RESUMEN
Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.
El paracetamol es una droga analgésica y antipirética comúnmente utilizada, que ha experimentado un aumento en su consumo en los últimos años en nuestro medio. También se ha observado un incremento en el número de sobredosis accidentales e intencionales que fueron atendidas por el sistema de salud. Su toxicidad es dosis dependiente y puede causar falla hepática fulminante, convirtiéndose en una de las principales razones de trasplante hepático en países angloparlantes. Se presenta el caso de una mujer de 28 años con antecedentes de depresión mayor y cinco intentos de suicidio previos, quien ingirió deliberadamente una cantidad significativa de comprimidos de paracetamol. Desarrolló una falla hepática fulminante y acidosis metabólica, por lo que fue sometida a un trasplante hepático de emergencia debido a la gravedad de su condición evolucionando favorablemente. La decisión de realizar un trasplante hepático en casos graves como este y bajo una condición de vulnerabilidad psiquiátrica grave, es un desafío y debe considerarse cuidadosamente. Este caso en particular ilustra la importancia de la atención multidisciplinaria incluyendo la evaluación psiquiátrica en pacientes con intoxicación por paracetamol.
Asunto(s)
Acetaminofén , Analgésicos no Narcóticos , Fallo Hepático Agudo , Trasplante de Hígado , Intento de Suicidio , Humanos , Acetaminofén/envenenamiento , Femenino , Adulto , Fallo Hepático Agudo/cirugía , Fallo Hepático Agudo/inducido químicamente , Analgésicos no Narcóticos/envenenamiento , Sobredosis de DrogaRESUMEN
Acute liver failure (ALF) is a severe condition secondary to a myriad of causes associated with poor outcomes. The prompt diagnosis and identification of the aetiology allow the administration of specific treatments plus supportive strategies and to define the overall prognosis, the probability of developing complications and the need for liver transplantation. Pivotal issues are adequate monitoring and the institution of prophylactic strategies to reduce the risk of complications, such as progressive liver failure, cerebral oedema, renal failure, coagulopathies or infections. In this article, we review the main aspects of ALF, including the definition, diagnosis and complications. Also, we describe the standard-of-care strategies and recent advances in the treatment of ALF. Finally, we include our experience of care patients with ALF.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Fallo Hepático Agudo/terapia , Acetaminofén/envenenamiento , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Amanita , Analgésicos no Narcóticos/envenenamiento , Biopsia , Trastornos de la Coagulación Sanguínea/sangre , Trastornos de la Coagulación Sanguínea/etiología , Trastornos de la Coagulación Sanguínea/terapia , Edema Encefálico/prevención & control , Edema Encefálico/terapia , Circulación Extracorporea , Femenino , Hemorragia/etiología , Hemorragia/terapia , Hepatitis B/terapia , Hepatitis Autoinmune/terapia , Humanos , Hipertensión Intracraneal/etiología , Hipertensión Intracraneal/terapia , Hígado/patología , Fallo Hepático Agudo/complicaciones , Fallo Hepático Agudo/patología , Trasplante de Hígado , Intoxicación por Setas/terapia , Intercambio Plasmático , Embarazo , Complicaciones del Embarazo/terapia , Terapia de Reemplazo Renal , Respiración Artificial , Medición de Riesgo , Sepsis/etiología , Sepsis/terapia , Desintoxicación por Sorción , TromboelastografíaRESUMEN
Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Evaluación Preclínica de Medicamentos , Proteínas Activadoras de GTPasa/metabolismo , Hígado/ultraestructura , Sistema de Señalización de MAP Quinasas , Masculino , Ratones Noqueados , Proteínas Supresoras de Tumor/antagonistas & inhibidoresRESUMEN
INTRODUCTION AND AIM: Procalcitonin is widely used as a biomarker to distinguish bacterial infections from other etiologies of systemic inflammation. Little is known about its value in acute liver injury resulting from intoxication with paracetamol. MATERIAL AND METHODS: We performed a single-center retrospective analysis of the procalcitonin level, liver synthesis, liver cell damage and renal function of patients admitted with paracetamol-induced liver injury to a tertiary care children's hospital. Children with acute liver failure due to other reasons without a bacterial or fungal infection served as the control group. Twelve patients with acute paracetamol intoxication and acute liver injury were compared with 29 patients with acute liver failure. RESULTS: The procalcitonin levels were higher in children with paracetamol intoxication than in patients with acute liver failure without paracetamol intoxication (median 24.8 (0.01-55.57) ng/mL vs. 1.36 (0.1-44.18) ng/mL; p < 0.005), although their liver and kidney functions were better and the liver cell injury was similar in both groups. Outcome analysis showed a trend towards better survival without transplantation in patients with paracetamol intoxication (10/12 vs. 15/29). Within each group, procalcitonin was significantly correlated with alanine aminotransferase and aspartate aminotransferase but was not correlated with the International Normalized Ratio or paracetamol blood levels in the paracetamol group. In conclusion, paracetamol intoxication leads to a marked increase in procalcitonin serum levels, which are significantly higher than those seen in acute liver failure. CONCLUSION: The underlying mechanism is neither caused by infection nor fully explained by liver cell death alone and remains to be determined.