A flowchart of our study is included in Fig. 1. This retrospective, single-center study enrolled 46 patients with TOF aged between 1-month and 12-month, who underwent CTS from July 1, 2017, to September 30, 2019. The study was in strict accordance with the Declaration of Helsinki and International Ethical Guidelines for Health-related Research Involving Humans. Demographic and clinical data were retrieved from the patients’ medical records.
Inclusion criteria for patients were: (1) age from 1-month to 12-month; (2) TOF was confirmed by preoperative echocardiography and intraoperative findings. TOF consists of a tetrad, or a group of 4 defects, which are ventricular septal defect, pulmonary stenosis, overriding aorta, and right ventricular hypertrophy (12); (3) the first time to receive CTS treatment and undergo complete surgical repair. Complete surgical repair includes closing the ventricular septal defect, resecting muscle bundles within the right ventricular outflow tract with or without patch augmentation (13); (4) complete clinical information such as history and laboratory examination.
The exclusion criteria were: (1) preexisting renal dysfunction (RD) or requirement of renal replacement therapy before surgery. RD was defined as kidney injury denoted by pathological changes, or other indicators such as abnormal blood, urine, or imaging findings or an estimated glomerular filtration rate (eGFR) of less than 60 ml/min*1.73 m2 for more than 3 months (14); (2) a history of nephrotoxic drug use within 7 days before surgery; (3)a lack of postoperative renal data; (4) delayed sternal closure or reoperation was required due to bleeding and other reasons.
Finally, 36 patients were included in the study, of which 17 had AKI. Diagnosis and staging of AKI were performed according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 clinical practice guidelines (15). Patients scheduled for CTS should have preoperative tests including the complete history, transthoracic echocardiography, and blood test. Venous blood used for the preoperative blood test was collected via scalp vein needle from scalp vein or femoral vein. The radial artery catheter was needed to obtain a sample of arterial blood for gas analysis and invasive monitoring. A central venous catheter (CVC) was placed through the femoral venous or jugular vein and central venous pressure (CVP) was measured hourly.
All postoperative children were admitted to the pediatric intensive care unit (PICU) and had real-time monitoring, which included measurement of vital signs (temperature, blood pressure, pulse, and respiration rate), quantification of all fluid intake and output. Blood used for routine postoperative test were collected from indwelling arterial lines after CTS, and simultaneous blood samples were obtained from a central venous catheter and an arterial catheter at 48 hours after surgery. Echocardiographic reexamination was performed on the 7th day after the operation. Postoperative management, systematic monitor and programmatic therapy were performed based on Handbook of Pediatric Cardiac Surgical Intensive Care (16).
Baseline data including demographics, clinical manifestation, and laboratory data were extracted and analyzed. Preoperative data included weight, height, age, sex, serum creatinine (SCr), eGFR, arterial oxygen pressure (PaO2), Hct, hemoglobin (Hb), McGoon ratio, Nakata index, pulmonary arterial pressure (PAP), left ventricular ejection fraction (LVEF) and fractional shortening (LVFS); surgical characteristics were CTS time, cardiopulmonary bypass (CPB) time and American Society of Anesthesiologists grade (ASA). Postoperative data including temperature, heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), lactic acid, arterial oxygen saturation (SaO2), PaO2 and urine output were recorded up to the first and second 24 hours after admission to PICU. Simultaneous monitoring of venous blood gas at 48 hours after CTS. The highest vasoactive inotrope score (VIS) within postoperative 48 hours was used to reflect the application of vasoactive drugs after CTS (17). Lengths of PICU and hospital stay were also recorded. To better show the oxygen metabolism in tissues, we calculated central venous-to-arterial carbon dioxide difference (Pv-aCO2), central arterial-to-venous oxygen saturation difference (Sa-vO2), central arterial-to-venous oxygen pressure difference (Pa-vO2), arterial-to-venous oxygen content difference (Ca-vO2), the rate of Pv-aCO2/Ca-vO2, and oxygen extraction ratio (O2 ER) according to the following formulas (18–20):
· CaO2 = (1.34 × SaO2 × Hb) + (0.003 × PaO2)
· CcvO2 = (1.34 × ScvO2 × Hb) + (0.003 × PcvO2)
· Ca − vO2 = CaO2 − CcvO2
· Pv-aCO2 = PcvCO2 − PaCO2
· Pv-aCO2 /Ca − vO2 ratio = Pv-aCO2 /Ca − vO2
· Pa − vO2 = PaO2 − PcvO2
· Sa − vO2 = SaO2 − ScvO2
· O2 ER = Ca-vO2 /CaO2
Shapiro-Wilk test was used to check the normality of the data; continuous variables with normal distribution were expressed in terms of mean and standard deviation. Group comparisons were analyzed by independent sample t-tests or ANOVA test. The continuous variables with the non-normal distribution were expressed as median (P25 and P75) and were compared using non-parametric factorial Kruskal-Wallis sum-rank test. Frequencies and proportions were estimated for categorical variables and were compared using the chi-squared test or Fisher's test. Odds ratios (ORs) with 95% confidence intervals (CIs) for the development of AKI in each group were calculated using a logistic regression model. Persistent AKI was defined as a continuance of AKI according to the KDIGO criteria beyond 48 h according to the consensus report of the ADQI 16 workgroup (21). Transient AKI was defined as AKI of less than 48 h duration. To investigate the relationship between preoperative PaO2 and postoperative AKI, Univariate analysis was performed on the general preoperative data, hemodynamic indexes and oxygen metabolism indexes of the 4 groups at 24 and 48 hours after operation and the incidence, severity, and duration of AKI in the 4 groups were compared. Subgroup analysis was performed to explore the relationship between oxygen metabolism index (Sa-vO2, Pa-vO2, Pv-aCO2, Ca-vO2, Pv-aCO2/Ca-vO2, O2ER) and persistent AKI. Single-factor regression analysis was performed to explore the risk factors with certain significance in univariate analysis (P < 0.05) of postoperative AKI and persistent AKI. All statistical analyses were performed with SPSS version 23 (IBM Corp. Released (2015) IBM SPSS Statistics for Windows. IBM Corp., Armonk, NY). The difference was considered significant when the two-tailed P-value was less than 0.05.