Prolonged N-acetylcysteine therapy in late acetaminophen poisoning associated with acute liver failure – a need to be more cautious 英文参考文献.docVIP

Available online /content/13/3/144 Commentary Prolonged N-acetylcysteine therapy in late acetaminophen poisoning associated with acute liver failure – a need to be more cautious? T Nimmi C Athuraliya and Alison L Jones Department of Clinical Pharmacology and Clinical Toxicology, School of Medicine and Public Health, Faculty of Health, University of Newcastle, Callaghan Drive, Newcastle, NSW 2308, Australia Corresponding author: Alison L Jones, alison.jones@.au Published: 14 May 2009 Critical Care 2009, 13:144 (doi:10.1186/cc7800) This article is online at /content/13/3/144 ? 2009 BioMed Central Ltd See related research by Yang et al., /content/13/2/R55 Abstract tered within 8 to 10 hours of ingestion of the overdose [2]. In later years, clinical use of NAC was extended to patients who present more than 10 hours after ingestion and to those with APAP-induced acute liver failure (ALF), and patients in such categories are routinely on NAC infusions for many days, even weeks [3,4]. The putative protective mechanisms of NAC in late-APAP poisoning and APAP-induced liver failure Since the 1970s, N-acetylcysteine (NAC) has shown proven efficacy as an antidote for acetaminophen (APAP) poisoning and APAP-induced liver failure for early presenters. The current evidence of benefits of NAC for late presenters is controversial because of the poor understanding of the mechanism of late toxicity. In the previous issue of Critical Care, Yang and colleagues use a mouse model to demonstrate that NAC in doses similar to those used therapeutically to treat APAP poisoning in humans impairs liver regenerative capacity and that the effect is more pronounced when administered for a longer duration. Studies based on cell cultures support this evidence. Cytokine and growth factor signalling pathways are recognised to be involved in the process of liver regeneration and