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

Mahmoud Abu-Amara, Kurinchi Selvan Gurusamy, George Glantzounis, Barry Fuller, Brian R Davidson
Cochrane Database of Systematic Reviews 2009, (4): CD008154

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 STRATEGY: 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.

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