Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning on Children Undergoing Cardiac Surgery

Cheung, Michael; Kharbanda, Rajesh K.; Konstantinov, Igor E.; Shimizu, Mikiko; Frndova, Helena; Li, Jia; Holtby, Helen; Cox, Peter N.; Smallhorn, Jeffrey F.; Arsdell, Glen S. Van; Redington, Andrew N.

doi:10.1016/j.jacc.2006.01.066

Cited by 500 publications

(434 citation statements)

References 28 publications

(27 reference statements)

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“…Despite initial success in children undergoing cardiac surgery 16 It is unclear from the published manuscripts whether or not supplementary oxygen was administered to the patients in these trials during the pre-or intraoperative period.…”

Section: Discussionmentioning

confidence: 99%

“…RIPC has been shown by our own group and others to ameliorate hepatic IR injury in small animal models 12,13,14,15 . It has also been translated into clinical benefit in patients undergoing both cardiac surgery 16 and major vascular surgery 17 . In major liver surgery, RIPC was shown in a pilot RCT to reduce liver IR injury as indicated by a reduction in post operative transaminases and increased ICG clearance.…”

Section: Discussionmentioning

confidence: 99%

“…RIPC has been shown by our own group and others to ameliorate hepatic IR injury in small animal models 12,13,14,15 . It has also been translated into clinical benefit in patients undergoing both cardiac surgery 16 The aims of this study was to perform a prospective randomized controlled feasibility study to address these issues and to obtain preliminary data on which to design a further prospective trial to determine efficacy and cost effectiveness. Patients above the age of 18 undergoing first elective deceased donor liver transplantation were enrolled with informed consent in the study for randomization.…”

mentioning

confidence: 99%

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Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Robertson

Goswami

Wright

et al. 2017

HPB

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Abstract:Ischaemia Reperfusion (IR) injury is a major cause of post-operative morbidity, mortality and graft loss following Orthotopic Liver Trasnplantation (OLT). There is no current accepted treatment for IR injury. The recent drive to implant more marginal grafts, which are more susceptible to IR injury makes this clinical problem a key research goal. Remote Ischaemic Preconditioning (RIPC) has been shown to ameliorate hepatic IR injury in small animal models. Whether recipient RIPC can reduce IR injury in human liver transplant recipients has not previously been investigated. Methods:Forty patients with end stage liver disease undergoing liver transplantation were randomized to RIPC or a sham control group. RIPC was induced through three 5 minute cycles of alternate ischaemia and reperfusion using an orthopaedic tourniquet to the left lower limb under general anaesthesia prior to commencement of the abdominal procedure. The aim of the study was to determine the safety and feasibility of limb RIPC in patients with end stage cirrhosis. Data on clinical outcomes was collected prospectively (minimum 3 month follow up) and the function of the graft was also evaluated. Plasma cytokine levels were measured at baseline, 2 hours post reperfusion and at 24 hours post-operatively. Results:45 of 51 patients approached (88%) were willing to enroll in the study. 5 patients were then excluded and 40 patients were randomized of which 20 underwent RIPC.RIPC was able to be performed in all patients randomized to the RIPC group. There was no evidence of localized complications following RIPC. One patient died in the control group and 1 further graft was lost in the control group due to a non-IR related 3 issue. Median AST levels on the third post-operative day showed a slightly higher trend in the RIPC group than in the control group (221iU vs 149iU, p=1.00) but this was not statistically significant. Conclusions:RIPC is acceptable and can be carried out safely in patients with advanced liver disease. This pilot feasibility study has not demonstrated evidence of a reduction in IR injury or clinical benefit. A longer follow up, a larger study or an altered preconditioning protocol may be required. 4Liver transplantation is the treatment of choice for both acute and chronic end stage liver disease. As outcomes following transplantation have improved, the indications for liver transplantation have been widened and a shortage of suitable organ donors has developed. This has resulted in an increased use of grafts from marginal donors such as the elderly and those with a fatty liver from obesity (extended criteria donors) and especially the use of grafts from donors following cardiac death (DCD). The use of liver DCD grafts in the UK has increased from 6.9% in 2005 1 to 19.1% of grafts implanted in 2013 2 .Ischaemia Reperfusion (IR) injury is the damage that happens to an organ when its blood supply is interrupted and reconstituted. It is a major cause of morbidity and mortality following liver transplantation and is believed to acc...

