Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional

Antecedentes: La intoxicación por acetaminofén (APAP) es una de las principales causas de lesión hepática aguda en todo el mundo. Sin embargo, los datos detallados de Colombia son limitados. Este estudio describe la presentación clínica, el manejo, la respuesta a la N-acetilcisteína (NAC) y los resu...

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Autores:
Berbeo Velásquez, Manuel Alejandro
Tipo de recurso:
Article of investigation
Fecha de publicación:
2025
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
spa
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/47477
Acceso en línea:
https://hdl.handle.net/10495/47477
Palabra clave:
Acetilcisteína
Acetaminofén - Toxicidad
Acetaminophen - Toxicity
Sobredosis de droga
Drug overdose
Acetilcisteína
Acetylcysteine
Enfermedad hepática inducida por sustancias y drogas
Chemical and drug induced liver injury
Estudio observacional
Observational study
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D000082
https://id.nlm.nih.gov/mesh/D062787
https://id.nlm.nih.gov/mesh/D000111
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D064888
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
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embargoedAccess
License
http://creativecommons.org/licenses/by-nc-sa/4.0/
id UDEA2_9556b71431f073ef5f192b6c026ec1a2
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/47477
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
title Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
spellingShingle Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
Acetilcisteína
Acetaminofén - Toxicidad
Acetaminophen - Toxicity
Sobredosis de droga
Drug overdose
Acetilcisteína
Acetylcysteine
Enfermedad hepática inducida por sustancias y drogas
Chemical and drug induced liver injury
Estudio observacional
Observational study
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D000082
https://id.nlm.nih.gov/mesh/D062787
https://id.nlm.nih.gov/mesh/D000111
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D064888
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
title_full Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
title_fullStr Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
title_full_unstemmed Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
title_sort Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad : un estudio observacional
dc.creator.fl_str_mv Berbeo Velásquez, Manuel Alejandro
dc.contributor.advisor.none.fl_str_mv Salgado Gómez, Tania Margarita
dc.contributor.author.none.fl_str_mv Berbeo Velásquez, Manuel Alejandro
dc.contributor.researcher.none.fl_str_mv Polo Hernández, Hernán David
Quintero Aguirre, Juliana
Rodríguez Jaramillo, Carlos Andrés
dc.subject.classification.none.fl_str_mv Acetilcisteína
topic Acetilcisteína
Acetaminofén - Toxicidad
Acetaminophen - Toxicity
Sobredosis de droga
Drug overdose
Acetilcisteína
Acetylcysteine
Enfermedad hepática inducida por sustancias y drogas
Chemical and drug induced liver injury
Estudio observacional
Observational study
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D000082
https://id.nlm.nih.gov/mesh/D062787
https://id.nlm.nih.gov/mesh/D000111
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D064888
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.decs.none.fl_str_mv Acetaminofén - Toxicidad
Acetaminophen - Toxicity
Sobredosis de droga
Drug overdose
Acetilcisteína
Acetylcysteine
Enfermedad hepática inducida por sustancias y drogas
Chemical and drug induced liver injury
Estudio observacional
Observational study
dc.subject.lcshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D056486
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D000082
https://id.nlm.nih.gov/mesh/D062787
https://id.nlm.nih.gov/mesh/D000111
https://id.nlm.nih.gov/mesh/D056486
https://id.nlm.nih.gov/mesh/D064888
