OBJECTIVE: To investigate the effects of continuous blood purification (CBP) combined with antibiotics on pulmonary surfactant protein D (SP-D), Clara cell protein-16 (CC-16), and prognosis in patients with severe acute pancreatitis (SAP) complicated by acute respiratory distress syndrome (ARDS). METHODS: A total of 128 patients with SAP and ARDS treated at Fudan University Shanghai Cancer Center from June 2021 to June 2023 were enrolled. Patients were divided into two groups: a control group (n=64) receiving routine treatment (gastrointestinal decompression, somatostatin administration, nutritional support, correction of water-electrolyte imbalance, and microcirculation improvement) and an observation group (n=64) treated with CBP combined with antibiotics. Clinical data, including the pancreatic edema resolution time, ventilator weaning time, and hospital stay, were compared between groups. Additional comparisons included intra-abdominal pressure (IAP), blood amylase (AMS), urinary amylase (UAMY), inflammatory markers [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β)], respiratory mechanics indices [airway peak pressure (Peak), airway plateau pressure (Plat), respiratory rate (F)], and blood oxygen levels [partial pressure of arterial oxygen (PaO RESULTS: The observation group demonstrated significantly better outcomes compared to the control group in terms of pancreatic edema resolution time, ventilator weaning time, hospital stay, and other indicators (all P<
0.05). The 28-day mortality rate in the observation group was significantly lower than in the control group (P<
0.05). Post-treatment levels of CC-16, SP-D, Peak, Plat, and other indicators improved significantly in both groups compared to baseline (all P<
0.05). The observation group exhibited significantly greater improvements in PaO CONCLUSION: CBP combined with antibiotics significantly improves clinical symptoms, reduces inflammatory markers, enhances prognosis, and lowers mortality rates in patients with SAP complicated by ARDS.