth by the Institute of Medicine for developing trustworthy guidelines and the Appraisal of Guidelines for Research and Evaluation Instrument. Systematic reviews are produced using the framework set in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Workgroup members jointly review the evidence and prepare statements on which they vote anonymously using a 9-point Likert scale. A two-round modified Delphi method is used to reach a consensus on clinical recommendations using the RAND/UCLA Appropriateness Method. Final recommendations are approved by unanimous consent of the workgroup and are expressed as both levels of evidence and strength of recommendations. LIMITATIONS: The major limitations of the Clinical Toxicology Recommendations Collaborative process centre around the amount and quality of evidence, the assessment of that evidence, and the voting of the panel. CONCLUSIONS: By using a transparent evidence- and consensus-based approach to produce systematic reviews and clinical recommendations, the Clinical Toxicology Recommendations Collaborative aims to create an international framework for clinical toxicology education and decision-making and foster positive change for the benefit of poisoned patients.

Characteristics of digoxin toxicity attended in Spanish emergency departments according to type of poisoning and administration of digoxin antibodies: the DIGITOX study. / Características de las intoxicaciones por digoxina atendidas en diversos servicios de urgencias españoles en función del tipo de intoxicación y de la administración de anticuerpos antidigoxina: estudio DIGITOX.

OBJECTIVES: Digoxin toxicity accounts for a small percentage of poisonings attended by emergency departments. This study aimed to describe differences between acute and chronic digoxin toxicity and assess the use of digoxin-specific antibody fragments (digoxin-Fab) as an antidote. MATERIAL AND METHODS: Retrospective, observational, multicenter study in 15 hospital emergency departments in 8 Spanish autonomous communities in 7 years. We collected patient, clinical and treatment variables, and discharge destination. Patients were classified according to whether toxicity was acute or chronic and whether digoxin-Fab was administered or not. RESULTS: Twenty-seven acute and 631 chronic digoxin poisonings were attended. The mean (SD) patient age was 83.9 (7.9) years, and 76.9% were women. Patients with acute toxicity were younger (80.0 [12] years) than those with chronic toxicity (84.1 [7.7] years) (P .038), and accidental poisoning was less common (in 85.2% vs 100% in chronic toxicity; P .001). Cases of acute toxicity were also more serious (Poison Severity Score (29.6% vs 12.5% in chronic toxicity; P .001). Thirty-four patients were treated with digoxin-Fab (5.4%). These patients were younger (78.7 [11.5] years vs 84.2 (7.6) years), their toxicity was more often acute (in 20.6% vs 3.2% in chronic toxicity), more had attempted suicide (8.8% vs 0.2% with chronic toxicity), and more had severe symptoms (50% vs 11.2%) (P .001, all comparisons). Hospital admission was required for 76.1%. Overall, mortality was 11.4%. CONCLUSION: Chronic toxicity accounts for most digoxin poisoning cases, and most patients are women. Acute toxicity is more serious. Patients who required digoxin-Fab have more severe poisoning. Such patients usually have acute toxicity, and attempted suicide is more often the reason for the emergency.

OBJETIVO: Las intoxicaciones por digoxina representan un pequeño porcentaje de las intoxicaciones atendidas en urgencias. El objetivo de este estudio fue describir las diferencias entre intoxicaciones agudas y crónicas y evaluar la administración de su antídoto específico: los anticuerpos antidigoxina (AcAD). METODO: Estudio retrospectivo, observacional y multicéntrico en 15 servicios de urgencias hospitalarios de 8 comunidades autónomas durante 7 años. Se recogieron datos de filiación, clínica, tratamiento y destino al alta. Los pacientes se dividieron según era la intoxicación aguda o crónica y según recibían o no AcAD. RESULTADOS: Se recogieron 27 intoxicaciones agudas y 631 crónicas. La edad media fue de 83,9 (7,9) años, y el 76,9% eran mujeres. Los pacientes con intoxicación aguda tenían menor edad media (80,0 (12) vs 84,1 (7,7) años; p 0,038), y porcentaje de causa accidental (85,2% vs 100%; p 0,001) y mayor gravedad en la escala Poison Severity Score (29,6% vs 12,5%; p 0,001). Treinta y cuatro pacientes recibieron AcAD (5,4%) y constituyen un grupo de menor edad [78,7 (11,5) vs 84,2 (7,6); p 0,001], con mayor porcentaje de intoxicaciones agudas (20,6% vs 3,2%), intencionalidad suicida (8,8% vs 0,2%) y gravedad (50% vs 11,2%, p 0,001 en todas las comparaciones). El 76,1% precisó ingreso. La mortalidad fue del 11,4%. CONCLUSIONES: Las intoxicaciones por digoxina suelen ser crónicas y predominan en mujeres. Las intoxicaciones agudas son de mayor gravedad. Los pacientes que precisaron administración de AcAD tenían intoxicaciones más graves y mayor porcentaje de intoxicaciones agudas y con intencionalidad suicida.

