Intervention Review

Pharmacological interventions for ischaemia reperfusion injury in liver resection surgery performed under vascular control

  1. Mahmoud Abu-Amara1,
  2. Kurinchi Selvan Gurusamy1,*,
  3. George Glantzounis2,
  4. Barry Fuller1,
  5. Brian R Davidson1

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 7 OCT 2009

Assessed as up-to-date: 19 JAN 2009

DOI: 10.1002/14651858.CD008154


How to Cite

Abu-Amara M, Gurusamy KS, Glantzounis G, Fuller B, Davidson BR. Pharmacological interventions for ischaemia reperfusion injury in liver resection surgery performed under vascular control. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD008154. DOI: 10.1002/14651858.CD008154.

Author Information

  1. 1

    Royal Free Hospital and University College School of Medicine, University Department of Surgery, London, UK

  2. 2

    University of Ioannina, Department of Surgery, School of Medicine, Ioannina, Greece

*Kurinchi Selvan Gurusamy, University Department of Surgery, Royal Free Hospital and University College School of Medicine, 9th Floor, Royal Free Hospital, Pond Street, London, NW3 2QG, UK. kurinchi2k@hotmail.com.

Publication History

  1. Publication Status: New
  2. Published Online: 7 OCT 2009

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Vascular occlusion used during elective liver resection to reduce blood loss results in significant ischaemia reperfusion (IR) injury. This in turn leads to significant postoperative liver dysfunction and morbidity. Various pharmacological drugs have been used in experimental settings to ameliorate the ischaemia reperfusion injury in liver resections.

Objectives

To assess the relative benefits and harms of using one pharmacological intervention versus another pharmacological intervention to decrease ischaemia reperfusion injury during liver resections where vascular occlusion was performed during the surgery.

Search methods

We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded until January 2009.

Selection criteria

We included randomised clinical trials, irrespective of language or publication status, comparing one pharmacological agent versus another pharmacological agent during elective liver resections with vascular occlusion.

Data collection and analysis

Two authors independently identified trials for inclusion and independently extracted data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We planned to calculate the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis. However, all outcomes were only reported on by single trials, and meta-analysis could not be performed. Therefore, we performed Fisher's exact test on dichotomous outcomes.

Main results

We identified a total of five randomised trials evaluating nine different pharmacological interventions (amrinone, prostaglandin E1, pentoxifylline, dopexamine, dopamine, ulinastatin, gantaile, sevoflurane, and propofol). All trials had high risk of bias. There was no significant difference between the groups in mortality, liver failure, or perioperative morbidity. The ulinastatin group had significantly lower postoperative enzyme markers of liver injury compared with the gantaile group. None of the other comparisons showed any difference in any of the other outcomes. However, there is a high risk of type I and type II errors because of the few trials included, the small sample size in each trial, and the risk of bias.

Authors' conclusions

Ulinastatin may have a protective effect against ischaemia reperfusion injury relative to gantaile in elective liver resections performed under vascular occlusion. The absolute benefit of this drug agent remains unknown. None of the drugs can be recommended for routine clinical practice. Considering that none of the drugs have proven to be useful to decrease ischaemia reperfusion injury, such trials should include a group of patients who do not receive any active intervention whenever possible to determine the pharmacological drug's absolute effects on ischaemia reperfusion injury in liver resections.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

No clear evidence that any pharmacological intervention is better than another in decreasing ischaemia reperfusion injury in liver resections

Elective liver surgery undertaken for a variety of reasons may require occlusion of the blood supply to the liver in order to reduce bleeding from the cut liver surface. This temporary interruption of blood supply causes liver damage for a variety of reasons. In experimental studies many drugs have shown some promise in decreasing liver damage caused by the occluded blood supply. The relative benefits of pharmacological agents compared with one another is unknown in the setting of liver damage caused by occlusion of the blood supply to the liver during surgery. We identified a total of five randomised trials evaluating nine different pharmacological interventions (amrinone, prostaglandin E1, pentoxifylline, dopexamine, dopamine, ulinastatin, gantaile, sevoflurane, and propofol). All trials had risk of bias ('systematic error') and risk of play of chance ('random errors'). There was no significant difference between the groups in mortality, liver failure, or postoperative complications. The ulinastatin group had significantly lower postoperative enzyme markers of liver injury compared with the gantaile group. None of the remaining pharmacological agents showed any significant difference in any of the remaining outcomes. However, there is a high risk of type I (erroneously concluding that an intervention is beneficial when it is actually not beneficial) and type II errors (erroneously concluding that an intervention is not beneficial when it is actually beneficial) because of the few trials included, the small sample size in each trial, and the risk of bias. Ulinastatin may have a protective effect relative to gantaile against liver injury sustained during elective liver surgery involving blood supply occlusion. The absolute benefit of ulinastatin in this setting remains unknown. None of the pharmacological agents can be recommended for routine clinical practice. Considering that none of the agents have been proven to be useful to decrease ischaemia reperfusion injury, such trials should include a group of patients who do not receive any active intervention whenever possible to determine their absolute effect on ischaemia reperfusion injury in liver resections.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

