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Clin Toxicol (Phila) ; 51(9): 855-63, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24134534

RESUMEN

CONTEXT: Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of "mitochondrial paralysis" (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases. CASE DETAILS: Three adults each presented comatose and acidemic 10 to ~18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 µM (900 µg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ~18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3-4 h of haemodialysis removed 10-20 g of acetaminophen (48-80% of remaining body burden), reduced serum acetaminophen concentrations by 56-84% (total clearance 3.4-7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure. DISCUSSION: When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.


Asunto(s)
Acetaminofén/envenenamiento , Acetilcisteína/farmacocinética , Analgésicos no Narcóticos/envenenamiento , Antídotos/farmacocinética , Sobredosis de Droga/terapia , Depuradores de Radicales Libres/farmacocinética , Diálisis Renal , Acetaminofén/antagonistas & inhibidores , Acetaminofén/sangre , Acetaminofén/farmacocinética , Acetilcisteína/administración & dosificación , Acetilcisteína/sangre , Acetilcisteína/uso terapéutico , Acidosis Láctica/etiología , Adulto , Anciano , Analgésicos no Narcóticos/antagonistas & inhibidores , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/farmacocinética , Antídotos/administración & dosificación , Antídotos/análisis , Antídotos/uso terapéutico , Coma/etiología , Monitoreo de Drogas , Sobredosis de Droga/sangre , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Droga/fisiopatología , Femenino , Depuradores de Radicales Libres/administración & dosificación , Depuradores de Radicales Libres/sangre , Depuradores de Radicales Libres/uso terapéutico , Semivida , Humanos , Fallo Hepático/etiología , Fallo Hepático/prevención & control , Masculino , Tasa de Depuración Metabólica , Persona de Mediana Edad , Diálisis Renal/efectos adversos , Adulto Joven
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