Ulinastatin Reduces Postoperative Pulmonary Complications in Cardiac Surgery: A Real-World Retrospective Study Integrating Network Pharmacology and Prospective Validation

Step Ⅰ: Retrospective Cohort Study of Intraoperative Ulinastatin and PPCs Risk This segment of the study is designed as a retrospective, multicenter observational investigation, encompassing adult patients who underwent elective cardiac surgery at three medical centers-specifically Tongji Guanggu Hospital, Tongji Zhongfa Hospital, and Tongji Hankou Hospital, all situated in Wuhan, China-between January 2014 and December 2022. Due to the retrospective design of the study, the sample size was pre-determined[14].

Participants Adult patients undergoing elective cardiac surgery, including open-heart valve repair, valve replacement with cardiopulmonary bypass, and off-pump coronary artery bypass grafting, were consecutively screened for eligibility. Exclusion criteria were as follows: (1) age < 18 years; (2) pregnant women; (3) history of prior cardiac surgery before the current hospitalization; (4) presence of acute respiratory diseases prior to surgery, such as respiratory tract infections, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and pneumonia; (5) administration of ulinastatin therapy prior to cardiac surgery during the current hospitalization; (6) The drug ulinastatin was utilized during the surgery, with a total intraoperative dose of less than 50,000 U; (7) history of malignancy or bone marrow transplantation.

Variables The primary exposure was intraoperative ulinastatin administration, defined by: (1) dosage: total intraoperative dose (≥50,000 U); (2) timing: first administration at anesthesia induction vs during cardiopulmonary bypass; (3) route: intravenous drip.

Demographic characteristics included age, gender, and smoking status, all ascertained at admission. Clinical comorbidities were documented based on clinical diagnoses in medical records, including hypertension, diabetes, chronic pulmonary diseases (chronic obstructive pulmonary disease, asthma, chronic bronchitis, bronchiectasis), and chronic renal failure. Preoperative laboratory indicators for patients consisted of venous blood test results obtained within 24 hours of admission, including white blood cell count and hemoglobin concentration.

Based on prior literature and biological plausibility, measured confounding factors included variables known or hypothesized to affect the risk of PPCs. These covariates comprised age, gender, body mass index (BMI), preoperative hemoglobin level, preoperative white blood cell count, preoperative blood pressure, and comorbidities. All covariates were pre-specified and incorporated into a multivariate adjustment model to address baseline imbalances and mitigate confounding bias in the assessment of clinical outcomes.