Differences in clinical signs and severity of intoxication due to street drugs in adolescents and young adults treated in emergency departments. / Características diferenciales en las manifestaciones clínicas y la gravedad de las intoxicaciones por drogas de abuso en adolescentes atendidos en servicios de urgencias en comparación con adultos jóvenes.

OBJECTIVES: To determine whether symptoms and levels of severity of intoxication from street drugs differ between adolescents and young adults who come to hospital emergency departments for treatment. MATERIAL AND METHODS: We studied a consecutive cohort of adolescents (aged 12-17 years) and young adults (aged 18-30 years) who were treated in 11 hospital emergency departments belonging to the Drug Abuse Network of Spanish Hospital Emergency Departments (REDURHE). Sociodemographic and clinical characteristics and level of severity were recorded for comparison between between adolescents and young adults, adjusted for sex, alcohol co-ingestion, and type of drug used. An intoxication was recorded as severe if at least 1 of the following indicators was present: cardiac arrest, tracheal intubation, intensive care unit admission, and in-hospital death. RESULTS: We included a total of 2181 patients: 249 adolescents (11.4%) and 1932 young adults (88.6%). Alcohol coingestion and use of multiple drugs were less common in adolescents, who had significantly more events related to cannabis (in 81.1% vs 49.0% of young adults) and benzodiazepines (13.3% vs 5.5%). The adolescents had significantly fewer intoxications from the use of cocaine (10.8% vs 45.1%), amphetamines (17.3% vs 32.3%), ketamine (0.4% vs 6.0%) and gamma-hydroxybutyrate (0.4% vs 4.0%). A higher proportion of adolescents than young adults presented with diminished consciousness (23.0% vs 16.9%), but fewer manifested anxiety (15.9% vs 26.3%), palpitations (11.0% vs 19.5%), or chest pain (2.8% vs 9.2%). The pattern of associations was similar in the subgroup of intoxications due to cannabis. The adjusted model confirmed that the adolescents were more likely to have diminished consciousness, with an odds ratio (OR) of 1.851 (95% CI, 1.204-2.844) and less likely to have anxiety (OR, 0.529 (95% CI, 0.347-0.807). Intoxication was severe in 46 patients overall (2.1%); in adolescents and young adults the proportions were 0.8% and 2.3%, respectively (P = 0.129). In adolescents, the OR was 0.568 (95% CI, 0.131-2.468) for severity; for component indicators, the ORs were 0.494 (95% CI, 0.063-3.892) for intubation and 0.780 (95% CI, 0.175-3.475) for intensive care unit admission. No deaths occurred. CONCLUSION: Adolescents requiring emergency care for street drug intoxication had co-ingested alcohol or taken multiple drugs less often than young adults. Cannabis was the drug most often used by adolescents, who presented more often with diminished consciousness but less often with anxiety. We detected no differences related to event severity.

