[Retrospective analysis of venlafaxine-induced hypoglycemia in patients with overdose]. / Análisis retrospectivo de las hipoglucemias inducidas por venlafaxina en pacientes con sobredosis.

INTRODUCTION: Recent publications relate the presence of hypoglycemia in venlafaxine (VLX) poisoning depending on the dose. Our aim was to analyze the clinical characteristics of patients who presented hypoglycemia induced by VLF overdose. PATIENTS AND METHODS: Retrospective study carried out in the Balearic Islands (2020-2023). INCLUSION CRITERIA: serum concentrations of VLX + O-desmethyl-venlafaxine (O-VLX)>800 ng/mL. The characteristics of patients with and without hypoglycemia were compared. RESULTS: Twenty-one patients were included, 8 (38.1%) with hypoglycemia. No differences were found in the doses referred to in both groups. Peak concentrations of VLX + O-VLX (ng/mL) were 9,783 [4,459-17,976] in patients with hypoglycemia and 1,413 [930-1,719] in patients without hypoglycemia (p<0.0001). The presence of hypoglycemia was associated with: lower age and level of consciousness; and higher frequency of suicide attempts, seizures, mydriasis, tachycardia and serotonin syndrome, invasive respiratory support, fluid therapy and ICU admission (p<0.05). CONCLUSIONS: The detection of hypoglycemia in a VLX overdose case is a readily available marker to suspect the severity of the patient. In any case, serum concentrations when available allow us to confirm intoxication.

Ketamine detection in urine samples from patients poisoned by recreational drugs: epidemiologic, clinical, and toxicologic profiles. / Detección de ketamina en pacientes intoxicados por drogas recreativas: perfil epidemiológico, clínico y toxicológico.

OBJECTIVES: To describe the epidemiologic, clinical, and toxicologic profiles of patients who used recreational ketamine and experienced acute poisoning. MATERIAL AND METHODS: Retrospective observational study of patients attended by several emergency medical services in the Balearic Islands for analytically confirmed acute poisoning after using ketamine between January 2016 and December 2020. Urine samples were analyzed by immunoassay and combined gas chromatography and mass spectrometry. RESULTS: One hundred twenty-two patients were studied. The mean (SD) age was 26.7 (6.5) years. The majority were men (77.9%) and not residents of the Balearic Islands (74.6%). Poisoning cases occurred mainly in the summer and in the island of Ibiza (84.4%). Ketamine use was declared by the patient or clinically suspected in 40.2%. The most common clinical signs were tachycardia (43.4%), hypertension (28.7%), mydriasis (27.0%), altered consciousness (25.4%), agitation/aggressiveness (25.4%), and hypothermia (21.3%). Seven patients (5.73%) required admission to the intensive care unit. The drugs most often detected along with ketamine were cocaine, in 93.4%, and 3,4-methylenedioxymethamphetamine (MDMA), in 78.7%. Multiple-drug use combining ketamine, cocaine, and MDMA, or on occasion additional substances, was detected in 98.4%. CONCLUSION: Detection of ketamine in urine samples from patients poisoned by recreational drugs is associated with a characteristic profile: young men who are not residents of the Balearic Islands, who attend electronic music concerts, and who have taken multiple drugs. A substantial percentage of such patients are unaware of drug intake.

