Protective Effects of Ischemic Preconditioning for Liver Resection Performed Under Inflow Occlusion in Humans

Clavien, Pierre‐Alain; Yadav, Siddharth; Sindram, David; Bentley, Rex C.

doi:10.1097/00000658-200008000-00001

Cited by 453 publications

(396 citation statements)

References 26 publications

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“…Another finding was the increased protective effects in patients with more than 30 minutes of ischemia. As 30 minutes is the minimal ischemia time associated with detectable injury after reperfusion, 38 it can be expected that the protective effect is more marked when the ischemic injury is long enough to induce permanent injury.…”

Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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Hepatic injury secondary to warm ischemia-reperfusion (I/R) injury and alterations in haemostatic parameters are often unavoidable events after major hepatic resection. The release of inflammatory mediator is believed to play a significant role in the genesis of these events. It has been suggested that preoperative steroid administration may reduce I/R injury and improve several aspects of the surgical stress response. The aim of this prospective randomized study was to investigate the clinical benefits on I/R injury and systemic responses of preoperatively administered corticosteroids. Seventy-six patients undergoing liver resection were randomized either to a steroid group or to a control group. Patients in the steroid group received preoperatively 500 mg of methylprednisolone. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, coagulation parameters, and inflammatory mediators, interleukin 6 and tumor necrosis factor alpha were compared between the 2 groups. Length of stay, and type and number of complications were recorded as well. Postoperative serum levels of ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in the steroid than in the control group at postoperative days 1 and 2. Changes in hemostatic parameters were also significantly attenuated in the steroid group. In conclusion, the incidence of postoperative complications in the steroid group tended to be significantly lower than the control group. It is of clinical interest that preoperative steroids administration before major surgery may reduce I/R injury, maintain coagulant/anticoagulant homeostasis, and reduce postoperative complications by modulating the inflammatory response. The human body reacts to surgical stimuli through various systemic responses including the endocrine, metabolic, coagulation, and immune systems. However, extended damage may result in an exaggerated systemic response with an overwhelming activation of immune cells and the release of various mediators of stress. [1][2][3] The systemic reaction to the operation is considered to be equivalent to the systemic inflammation response syndrome, mainly caused by cytokine networks. 4,5 Raised levels of inflammatory cytokines have been related to higher postoperative mortality and morbidity rates. 2,3,6 Therefore, increased attention has evolved toward modulating potentially deleterious inflammatory response to the operation.The anti-inflammatory and immune modulating effects of steroids have been known for decades and have found extensive therapeutic use in a wide range of diseases in which inflammatory responses play major role. 7,8 Several trials have investigated the benefits of administering corticosteroids as a modulator of cytokine response in patients undergoing elective cardiothoracic or gastrointestinal surgery, as well as in cases of septic shock, suggesting that several aspects of the surgical stress responses, organ dysfunction, and postAbbreviations: POD, postoperative day; ALT, alanine aminotr...

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Section: Discussionmentioning

confidence: 99%

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

et al. 2006

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“…Two recent publications prompted us to test the use of IIO in living donor hepatectomy. 8,10 Imamura et al recently showed that the Pringle maneuver actually diminished graft injury (as measured by AST and ALT levels) and reduced transection time and blood loss in living donors. They postulated that ischemic preconditioning was in part responsible for the benefit to the graft; unfortunately, they did not report detailed results of remnant function or the donors' postoperative course.…”

Section: Discussionmentioning

confidence: 99%

“…10 The issue of ischemic preconditioning has been extensively studied by Clavien. 8 Inducing a period of ischemia followed by a period of reperfusion prevents the apoptosis associated with prolonged warm ischemia. It has been suggested that the short initial period of ischemia and reperfusion stimulates the generation and release of adenosine and its metabolites, which improve the endothelin-nitric oxide (NO) balance and paradoxically prevent ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