OBJETIVO: Investigar si existen diferencias en las drogas, sintomatología y gravedad entre adolescentes y jóvenes atendidos por intoxicación por drogas en servicios de urgencias hospitalarios (SUH). METODO: Entre los pacientes consecutivos atendidos por consumo de drogas en los 11 SUH de la REDURHE (Red de estudio de Drogas en Urgencias Hospitalarios en España), se seleccionaron los adolescentes (edad = 12-17 años) y los jóvenes (edad = 18-30 años). Se compararon las características sociodemográficas, clínicas y la gravedad (evento adverso combinado ­EAC­: parada cardiorrespiratoria, intubación endotraqueal, ingreso en cuidados intensivos o muerte intrahospitalaria) en adolescentes y jóvenes, ajustadas por sexo, coingesta de etanol y drogas involucradas. RESULTADOS: Se incluyeron 2.181 pacientes (adolescentes = 249, 11,4%; jóvenes = 1.932, 88,6%). En adolescentes, la coingesta de etanol y múltiples drogas fue menos frecuente. Hubo significativamente más asistencias por cannabis (81,1% vs 49,0%) y benzodiacepinas (13,3% vs 5,5%) y menos por cocaína (10,8% vs 45,1%), anfetamínicos (17,3% vs 32,3%), ketamina (0,4% vs 6,0%) y gamma-hidroxibutirato (0,4% vs 4,0%). Los adolescentes presentaron más disminución de consciencia (23,0% vs 16,9%) y menos ansiedad (15,9% vs 26,3%), palpitaciones (11,0% vs 19,5%) y dolor torácico (2,8% vs 9,2%). Estas asociaciones se mantuvieron al analizar el subgrupo de intoxicados por cannabis. En el modelo ajustado, los adolescentes presentan más disminución de consciencia con (OR = 1,851, IC 95%: 1,204-2,844) y menos ansiedad (OR = 0,529, IC 95%: 0,347-0,807). Se observó EAC en 46 pacientes (2,0%; 0,8% vs 2,3%, p = 0,129). La OR ajustada en adolescentes para EAC fue 0,568 (IC 95%: 0,131-2,468), y para intubación 0,494 (IC 95%: 0,063-3,892) y para ingreso en intensivos 0,780 (IC 95%: 0,175-3,475). No hubo fallecimientos. CONCLUSIONES: Los adolescentes intoxicados por drogas atendidos en SUH presentan con menor frecuencia coingesta de etanol o múltiples drogas. La droga más frecuentemente implicada es el cannabis, y presentan más disminución de consciencia y menos ansiedad. No detectamos diferencias en la gravedad entre adolescentes y jóvenes.

Spanish Research Network on Drugs in Hospital Emergency Departments - the REDUrHE registry: general analysis and comparisons between weekend and weekday poisonings. / Red de Estudio de Drogas en Urgencias Hospitalarias en España (Registro REDUrHE): análisis general y comparación según asistencia en día laborable o festivo.

OBJECTIVES: To describe the sociodemographic characteristics, drug use patterns, and the severity of drug overdoses treated in hospital emergency departments according to the registry of the Spanish Research Network on Drugs in Hospital Emergency Departments (REDUrHE project), and to identify differences between patterns on weekdays and weekends/national holidays. MATERIAL AND METHODS: Eleven hospitals participated in the REDUrHE project, studying consecutive patients with symptoms of drug overdose over a 24-month period. The drugs implicated were extracted from clinical records or toxicology reports. An overdose was considered severe if management required intubation, cardiopulmonary resuscitation, or admission to the intensive care unit, or if in-hospital death occurred (composite event). Each of these variables was also analyzed by itself. RESULTS: A total of 4526 patients were studied (2218 [49%] on weekends/holidays; 2308 [51%] on workdays). The mean (SD) age was 33 (11) years, and 75.5% were men. The most commonly used drugs were cocaine (47.8%), paciencannabis (44.4%), amphetamine derivatives (25.5%), benzodiazepines (8.8%), and opioids (7.3%). Patients treated on weekends/holidays were younger (32.1 vs 33.1 years on weekdays, P = .006), and they were more often taken to the hospital in an ambulance (60.5% vs 57.3%, P = .035). Hospitals in large cities (Barcelona and Madrid) saw more patients on weekends/holidays (55.8%). Major tourist destinations (the Balearic and Canary Islands) saw fewer patients on weekends/holidays (44.7%, P .001). Alcohol was ingested along with a drug by 58.2%; this combination was more common on weekends/holidays (in 63.3% vs 52.9% on weekdays, P .001), and 39.4% used more than 1 drug. Use of more than 1 drug was less common on weekends (in 37.6% vs 41.2%, P = .013). Opioid emergencies were also less frequent on weekends (6.0% vs 8.6%, P = .001), when gamma-hydroxybutyrate (GHB) overdoses were more common (5.8% vs 3.6%, P .001). Severity indicators were present (the composite event) more often on weekends (in 3.6% vs 2.2%, P = .006). Likewise, weekends saw more intubations (in 2.3% vs 1.0%, P = .001) and intensive care unit admissions (2.4% vs 1.6%, P = .047). Twelve patients (0.3%) died; mortality was similar on weekends (0.2%) and weekdays (0.3%) (P = .826). After adjusting for age, sex, combined use of alcohol, and type of drug, the risk of the severe-event composite was greater on weekends (odds ratio, 1.569; 95% CI, 1.088-2.263). CONCLUSION: Weekend and holiday emergencies due to drug overdoses are more frequent in large city hospitals. Weekend emergencies share certain distinctive characteristics: patients are younger, alcohol more often is ingested with drugs but multiple-drug combinations are less common, and GHB is used more often while opioids are used less often. Severe poisonings occur more often on weekends and holidays.