OBJETIVO: Identificar el perfil epidemiológico, clínico y toxicológico de los pacientes consumidores de ketamina en el contexto de una intoxicación aguda por drogas recreativas. METODO: Estudio observacional retrospectivo en pacientes atendidos en varios servicios de urgencias (SU) en Baleares por intoxicaciones agudas por drogas recreativas con exposición a ketamina confirmada analíticamente, entre enero de 2016 y diciembre de 2020. El análisis toxicológico en muestras de orina se realizó mediante inmunoensayo y cromatografía de gases acoplada a espectrometría de masas. RESULTADOS: Se incluyeron 122 pacientes. La edad media fue de 26,7 (DE 6,5) años. La mayoría eran hombres (77,9%) y no residentes en las Islas Baleares (74,6%). Los casos se detectaron mayoritariamente en verano y en Ibiza (84,4%). El uso de ketamina solo fue declarado por el paciente o fue clínicamente sospechado por el médico en el 40,2%. Los signos clínicos más frecuentes fueron taquicardia (43,4%), hipertensión (28,7%), midriasis (27,0%), disminución de la consciencia (25,4%), agitación/agresividad (25,4%) e hipotermia (21,3%). Siete pacientes (5,7%) requirieron ingreso en la unidad de cuidados intensivos (UCI). La cocaína (93,4%) y la 3,4-metilendioximetanfetamina (MDMA) (78,7%) fueron las drogas más detectadas junto con la ketamina. El policonsumo fue habitual (98,4%), combinando ketamina, cocaína y MDMA, en algunos casos asociado a otras sustancias. CONCLUSIONES: La detección de ketamina en intoxicaciones por drogas recreativas se asocia a consumidores con un perfil característico (varones jóvenes, no residentes, asistentes a eventos de música electrónica y policonsumo) y un alto porcentaje desconocen de este consumo.

Detection of unsuspected cathinone and piperazine-type drugs in urine samples positive for methamphetamine and amphetamine collected in emergency departments. / Detección no sospechada de catinonas y piperacinas en pacientes consumidores de metanfetamina y anfetamina atendidos en servicios de urgencias hospitalarios.

OBJECTIVES: To detect the presence of unsuspected and/or undeclared cathinone and piperazine-type designer drugs in methamphetamine (METH) and amphetamine users treated in emergency departments, and to compare clinical and toxicologic profiles. MATERIAL AND METHODS: Retrospective observational study of emergency department patients treated for confirmed acute intoxication by recreational drugs (METH and amphetamines) between March 2019 and December 2020. We ordered high-performance liquid chromatography with tandem mass spectrometry to detect cathinones (methylone, fluoromethcathinone, mexedrone, fluoromethamphetamine, mephedrone, methylenedioxypyrovalerone) and synthetic piperazines (meta-chlorophenylpiperazine and trifluoromethylphenylpiperazine). Demographic, clinical, and toxicologic variables were analyzed with SPSS software (version 23). RESULTS: Thirty-nine patients were included: 24 (61.5%) had used METH and 15 (38.5%) an amphetamine. Synthetic cathinones were detected in samples from 11 patients (28.2%), 10 (90.9%) in the METH group and 1 (9.1%) in the amphetamine group (P = .028). The METH users had taken mephedrone (8 patients) or methylone (2 patients); the amphetamine user had taken mephedrone. None of the patients had declared use of a cathinone; nor was use suspected. The mean (SD) number of substances involved was higher among users of cathinones (3.5 [1.13] vs 2.5 [1.40] in those who took no cathinones; P = .036). Among the cathinone users, 90.9% were men, 90.9% had used METH, and 45.5% had practiced chemsex. HIV positivity was significantly associated with cathinone use (in 45.5% vs 10.7% of those not using cathinones; P = .028). All 5 of the patients who had taken cathinones and also practiced chemsex were HIV positive. Significantly more patients who had taken cathinones presented with anxiety (72.7% vs 21.43%; P = .007). No differences in clinical management were found. CONCLUSION: Detection of METH in intoxicated patients should raise suspicion of probable use of a synthetic cathinone. Patients in whom new psychoactive substances are detected should be kept under observation, and clinical protocols should include referring them to addiction treatment centers.

