Effects of two ventilation strategies on systemic proinflammatory cytokines during minimally invasive esophagectomy in the prone position: a randomized controlled trial

Background During the thoracic phase of minimally invasive esophagectomy (MIE) in the prone position, different ventilation strategies can be used to facilitate surgical exposure while maintaining gas exchange. We compared the effects of two ventilation strategies on systemic proinflammatory cytokine responses during MIE. Methods Patients undergoing MIE for esophageal cancer in the prone position were randomized to one-lung ventilation (OLV) using a bronchial blocker with 5 cmH₂O positive end-expiratory pressure (PEEP) or two-lung ventilation (TLV) without a bronchial blocker and with zero PEEP during the thoracic phase both under capnothorax. The primary outcome was serum interleukin (IL)-6 concentration at the end of the thoracic phase, analyzed with adjustment for baseline IL-6 and randomization stratum. Prespecified secondary outcomes were serum tumor necrosis factor (TNF)-α concentration, plasma IL-8 concentration, and postoperative pulmonary complications (PPCs). Arterial oxygenation and operative-lung deflation were evaluated as exploratory outcomes. Results Fifty-seven randomized patients were included in the intention-to-treat analysis (OLV, n = 29; TLV, n = 28). IL-6 concentrations at the end of the thoracic phase were 34.0 [24.0–50.2] pg/mL with OLV and 25.5 [19.0–48.5] pg/mL with TLV (the adjusted geometric mean ratio, TLV versus OLV, 0.895; 95% CI, 0.634–1.263; P = 0.521). For TNF-α, the adjusted geometric mean ratio was 0.956 (95% CI, 0.836–1.093; P = 0.503). IL-8 quantifiability showed no evidence of a group-by-time interaction ( P = 0.954). PPCs occurred in 7/29 (24.1%) OLV patients and 5/28 (17.9%) TLV patients (risk difference, TLV minus OLV, − 6.3% points; 95% CI, − 26.8 to 15.1). In exploratory analyses, operative-lung deflation scores were higher with OLV at 10 and 20 min (Holm-adjusted P = 0.012 and P = 0.003, respectively). At 20 min, arterial oxygen tension was higher with TLV (adjusted mean difference, 43.4 mmHg; 95% CI, 11.2–75.5; Holm-adjusted P = 0.042). Conclusions In patients undergoing MIE in the prone position, no statistically significant difference in serum IL-6 concentration at the end of the thoracic phase was detected between the two ventilation strategies. However, the confidence interval was wide enough to include clinically relevant differences, and equivalence between the strategies cannot be concluded. Trial registration University Hospital Medical Information Network (UMIN) (ID UMIN000045319).