OBJETIVO: Conocer las características sociodemográficas, el patrón de consumo y la gravedad de los pacientes atendidos en servicios de urgencias hospitalarios (SUH) españoles por intoxicación por drogas (Proyecto REDUrHE) e investigar si existen diferencias entre los días festivos y los días laborables. METODO: Once SUH integrantes del proyecto REDUrHE incluyeron durante 24 meses de forma consecutiva a los pacientes atendidos por sintomatología derivada del consumo de drogas ilegales. Estas se determinaron por la historia clínica o la determinación toxicológica. El indicador primario de gravedad fue el evento adverso combinado formado por intubación, parada cardiorrespiratoria, ingreso en cuidados intensivos o muerte intrahospitalaria y los indicadores secundarios cada uno de estos eventos adversos considerado individualmente. RESULTADOS: Se incluyeron 4.526 pacientes (festivo: 2.218, 49%; laborables: 2.308, 51%), con edad media de 33 años (DE 11) y 75,5% hombres. Las drogas más frecuentemente involucradas fueron cocaína (47,8%), cannabis (44,4%), derivados anfetamínicos (25,5%), benzodiacepinas (8,8%) y opiáceos (7,3%). Los pacientes atendidos en festivos eran más jóvenes (32,1 vs 33,1 años, p = 0,006) y más frecuentemente traídos al SUH en ambulancia (60,5% vs 57,3%, p = 0,035). Los SUH de grandes ciudades (Barcelona, Madrid) tuvieron la mayor afluencia en festivo (55,8%) y los de zonas de alto turismo lúdico (Baleares, Canarias) los de menor afluencia (44,7%; p 0,001). El 58,2% ingirió simultáneamente etanol (más en festivos, 63,3% vs 52,9%, p 0,001) y el 39,4% más de una droga (menos en festivos, 37,6% vs 41,2%, p = 0,013). En festivo, los opiáceos fueron menos frecuentes (6,0% vs 8,6%, p = 0,001) y el gamma- hidroxibutirato más (5,8% vs 3,6%, p 0,001). También en festivo, hubo más eventos combinados adversos (3,6% vs 2,2%; p = 0,006), más intubaciones (2,3% vs 1,0%, p = 0,001) y más ingresos en cuidados intensivos (2,4% vs 1,6%, p = 0,047). Fallecieron 12 pacientes (0,3%), sin diferencias entre grupos (0,2% vs 0,3%, p = 0,826). Al ajustar por edad, sexo, ingesta combinada de etanol y tipos de drogas implicadas, los pacientes atendidos en festivos tuvieron más riesgo de evento adverso combinado, con OR = 1,569 (IC 95% = 1,088-2,263). CONCLUSIONES: Las intoxicaciones por drogas atendidas en SUH en día festivo suceden con mayor frecuencia en grandes ciudades y presentan ciertas características distintivas (pacientes más jóvenes, más ingesta conjunta con etanol, menos combinación de drogas, más frecuente gamma-hidroxibutirato y menos frecuente piáceos). Durante los festivos, las intoxicaciones atendidas son de mayor gravedad.