OBJETIVO: Determinar la incidencia de catinonas y piperazinas, no sospechadas y/o declaradas en consumidores de metanfetamina (MANF) y anfetamina (ANF) atendidos en servicios de urgencias hospitalarios (SUH) y comparar los perfiles clínicos y toxicológicos. METODO: Estudio retrospectivo de pacientes con intoxicación aguda por drogas recreativas con MANF y ANF confirmadas analíticamente atendidos en 3 SUH entre marzo de 2019 y diciembre de 2020. Se detectaron por HPLC-MS/MS las catinonas [metilona, fluorometcatinona, mecedrona, fluorometanfetamina, mefedrona, metilendioxipirovalerona (MDPV)] y las piperazinas sintéticas [meta-clorofenilpiperazina (mCPP), trifluorometilfenilpiperazina (TFMPP)]. RESULTADOS: Se incluyeron 39 pacientes: 24 (61,5%) en el grupo MANF y 15 (38,5%) en el ANF. En 11 (28,2%), se detectaron catinonas sintéticas (grupo CAT), 10 en el grupo MANF (8 mefedrona, 2 metilona) y 1 en el grupo ANF (1 mefedrona) (90,9% vs 9,1%; p = 0,028). Ninguno de los pacientes declaró consumo de catinonas. El número de drogas implicadas en la intoxicación fue superior en el grupo CAT (3,5 [1,13] vs 2,5 [1,40]; p = 0,036). El perfil clínico del grupo CAT fue: varón (90,9%), consumidor de MANF (90,9%) y usuario de chemsex (45,5%). El diagnóstico de VIH se asoció significativamente al grupo CAT (45,5% vs 10,7%; p = 0,028). Los pacientes del grupo CAT presentaron mayor ansiedad (72,7% vs 21,4%; p = 0,007). No se hallaron diferencias en su manejo clínico. CONCLUSIONES: La detección de MANF debería considerarse un dato de sospecha de consumo de catinonas sintéticas, y en esos casos debería contemplarse la detección de nuevas sustancias psicoactivas de abuso.

Sudden cardiac death in persons aged 50 years or younger: diagnostic yield of a regional molecular autopsy program using massive sequencing.

INTRODUCTION AND OBJECTIVES: Sudden cardiac death (SCD) in young people often has a genetic cause. Consequently, the results of "molecular autopsy" may have important implications for their relatives. Our objective was to evaluate the diagnostic yield of a molecular autopsy program using next-generation sequencing. METHODS: We performed a prospective study of a cohort of consecutive patients who died from nonviolent SCD, aged ≤ 50 years, and who underwent molecular autopsy using large panels of next-generation sequencing, with subsequent clinical and genetic family screening. We analyzed demographic, clinical, toxicological, and genetic data. RESULTS: We studied 123 consecutive cases of SCD in persons aged ≤ 50 years. The incidence of SCD was 5.8 cases/100 000 individuals/y, mean age was 36.15±12.7 years, and 95 were men (77%). The cause was cardiac in 53%, unexplained SCD in 24%, toxic in 10.6%, and infant SCD in 4%. Among cardiac causes, ischemic heart disease accounted for 38% of deaths, arrhythmogenic cardiomyopathy for 7%, hypertrophic cardiomyopathy for 5%, and idiopathic left ventricular hypertrophy for 11%. Genetic analysis was performed in 62 cases (50.4%). Genetic variants were found in 42 cases (67.7%), with a mean of 3.4±4 genetic variants/patient, and the variant found was considered to be pathogenic or probably pathogenic in 30.6%. In unexplained SCD, 70% showed some genetic variant. Family screening diagnosed 21 carriers or affected individuals, 5 of whom were at risk, indicating an implantable cardiac defibrillator. CONCLUSIONS: Protocol-based and exhaustive study of SCD from cardiac causes in persons aged ≤ 50 years is feasible and necessary. In a high percentage of cases, the cause is genetic, indicating the existence of relatives at risk who could benefit from early diagnosis and treatment to avoid complications.

Amphetamine and methamphetamine poisonings attended in hospital emergency departments: clinical features and the usefulness of laboratory confirmation. / Intoxicaciones por anfetamina y metanfetamina atendidas en los servicios de urgencias: características clínicas y utilidad de la confirmación analítica.

