Non-steroidal anti-inflammatory drugs (NSAIDs) reduced pleural adhesion in animal studies, but its effect on human had not been studied. A retrospective study was carried out for patients with solitary pulmonary nodules without a pre-operative tissue diagnosis positive for malignancy. The impact of the use of NSAIDs after stage one wedge resection was assessed by the degree of pleural adhesions encountered during second-stage, redo completion lobectomy. From April 2016 to March 2022, 50 consecutive patients meeting the inclusion criteria were included, and 44 patients were selected for analysis after exclusion (Treatment group with NSAID: N = 27; Control group without NSAID: N = 17). The preoperative characteristics and the final tumor pathologies were similar between the groups. The use of NSAID was significantly associated with lower risk of severe pleural adhesions and complete pleural symphysis (risk difference = -29%, p = 0.03). After controlling the effect of tumor size and chest drain duration, only the use of NSAID was statistically associated with the lowered risk of severe pleural adhesions and complete pleural symphysis. No statistically significant effects of NSAID on operative time (p = 0.86), blood loss (p = 0.72), and post-operative length of stay (p = 0.72) were demonstrated. In human, NSAIDs attenuated the formation of pleural adhesions after pleural disruptions. Physicians and surgeons should avoid the use of NSAIDs when pleural adhesion formation is the intended treatment outcome.
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