[Acute poisoning by chemical products: analysis of the first 15 years of the Spanish Toxic Surveillance System (SETv)]. / Intoxicaciones agudas por productos químicos: análisis de los primeros 15 años del Sistema Español de Toxicovigilancia (SETv).

OBJECTIVE: There are few epidemiological studies on acute poisonings from pesticides, industrials and household products in Spain. The objective of this work is to describe the epidemiological and clinical profile of acute poisonings by chemical products in our country, and analyze their annual evolution. METHODS: The Spanish Toxicovigilance System (SETv) is a prospective registry that includes 32 Emergency Departments and Intensive Care Units in Spain. An observational descriptive study of acute poisoning by chemical agents (excluding pharmacological products and illicit drugs) was carried out, within 1999-2014. Statistical analysis was performed using Chi-square or exact Fisher's tests. Non-parametric continuous variables were compared using the Mann-Whitney U test. P-value less than 0.05 were considered significant. RESULTS: The 10,548 cases studied had a mean age of 38.41 (±22.07) years, being significantly higher in women (p=0.0001). 67.7% of the poisonings occurred at home, and the most frequent routes of exposure were respiratory (48.3%), digestive (35.3%) and ocular (13.1%). The most frequent toxic groups were toxic gases (31%), caustics (25.6%) and irritant gases (12.1%). Of the patients that required treatment (76.2%), antidotes were used in 27.2%. 20.6% of the patients were admitted at Hospital, with a median stay of 32 (±151.94) days, with significant differences for pesticides and solvents (p=0.02). Sequelae were presented at discharge in 2.1% of patients. Mortality was 1.4% (146 patients) with a mean age of 62.08 years (±19.58) (p=0.0001). CONCLUSIONS: The reduction of chemical poisonings should be prevented in the domestic environment, taking into account the sources of exposure to carbon monoxide and the handling of household cleaning products, both caustic liquids and the generation of irritating gases when mixed.

OBJETIVO: Existen pocos estudios epidemiológicos, sobre todo de tipo multicéntrico, sobre las intoxicaciones agudas a causa de productos químicos agroindustriales y del hogar en España. El objetivo de este trabajo fue describir el perfil epidemiológico y clínico de estas intoxicaciones en nuestro país, y analizar su evolución temporal. METODOS: El Sistema Español de Toxicovigilancia (SETv) es un registro prospectivo que incluye a 32 Servicios de Urgencias y Unidades de Cuidados intensivos de España. Se realizó un estudio descriptivo observacional de las intoxicaciones agudas por agentes químicos (excluyendo drogas y fármacos) en sus primeros 15 años de funcionamiento (1999-2014). Las comparaciones de proporciones se realizaron mediante las pruebas de Chi-cuadrado o exacta de Fisher, y entre pares de grupos independientes con la prueba de Mann-Whitney. Se consideraron significativos los valores de probabilidad menores de 0,05. RESULTADOS: Los 10.548 casos estudiados presentaban una edad media de 38,41 (±22,07) años, siendo significativamente superior en las mujeres (p=0,0001). El 67,7% de las intoxicaciones ocurrieron en el hogar, y las vías de entrada más frecuentes fueron la respiratoria (48,3%), la digestiva (35,3%) y la ocular (13,1%). Los grupos tóxicos más frecuentes fueron los gases tóxicos (31%), los cáusticos (25,6%) y los gases irritantes (12,1%). Un 76,2% de los casos requirieron tratamiento (27,2% con antídotos). Ingresó en un centro hospitalario un 20,6% de las personas, con una estancia media de 32 (±151,94) días, con diferencias significativas para los plaguicidas y disolventes (p=0,02). Presentaron secuelas al alta un 2,1%. La mortalidad fue del 1,4% (146 pacientes), con una edad media de 62,08 años (±19,58; p=0,0001). CONCLUSIONES: En las intoxicaciones por productos químicos, las medidas preventivas deben centrarse fundamentalmente en el ámbito doméstico, controlando las fuentes de exposición al monóxido de carbono y la manipulación de los productos de limpieza, fundamentalmente los líquidos cáusticos y la generación de gases irritantes al mezclarlos.

