Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials

Bonanni, Alice; Bruschi, Maurizio; Alicino, Cristiano; Signori, Alessio

doi:10.1093/ndt/gfx210

Cited by 38 publications

(25 citation statements)

References 68 publications

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“…The potential interaction between anaesthetic regimen and the effect of RIPC is debatable. Results from meta-analyses and clinical studies are contradictory and primarily from cardiac surgery 29303536. To the best of our knowledge, no clinical trial has specifically investigated the influence of an anaesthetic regimen on the effect of RIPC.…”

Section: Discussionmentioning

confidence: 99%

The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial

Ekeloef

Homilius

Stilling

et al. 2019

BMJ

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ObjectiveTo investigate whether remote ischaemic preconditioning (RIPC) prevents myocardial injury in patients undergoing hip fracture surgery.DesignPhase II, multicentre, randomised, observer blinded, clinical trial.SettingThree Danish university hospitals, 2015-17.Participants648 patients with cardiovascular risk factors undergoing hip fracture surgery. 286 patients were assigned to RIPC and 287 were assigned to standard practice (control group).InterventionThe RIPC procedure was initiated before surgery with a tourniquet applied to the upper arm and consisted of four cycles of forearm ischaemia for five minutes followed by reperfusion for five minutes.Main outcome measuresThe original primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more caused by ischaemia. The revised primary outcome was myocardial injury within four days of surgery, defined as a peak plasma cardiac troponin I concentration of 45 ng/L or more or high sensitive troponin I greater than 24 ng/L (the primary outcome was changed owing to availability of testing). Secondary outcomes were peak plasma troponin I and total troponin I release during the first four days after surgery (cardiac and high sensitive troponin I), perioperative myocardial infarction, major adverse cardiovascular events, and all cause mortality within 30 days of surgery, length of postoperative stay, and length of stay in the intensive care unit. Several planned secondary outcomes will be reported elsewhere.Results573 of the 648 randomised patients were included in the intention-to-treat analysis (mean age 79 (SD 10) years; 399 (70%) women). The primary outcome occurred in 25 of 168 (15%) patients in the RIPC group and 45 of 158 (28%) in the control group (odds ratio 0.44, 95% confidence interval 0.25 to 0.76; P=0.003). The revised primary outcome occurred in 57 of 286 patients (20%) in the RIPC group and 90 of 287 (31%) in the control group (0.55, 0.37 to 0.80; P=0.002). Myocardial infarction occurred in 10 patients (3%) in the RIPC group and 21 patients (7%) in the control group (0.46, 0.21 to 0.99; P=0.04). Statistical power was insufficient to draw firm conclusions on differences between groups for the other clinical secondary outcomes (major adverse cardiovascular events, 30 day all cause mortality, length of postoperative stay, and length of stay in the intensive care unit).ConclusionsRIPC reduced the risk of myocardial injury and infarction after emergency hip fracture surgery. It cannot be concluded that RIPC overall prevents major adverse cardiovascular events after surgery. The findings support larger scale clinical trials to assess longer term clinical outcomes and mortality.Trial registrationClinicalTrials.gov NCT02344797.

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Section: Discussionmentioning

confidence: 99%

The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial

Ekeloef

Homilius

Stilling

et al. 2019

BMJ

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“…Similarly, the long-term effects of repetitive weekly bursts of subclinical injury in individuals practicing high-intensity exercises are unknown. However, it is also possible that some individuals may develop improved resilience to renal insults, as observed with remote ischemic preconditioning preventing AKI, which enhanced the renal recovery in patients with AKI and reduced the long-term incidence of major adverse kidney events in high-risk patients undergoing cardiac surgery [ 41 ]. Likewise, acute exercise or continuous training schedules may induce or activate heat shock proteins, a group of proteins that is crucial in the preservation of protein and cell homeostasis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals

