STUDY DESIGN Single-center, prospective, observational cohort study conducted at Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea. There is no group allocation, no randomization, and no blinding of treatment. All participants receive the same standard anesthetic, surgical, and postoperative care regardless of study participation.
PARTICIPANTS AND SCREENING Adults aged 19 years or older scheduled for elective off-pump coronary artery bypass (OPCAB) are approached on the day before surgery. Written informed consent is obtained by an investigator in a private counseling room, with at least 3 hours allowed for consideration before consent is signed. After arrival in the operating room, willingness to participate is reconfirmed and, before anesthetic induction, ultrasonography is performed with the patient temporarily placed in the lateral decubitus position to measure the depth from the skin to the erector spinae muscle and to the renal cortex at the level of the left renal hilum. Only participants in whom the skin-to-erector spinae muscle depth is less than 2.0 cm, so that a stable NIRS measurement is considered feasible, are finally enrolled. Participants who do not meet this criterion are classified as screen failures, no sensor is applied, and no further study data are collected.
MEASUREMENTS NIRS sensors are applied over the left erector spinae muscle at the renal hilum level and over the ipsilateral renal cortex. Regional oxygen saturation is recorded continuously with an INVOS oximeter (Medtronic, Minneapolis, MN, USA), which is already installed in all operating rooms of the institution; no additional monitoring equipment is introduced for the study. Baseline values are recorded before anesthetic induction while the participant breathes room air. Recording continues until the end of surgery. The start and the end of mechanical displacement of the heart (from the deep pericardial stitch to heart return) are tagged as events, so that the period before cardiac displacement and the cardiac displacement period can be analyzed separately. The area under the threshold (AUT), defined as the integral of the magnitude and duration of desaturation below a given threshold, and the duration under the threshold are computed with the INVOS Analytics Tool Software.
OBSERVATIONAL INTEGRITY ESrSO2 and renal rSO2 are collected for research purposes only. The corresponding channel displays are physically masked during surgery, no alarms are set for these channels, and the values are not available to the clinical team and are not used for intraoperative or postoperative management. Data are retrieved after surgery from the device. Cerebral rSO2 remains part of standard institutional monitoring for OPCAB and is used and managed as usual.
DATA COLLECTED Preoperative: demographics, comorbidities, medications, New York Heart Association class, Canadian Cardiovascular Society class, EuroSCORE II, Society of Thoracic Surgeons risk score, hemodynamic variables, complete blood count and chemistry including serum creatinine, estimated glomerular filtration rate and serum albumin, echocardiography, and coronary angiography. All of these are part of the routine preoperative work-up for OPCAB and none are performed additionally for the study.
Intraoperative: ESrSO2, renal rSO2, cerebral rSO2, bispectral index, anesthesia and operation time, timing of cardiac displacement, ischemic time for anastomosis, arterial, pulmonary arterial and central venous pressures, heart rate, cardiac index, mixed venous oxygen saturation, rhythm, vasopressor and inotrope use, fluids, transfusion, cell saver volume, and urine output.
Postoperative: daily maximum serum creatinine for 7 days, fluid balance and transfusion for 48 hours, bleeding, urine output, use of continuous renal replacement therapy, hemodynamic and respiratory variables, mechanical ventilation and reintubation, intensive care unit and hospital length of stay, reoperation, intensive care unit readmission, complications according to the Society of Thoracic Surgeons definitions, days alive and out of hospital at 30 days, 30-day readmission, in-hospital and 30-day mortality, AKI by KDIGO criteria, and major adverse kidney events at 30 days.
DEFINITION OF AKI AKI is defined according to the KDIGO criteria as an increase in serum creatinine of 0.3 mg/dL or more within 48 hours, an increase to 1.5 times or more of the baseline value within 7 days, or urine output of less than 0.5 mL/kg/h for 6 hours.
SAMPLE SIZE The incidence of AKI after OPCAB at the participating institution is approximately 25%, and the reported predictive performance of cerebral oximetry for AKI corresponds to an area under the receiver operating characteristic curve (AUROC) of approximately 0.68. Assuming a target AUROC of 0.80 for ESrSO2 and a 95% confidence interval of 0.70 to 0.90, the Hanley and McNeil method yields a minimum required sample size of 124 participants. Allowing for approximately 10% attrition, the target enrollment is 138 participants.
STATISTICAL ANALYSIS Continuous variables are compared with the independent t test or the Mann-Whitney U test according to normality and are presented as mean with standard deviation or as median with interquartile range. Categorical variables are compared with the chi-square test or the Fisher exact test and are presented as number with percentage. A two-sided p value below 0.05 is considered significant, with Bonferroni correction for multiple comparisons. Analyses are performed with R software.
For the primary objective, receiver operating characteristic curves are constructed for each ESrSO2 variable and AUROC values are compared to identify the variable with the highest predictive performance.
For the secondary objectives, this study is explicitly framed as a pilot and exploratory study and does not aim to derive or validate a definitive prediction model. Given the expected number of AKI events and the resulting constraint on events per variable, adjustment variables are pre-specified on the basis of clinical importance and previous OPCAB-AKI literature, namely age, preoperative renal function (baseline estimated glomerular filtration rate or chronic kidney disease), diabetes mellitus, and hypoalbuminemia. These four variables are not re-tested for significance in this cohort but are fixed as an established background risk model and combined into a single linear predictor. The only term formally tested is the ESrSO2 variable, which is added to the pre-specified baseline model as an incremental term. Firth penalized logistic regression with bootstrap internal validation is used to reduce small-sample bias. Improvement in discrimination is assessed with the DeLong test for the difference in AUROC, and clinical usefulness is explored with decision curve analysis (net benefit). Reclassification indices are not used. The predictive performance of ESrSO2, cerebral rSO2, and renal rSO2 is compared in the same way, and the same approach is applied to severe AKI (KDIGO stage 2 to 3) and persistent AKI (lasting 48 hours or longer).
WITHDRAWAL AND DISCONTINUATION Participants are discontinued if conversion to on-pump coronary artery bypass occurs, if a ventricular assist device is inserted, if cardiopulmonary resuscitation or another emergency situation occurs, if continuous ESrSO2 measurement becomes technically impossible, or if consent is withdrawn.
RISK The only study-related procedure is application of non-invasive skin sensors and a brief ultrasound examination. The anticipated risk is limited to mild transient skin irritation at the sensor site, and the study is therefore considered to involve minimal risk.
