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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.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: October 7, 2009

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.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: October 7, 2009

Blood cardioplegia in cardiac surgery contains leukocytes, which causes the inflammatory reaction and promotes myocardial reperfusion injury. The removal of leukocytes from the cardioplegia line, using specialized filters, has been proposed as one of the effective methods in attenuating the inflammatory response. We performed a two-level search to identify randomized, controlled trials concerning the effects of leukocyte-depleted blood cardioplegia on myocardial reperfusion injury. Sixteen studies, comprising 738 patients, met the selection criteria. There are significant reductions in creatinine kinase isoenzyme MB (CK-MB) during 4-8h postoperatively (SMD - 0.577; 95% CI -0.795 to -0.358; p=0.000), CK-MB peak (SMD - 0.713; 95% CI -1.027 to -0.400; p=0.000), troponin in the period of 4-8h postoperatively (SMD - 0.502; 95% CI -0.935 to -0.069; p=0.023), troponin peak (SMD - 0.826; 95% CI -1.373 to -0.279; p=0.003) and inotropic support (RR, 0.500; 95% CI 0.269 to 0.931; p=0.029). Leukocyte-depleted blood cardioplegia may reduce myocardial reperfusion injury in the early postoperative period, but there has been no evidence to support the clinically significant difference. Larger and more precise randomized control trials are needed to further elucidate the cardioprotective effects of cardioplegia leukofiltration.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

Ischaemic preconditioning is a mechanism for reducing organ ischaemia reperfusion injury by a brief period of organ ischaemia, ie, decrease the injury caused by return of blood supply to the organ after a period of decreased or absent blood supply by exposing the organ to shorter periods of decreased blood supply. There is considerable controversy regarding whether ischaemic preconditioning during donor liver retrieval has beneficial effect on the outcome of liver transplantation. This systematic review includes five randomised clinical trials assessing the advantages and disadvantages of ischaemic preconditioning during donor hepatectomy for liver transplant recipients. In four trials, 270 cadaveric liver donor retrievals were randomised; 131 to ischaemic preconditioning and 139 to no ischaemic preconditioning; and in one trial, 15 living donor liver retrievals were randomised; 10 to ischaemic preconditioning and 5 to no ischaemic preconditioning. All the trials were high bias‐risk trials. There was no statistically significant difference in mortality, initial poor function, re‐transplant, primary graft non‐function, or in any other outcome other than enzyme markers of liver injury, which was in different directions in different trials. There is currently no evidence to support or refute the use of ischaemic preconditioning in donor liver retrievals. Further studies are necessary to identify the optimal ischaemic preconditioning stimulus.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: January 23, 2008

More than 1000 elective liver resections (planned operation) are performed annually in the United Kingdom alone. When liver resection is performed, the inflow of blood to the liver can be blocked (vascular occlusion), thereby reducing the blood loss. There are concerns about liver damage when the blood supply is blocked. Ischaemic preconditioning involves ischaemia (blocking the blood supply) and reperfusion (unblocking the blood supply) for a short period of time before exposure to prolonged vascular occlusion. The aim of this review was to assess the role of ischaemic preconditioning in liver resections performed utilising vascular occlusion. Four randomised clinical trials including 271 patients undergoing open liver resections fulfilled the inclusion criteria of this review. The patients were randomised to ischaemic preconditioning (n = 135) and no ischaemic preconditioning (n = 136) prior to continuous vascular occlusion. All the trials excluded cirrhotic patients. We assessed all the four trials as having high risk of bias (high risk of systematic error). There was no difference in mortality, liver failure, post‐operative complications, hospital stay, intensive therapy unit stay, and operating time between the two groups. The proportion of patients requiring blood transfusion was lower in the ischaemic preconditioning group. The reasons for this are not clear. There was no difference in blood loss or enzyme markers of liver function between the two groups. The enzyme markers of liver injury were lower in the ischaemic preconditioning group on the first post‐operative day. Currently, there is no evidence to suggest a protective effect of ischaemic preconditioning in non‐cirrhotic patients undergoing liver resection under continuous vascular occlusion. Ischaemic preconditioning reduces the blood transfusion requirements in patients undergoing liver resection. Further high quality randomised clinical trials are necessary to assess the role of ischaemic preconditioning. Further studies are necessary to understand the mechanism of ischaemic preconditioning.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: January 21, 2009

When myocardial blood flow is acutely impaired (ischaemia), and often not provoked by exertion, a person will commonly suffer more prolonged pain; this is referred to as acute coronary syndrome (ACS). The underlying common pathophysiology of ACS involves the erosion or sudden rupture of an atherosclerotic plaque within the wall of a coronary artery. Exposure of the circulating blood to the cholesterol-rich material within the plaque stimulates blood clotting (thrombosis), which obstructs blood flow within the affected coronary artery. This coronary obstruction may be of short duration, and may not result in myocardial cell damage (necrosis), in which case the clinical syndrome is termed unstable angina. Unstable angina may result in reversible changes on the electrocardiogram (ECG) but does not cause a rise in troponin, a protein released by infarcting myocardial cells. Ischaemia which causes myocardial necrosis (infarction) will result in elevated troponin. When the ischaemia-causing infarction is either short-lived or affects only a small territory of myocardium the ECG will often show either no abnormality or subtle changes. This syndrome is termed non-ST-segment elevation myocardial infarction (NSTEMI). The diagnosis and immediate management of STEMI and the management of unstable angina and NSTEMI is addressed in other NICE Clinical Guidelines (CG95 and CG94).

