This retrospective cohort study was approved by our institutional review board (approval No. 2017-11-004). The need for written informed consent from participant was waived because of non-interventional retrospective design. Electronic medical records for all patients who underwent esophagectomy from January 2010 to December 2015 in our institute, were reviewed in this study (n=1,041). Patients who received corticosteroid to prevent ARDS during operation were assigned to the Steroid group and patients who did not receive corticosteroid during the same period were assigned to the Control group. Preventive use of corticosteroid waspure ARDSc leak problem defined as an intravenous corticosteroid administered during operation for the preventive purpose of ARDS. A single bolus dose of 100 mg of hydrocortisone was usually administered during the surgery by anesthesiologist H. J. A. and thoracic surgeon Y. S. C. These two physicians routinely administered corticosteroid in esophagectomy for the prevention of ARDS during the study period. Other anesthesiologists and thoracic surgeons did not use corticosteroid for the preventive purpose.
Information collected from patient’s medical record included administration of perioperative corticosteroids, age, gender, comorbidities, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status, duration and type of surgery, preoperative hemoglobin and albumin, intraoperative administration of inotrope or vasopressor, perioperative transfusion, net volume of fluid administrated during and within 24 hours after the surgery, and method of postoperative analgesia (thoracic epidural analgesia or intravenous patient-controlled analgesia). Comorbid conditions included hypertension, diabetes mellitus, renal dysfunction (serum creatinine > 1.2 mg/dl), cerebrovascular disease, cardiac disease, and pulmonary dysfunction. Cerebrovascular disease included a history of cerebral infarction, cerebral hemorrhage, and Parkinson’s disease/dementia/Alzheimer’s disease. Cardiac disease included coronary artery disease, arrhythmia and heart failure. Pulmonary dysfunction included lung diseases (i.e., chronic obstructive pulmonary disease, bronchiectasis, asthma, and interstitial lung disease), preoperative forced expiratory volume in one-second (FEV1) < 60% of predicted value, and current smoker. Current smoker was defined as patients who were smoking or had stopped smoking within 1 month before surgery.
Definition of postoperative complications
Composite complication was the primary outcome of this study. Three categories of complication until discharge were included: ARDS, graft dehiscence, and infection. ARDS was defined in according to the 2012 Berlin definition as acute (within one week of a known clinical insult) hypoxemic respiratory failure (a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen [PaO2/FiO2] less than 300 mm Hg) requiring positive end-expiratory pressure (PEEP) of 5 cm H2O or greater with bilateral opacities on chest imaging that are not fully explained by cardiac failure or fluid overload . Graft dehiscence included the development of anastomotic leakage, significant esophageal fistula, perforation of bowel or stomach, bronchopulmonary fistula, and graft failure. Infection included pneumonia, empyema, surgical site infection, and catheter-related infection.
Anesthesia and postoperative management
Anesthesia and postoperative management were performed according to our institutional protocol. Most patients received a balanced anesthesia, which was a combination of volatile anesthetic agents, non-depolarizing neuromuscular blocking agents, and a continuous intravenous infusion of remifentanil. Maintenance fluid was lactated Ringer’s solution, infused at a rate of 3 - 5 ml/kg/h. If volume deficiency was suspected, 5% human albumin (Green Cross Corp., Gyeonggi, Korea) or 6% hydroxyethyl starch (Fresenius Kabi, Seoul, Korea) was infused to the patients. In case of intraoperative bleeding, transfusion was performed for effective resuscitation (transfusion cut-off: hemoglobin < 8 g/dl). The protective ventilation protocol was applied to all patients. Mechanical ventilation during OLV was maintained with a tidal volume of 5-6 ml/kg predicted body weight at 5 cm H2O PEEP. A recruitment maneuver to the dependent lung was performed immediately after OLV and at the restart of two lung ventilation.
For postoperative management, patients stayed in the intensive care unit (ICU) for two days. The postoperative analgesic methods were determined by surgeon’s preference and existence of contraindications for regional analgesia. Maintenance fluid was administered at a rate of 2-3 ml/kg/h. ICU intensivists administered additional fluid based on the patient’s vital sign. Patients were encouraged to ambulate from postoperative day (POD) 1 and received a daily physiotherapy program, which included deep-breathing exercises, incentive spirometry, and chest physiotherapy by physiotherapists and attending nurses during the ICU and the ward stays.
Patient demographic and clinical data were summarized as frequency (percentage) for categorical variables and median (interquartile range) for continuous variables. Wilcoxon rank sum test was used to determine the significant differences in continuous variables between the Steroid and Control groups. Chi-square test or Fisher’s exact test was used to compare categorical variables between the two groups. Multivariable logistic regression analysis was used for the risk factors of postoperative complications. Univariable analysis was done for all variables and variables with P <0.2 were further analyzed by multivariable analysis. Propensity score matching (PSM) was performed between the two groups. Matched variables were gender, age, body mass index, ASA classification, hypertension, diabetes mellitus, cardiac disease, pulmonary dysfunction, renal dysfunction, cerebrovascular disease, liver disease, preoperative hemoglobin, preoperative albumin, duration of surgery, intraoperative inotrope or vasopressor, transfusion, intraoperative fluid balance, minimally invasive surgery, and thoracic epidural analgesia. Based on the standard deviation of the logit of the estimated propensity score, one to one matching was performed using the nearest-neighbor method with a caliper width of 0.2 in pairwise manner. The matched data included n=115 for each group. For all analyses, a 2-sided P <0.05 was considered significant. Data were analyzed using SAS 9.4 software (SAS Institute, Inc, NC, USA).