Study design and population
This is a retrospective cohort analysis of patients with tetralogy of Fallot between March 2012 and December 2018 at Teda Cardiovascular Hospital. Consecutive patients were included if they underwent complete repair of tetralogy of Fallot with CPB at 6–72 months. We excluded patients who had received extracorporeal membrane oxygenation, intra-aortic balloon pump, ventricular assist device, mechanical ventilatory support, or renal replacement therapy before this current surgery. Additional exclusion criteria were incomplete PpO2 records and missing outcome data for identification of postoperative myocardial dysfunction.
The Institutional Review Board of Teda Cardiovascular Hospital approved the study. This study followed the Declaration of Helsinki and the ethical standards of the responsible committee on human experimentation. Informed consent was waived for this retrospective study. This study was registered with Clinical Trials. gov number NCT03568357.
Patients were totally heparinized, and an activated clotting time of more than 480 secs was confirmed before the initiation and duration of CPB. Pump flow was settled at approximately 2.8 L/min/m2 at the outset of CPB and subsequently adjusted according to patient’s core temperature (usually a 20% decrease for core temperatures between 30 and 34 °C and an additional 10% decrease for core temperatures < 30 °C). The hemodilution level was decreased to 25–30% during hypothermic CPB according to the routine protocol of our institution .
We hypnotized that exposure to hyperoxic CPB would lead to reoxygenation injury in cyanotic patients, so we used the highest PpO2 during aortic occlusion for analysis. Patients were divided into two groups: lower PpO2 group (< 250 mmHg) and higher PpO2 group (> 250 mmHg). PpO2 was available from online blood gas analyzers and confirmed by an independent manual check of extracorporeal circulation records by blinded trained staff.
Primary outcome was myocardial dysfunction, which was confirmed if any of the following is true:
need for higher doses of vasoactive drug to maintain blood pressure in normal range (vasoactive-inotropic score [VIS] of greater than 15 points );
decrease in blood pressure < 5th percentile for age or systolic blood pressure < 2 SD below normal for age ;
two of the following: unexplained metabolic acidosis, oliguria, prolonged capillary refill > 5 s, core to peripheral temperature gap > 3 °C ; OR
Postoperative use of renal replacement therapy, extracorporeal membrane oxygenation, intra-aortic balloon pump, or ventricular assist device .
Myocardial dysfunctions were determined throughout postoperative 7 days, hospital discharge, or death, whichever occurred first. Secondary outcome included inotropic score, ICU stay, mechanical ventilation support time, postoperative stay, and hospital cost, as well as the rate of postoperative acute lung injury  and systemic inflammatory response syndrome .
Baseline clinical characteristics included age at surgery, sex, body mass index (BMI), hematocrit, percutaneous saturation (SpO2), left ventricular end-diastolic volume (LVEDV), and NYHA classification. Disease-specific pathologies included McGoon ratio, pulmonary annular Z-score, and aortopulmonary collateral arteries (APCAS). Procedural characteristics included cardioplegia types, transannular patch, tricuspid valve detachment, CPB time, and intraoperative blood transfusion, as well as immediately postoperative central venous pressure (post-CVP) and transpulmonary gradient (post-TPG).
Continuous data were presented as mean (SD) or median (IQRs) and compared using a t-test or Kruskal–Wallis testing depending on distributed characteristics, and categorical data were reported as percentages (%) and compared using χ2 or Fisher’s exact testing. The odd ratio (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Baseline adjustments included age at surgery, sex, BMI, hematocrit, SpO2, LVEDV, and NYHA classification. Clinical adjustments included McGoon ratio, pulmonary annular Z-score, and APCAS. Procedural adjustments included cardioplegia types, transannular patch, tricuspid valve detachment, CPB time, intraoperative blood transfusion, post-CVP, and post-TPG.
We conducted stratified risk analyses by disease-specific characteristics (pulmonary annular Z-score, McGoon ratio, and APCAS). Heterogeneity of these stratified estimates was evaluated using the likelihood ratio test of the interaction terms between PpO2 and each covariate.
All covariates showing relative strong associations (P value < 0.1) with myocardial dysfunction in univariate analysis were modelled together to investigate independent risk factors of myocardial dysfunction using multivariate logistic regression. All statistical analysis were performed using Stata version 14 (Stata Corp, College Station, TX, USA) and R software (version 3.2.0). P values of less than 0.05 were considered statistically significant.
All methods were carried out in accordance with relevant guidelines and regulations.