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Fallo Hepático Agudo/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Adolescente , Factores de Edad , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Niño , Preescolar , Femenino , Alemania , Humanos , Lactante , Pruebas de Función Renal , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/diagnóstico , Pruebas de Función Hepática , Masculino , Estudios Retrospectivos , Factores de Riesgo , Regulación hacia ArribaRESUMEN
Essential oils of green cumin (Cuminum cyminum) and chamomile (Chamomilla recutita) have antioxidant and anti-inflammatory effects. Acetaminophen, N-acetyl-p-amino-phenol, is an over-the-counter analgesic and antipyretic. Despite being safe at therapeutic doses, acetaminophen overdose is a leading cause of acute liver failure. This study aimed to compare the possible protective effects of cumin and chamomile essential oils against acute acetaminophen hepatotoxicity in male rats. Cumin oil (400 mg/kg) and chamomile oil (250 mg/kg) were orally administered for 2 weeks prior to a single acetaminophen dose (1g/kg). Serum liver function enzymes, oxidative stress markers in the liver and histopathological features were evaluated. Acetaminophen caused marked damage to hepatocytes evidenced by a significant rise in the levels of liver function enzymes, including alanine aminotransferase and aspartate aminotransferase, and disruption to the liver antioxidant protective system. Whereas the cumin oil normalized acetaminophen-induced liver enzymes elevation, the chamomile oil slightly attenuated the increase in alanine aminotransferase levels in acetaminophen-intoxicated rats. The Chamomile oil moderately ameliorated glutathione depletion and the decrease in superoxide dismutase activity in the liver of acetaminophen-administered rats. The Cumin oil preserved the liver structure to a greater extent than chamomile oil in acetaminophen-intoxicated rats. Essential oils of cumin and chamomile partially counteracted acute acetaminophen hepatotoxicity.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Manzanilla/química , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Cuminum/química , Aceites Volátiles/uso terapéutico , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Masculino , Aceites Volátiles/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/aislamiento & purificación , Sustancias Protectoras/aislamiento & purificación , Ratas , Ratas WistarRESUMEN
INTRODUCTION: While a nationwide poison control registry exists in Chile, reporting to the center is sporadic and happens at the discretion of the treating physician or by patients' self-report. Moreover, individual hospitals do not monitor accidental or intentional poisoning in a systematic manner. The goal of this study was to identify all cases of intentional medication overdose (MO) that occurred over two years at a large public hospital in Santiago, Chile, and examine its epidemiologic profile. METHODS: This study is a retrospective, explicit chart review conducted at Hospital Sótero del Rio from July 2008 until June 2010. We included all cases of identified intentional MO. Alcohol and recreational drugs were included only when they were ingested with other medications. RESULTS: We identified 1,557 cases of intentional MO and analyzed a total of 1,197 cases, corresponding to 0.51% of all emergency department (ED) presentations between July 2008 and June 2010. The median patient age was 25 years. The majority was female (67.6%). Two peaks were identified, corresponding to the spring of each year sampled. The rate of hospital admission was 22.2%. Benzodiazepines, selective serotonin reuptake inhibitors, and tricyclic antidepressants (TCA) were the causative agents most commonly found, comprising 1,044 (87.2%) of all analyzed cases. Acetaminophen was involved in 81 (6.8%) cases. More than one active substance was involved in 35% of cases. In 7.3% there was ethanol co-ingestion and in 1.0% co-ingestion of some other recreational drug (primarily cocaine). Of 1,557 cases, six (0.39%) patients died. TCA were involved in two of these deaths. CONCLUSION: Similar to other developed and developing nations, intentional MO accounts for a significant number of ED presentations in Chile. Chile is unique in the region, however, in that its spectrum of intentional overdoses includes an excess burden of tricyclic antidepressant and benzodiazepine overdoses, a relatively low rate of alcohol and recreational drug co-ingestion, and a relatively low rate of acetaminophen ingestion.