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      Insuficiencia hepática aguda por sobredosis accidental de paracetamol. Causas Translated title: Acute hepatic failure due to accidental overdose of paracetamol. Causes

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          Abstract

          RESUMEN Objetivo: Determinar la prevalencia de sobredosis accidental con paracetamol que ocasionaron insuficiencia hepática aguda en el paciente y las causas de las sobredosis. Método: Búsqueda bibliográfica de estudios de investigación originales, publicados desde enero del año 2010 hasta noviembre del 2018. Resultados: Los pacientes ADULTOS que desarrollaron insuficiencia hepática aguda por sobredosis accidental con paracetamol, la gran mayoría eran polimedicados con opiáceos, pacientes que buscaban calmar el dolor, con una deficiente supervisión del tratamiento por parte de los médicos prescriptores y de los farmacéuticos, lo que dio lugar a la automedicación, la duplicidad, y como consecuencia “la sobredosis”. En los NIÑOS, menores de 18 años, la principal causa fue ocasionada por errores de los cuidadores: confusión en la pauta de alternancia con ibuprofeno, por confundir la dosis y por pauta incorrecta a la edad y peso. Conclusión: Existen casos de insuficiencia hepática aguda por sobredosis accidental con paracetamol, siendo las causas principales las ocasionadas por el sistema sanitario: deficiente gestión y supervisión del tratamiento por centros médicos y farmacias. El grado de conocimiento de la medicación por el paciente es alarmante la percepción de “inocuo”, independiente de la dosis, entendida como la ausencia de toxicidad.

          Translated abstract

          ABSTRACT Objective: To determine the scientific evidences of accidental overdose with acetaminophen that caused acute liver failure in patients and the causes of the overdose. Method: Bibliographic search of original research studies, published from January of 2010 to November of 2018. Results: Of the patients that developed acute liver failure due to accidental overdose with acetaminophen, the great majority were polymedicated with opiates; patients that seeked to calm the pain, thus a poor supervision of the treatment by the prescribing doctors and the pharmacists, gave place to self-medication, duplicity, and overdose. In children, younger than 18 years of age, the principal cause was produced by mistakes of the caregivers: confusion in the alternating pattern with ibuprofen, due to confusion of the dose and correct guideline of age and weight. Conclusion: Cases of hepatotoxicity and acute liver failure exist due to accidental overdose with acetaminophen, being the main causes those produced by the health system: poor management and supervision of treatment by medical centers and pharmacies. Patient medication knowledge: on the part of the patients, the perception of “innocuous” is alarming, regardless of the dose, understood as the absence of toxicity.

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          Most cited references35

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          Acetaminophen-related hepatotoxicity.

          Acetaminophen (APAP) is the leading worldwide cause of drug overdose and acute liver failure (ALF). Single overdose ingestion and therapeutic misadventure may cause hepatotoxicity. Several factors, such as concomitant alcohol use or abuse, concurrent medications, genetic factors, and nutritional status, can influence the susceptibility and severity of APAP hepatotoxicity. Early manifestations of APAP hepatotoxicity are nonspecific, but require prompt recognition by physicians. Patients with repeated overdose tend to present late, and in such hepatotoxicity may have already evolved. N-acetylcysteine is a very effective antidote when giving within 8 hours, and is also recommended after a presentation of hepatotoxicity and ALF. The prognosis of patients with APAP-induced ALF is better than other causes of ALF. Liver transplantation should be offered to those who are unlikely to survive. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure.

            Despite extensive investigations, the cause of liver injury in 14% of patients with acute liver failure remains unknown (indeterminate). In a pilot study using a novel assay, highly specific acetaminophen-cysteine adducts were detected in 7 of 36 indeterminate patients (19%). To extend these observations, sera from 110 subjects enrolled in the Acute Liver Failure Study Group registry with indeterminate acute liver failure were analyzed with a similar but more efficient and sensitive adduct assay. As positive controls, another 199 patients with known or presumed acetaminophen-induced liver failure were assessed for the presence and quantity of adducts. Clinical, laboratory, and outcome data were compared for the two groups. On the basis of previous data for known therapeutic exposures and acetaminophen overdoses, an adduct concentration ≥1.0 nmol/mL of serum indicated a definite acetaminophen overdose. Among the 110 indeterminate cases, 18% had assay values ≥1.0 with a median level of 9.2 nmol/mL; 94.5% of the positive controls (known acetaminophen cases) had values ≥1.0 nmol/mL. Regardless of the initial diagnosis, subjects with elevated adduct levels demonstrated the clinical profile and hyperacute biochemical injury pattern associated with acetaminophen overdose: a predominance of female gender, very high aminotransferase levels, and low bilirubin levels. These data confirm and extend previous observations regarding the high (18%) prevalence of unrecognized or uncertain acetaminophen toxicity among subjects with indeterminate acute liver failure. N-Acetylcysteine use was limited in this group, presumably because of the lack of a specific diagnosis of acetaminophen toxicity. Copyright © 2010 American Association for the Study of Liver Diseases.
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              Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity.

              Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P < 0.001). The King's College poor prognostic criteria had reduced sensitivity in unintentional overdoses (77.8%, 95% confidence intervals (CI) 62.9, 88.8) compared with intentional overdoses (89.9%, 95% CI 83.4, 94.5). Unintentional overdose was independently predictive of death or liver transplantation on multivariate analysis (odds ratio 1.91 (95% CI 1.07, 3.43), P = 0.032). Unintentional paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.
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                Author and article information

                Journal
                ars
                Ars Pharmaceutica (Internet)
                Ars Pharm
                Universidad de Granada (Granada, Granada, Spain )
                2340-9894
                September 2019
                : 60
                : 3
                : 177-184
                Affiliations
                [1] orgnameRedfarma
                Article
                S2340-98942019000500006 S2340-9894(19)06000300006
                10.30827/ars.v60i3.8775
                34fc5ebc-2a41-47c0-8bd7-79d6a15ec07f

                This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

                History
                : 28 February 2019
                : 24 June 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 35, Pages: 8
                Product

                SciELO Spain

                Categories
                Artículos de Revisión

                paracetamol,fallo hepático agudo,Paracetamol,acetaminofeno,sobredosis,causas,Causes,Acetaminophen,Acute Liver Failure,Drug Overdose

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