et al. 2018

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PurposeHigh-intensity interval resistance training (HIIRT) is an increasingly popular exercise program that provides positive results with short sessions. This study aimed to evaluate whether an HIIRT session causes muscle and kidney damage.MethodsFifty-eight healthy volunteers (median age 24 years, 50% women) participated in this study and performed a HIIRT session. The Borg CR10 scale for pain (CR10P) and blood and urine samples were collected before (baseline) and 2 and 24 hours after the HIIRT session. Blood samples were analyzed for serum creatinine (SCr), creatine kinase (CK) and myoglobin. Urine samples were assessed for creatinine, neutrophil gelatinase-associated lipocalin, interleukin 18, calbindin, microalbuminuria, trefoil factor-3 and β-2 microglobulin.ResultsCR10P had a significant increase at 2 and 24 hours post-workout, and CK increased significantly at 2 hours and increased further at 24 hours. Myoglobin increased significantly at 2 hours and remained elevated at 24 hours. SCr increased modestly but significantly at 24 hours only in men. Three men met the KDIGO diagnostic criteria for acute kidney injury. The urinary kidney injury biomarkers increased significantly at 2 hours and returned to the baseline values 24 hours after HIIRT.ConclusionsA single HIIRT session caused early and significant elevations in CK, myoglobin, SCr, microalbuminuria and urinary biomarkers indicative of kidney tubular injury, suggesting the occurrence of muscle and kidney damage.

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“…Recently performed large meta-analyses demonstrated that postoperative cardiac biomarker concentrations were lower in cardiac surgery patients after RIPC. [14][15][16] To date, a cardioprotective effect of RIPC was not observed in patients undergoing major abdominal surgery. A previous randomized trial with RIPC in abdominal surgery patients (>90% of patients underwent colon surgery) found no differences in hs-cTnT concentrations until 72 hours after surgery.…”

Section: Discussionmentioning

confidence: 99%

“…A possible interference of propofol with the cardioprotective effects of RIPC, which has been extensively described in prior studies, was ruled out by our study design. 14,[16][17][18] Surgical tissue injury triggers pro-and anti-inflammatory pathways. An excessive activation of the immune system, as reflected by high concentrations of IL-6, has been associated with adverse .…”

Section: Discussionmentioning

confidence: 99%

“…Studies in cardiac surgery patients have demonstrated a cardioprotective effect of remote ischemic preconditioning (RIPC) but were unable to show an improvement in postoperative outcome. [14][15][16] This might have been the result of an interference with anesthetic drugs (i.e. propofol), although the exact mechanism of this interaction remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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The effect of remote ischemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial

Zeggeren

Visser

Vernooij

et al. 2020

Preprint

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BackgroundCardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. Remote ischemic preconditioning (RIPC) may protect organs from ischemic insults during and after cardiac surgery, but the effect in major abdominal surgery is largely unknown.ObjectiveTo study the effect of RIPC on cardiac and inflammatory biomarkers in patients undergoing pancreatic resection.MethodsSingle-center, double-blind, randomized controlled trial in ninety patients undergoing elective pancreatic resection between March 2017 and February 2019. Three cycles of upper-limb ischemia and reperfusion (each 5 minutes) were applied before surgery. The primary endpoint was the maximum postoperative high-sensitive cardiac troponin (hs-cTn) T concentration within 48 hours after surgery. Secondary endpoints were postoperative myocardial injury (PMI, defined as a postoperative hs-cTnT ≥14 ng L-1), the maximum concentration of interleukin (IL)-6 within 48 hours after surgery, and postoperative complications within 30-days of surgery.ResultsRIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng L-1 vs 16.6 ng L-1 in the control group (P=0.23), nor did it lessen the incidence of PMI (15 (33.3%) patients in the RIPC group versus 19 (42.2%) controls, P=0.93). The maximum postoperative IL-6 concentration was 239 pg mL-1 [115-360] in the RIPC group, as compared to 317 pg mL-1 [174-909] in the control group (P=0.13). A postoperative complication occurred in 23 (51%) RIPC patients and 24 (53%) controls.ConclusionsRemote ischemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were not statistically different between RIPC patients and controls.Trial RegistrationClinicaltrials.gov identifier NCT03460938FundingFunding for biomarker analysis was provided by Roche Diagnostics. Roche Diagnostics had no role in design and conduct of the study, analysis and interpretation of the data, preparation and approval of the manuscript.Article summaryStrengths and limitations of this studyWell-designed clinical trial in a selected group of high-risk abdominal surgery patients.Serial assessment of high-sensitive cardiac troponin T and interleukin-6 concentrations.Postoperative cardiac biomarker concentrations were relatively low.This trial was not primarily designed to detect differences in IL-6 concentrations and postoperative complications.

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Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials

Abstract: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.

Cited by 38 publications

References 68 publications

The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial

The effect of remote ischaemic preconditioning on myocardial injury in emergency hip fracture surgery (PIXIE trial): phase II randomised clinical trial

High intensity resistance training causes muscle damage and increases biomarkers of acute kidney injury in healthy individuals

The effect of remote ischemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial

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