OBJECTIVES: To determine whether clinical and toxicologic findings differed between cases of amphetamine (AMP) and methamphetamine (mAMP) poisoning attended in 2 Balearic Island hospital emergency departments. MATERIAL AND METHODS: Retrospective observational study of AMP and mAMP cases with laboratory confirmation between 2013 and 2018. We compared clinical and toxicologic variables as well as clinical management between groups. RESULTS: 1) A total of 120 cases were found: 86 (71.7%) with AMP poisoning and 34 (28.3%) with mAMP poisoning. 2) Drug poisoning was confirmed by gas chromatography associated with mass spectrometry (GC-MS) in 787 urine samples found to be positive during screening. One hundred fifty-four (19.6%) were confirmed by GC-MS. Thirtyfour of them did not meet the inclusion criteria. 3) Significant differences between AMP and mAMP cases were found for age (32.3 vs 28.4 y, respectively); sex (72.1% vs 94.1% men); and Spanish nationality (64.0% vs 29.4%). Reasons for admission and clinical features also differed: the reasons were aberrant behavior (15.1% in the AMP group vs 0% in the mAMP group) and palpitations (1.2% vs 20.6%); agitation was observed in 27.9% and 8.8%, respectively. Clinical management was similar in the 2 groups. Multiple drug poisoning was detected in 76.6% patients and was more common in patients in the AMP group (82.6% vs 61.8%). The additional drugs in these cases were mainly cocaine (63.0%), cannabis (48.9%), 3,4-methylenedioxy-N-methamphetamine (MDMA) (38.0%), and alcohol (35.9%). Cannabis was detected in a significantly higher proportion in the AMP group (45.3%) than in the mAMP group (17.6%). False positives were found in 78.7% of the samples. The culprit drug was most often MDMA (71.2%). CONCLUSION: AMP poisonings were associated with age over 30 years, Spanish nationality, aberrant behavior, agitation, multiple drug findings, and the use of cannabis. Poisonings caused by mAMP abuse were associated with age under 30 years, non-Spanish nationality, palpitations, and single-drug use.

OBJETIVO: Investigar si existen diferencias clínicas y toxicológicas en pacientes intoxicados por anfetamina (ANF) y metanfetamina (MANF) atendidos en servicios de urgencias. METODO: Estudio observacional retrospectivo de intoxicaciones por ANF y MANF con confirmación analítica en Baleares (2013-2018). Se compararon variables clínicas, toxicológicas y de manejo clínico entre grupos. RESULTADOS: 1) Se incluyeron 120 pacientes, 86 (71,7%) grupo ANF y 34 (28,3%) grupo MANF. 2) La confirmación de derivados anfetamínicos se realizó por cromatografía de gases-espectrometría de masas en 787 muestras de orina previamente positivas mediante un método de cribado cualitativo. Se confirmaron 154 (19,6%) muestras. De ellas, 34 fueron excluidas. 3) Se encontraron diferencias significativas entre ANF y MANF en: edad (32,3 vs 28,4 años); sexo (72,1 vs 94,1% hombres); nacionalidad española (64,0 vs 29,4%); en motivos de admisión: alteración de conducta (15,1 vs 0%) y palpitaciones (1,2 vs 20,6%); y en características clínicas: agitación (27,9 vs 8,8%). No hubo diferencias de manejo clínico. El 76,6% de casos fueron polintoxicaciones, más comunes en ANF (82,6 vs 61,8%). En estos casos se detectó principalmente cocaína (63,0%), cannabis (48,9%), MDMA (38,0%) y alcohol (35,9%). La mayor asociación del cannabis con el grupo de ANF fue estadísticamente significativa (45,3 vs 17,6%). La causa de los falsos positivos se identificó en el 78,7% de muestras, siendo el MDMA (71,2%) la principal. CONCLUSIONES: Se observaron diferencias entre ANF y MANF en cuanto a variables demográficas y motivo de asistencia; no obstante en esta serie hubo un alto porcentaje de polintoxicaciones.

Acute extensive myelopathy after single heroin and cocaine exposure in a patient with toxicological evidence of long-term drug abstinence.

Heroin-related myelopathy is an uncommon but often devastating complication of heroin intake. It is usually reported in individuals exposed to intravenous heroin after a variable drug-free period, leading to acute and complete spinal cord injury with poor long-term outcome. We describe an original case of acute longitudinally extensive transverse myelopathy following single heroin and cocaine intravenous exposure after a long period of abstinence confirmed by toxicological hair and retrospective urine drug analysis. This case could provide new insights in the understanding of this rare neurological complication.

[Factors associated with death due to lactic acidosis in patients with type-2 diabetes treated with metformin]. / Factores asociados a mortalidad por acidosis láctica en pacientes diabéticos tratados con metformina.