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Antecedentes: La intoxicación por acetaminofén (APAP) es una de las principales causas de lesión hepática aguda en todo el mundo. Sin embargo, los datos detallados de Colombia son limitados. Este estudio describe la presentación clínica, el manejo, la respuesta a la N-acetilcisteína (NAC) y los resultados entre los pacientes tratados en un hospital de referencia nacional. Métodos: Se realizó un estudio observacional retrospectivo que incluyó a pacientes ingresados por intoxicación por APAP en el Hospital Universitario San Vicente Fundación (Medellín, Colombia) desde enero de 2012 hasta diciembre de 2023. Se recopilaron datos demográficos, clínicos y de laboratorio, y se analizaron por fase de intoxicación. Las variables de tratamiento incluyeron las medidas de descontaminación y el tiempo hasta el inicio de la NAC (menos de 8 horas, de 8 a 15 horas, más de 15 horas). Los resultados incluyeron lesión hepática aguda grave, duración de la estancia hospitalaria y mortalidad. Se utilizaron estadísticas descriptivas y comparaciones de grupos (pruebas de Chi-cuadrado y Kruskal-Wallis). Resultados: Entre 227 pacientes, el 71.4% eran mujeres y el 53% eran estudiantes. Más del 90% de los casos fueron por ingestión intencional, y el 56% tenía comorbilidades psiquiátricas. Se inició la NAC en las primeras 8 horas en el 57.7% de los casos. Los pacientes que recibieron NAC en menos de 8 horas mantuvieron las transaminasas dentro de los límites normales a lo largo de las fases de intoxicación. Por otro lado, la administración tardía de NAC (más de 8 horas) se asoció con niveles más altos de transaminasas en las fases III-IV. La lesión hepática aguda grave ocurrió en el 9.7% de los pacientes. No se registraron muertes ni trasplantes de hígado. Se produjeron reacciones adversas relacionadas con la NAC en el 14.1% de los casos, la mayoría leves. Conclusiones: En esta cohorte colombiana, la intoxicación por APAP afectó predominantemente a mujeres jóvenes con antecedentes psiquiátricos. La administración temprana de NAC (igual o menos de 8 horas) se asoció con la prevención de elevaciones significativas de las enzimas hepáticas. El inicio rápido del antídoto puede reducir las necesidades de monitoreo y optimizar el uso de los recursos.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-10-01T12:34:52Z
dc.date.issued.none.fl_str_mv 2025
dc.date.available.none.fl_str_mv 2027-10-01
dc.type.none.fl_str_mv Trabajo de grado - Especialización
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.content.none.fl_str_mv Text
dc.type.coarversion.none.fl_str_mv http://purl.org/coar/version/c_b1a7d7d4d402bcce
dc.type.driver.none.fl_str_mv info:eu-repo/semantics/other
dc.type.version.none.fl_str_mv info:eu-repo/semantics/draft
format http://purl.org/coar/resource_type/c_2df8fbb1
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dc.identifier.citation.none.fl_str_mv Manuel Alejandro Berbeo Velásquez, Hernán David Polo Hernández, Juliana Quintero Aguirre, Carlos Andrés Rodríguez Jaramillo y Tania Margarita Salgado Gómez, “Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad: un estudio observacional” (Trabajo de grado especialización, Universidad de Antioquia, 2025).
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/47477
identifier_str_mv Manuel Alejandro Berbeo Velásquez, Hernán David Polo Hernández, Juliana Quintero Aguirre, Carlos Andrés Rodríguez Jaramillo y Tania Margarita Salgado Gómez, “Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad: un estudio observacional” (Trabajo de grado especialización, Universidad de Antioquia, 2025).
url https://hdl.handle.net/10495/47477
dc.language.iso.none.fl_str_mv spa
language spa
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spelling Salgado Gómez, Tania MargaritaBerbeo Velásquez, Manuel AlejandroPolo Hernández, Hernán DavidQuintero Aguirre, JulianaRodríguez Jaramillo, Carlos Andrés2025-10-01T12:34:52Z2027-10-012025Manuel Alejandro Berbeo Velásquez, Hernán David Polo Hernández, Juliana Quintero Aguirre, Carlos Andrés Rodríguez Jaramillo y Tania Margarita Salgado Gómez, “Caracterización de la intoxicación por acetaminofén en un centro de alta complejidad: un estudio observacional” (Trabajo de grado especialización, Universidad de Antioquia, 2025).https://hdl.handle.net/10495/47477Antecedentes: La intoxicación por acetaminofén (APAP) es una de las principales causas de lesión hepática aguda en todo el mundo. Sin embargo, los datos detallados de Colombia son limitados. Este estudio describe la presentación clínica, el manejo, la respuesta a la N-acetilcisteína (NAC) y los resultados entre los pacientes tratados en un hospital de referencia nacional. Métodos: Se realizó un estudio observacional retrospectivo que incluyó a pacientes ingresados por intoxicación por APAP en el Hospital Universitario San Vicente Fundación (Medellín, Colombia) desde enero de 2012 hasta diciembre de 2023. Se