Terlipressin for acute esophageal variceal hemorrhage
Editorial Group: Cochrane Hepato-Biliary Group
Published Online: 20 JAN 2003
Assessed as up-to-date: 29 OCT 2002
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Ioannou GN, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD002147. DOI: 10.1002/14651858.CD002147.
- Publication Status: Edited (no change to conclusions)
- Published Online: 20 JAN 2003
Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal haemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain.
To determine if treatment with terlipressin improves outcome in acute oesophageal variceal haemorrhage and is safe.
Randomized clinical trials were identified by searching the following databases (November 1999): The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register on The Cochrane Library (Issue 3, 1999), MEDLINE, EMBASE, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. For the update of this review, no new randomised clinical trials were identified on any of the databases (October 2002).
All randomised clinical trials, which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal haemorrhage.
Data collection and analysis
Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial haemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalisation.
Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide, and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no significant difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication.
On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.
Plain language summary
Terlipressin is a safe and effective treatment for bleeding from oesophageal varices which is a life threatening complication of cirrhosis of the liver
Esophageal varices are abnormal dilatations of veins in the lower part of the swallowing tube (oesophagus) that may develop in patients with chronic liver damage (cirrhosis). Bleeding from these varices is a life threatening complication with mortality between 20 and 50 per cent. Bleeding from varices may be treated with medications and/or with an endoscope which is a flexible tube with a camera at the end which allows direct visualization and treatment of bleeding varices. The reviewers evaluated the safety and effectiveness of a drug called terlipressin: they reported that terlipressin appears to be as safe as other treatments and that terlipressin may reduce the mortality from variceal bleeding as compared to placebo. The reviewers did not have sufficient data to decide whether terlipressin was better or worse than other available treatments such as other drugs (somatostatin, octreotide) or endoscopic treatment.
Terlipressin(triglycyl lysine vasopressin)是垂體後葉荷爾蒙(vasopressin)的合成物，用來治療急性靜脈曲張出血。相較於垂體後葉荷爾蒙，Terlipressin可以通過間歇性注射的方法給與，代替持續性靜脈內灌注，具有較安全的不良反應，但是，該藥物的有效性還不是非常明確。
透過研究下列資料庫(1999年9月)，確定隨機臨床試驗：The Cochrane HepatoBiliary Group Controlled Trials Register, Cochrane Library的The Cochrane HepatoBiliary Group Controlled Trials Register (1999年第3期)、MEDLINE、EMBASE、Biosis和Current Contents。檢閱已找出之的發表文章的書目。 聯繫該領域的專家和Terlipressin廠商。 為了更新本次文獻回顧，直到2002年10月為止沒有從任何的資料庫找到新的隨機臨床試驗。
所有在急性靜脈曲張出血的情況下使用Terlipressin對照下列療法的隨機臨床試驗: (a) 安慰劑或無治療、(b) 氣囊填塞法、(c)內視鏡治療、(d) octreotide、(e) 生長激素抑制素(somatostatin)、(f) 垂體後葉荷爾蒙。
所有控制組一共找到20個研究，共1609 位病人。有7個研究 (443位病人)比較Terlipressin和安慰劑，根據Jadad量表，5個研究被認為屬於品質較高。統合分析指出，和安慰劑相比，Terlipressin可以明顯降低所有原因造成的死亡率 ((relative risk 0.66, 95% CI 0.49 0.88)。有3個研究比較Terlipressin和生長激素抑制素 (302位病人)，其中2個研究具有較高的品質；只有一個品質較高的研究比較(219 位病人)Terlipressin和內視鏡治療。在病人數量較少的有限檢力(power)範圍內，Terlipressin和生長激素抑制素或內視鏡治療沒有在任何結果上顯示有統計上顯著的差異。其餘對照組被確定為研究規模小、品質低，包括Terlipressin對照氣囊填塞法，Terlipressin對照octreotideTerlipressin對照垂體後葉荷爾蒙，在所有主要結果方面沒有顯示有差異。 Terlipressin組和所有對照組在引起死亡或治療中斷等不良事件的數量方面，沒有顯著差異。
此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。
Terlipressin能夠安全有效地治療威脅生命的肝硬化併發症食管靜脈曲張出血。 食管靜脈曲張是指吞咽管(食道)下端的靜脈發生異常擴張，其這種可能出現在慢性肝損傷(肝硬化)的病人。靜脈曲張出血是威脅生命的一大併發症，死亡率大約為20% – 50%。血管曲張出血可以使用藥物和內視鏡治療，內視鏡是一根可彎曲的管子，底部有一個鏡頭，可以直接目測和治療出血靜脈曲張。回顧作者評估一種叫做Terlipressin的藥物其安全性和有效性。Terlipressin似乎和其他治療方法一樣安全，和安慰劑相比，Terlipressin可能降低因為靜脈曲張出血導致的死亡率。作者沒有足夠的資料決定是否Terlipressin優於或不如其他使用的治療方法，例如其他藥物(生長激素抑制素, octreotide)或內視鏡治療。