EN: To identify analytical factors associated with mortality in patients with type-2 diabetes under long-term treatment with metformin who come to the emergency department with acute symptoms of lactic acidosis. Retrospective observational analysis of patient records in a referral hospital. We collected clinical data and laboratory results for a series of metformin-treated patients with type-2 diabetes who developed lactic acidosis, stratified by severity. Factors related to the episode were analyzed for associations with mortality or survival. Of 16 patients studied (mean age 70 years; range, 60-77 years), 75% had gastrointestinal symptoms in the 5 days before they came to the emergency department. Mortality (19%) was associated with sepsis on arrival; elevated white blood cell counts, particularly neutrophil counts; low platelet counts; high C-reactive protein (CRP) and procalcitonin levels; and 1 or more chronic concomitant diseases. Metformin concentration was not significantly associated with mortality. Signs of sepsis, high neutrophil counts with low platelet counts, elevated CRP and procalcitonin levels, and the presence of 1 or more concomitant diseases may be risk factors for death in metformin-treated patients with lactic acidosis.

ES: El objetivo de este estudio es la detección de parámetros analíticos asociados a la mortalidad en los pacientes con diabetes mellitus tipo 2 (DM2) con tratamiento crónico con metformina que acuden a urgencias por un cuadro clínico agudo con presencia de acidosis láctica. Se trata de un estudio observacional-analítico retrospectivo realizado en un hospital de tercer nivel. Se recogieron datos clínicos y analíticos en una serie de pacientes con acidosis láctica, estratificada por gravedad, y tratamiento con metformina para DM2. Se compararon los resultados en función de la mortalidad o supervivencia del episodio. De 16 pacientes estudiados, con una edad media de 70 años (rango de 60 a 77), el 75% presentó sintomatología gastrointestinal los 5 días previos a su ingreso. La mortalidad total observada fue del 19%, que se asoció a la presencia de sepsis al ingreso, leucocitosis con neutrofilia, plaquetopenia, elevación de proteína C reactiva (PCR), valores altos de procalcitonina y la comorbilidad con una o más patologías crónicas. Las cifras séricas de metformina no se correlacionaron significativamente con la mortalidad. Se concluye que en pacientes con acidosis láctica y tratamiento con metformina pueden ser factores asociados a la mortalidad la presencia de criterios de sepsis, neutrofilia con plaquetopenia, elevación de PCR y de procalcitonina y la existencia de una o más patologías comórbidas.

[Usefulness of testing for paracetamol concentration in urine when poisoning is suspected in children]. / Estudio piloto sobre la utilidad de la determinación de paracetamol urinario en la sospecha de intoxicación del paciente pediátrico.

OBJECTIVES: To analyze the diagnostic yield of a cut-point of 3 µg/mL for paracetamol in urine to screen for poisoning in children. MATERIAL AND METHODS: Prospective case-control observational study in a pediatric intensive care unit (PICU). All enrolled patients had been admitted to the PICU. Cases were children receiving a therapeutic dose of intravenous paracetamol. Controls were not receiving paracetamol. Urine samples were collected early in the morning and 4 hours after a dose of paracetamol was received by case patients. Paracetamol concentration was measured in all samples. We compared the percentages of cases and controls who had a concentration of 3 µg/mL or more. The sensitivity, specificity, and predictive values of the cut-point were calculated. RESULTS: Forty children aged between 1 month and 19 years (20 per matched group) were enrolled. Paracetamol was not detected in any of the control samples. The sensitivity of the test in early morning urine was 95% (95% CI, 85.5%-100%); specificity was 100%. The positive predictive value was 100%; the negative predictive value was 95.2% (95% CI, 86.1%-100%). Paracetamol was detected in all of the second samples collected from cases. CONCLUSION: Measuring the paracetamol concentration in urine within 4 hours of dosing is useful to rule out prior intake of paracetamol and overdosing in PICU patients. Studies to validate the new cut-point of 3 µg/mL for paracetamol in urine are required with a view to possibly including it in a diagnostic protocol for suspected acute poisoning.