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Antidepresivos Tricíclicos/envenenamiento , Sobredosis de Droga/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Intento de Suicidio/estadística & datos numéricos , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Atención Ambulatoria , Chile/epidemiología , Medicina Basada en la Evidencia , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Paracetamol (acetaminophen) is an analgesic and antipyretic drug widely used across the world. Its ingestion is one of the most common causes of drug overdose. In the United States is the first cause of acute hepatitis in adults. AIM: To describe the epidemiological profile of paracetamol overdose in Chile. MATERIAL AND METHODS: Cross sectional retrospective study that included all the phone call inquiries received at the Poison Control Center of the Pontificia Universidad Catolica de Chile (CITUC) during 2009. RESULTS: Nine hundred fifty nine inquiries involving acute paracetamol exposures were received. Women represented a 63.1% of the cases. Half of the cases were suicide attempts, of which 74.8% were women. Accidental exposures occurred mainly in children. In 29.3% of the patients, the exposure was considered to involve a hepatotoxic dose. Women had 2.7 times the risk of men to ingest a toxic dose of paracetamol with suicidal purpose (Odds ratio (OR) = 2.7; 95% confidence interval (Cl): 2.1-3.6; p < 0.001). Adolescents had 3.4 times the risk of the general consultants (OR: 3.4; 95% Cl: 2.4-4.7; p < 0.001). CONCLUSIONS: Paracetamol overdose is common in Chile. Authorities should carry out preventive measures. Antidotes and the capacity to measure plasma levels of paracetamol should be available in healthcare centers.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Sobredosis de Droga/epidemiología , Adolescente , Adulto , Factores de Edad , Niño , Preescolar , Chile/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Intento de Suicidio/estadística & datos numéricos , Adulto JovenRESUMEN
Background: Paracetamol (acetaminophen) is an analgesic and antipyretic drug widely used across the world. Its ingestion is one of the most common causes of drug overdose. In the United States is the first cause of acute hepatitis in adults. Aim: To describe the epidemiological profile of paracetamol overdose in Chile. Material and Methods: Cross sectional retrospective study that included all the phone call inquiries received at the Poison Control Center of the Pontificia Universidad Catolica de Chile (CITUC) during 2009. Results: Nine hundred fifty nine inquiries involving acute paracetamol exposures were received. Women represented a 63.1% of the cases. Half of the cases were suicide attempts, of which 74.8% were women. Accidental exposures occurred mainly in children. In 29.3% of the patients, the exposure was considered to involve a hepatotoxic dose. Women had 2.7 times the risk of men to ingest a toxic dose of paracetamol with suicidal purpose (Odds ratio (OR) = 2.7; 95% confidence interval (Cl): 2.1-3.6; p < 0.001). Adolescents had 3.4 times the risk of the general consultants (OR: 3.4; 95% Cl: 2.4-4.7; p < 0.001). Conclusions: Paracetamol overdose is common in Chile. Authorities should carry out preventive measures. Antidotes and the capacity to measure plasma levels of paracetamol should be available in healthcare centers.
Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Adulto Joven , Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Sobredosis de Droga/epidemiología , Factores de Edad , Chile/epidemiología , Estudios Transversales , Centros de Control de Intoxicaciones/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Intento de Suicidio/estadística & datos numéricosRESUMEN
Acetaminophen is a dose dependent hepatotoxin which is frequently associated with intentional self-harm. Forty-nine cases of parasuicide attempts involving paracetamol only or in combination with another drug were treated at the UHWI, Jamaica, between 1994-2004. The majority were women (84%) and the mean age was 23 years. Acetaminophen was the only agent ingested in 71% of cases; 29% involved an additional drug. Patients presented an average of 6.5 hours after ingestion (range 1-45 hours). Serum transaminases were elevated in 18% of cases and N-acetylcysteine (NAC) therapy given in 55%. The mean duration of hospitalization was three days. One patient developed liver failure and there were no deaths. Education of the public and medical profession is needed to increase awareness of the potential toxic effects of acetaminophen overdose. N-acetylcysteine therapy should be given early in suspected cases.