於血流控制下進行肝切除手術造成缺血性再灌流損傷的藥物治療

擇期肝切除手術中以血管阻斷降低失血,會造成嚴重缺血性再灌流傷害。進而導致嚴重術後肝功能受損與併發症。許多試驗利用不同藥物改善肝切除手術時的缺血性再灌流損傷。

目標

評估經兩種不同藥物處理對於降低肝切除手術中進行血管阻斷術之缺血性再灌流損傷之相對效益與傷害。

搜尋策略

我們搜尋至2009年1月前`Cochrane Library的 Cochrane HepatoBiliary Group Controlled Trials Register與Cochrane Central Register of Controlled Trials (CENTRAL)、MEDLINE、EMBASE,以及Science Citation Index Expanded資料庫。

選擇標準

不限制發表語言或出版狀態,收納比較兩種不同藥物用於進行血管阻斷術擇期肝切除手術的隨機臨床試驗。

資料收集與分析

兩位作者獨立篩選欲納入的試驗並擷取數據。利用Rev Man分析軟體兼以固定效應與隨機效應模型分析。並擬根據意向性治療分析或現有個案分析計算風險比(RR)與平均差(MD)及其95%信賴區間(CI)。然而因所有結果都只有單一試驗發表,無法進行統合分析。因此我們利用Fisher氏精確檢驗法評估二分法結果。

主要結論

我們收納5個隨機臨床試驗評估9種不同藥物處置(amrinone、prostaglandin E1、pentoxifylline、dopexamine、dopamine、ulinastatin、gantaile、sevoflurane以及propofol)。所有臨床試驗都有高偏誤風險。各組間死亡率、肝衰竭或術後併發症並無顯著差異。ulinastatin組手術後肝臟受損的標記酵素值顯著低於gantaile組。其他比較結果則沒有任何差異。然而由於納入的臨床試驗少、各試驗之樣本數低,與偏誤風險,因此發生第一型與第二型誤差的風險較高。

作者結論

相較於gantaile,ulinastatin對擇期性肝切除手術進行血管阻斷所產生之缺血性再灌流損害可能具有保護作用。此藥的絕對效益尚未明確。上述藥物不建議用於常規臨床治療。基於沒有藥物證實可降低缺血性再灌流損傷,此類試驗應增加一組未接受任何療效藥物處置的患者,藉以探討藥物對肝臟切除術時所產生之缺血性再灌流損傷的絕對影響。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

無明確證據顯示有任何藥物在減少肝臟切除手術時缺血性再灌流損傷上優於其他藥物。因各種原因而進行擇期性肝臟手術時,為降低肝臟切面之出血須阻斷流至肝臟的血液。這暫時阻斷供血因不同原因會造成肝臟受損。在研究室實驗許多藥物呈現某程度減少因阻斷供血所造成之肝臟受損的能力。這些藥物對手術中阻斷供血至肝臟會造成肝臟受損的相對效益比較仍然未知。我們收納5個隨機臨床試驗評估9種不同藥物(amrinone、prostaglandin E1、pentoxifylline、dopexamine、dopamine、ulinastatin、gantaile、sevoflurane及propofol)。所有試驗都有偏誤(系統性誤差)風險與機會風險(隨機誤差)。各組間死亡率、肝衰竭或術後併發症並無顯著差異。ulinastatin組術後肝臟受損的標記酵素顯著低於gantaile組,而其他藥劑在其他結果未出現任何差異。然而由於納入的臨床試驗數少、各試驗之樣本數低,且存在偏誤的風險,因此發生第一型(誤將無效之藥物介入判為有效)與第二型(誤將有效之藥物介入判為無效)誤差的風險較高。相較於gantaile,ulinastatin在擇期性肝切除手術經血管阻斷後造成缺血性再灌流損害可能具有保護作用。但此藥物的絕對效益尚未明確。上述藥物不建議用於常規臨床治療。基於沒有藥物證實可降低缺血性再灌流損傷,此類試驗應增加一組未接受任何療效藥物處置的患者,藉以探討藥物對肝臟切除術時所產生之缺血性再灌流損傷的絕對影響。