NICE Clinical Guidelines - National Clinical Guideline Centre (UK).

Version: July 2013

BACKGROUND: Remote ischemic conditioning is gaining interest as potential method to induce resistance against ischemia reperfusion injury in a variety of clinical settings. We performed a systematic review and meta-analysis to investigate whether remote ischemic conditioning reduces mortality, major adverse cardiovascular events, length of stay in hospital and in the intensive care unit and biomarker release in patients who suffer from or are at risk for ischemia reperfusion injury.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

The kidney is highly sensitive to shortage in blood flow and thus oxygen supply. This may cause irreversible kidney injury leading to haemodialysis or death. Kidney injury does not only relate to the temporary lack of oxygen supply, but is also due to the re‐saturation of blood flow. At this stage, toxic products are released and initiate a reaction of the body causing further cellular damage within the kidney, the so called ‘ischaemia‐reperfusion injury’. A lack of oxygen supply to the kidney injury may have many different causes, for example blood pressure changes that may occur during major surgery.

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet] - John Wiley & Sons, Ltd.

Version: March 4, 2017

OBJECTIVES: The purpose of this study was to assess the effect of remote ischemic precondition (RIPC) on the incidence of myocardial and renal injury in patients undergoing cardiovascular interventions as measured by biomarkers. Clinical data were pooled to evaluate the usefulness of RIPC to benefit clinical outcomes.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

The authors concluded that perioperative steroids had a favourable impact on postoperative outcomes after liver resection. These conclusions seem to reflect the results of the review, but their reliability is uncertain due to small samples, poor-quality of evidence, and analyses with wide variations.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

BACKGROUND: Although remote ischemic conditioning (RIC) by transient limb ischemia in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) has shown favorable effects on myocardial (ischemia-reperfusion) injury, recent trials provide inconsistent results. The aim of the present study was to assess the effect of RIC in PCI or CABG.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

BACKGROUND: Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

BACKGROUND: Remote ischemic preconditioning (RIPC) appears to protect distant organs from ischemia-reperfusion injury. We undertook meta-analysis of clinical studies to evaluate the effects of RIPC on organ protection and clinical outcomes in patients undergoing cardiac surgery.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2014

BACKGROUND: Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

BACKGROUND: Studies evaluating intracoronary administration of adenosine for prevention of microvascular dysfunction and ischemic-reperfusion injury in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) have yielded mixed results. Therefore, we performed a meta-analysis of these trials to evaluate the safety and efficacy of intracoronary adenosine administration in patients with AMI undergoing primary PCI.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

Brain injuries resulting from trauma and stroke are common and costly. Cooling therapy may reduce damage and potentially improve outcome. Head cooling targets the site of injury and may have fewer side effects than systemic cooling, but there has been no systematic review and the evidence base is unclear.

Health Technology Assessment - NIHR Journals Library.

Version: November 2012

A systematic assessment of diagnostic and therapeutic devices in common use as blood management tools in cardiac surgery did not demonstrate clinical effectiveness or cost-effectiveness.

Programme Grants for Applied Research - NIHR Journals Library.

Version: September 2017

Bibliographic details: Chen QJ, Yang YN, Ma YT, LI XM, Xie X, Yu ZX, Guo H.  Effectiveness of nicorandil for reperfusion of acute myocardial infarction: a meta-analysis. Chinese Journal of Evidence-Based Medicine 2012; 12(11): 1330-1338

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

INTRODUCTION: Custodiol cardioplegia is attractive for minimally invasive cardiac surgery, as a single dose provides a long period of myocardial protection. Despite widespread use in Europe, there is little data confirming its efficacy compared with conventional (blood or crystalloid) cardioplegia. There is similar enthusiasm for its use in organ preservation for transplant, but also a lack of data. This systematic review aimed to assess the evidence for the efficacy of Custodiol in myocardial protection and as a preservation solution in heart transplant.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2013

AIM: Randomised trials exploring remote ischaemic preconditioning (RIPC) in patients undergoing coronary artery bypass graft (CABG) surgery have yielded conflicting data regarding potential cardiovascular and renal protection, and are individually flawed by small sample size.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet] - Centre for Reviews and Dissemination (UK).

Version: 2012

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