Effects of Permissive Hypercapnia During Lung Surgery on Inflammatory Biomarkers in Serum and Bronchoalveolar Lavage Fluid: A Randomized Controlled Trial

Introduction: Permissive hypercapnia has become an integral component of lung-protective ventilation strategies during one-lung ventilation (OLV), particularly in thoracic surgery. Its potential immunomodulatory effects have attracted increasing interest; however, clinical evidence remains limited and inconsistent. The Aim: The primary objective was to evaluate the effects of permissive hypercapnia on inflammatory biomarkers in bronchoalveolar lavage fluid and serum during one-lung ventilation. The secondary objective was to assess the influence of different ventilation modes on these inflammatory responses. Methods: Forty patients undergoing elective lung surgery requiring OLV were prospectively enrolled and allocated to either a normocapnic (n = 20) or hypercapnic group (n = 20). BAL concentrations of TNF-α, IL-1β, IL-6, and IL-8 were measured before and after intervention. Serum IL-6, C-reactive protein (CRP), and leukocyte counts were also assessed. Outcome Measures: Primary outcome: Change in bronchoalveolar lavage (BAL) levels of preselected biomarkers for inflammation (TNF-α, IL-1β, IL-6, and IL-8) and in serum (IL-6, CRP, and WBC) between the normocapnic and hypercapnic groups during one-lung ventilation. Secondary outcome: Whether the inflammatory response differed according to the ventilation mode (pressure-controlled versus volume-controlled ventilation). Results: Baseline and post-intervention BAL concentrations of TNF-α, IL-1β, IL-6, and IL-8 were generally comparable between the hypercapnic and normocapnic groups. No significant differences were observed in post-intervention BAL concentrations of TNF-α, IL-1β, or IL-6 among the ventilated subgroups. However, post hoc analysis demonstrated significantly lower IL-8 concentrations in the hypercapnic-PC subgroup compared with the normocapnic-PC subgroup (p = 0.034). Within the normocapnic cohort, BAL IL-8 concentrations were significantly higher in the PC subgroup than in the VC subgroup (p = 0.012). In serum, postoperative IL-6 concentrations were significantly higher in the hypercapnic than in the normocapnic group (p = 0.003). Conclusions: Permissive hypercapnia was not associated with a reduction in BAL concentration of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8. However, postoperative serum IL-6 concentrations were significantly higher in patients exposed to hypercapnia. As the duration of surgery, one-lung ventilation, and mechanical ventilation was longer in the hypercapnic group, the observed increase in serum IL-6 cannot be attributed solely to hypercapnia. Further large-scale randomized studies are required to clarify the immunological effects of permissive hypercapnia during thoracic surgery.