Postoperative Neurocognitive Dysfunction in Patients Undergoing Cardiac Surgery after Remote Ischemic Preconditioning: A Double-Blind Randomized Controlled Pilot Study

Patrick Meybohm,Jochen Renner,Jochen Cremer,Martin Albrecht,Jens Scholz,Nils Haake,Kai Zacharowski,Berthold Bein,Ole Broch,Dorothee Caliebe

doi:10.1371/journal.pone.0064743

Abstract

BackgroundRemote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery.MethodsWe conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion).ResultsAccording to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L].ConclusionsWe failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed.Trial RegistrationClinicalTrials.gov NCT00877305

Highlights

Cardiac surgery is associated with a predictable incidence of myocardial, neurologic, and renal ischemia/reperfusion injury
Transient sublethal episodes of ischemia in nonvital tissue have been shown to enhance the tolerance of remote vital organs to subsequent prolonged ischemia/reperfusion injury in a number of clinical conditions, a phenomenon known as remote ischemic preconditioning (RIPC)
The first proof of principle studies suggested that transient limb ischemia has the potential to attenuate cardiac troponin I or T release during coronary artery surgery [2,3], congenital heart surgery [4], and noncardiac surgery in high-risk patients [5]

Summary

Introduction

Cardiac surgery is associated with a predictable incidence of myocardial, neurologic, and renal ischemia/reperfusion injury. Transient sublethal episodes of ischemia in nonvital tissue (e.g., skeletal muscles) have been shown to enhance the tolerance of remote vital organs (e.g., the heart, brain, and kidney) to subsequent prolonged ischemia/reperfusion injury in a number of clinical conditions, a phenomenon known as remote ischemic preconditioning (RIPC). RIPC has been extended to different organs, representing a general form of interorgan protection against the detrimental effects of acute ischemia/reperfusion injury [6]. This hypothesis is further supported by previous experimental findings suggesting that RIPC offers advantages with respect to cerebral ischemia/reperfusion injury [7,8]. We hypothesized that RIPC reduces the incidence and severity of neurocognitive dysfunction in patients undergoing cardiac surgery with a cardiopulmonary bypass. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery

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Conclusion