Hepatic encephalopathy may be associated with accumulation of substances that bind to a receptor-complex in the brain resulting in neural inhibition. Benzodiazepine receptor antagonists may have a beneficial effect on patients with hepatic encephalopathy.
To evaluate the beneficial and harmful effects of benzodiazepine receptor antagonists for patients with hepatic encephalopathy.
Eligible trials were identified through The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library, MEDLINE and EMBASE (last search: January 2004), reference lists of relevant articles, authors of trials, and pharmaceutical companies.
Randomised trials comparing any benzodiazepine receptor antagonist versus placebo or no intervention for hepatic encephalopathy.
Data collection and analysis
Two reviewers independently included trials and extracted data. Binary outcomes are reported as risk difference (RD) with 95% confidence intervals (CI) based on a random effects model. Statistical heterogeneity was explored by a chi-squared test with significance set at P < 0.1. The inconsistency across trials was assessed by I2. Potential sources of heterogeneity were explored through subgroup analyses.
Thirteen randomised trials with 805 patients were included. Eight trials used a crossover design. All trials were double-blind and assessed flumazenil versus placebo. Data on all outcomes could not be extracted from all trials. The included patients had a favourable prognosis (361/390 [93%] survived in the flumazenil group versus 345/376 [92%] in the placebo group). Flumazenil had a significant beneficial effect on improvement of hepatic encephalopathy at the end of treatment (RD 0.28; 95% CI 0.20 to 0.37, eight trials). Flumazenil had no significant effect on recovery (RD 0.13; 95% CI -0.09 to 0.36, two trials) or mortality RD 0.01; 95% CI -0.05 to 0.07, 10 trials). Flumazenil may be associated with adverse events, but trial results were heterogeneous.
Flumazenil had a significant beneficial effect on short-term improvement of hepatic encephalopathy in patients with cirrhosis and a highly favourable prognosis. Flumazenil had no significant effect on recovery or survival. Considering the fluctuating nature of hepatic encephalopathy, future trials should use a parallel design and assess if treatment with flumazenil leads to a sustained improvement or increased recovery and survival. Until this has been demonstrated, flumazenil may be considered for patients with chronic liver disease and hepatic encephalopathy, but cannot be recommended for routine clinical use.
經由Cochrane HepatoBiliary Group Controlled Trials Register、Cochrane Library的Cochrane Controlled Trials Register 、MEDLINE和EMBASE (最近一次搜索: 2004年1月)，相關文章的參考文獻清單、試驗作者和製藥公司，找出符合資格的試驗。
兩位作者獨立收錄試驗和提取資料。根據隨機效應模型，二分法結果以風險差異(risk difference，RD)與其95%信賴區間(CI)呈現。統計學意義異質性以卡方檢驗探究，顯著性設定為P < 0.1。 試驗間不一致性以I2評估。潛在異質性的來源經由亞組分析來評估。
共收納13項隨機試驗，共805位病人參與。8項試驗使用交叉設計。所有試驗採取雙盲法，評估Flumazenil相對安慰劑的結果。無法從所有試驗中擷取到所有結果的資料。參與試驗的病人中Flumazenil組的病人存活預後良好 (361/390 [93%]，相對於安慰劑組的病人是345/376 [92%])。治療結束時，Flumazenil可顯著改善肝性腦病變(RD 0.28; 95% CI 0.20 – 0.37, 8項試驗)。Flumazenil對於痊癒(RD 0.13; 95% CI −0.09 0.36, 2項試驗)或死亡率(RD 0.01; 95% CI −0.05 – 0.07, 10項試驗)沒有顯著影響。 Flumazenil可能造成不良事件，但是各試驗的結果卻各不相同。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。