recopilaron datos demográficos, clínicos y de laboratorio, y se analizaron por fase de intoxicación. Las variables de tratamiento incluyeron las medidas de descontaminación y el tiempo hasta el inicio de la NAC (menos de 8 horas, de 8 a 15 horas, más de 15 horas). Los resultados incluyeron lesión hepática aguda grave, duración de la estancia hospitalaria y mortalidad. Se utilizaron estadísticas descriptivas y comparaciones de grupos (pruebas de Chi-cuadrado y Kruskal-Wallis). Resultados: Entre 227 pacientes, el 71.4% eran mujeres y el 53% eran estudiantes. Más del 90% de los casos fueron por ingestión intencional, y el 56% tenía comorbilidades psiquiátricas. Se inició la NAC en las primeras 8 horas en el 57.7% de los casos. Los pacientes que recibieron NAC en menos de 8 horas mantuvieron las transaminasas dentro de los límites normales a lo largo de las fases de intoxicación. Por otro lado, la administración tardía de NAC (más de 8 horas) se asoció con niveles más altos de transaminasas en las fases III-IV. La lesión hepática aguda grave ocurrió en el 9.7% de los pacientes. No se registraron muertes ni trasplantes de hígado. Se produjeron reacciones adversas relacionadas con la NAC en el 14.1% de los casos, la mayoría leves. Conclusiones: En esta cohorte colombiana, la intoxicación por APAP afectó predominantemente a mujeres jóvenes con antecedentes psiquiátricos. La administración temprana de NAC (igual o menos de 8 horas) se asoció con la prevención de elevaciones significativas de las enzimas hepáticas. El inicio rápido del antídoto puede reducir las necesidades de monitoreo y optimizar el uso de los recursos.Background: Acetaminophen (APAP) poisoning is a leading cause of acute liver injury worldwide, yet detailed data from Colombia are limited. This study describes clinical presentation, management, response to N-acetylcysteine (NAC), and outcomes among patients treated at a national referral hospital. Methods: We conducted a retrospective observational study including patients admitted for APAP poisoning to San Vicente Foundation Hospital (Medellín, Colombia) from January 2012 to December 2023. Demographic, clinical and laboratory data were collected and analyzed by intoxication phase. Treatment variables included decontamination measures and time to NAC initiation (<8 h, 8–15 h, >15 h). Outcomes comprised severe acute liver injury, length of stay, and mortality. Descriptive statistics and group comparisons (Chi-square and Kruskal–Wallis tests) were used. Results: Among 227 patients, 71.4% were female and 53% were students; >90% of cases were intentional ingestions, and 56% had psychiatric comorbidities. NAC was initiated within 8 hours in 57.7% of cases. Patients receiving NAC within 8 hoursmaintained transaminases within normal limits across intoxication phases, while delayed NAC (>8 h) was associated with higher transaminase levels in phases III–IV. Severe acute liver injury occurred in 9.7% of patients; no deaths or liver transplants were recorded. NAC-related adverse reactions occurred in 14.1%, mostly mild. Conclusions: In this Colombian cohort, APAP poisoning predominantly affected young women with psychiatric histories. Early NAC administration (≤8 h) was associated with prevention of significant liver enzyme elevations. Rapid antidote initiation may reduce monitoring needs and optimize resource use.EspecializaciónEspecialista en Toxicología Clínica38 páginasapplication/pdfspaUniversidad de AntioquiaEspecialización en Toxicología ClínicaDepartamento de Farmacología y ToxicologíaMedellín, ColombiaFacultad de MedicinaCampus en el Área de la saludhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/embargoedAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_f1cfAcetilcisteínaAcetaminofén - ToxicidadAcetaminophen - ToxicitySobredosis de drogaDrug overdoseAcetilcisteínaAcetylcysteineEnfermedad hepática inducida por sustancias y drogasChemical and drug induced liver injuryEstudio observacionalObservational studyhttps://id.nlm.nih.gov/mesh/D056486https://id.nlm.nih.gov/mesh/D000082https://id.nlm.nih.gov/mesh/D062787https://id.nlm.nih.gov/mesh/D000111https://id.nlm.nih.gov/mesh/D056486https://id.nlm.nih.gov/mesh/D064888ODS 3: Salud y bienestar. 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Internationalembargo2027-10-01https://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de 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