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Section: Discussionmentioning

confidence: 99%

“…RIPC has been shown by our own group and others to ameliorate hepatic IR injury in small animal models 12,13,14,15 . It has also been translated into clinical benefit in patients undergoing both cardiac surgery 16 and major vascular surgery 17 . In major liver surgery, RIPC was shown in a pilot RCT to reduce liver IR injury as indicated by a reduction in post operative transaminases and increased ICG clearance.…”

Section: Discussionmentioning

confidence: 99%

“…RIPC has been shown by our own group and others to ameliorate hepatic IR injury in small animal models 12,13,14,15 . It has also been translated into clinical benefit in patients undergoing both cardiac surgery 16 The aims of this study was to perform a prospective randomized controlled feasibility study to address these issues and to obtain preliminary data on which to design a further prospective trial to determine efficacy and cost effectiveness. Patients above the age of 18 undergoing first elective deceased donor liver transplantation were enrolled with informed consent in the study for randomization.…”

mentioning

confidence: 99%

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Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Robertson

Goswami

Wright

et al. 2017

HPB

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“…The merits of this composite endpoint were discussed in the Severity of Ischemia and RP Injury section, subsection Liver Transplantation. Remote preconditioning via limb ischemia 81,82 (1) Applicable to DCD donors; (2) Inexpensive Hypertonic saline dextran 83,84 (1) Volume enhancement, especially in donors and applicable to DCD donors; (2) Inexpensive Anesthetic preconditioning (volatile anesthetics, nitric oxide) 3,4,85 (1) May not be feasible in all donor hospitals; (2) Nitric oxide is expensive Pharmacologic preconditioning (nitrites, adenosine, interleukin-10) 2,6,7 (1) More expensive; (2) Potential side effects of agents NOTE: In contradistinction to ischemic preconditioning, all listed modalities are applicable in both liver donors and recipients. They share avoidance of direct organ ischemia and, when used in deceased donors, have the potential to benefit recipients of many organs.…”

Section: Criteria and Reporting Of Rp Injurymentioning

confidence: 99%

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

et al. 2008

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Utilization of ischemic preconditioning to ameliorate ischemia/reperfusion injury has been extensively studied in various organs and species for the past two decades. While hepatic ischemic preconditioning in animals has been largely beneficial, translational efforts in the two clinical contexts-liver resection and decreased donor liver transplantation-have yielded mixed results. This review is intended to critically examine the translational data and identify some potential reasons for the disparate clinical results, and highlight some issues for further studies.

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“…1 Apart from the local effects, the protection of remote tissues can also be achieved through brief periods of arterial occlusions of the intestine, kidneys, and many other organs. 2,3 Although the remote effects of intraabdominal IPC may be notable, the extremities provide better opportunities for clinical purposes. IPC of the limbs in humans can be easily performed, the risk of surgical complications is low, and moreover, the large tissue mass may theoretically provide strong defense-triggering IPC signals.…”

mentioning

confidence: 99%

Ischemic limb preconditioning downregulates systemic inflammatory activation

Szabó

Varga

Keresztes

et al. 2008

Journal Orthopaedic Research

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We examined local and systemic antiinflammatory consequences of ischemic preconditioning (IPC) in a rat model of limb ischemia-reperfusion (I-R) by characterizing the leukocyte-endothelial interactions in the periosteum and the expression of adhesion molecules playing a role in leukocyte-mediated inflammatory processes. IPC induction (2 cycles of 10 min of complete limb ischemia and 10 min of reperfusion) was followed by 60 min of ischemia/180 min of reperfusion or sham-operation. Data were compared with those on animals subjected to I-R and sham-operation. Neutrophil leukocyte-endothelial cell interactions (intravital videomicroscopy), intravascular neutrophil activation (CD11b expression changes by flow cytometry), and soluble and tissue intercellular adhesion molecule-1 (ICAM-1; ELISA and immunohistochemistry, respectively) expressions were assessed. I-R induced enhanced leukocyte rolling and adherence in the periosteal postcapillary venules after 120 and 180 min of reperfusion. This was associated with a significantly enhanced CD11b expression (by $80% and 72%, respectively) and moderately increased soluble and periosteal ICAM-1 expressions. IPC prevented the I-R-induced increases in leukocyte adherence and CD11b expression without influencing the soluble and tissue ICAM-1 levels. The results show that limb IPC exerts not only local, but distant antiinflammatory effects through significant modulation of neutrophil recruitment. ß

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Randomized Controlled Trial of the Effects of Remote Ischemic Preconditioning on Children Undergoing Cardiac Surgery

Abstract: This study demonstrates the myocardial protective effects of RIPC using a simple noninvasive technique of four 5-min cycles of lower limb ischemia and reperfusion. These novel data support the need for a larger study of RIPC in patients undergoing cardiac surgery.

Cited by 500 publications

References 28 publications

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Remote ischaemic preconditioning in orthotopic liver transplantation (RIPCOLT trial): a pilot randomized controlled feasibility study

Ischemic preconditioning of the liver: A few perspectives from the bench to bedside translation

Ischemic limb preconditioning downregulates systemic inflammatory activation

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