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.