El acetaminofén es una hepatotoxina dosis-dependiente, frecuentemente asociada con intenciones auto-destructivas. Cuarenta y nueve casos de intentos parasuicidas que involucraban paracetamol o combinación con otra droga, fueron tratados en el UHWI, Jamaica, entre 1994-2004. En la mayoría de los casos se trataba de mujeres (84%) y la edad promedio fue 23 años. El acetaminofén fue el único agente ingerido en 71% de los casos; 29% involucraron un medicamento adicional. Las transaminasas en suero fueron elevadas en 18% de los casos y se aplicó terapia de N-acetilcisteína en el 55% de los casos. La duración promedio de hospitalización fue de tres días. Uno de los pacientes tuvo un fallo hepático y no hubo muertes. Se requiere la educación del público y la profesión médica a fin de aumentar la conciencia sobre los efectos tóxicos potenciales de la sobredosis de acetaminofén. La terapia con N-acetilcisteína (NAC) debe aplicarse tan pronto como el caso despierte sospecha.
Asunto(s)
Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Fallo Hepático Agudo/inducido químicamente , Intento de Suicidio/estadística & datos numéricos , Sobredosis de Droga , Jamaica/epidemiología , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/epidemiología , Pruebas de Función Hepática , Estudios RetrospectivosRESUMEN
Acetaminophen is a dose dependent hepatotoxin which is frequently associated with intentional self-harm. Forty-nine cases of parasuicide attempts involving paracetamol only or in combination with another drug were treated at the UHWI, Jamaica, between 1994-2004. The majority were women (84%) and the mean age was 23 years. Acetaminophen was the only agent ingested in 71% of cases; 29% involved an additional drug. Patients presented an average of 6.5 hours after ingestion (range 1-45 hours). Serum transaminases were elevated in 18% of cases and N-acetylcysteine (NAC) therapy given in 55%. The mean duration of hospitalization was three days. One patient developed liver failure and there were no deaths. Education of the public and medical profession is needed to increase awareness of the potential toxic effects of acetaminophen overdose. N-acetylcysteine therapy should be given early in suspected cases.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Fallo Hepático Agudo/inducido químicamente , Intento de Suicidio/estadística & datos numéricos , Adolescente , Adulto , Sobredosis de Droga , Femenino , Humanos , Jamaica/epidemiología , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/epidemiología , Pruebas de Función Hepática , Masculino , Estudios Retrospectivos , Adulto JovenAsunto(s)
Acetaminofén/envenenamiento , Acetilcisteína/uso terapéutico , Analgésicos no Narcóticos/envenenamiento , Depuradores de Radicales Libres/uso terapéutico , Hepatopatías/prevención & control , Adolescente , Enfermedad Hepática Inducida por Sustancias y Drogas , Niño , Preescolar , Toma de Decisiones , Sobredosis de Droga/tratamiento farmacológico , Humanos , Lactante , Hepatopatías/diagnóstico , Pruebas de Función Hepática , Factores de TiempoRESUMEN
OBJECTIVE: Shortened courses of N-acetylcysteine may be acceptable in patients with acetaminophen poisoning who are at low risk for toxicity. The goal of this study was to determine which clinical findings best identified patients at lowest risk for acetaminophen-related hepatotoxicity after an acute overdose. STUDY DESIGN: This was a retrospective analysis, throughout 10 years, of hospital admissions for acute acetaminophen poisoning, with inclusion criteria being an acetaminophen concentration above the possible toxicity line by nomogram, arrival within 24 hours, and an initial prothrombin time (PT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) measured within 24 hours of ingestion. Clinical parameters capable of identifying patients most and least likely to have hepatotoxicity were evaluated by using sensitivity and specificity testing. RESULTS: Of 95 patient charts identified, 41 met all inclusion criteria, with 16 patients having hepatotoxicity. PT, AST, and ALT within the first 24 hours postingestion did not identify all patients who had hepatotoxicity. The best predictor of a low risk of toxicity was the presence of normal values for the PT, AST, or ALT within 48 hours of ingestion. CONCLUSIONS: These data suggest that all patients with an acute acetaminophen overdose should be observed and treated for at least 48 hours postingestion.