“…[5][6][7] IIO mimics the benefits of ischemic preconditioning and can safely extend periods of ischemia during hepatic surgery. 8 Adult-to-adult living donor liver transplantation (LDLT) is now widely used at transplantation centers throughout the world because of the severe shortage of cadaveric organs and the increasing number of patients waiting for transplantation. The paramount concern in LDLT is donor safety.…”

Section: Introductionmentioning

confidence: 99%

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Intermittent inflow occlusion in living liver donors: Impact on safety and remnant function

et al. 2004

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Clamping of the portal triad accomplishes complete inflow occlusion. This maneuver is commonly used during liver surgery to minimize blood loss but is not widely used in living donors undergoing resection for liver transplantation. We compared outcomes in living donors who underwent resection with and without inflow occlusion. We reviewed data on 2 nonsimultaneous living liver donor cohorts. The first 20 donors (group 1) underwent resection without inflow occlusion. In the next 15 donors (group 2), inflow occlusion was used during parenchymal transection, using cycles of 10 -15 minutes occlusion and 6 minutes reperfusion. In donors, we recorded type of resection; ischemia times; blood loss; transfusions; peak ALT, AST, bilirubin, and INR in the first 5 days; hospital length of stay (LOS), and major complications. In recipients, we recorded peak ALT. In group 1, 19 of 20 donors underwent right hepatectomy. In group 2, 8 donors underwent right hepatectomy, and 7 donors had left lobectomies. Total ischemic time ranged from 16 -49 minutes (mean, 31 ؎ 9 minutes). In group 1, two donors received a total of 5 U of allogeneic blood. In group 2, no donor required transfusion. Mean peak ALT was significantly higher in group 1 (521 ؎ 336 U/L) than group 2 (322 ؎ 162 U/L; P ‫؍‬ 0.03). Mean INR was significantly higher in group 1 (1.8 ؎ 0.2) vs. group 2 (1.5 ؎ 0.2; P ‫؍‬ 0.001). There were 4 major complications in group 1 (incisional hernia, transient liver failure, biliary stricture, and biliary leak) and no major intraoperative or postoperative complications in group 2. Mean LOS was significantly longer in group 1 (7.9 ؎ 2.9 days) than group 2 (6.2 ؎ 1.1 days; P ‫؍‬ 0.04). Mean peak ALT in recipients trended lower in group 2. In conclusion, inflow occlusion was associated with reduced blood loss and less ischemic injury to hepatic remnants in the donors and the grafts in the recipients. These benefits were associated with a diminished incidence of major complications and shorter LOS. Inflow occlusion should be an essential part of living donor hepatectomy. (Liver Transpl 2004;10:244 -247.)

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“…We did not encounter any major immunological problems. These excellent results may be explained by the fact that these case reports represent a very selected organ-donor group and also by the fact that these grafts might benefit from protective ischemic pre-conditioning, as described in major hepatic-resection procedures [2].…”

Section: Discussionmentioning

confidence: 90%

Re-use of a liver allograft; an exceptional opportunity to enlarge the organ donor pool

Rubay

Wittebolle

Ciccarelli

et al. 2003

Transplant International

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Liver allograft re-use is an exceptional way of enlarging the donor pool. We describe here a case of a re-used liver allograft, originating from an insulin-intoxicated donor and transplanted at first into a recipient presenting with hyperacute liver failure due to paracetamol intoxication. Because the original recipient developed an irreversible cerebral oedema, the allograft was re-implanted electively 55.5 h later into a patient with post-viral C cirrhosis and solitary hepatocarcinoma. Both donor and recipient operations were technically successful; liver function after the second use of the graft was normal.

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Protective Effects of Ischemic Preconditioning for Liver Resection Performed Under Inflow Occlusion in Humans

Cited by 453 publications

References 26 publications

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

Impact of preoperative steroids administration on ischemia-reperfusion injury and systemic responses in liver surgery: A prospective randomized study

Intermittent inflow occlusion in living liver donors: Impact on safety and remnant function

Re-use of a liver allograft; an exceptional opportunity to enlarge the organ donor pool

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