Toxicogenomics and clinical toxicology: an example of the connection between basic and applied sciences.

The relationship between basic research and its potential clinical applications is often a difficult subject. Clinical toxicology has always been very dependent on experimental research whose usefulness has been impaired by the existence of huge differences in the toxicity expression of different substances, inter- and intra-species which make it difficult to predict clinical effects in humans. The new methods in molecular biology developed in the last decades are furnishing very useful tools to study some of the more relevant molecules implied in toxicokinetic and toxicodynamic processes. We aim to show some meaningful examples of how recent research developments with genes and proteins have clear applications to understand significant clinical matters, such as inter-individual variations in susceptibility to chemicals, and other phenomena related to the way some substances act to induce variations in the expression and functionality of these targets.

Incidence, factors related to presentation, course and mortality of metformin-associated lactic acidosis in the healthcare area of a tertiary hospital. / Incidencia, factores relacionados con la presentación, evolución y mortalidad de la acidosis láctica asociada a metformina en el área sanitaria de un hospital de tercer nivel.

OBJECTIVES: To determine the incidence of metformin-induced lactic acidosis during the period January 2014 to March 2017 in Aragon Healthcare Area III. To analyse the associated clinical and analytical factors and mortality. RESULTS: A total of 31 cases (61.3% males). Incidence: 79.76 cases/100,000 patients-year; mean age 75.39±9.34 years; 23 of them with levels of serum metformin (21.91±15.52 mcg/ ml); milligrams/day of metformin ingested: 1790.32±499; 96.8% of cases in the context of acute kidney failure; 11 cases with a history of chronic kidney disease (35.5%); 12 required intensive care (38.7%); 13 required purification treatment (41.9%; 3 haemodiafiltration, 10 haemodialysis). There was a significant correlation between daily milligrams of metformin ingested and drug levels; levels of metformin; and peak creatinine, pH and lactate. Mortality was 25.8%. There were only significant differences between the deceased and survivors regarding the duration of stay and final creatinine. Multivariate logistic regression did not detect any study variables associated with mortality. CONCLUSIONS: The incidence in our healthcare area is higher than in other series, with a 25.8% mortality rate. Virtually all cases were in the context of prerenal acute kidney failure. In 29% of cases, there was an overdose. Patients must be warned about the most common lactic acidosis-inducing situations, especially dehydration, if they continue taking the drug at such times.

Polychlorinated dibenzo-p-dioxins and the human immune system: 4 studies on two Spanish families with increased body burdens of highly chlorinated PCDDs.

The consequences of exposure of people to highly chlorinated polychlorodibenzo-p-dioxins (PCDDs) are much less known than those of TCDD. We report on levels of PCDDs (and PCDFs) in 13 members of two families poisoned by contaminated cooking oil. Originally, all persons displayed chloracne as an early symptom. Persisting hexa- and higher chlorinated PCDDs could be analysed many years after exposure. Highest values found in blood lipids were: OCDD 660,000 pg/g; HpCDD 58,000 pg/g; HxCDDs: 3500 pg/g. None of the participants exhibited increased TCDD levels at the time of study. During a period of 6 years, HpCDD and OCDD disappeared from the blood lipids much faster in persons exposed as children or young adults, than from lipids of their parents. Surface receptors on blood lymphocytes of the members of the two families and the proliferative capacity of these blood cells in the presence of typical stimulants were analysed. Even in family members with the highest body burdens of hexa- to octachlorinated PCDDs we could not detect pronounced changes from a reference population with respect to the immunological markers. Minor deviations of levels of some receptors in a few, but not all, highly exposed persons suggested a similar trend to those reported in previous studies of persons with body burdens of > or =3000 pg TCDD/g blood lipids. An increase in the number of total blood lymphocytes in some subjects exposed as children may have similarity with highly TCDD-exposed children in Seveso.