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Enfermedad Hepática Inducida por Sustancias y Drogas , Hepatopatías/diagnóstico , Pruebas de Función Hepática , Acetilcisteína/uso terapéutico , Adolescente , Alanina Transaminasa/sangre , Arkansas/epidemiología , Aspartato Aminotransferasas/sangre , Niño , Preescolar , Toma de Decisiones , Sobredosis de Droga/tratamiento farmacológico , Femenino , Depuradores de Radicales Libres/uso terapéutico , Humanos , Lactante , Hepatopatías/prevención & control , Masculino , Valor Predictivo de las Pruebas , Tiempo de Protrombina , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation. After 7 days animals were injected with paracetamol (BDL-APAP group). Sham-operated rats were injected at day 7 with paracetamol (APAP group). Cholestatic and sham-operated rats injected with vehicle (BDL and control groups). UDP-GT activity was measured by a kinetic method for different substrates. Microsomal membrane phospholipid composition, cholesterol content and ultrastructure were determined. BDL-APAP group showed an increment in the UDP-GT activity except for chloramphenicol, morphine and paracetamol if compared to controls and to BDL group. The same increment was observed when BDL-APAP was compared to APAP except for chloramphenicol and lorazepam. Between BDL and APAP groups similar levels of activity were detected except for paracetamol. Microsomal phospholipid profile: phosphatidylcholine showed the lowest content in the BDL group, with a significant recovery in the BDL-APAP and APAP groups. Phosphatidylserine was markedly decreased in the APAP group compared to the rest and phosphatidylinositol was decreased in all the groups if compared to control values. An increment of phosphatidylethanolamine was seen in the APAP and BDL-APAP groups if compared to BDL and control values. A significant increment of microsomal cholesterol content was seen in BDL. Under these conditions, a different lipid microenvironment is produced, resulting in an increment of the enzyme activity for a variety of substrates.
Asunto(s)
Acetaminofén/envenenamiento , Analgésicos no Narcóticos/envenenamiento , Colestasis/metabolismo , Glucuronosiltransferasa/metabolismo , Microsomas Hepáticos/metabolismo , Fosfolípidos/metabolismo , Acetaminofén/sangre , Analgésicos no Narcóticos/sangre , Animales , Conductos Biliares/metabolismo , Ligadura , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Ratas , Ratas WistarAsunto(s)
Acetaminofén/sangre , Acetaminofén/envenenamiento , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/envenenamiento , Monitoreo de Drogas/métodos , Factores de Edad , Antídotos/uso terapéutico , Carbón Orgánico/uso terapéutico , Niño , Composición de Medicamentos , Sobredosis de Droga/sangre , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/tratamiento farmacológico , Humanos , Absorción Intestinal , Anamnesis , Factores de TiempoRESUMEN
OBJECTIVE: To predict serum concentrations to evaluate and improve guidelines for the treatment of children (1 to 5 years) with accidental ingestion of acetaminophen elixir. METHODS: Acetaminophen concentrations for 1000 children were simulated with pharmacokinetic parameters and their expected variability. The distribution of concentrations arising from a 300 mg/kg dose at different age groups was predicted. These predictions were validated by comparison with concentrations obtained at 4 hours from 121 children with accidental ingestion of acetaminophen elixir. RESULTS: No child who presented with overdose had a concentration in the probable risk area of the Rumack-Matthew toxicity nomogram. Enteral charcoal administered 98 minutes (SD 44) after ingestion had no effect on serum concentrations. The simulation predicted that an acetaminophen dose of 300 mg/kg would result in concentrations of 32 to 208 mg/L (95% CI) at 4 hours after ingestion. The maximum concentration occurred before 2 hours in 95% of simulated children. CONCLUSION: Children (1 to 5 years) with reported ingestion of >250 mg/kg acetaminophen elixir should have serum concentrations measured at 2 hours after ingestion rather than at the 4-hour time point recommended in adults. This can be expected to speed discharge and reduce anxiety. The use of enteral charcoal is unlikely to enhance acetaminophen elimination, unless it is given within an hour of acetaminophen ingestion.
