The Risk of Oxygen during Cardiac Surgery (ROCS) trial: study protocol for a randomized clinical trial

Marcos G Lopez, Mias Pretorius, Matthew S Shotwell, Robert Deegan, Susan S Eagle, Jeremy M Bennett, Bantayehu Sileshi, Yafen Liang, Brian J Gelfand, Adam J Kingeter, Kara K Siegrist, Frederick W Lombard, Tiffany M Richburg, Dane A Fornero, Andrew D Shaw, Antonio Hernandez, Frederic T Billings 4th, Marcos G Lopez, Mias Pretorius, Matthew S Shotwell, Robert Deegan, Susan S Eagle, Jeremy M Bennett, Bantayehu Sileshi, Yafen Liang, Brian J Gelfand, Adam J Kingeter, Kara K Siegrist, Frederick W Lombard, Tiffany M Richburg, Dane A Fornero, Andrew D Shaw, Antonio Hernandez, Frederic T Billings 4th

Abstract

Background: Anesthesiologists administer excess supplemental oxygen (hyper-oxygenation) to patients during surgery to avoid hypoxia. Hyper-oxygenation, however, may increase the generation of reactive oxygen species and cause oxidative damage. In cardiac surgery, increased oxidative damage has been associated with postoperative kidney and brain injury. We hypothesize that maintenance of normoxia during cardiac surgery (physiologic oxygenation) decreases kidney injury and oxidative damage compared to hyper-oxygenation.

Methods/design: The Risk of Oxygen during Cardiac Surgery (ROCS) trial will randomly assign 200 cardiac surgery patients to receive physiologic oxygenation, defined as the lowest fraction of inspired oxygen (FIO2) necessary to maintain an arterial hemoglobin saturation of 95 to 97%, or hyper-oxygenation (FIO2 = 1.0) during surgery. The primary clinical endpoint is serum creatinine change from baseline to postoperative day 2, and the primary mechanism endpoint is change in plasma concentrations of F2-isoprostanes and isofurans. Secondary endpoints include superoxide production, clinical delirium, myocardial injury, and length of stay. An endothelial function substudy will examine the effects of oxygen treatment and oxidative stress on endothelial function, measured using flow mediated dilation, peripheral arterial tonometry, and wire tension myography of epicardial fat arterioles.

Discussion: The ROCS trial will test the hypothesis that intraoperative physiologic oxygenation decreases oxidative damage and organ injury compared to hyper-oxygenation in patients undergoing cardiac surgery.

Trial registration: ClinicalTrials.gov, ID: NCT02361944 . Registered on the 30th of January 2015.

Keywords: Acute kidney injury; Cardiac surgery; Clinical trial; Delirium; Endothelial dysfunction; Hyper-oxygenation; Hyperoxia; Isofurans; Isoprostanes; Normoxia; Oxidative stress; Physiologic oxygenation; Reactive oxygen species.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) figure
Fig. 2
Fig. 2
Schematic of oxygen titration protocol
Fig. 3
Fig. 3
Expected oxygen exposures during surgery (based on preliminary subjects). The hyper-oxygenation curve is shifted 1% left and 1% up to improve discrimination compared to the physiologic oxygenation curve

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Source: PubMed

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