OBJETIVO: Analizar el rendimiento de un punto de corte de 3 µg/mL en la determinación de paracetamol urinario (PCTo) como método de cribado para detectar paracetamol en posibles sobreingestas en población pediátrica. METODO: Estudio de caso-control, observacional, analítico y prospectivo realizado en una unidad de cuidados intensivos pediátricos (UCIP). Se seleccionó una muestra compuesta por aquellos pacientes ingresados en UCIP, considerando el grupo de casos aquellos con administración pautada de una dosis terapéutica endovenosa de paracetamol y un grupo control sin administración del fármaco. Se recogió una muestra de orina dentro de la primera hora y una segunda muestra pasadas 4 horas de la dosis del fármaco. En todos se determinó PCTo cuantitativamente. Se comparó la proporción de pacientes con PCTo STX 3 µg/mL. Se calcularon sensibilidad, especificidad y valores predictivos. RESULTADOS: Se incluyeron 40 niños de edades entre 1 mes y 19 años (20 en cada grupo). No se obtuvo ningún paciente de control con PCTo positiva. La sensibilidad de la prueba en la primera orina recogida fue del 95% (IC 95%: 85,5-100%) y su especificidad del 100%. El valor predictivo positivo fue 100%, y el negativo del 95,2% (IC 95%: 86,1-100%). En las segundas orinas recogidas todos los valores de rendimiento del test fueron del 100%. CONCLUSIONES: La detección de PCTo antes de las 4 horas es útil para descartar la ingesta de paracetamol en población pediátrica. Se requieren estudios que permitan validar el nuevo punto de corte de 3 µg/mL para su posible inclusión en el algoritmo de sospecha de intoxicación aguda.

[Consensus document on the prevention of exposure to methylmercury in Spain]. / Documento de consenso sobre la prevención de la exposición al metilmercurio en España.

The beneficial effects of fish consumption in both children and adults are well known. However, the intake of methylmercury, mainly from contaminated fish and shellfish, can have adverse health effects. The study group on the prevention of exposure to methylmercury (GEPREM-Hg), made up of representatives from different Spanish scientific societies, has prepared a consensus document in a question and answer format, containing the group's main conclusions, recommendations and proposals. The objective of the document is to provide broader knowledge of factors associated with methylmercury exposure, its possible effects on health among the Spanish population, methods of analysis, interpretation of the results and economic costs, and to then set recommendations for fish and shellfish consumption. The group sees the merit of all initiatives aimed at reducing or prohibiting the use of mercury as well as the need to be aware of the results of contaminant analyses performed on fish and shellfish marketed in Spain. In addition, the group believes that biomonitoring systems should be set up in order to follow the evolution of methylmercury exposure in children and adults and perform studies designed to learn more about the possible health effects of concentrations found in the Spanish population, ta king into account the lifestyle, eating patterns and the Mediterranean diet.

Los efectos beneficiosos del consumo de pescado tanto en niños como en adultos han sido bien reconocidos. Sin embargo, la ingesta de metilmercurio principalmente a través del pescado y marisco contaminado puede producir efectos adversos en la salud. El grupo de estudio para la prevención de la exposición al metilmercurio (GEPREM-Hg), constituido por representantes de diferentes sociedades científicas españolas, ha elaborado un documento de consenso donde se recogen en forma de preguntas y respuestas las principales conclusiones, recomendaciones y propuestas planteadas en el grupo. El objetivo del documento es profundizar en el conocimiento de los factores asociados a la exposición al metilmercurio, los posibles efectos sobre la salud en la población española, los métodos de análisis, la interpretación de los resultados, el coste económico y establecer finalmente recomendaciones de consumo de pescados y mariscos. El grupo considera acertadas todas las iniciativas encaminadas a reducir o prohibir el uso del mercurio y la necesidad de conocer los resultados de los análisis de contaminantes que se realizan en los pescados y mariscos que se comercializan en España. Además, opina que se deberían establecer sistemas de biomonitorización para conocer la evolución de la exposición al metilmercurio en niños y adultos y realizar estudios diseñados para conocer los posibles efectos sobre la salud de las concentraciones halladas en la población española, teniendo en cuenta el estilo de vida, los patrones de consumo alimentarios y la dieta mediterránea.