Asunto(s)
Acetaminofén/sangre , Acetaminofén/envenenamiento , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/envenenamiento , Monitoreo de Drogas/métodos , Acetaminofén/farmacocinética , Adulto , Factores de Edad , Analgésicos no Narcóticos/farmacocinética , Antídotos/uso terapéutico , Peso Corporal , Carbón Orgánico/uso terapéutico , Preescolar , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/metabolismo , Tratamiento de Urgencia , Humanos , Lactante , Absorción Intestinal , Tasa de Depuración Metabólica , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de TiempoRESUMEN
STUDY OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (N-AC) alone or combined with multiple-dose activated charcoal (AC) in the treatment of acetaminophen (ACT) overdose. DESIGN: Prospective observational case series of 14 consecutive pediatric patients. Group A (n = 7) were treated only with N-AC and group B (n = 7) with N-AC combined with AC. Plasma ACT concentrations were measured at 0.0, 24 and 48 h. As a measure of ACT disappearance, half-life of elimination (t1/2 beta) and exogenous body clearance (ClB) were calculated. RESULTS: Group A, Initial and final mean ACT plasmatic levels were 27 micrograms/mL and 4 micrograms/mL; t1/2 beta of 17 h and ClB 0.640 mL.kg.min. Group B, 27 micrograms/mL and 0.66 microgram/mL; t1/2 beta of 10 h and ClB 1.092 mL.kg.min. For both t1/2 beta and ClB differences, p < 0.05 (SS). CONCLUSION: N-AC significantly decreased the plasma ACT levels in both treatments; however, there were several advantages with the combined therapy: AC enhanced the efficacy of N-AC according with the higher eliminatión of the overdosed drug (97.6% vs. 85.2%), the t1/2 beta decreased 42%, and the ClB increased 70% in relation to the group A. Data of this study suggested that N-AC plus AC is more effective than N-AC alone in enhancing ACT elimination in overdosed patients and that it provided additional hepatoprotective benefit.
Asunto(s)
Acetaminofén/envenenamiento , Acetilcisteína/uso terapéutico , Analgésicos no Narcóticos/envenenamiento , Antídotos/uso terapéutico , Carbón Orgánico/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Niño , Preescolar , Terapia Combinada , Sobredosis de Droga , Femenino , Humanos , Lactante , Masculino , Estudios ProspectivosRESUMEN
Objetivo. Evaluar comparativamente la eficacia de la N-acetilcisteina (N-AC) administrada como monofármaco o combinada con diálisis gastrointestinal con carbón activado (CA) en el tratamiento de la sobredosis por acetaminofén (ACT). Diseño. Estudio prospectivo observacional de una serie consecutiva de 14 niños. Al grupo A (n=7) se le administró unicamente N-AC, el grupo B (n=7) se le administró N-AC combinada con CA. Se midieron las concentraciones plasmáticas de ACT a las 0.0, 24 y 48 h. Como medida de la eliminación del fármaco se calculó la vida media de eliminación (t ½ ß) y la depuración corporal exógena-no renal (Cl B). Resultados. Grupo A: niveles promediados de acetaminofén plasmático, al inicio y final del tratamiento, 27 µg/mL; t ½ ß 17 h y Cl B 0.640 mL.kg.min. Grupo B: 27 µg/mL y 0.66 µg/mL; t ½ ß 10 h y Cl B 1.092 mL.kg.min. Para las diferencias entre t ½ ß y Cl B, p < 0.05 (ES). Conclusiones. Ambos grupos mostraron una depuración significativa de las concentraciones de ACT con algunas diferencias a favor del tratamiento combinado (grupo B): el porcentaje de eliminación plasmática fue mayor (97.6 porciento vs 85.2 por ciento), la t ½ ß se redujo 42 por ciento y la Cl B se incrementó 70 por ciento. Los resultados sugieren la mayor utilidad de la combinación N-AC más CA en el tratamiento preventivo de la hepatoxicidad por ACT