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Pharmacological interventions versus no pharmacological intervention for ischaemia reperfusion injury in liver resection surgery performed under vascular control

  • Review
  • Intervention

Authors


Abstract

Background

Vascular occlusion to reduce blood loss is used during elective liver resection but results in significant ischaemia reperfusion injury. This, in turn, might lead to significant postoperative liver dysfunction and morbidity. Various pharmacological drugs have been used with an intention to ameliorate the ischaemia reperfusion injury in liver resections.

Objectives

To assess the benefits and harms of different pharmacological agents versus no pharmacological interventions 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 any pharmacological agent versus placebo or no pharmacological agent during elective liver resections with vascular occlusion.

Data collection and analysis

Two authors independently identified trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and the random-effects models using RevMan Analysis. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on intention-to-treat analysis or available case analysis.

Main results

We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046 (a thromboxane A2 synthetase inhibitor)). All trials had high risk of bias. There were no significant differences between the groups in mortality, liver failure, or perioperative morbidity. The trimetazidine group had a significantly shorter hospital stay than control (MD -3.00 days; 95% CI -3.57 to -2.43). There were no significant differences in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared with controls. 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

Trimetazidine, methylprednisolone, and dextrose may protect against ischaemia reperfusion injury in elective liver resections performed under vascular occlusion, but this is shown in trials with small sample sizes and high risk of bias. The use of these drugs should be restricted to well-designed randomised clinical trials before implementing them in clinical practice.

アブストラクト

血管コントロール下で施行される肝切除術時の虚血性再灌流傷害に対する薬理学的介入と無薬理学的介入との比較

背景

待期的肝切除時に出血を軽減させるために血管閉塞術が使用されているが、その結果、有意な虚血性再灌流傷害が引き起こされる。このことにより、さらに有意な術後肝機能障害および病的状態へとつながることもある。肝切除時の虚血性再灌流傷害を改善させるために様々な薬理学的薬剤が使用されている。

目的

術中に血管閉塞術が行われた肝切除時の虚血性再灌流傷害を軽減させるために使用される各種薬理学的薬剤の利益と有害性を無薬理学的介入と比較評価する。

検索戦略

Cochrane Hepato-Biliary Group Controlled Trials Register、コクラン・ライブラリのCochraneCentral Register of Controlled Trials(CENTRAL)、MEDLINE、EMBASE、およびScienceCitation Index Expandedを2009年1月まで検索した。

選択基準

言語や発表の状況にかかわりなく、血管閉塞術を伴う待期的肝切除時の薬理学的薬剤をプラセボまたは無薬理学的薬剤と比較したランダム化臨床試験を含めた。

データ収集と分析

2名のレビューアが含める試験を独立に同定し、独自にデータを抽出した。RevMan解析を用いて固定効果およびランダム効果の両モデルでデータを解析した。ITT解析または利用可能な症例分析に基づいて、リスク比(RR)または平均差(MD)と95%信頼区間(CI)を計算した。

主な結果

11種類の薬理学的介入(メチルプレドニゾロン、複合ビタミン剤アンチオキシダント注入、ビタミンE注入、アムリノン、プロスタグランジンE1、ペントキシフィリン、マンニトール、トリメタジジン、デキストロース、アロプリノール、およびOKY 046(トロンボキサンA2合成酵素阻害薬))を評価していた計15件のランダム化試験を同定した。試験はすべて、バイアス・リスクが高かった。死亡率、肝不全、周術期の罹病率に群間で有意差を認めなかった。トリメタジジン群はコントロール群よりも在院期間が有意に短かった(MD -3.00日、95%CI-3.57~-2.43)。その他の比較でも、臨床的に関連性のあるアウトカムのいずれも有意差を認めなかった。メチルプレドニゾロンは肝機能の酵素マーカを改善させ、トリメタジジン、メチルプレドニゾロン、およびデキストロースは、コントロールと比較して、肝障害を示す酵素マーカを低下させた。しかし、含まれた試験は少ししかなく、各試験のサンプル・サイズは小さく、バイアス・リスクがあるため、第1型の過誤および第2種の過誤のリスクが高い。

著者の結論

トリメタジジン、メチルプレドニゾロン、およびデキストロースは、血管閉塞の下で施行される待機的肝切除時の虚血性再灌流傷害を予防すると思われるが、これらの所見はサンプル・サイズが小さく、バイアス・リスクが高い試験からのものである。これらの薬剤の使用については、臨床診療に先立ち、適切にデザインされたランダム化臨床試験によって再検討されるべきである。

訳注

Translated by: MINDS

Translation supported by:

Plain language summary

Pharmacological interventions show potential for a protective role against 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 blood supply interruption can cause 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. We identified a total of 15 randomised trials evaluating 11 different pharmacological interventions (methylprednisolone, multivitamin antioxidant infusion, vitamin E infusion, amrinone, prostaglandin E1, pentoxifylline, mannitol, trimetazidine, dextrose, allopurinol, and OKY 046). All trials had risk of bias ('systematic errors') and risk of play of chance ('random errors'). There was no significant difference between the groups in mortality, liver failure, or post-operative complications. The trimetazidine group had a significantly shorter hospital stay, and the vitamin E group had a significantly shorter intensive therapy unit stay than the respective controls. There was no significant difference in any of the clinically relevant outcomes in the remaining comparisons. Methylprednisolone improved the enzyme markers of liver function and trimetazidine, methylprednisolone, and dextrose reduced the enzyme markers of liver injury compared to controls. 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 risks of bias. Three pharmacological drugs - trimetazidine, methylprednisolone, and dextrose - have potential for a protective role against liver injury in elective liver surgery involving blood supply occlusion. However, based on the current evidence it is recommended that the use of these agents should be restricted to well-designed trials in patients undergoing resection.