Scottish Liver Transplantation Unit, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 4SA, UK.
Br J Clin Pharmacol. 2011 Feb;71(2):273-82. doi: 10.1111/j.1365-2125.2010.03819.x.
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.
对乙酰氨基酚(扑热息痛)肝毒性是英国急性肝衰竭(ALF)最常见的原因。据报道,不同过量模式导致的扑热息痛引起的 ALF 的结果存在相互矛盾的数据。
使用前瞻性定义的标准,我们分析了苏格兰肝移植中心收治的 938 例急性严重肝损伤患者中过量模式对结局的影响。
1992 年至 2008 年期间,663 例患者因扑热息痛引起的急性严重肝损伤入院。其中,500 例(75.4%)有意服用扑热息痛过量,110 例(16.6%)无意过量。53 例(8.0%)无法明确确定过量模式。无意过量的患者年龄较大,更可能滥用酒精,并且更常过量服用复方麻醉/扑热息痛镇痛药,而有意过量的患者则较少。无意过量患者入院时的乙酰氨基酚和丙氨酸氨基转移酶浓度明显低于有意过量患者。然而,无意过量患者入院时器官功能障碍更严重,死亡率更高(无意 42/110(38.2%),有意 128/500(25.6%),P<0.001)。与有意过量相比,King's College 不良预后标准在无意过量中的敏感性降低(77.8%,95%置信区间[CI]62.9,88.8)(89.9%,95%CI 83.4,94.5)。多变量分析显示,无意过量是死亡或肝移植的独立预测因素(比值比 1.91(95%CI 1.07,3.43),P=0.032)。
与有意扑热息痛过量相比,无意扑热息痛过量尽管入院时乙酰氨基酚浓度较低,但与死亡率增加相关。可能需要针对无意扑热息痛过量的替代预后标准。