Clinical significance of perioperative carbon dioxide levels during healing of intestinal anastomoses

Background Up to 10% of patients undergoing colorectal surgery develop anastomotic leakage (AL). In a preclinical mouse model, we could recently show that enhanced pro-inflammatory (M1) macrophage infiltration impairs healing of intestinal anastomoses. Elevated carbon dioxide levels (CO₂) mitigate pro-inflammatory signaling and attenuate macrophage migration. We thus investigated the clinical significance of pro-inflammatory signaling during AL and whether perioperative carbon dioxide levels affect healing of intestinal anastomoses.

Methods A prospective database recording clinical data and outcome of 360 patients undergoing colorectal surgery due to colorectal cancer was established and retrospectively analyzed. Expression of pro-inflammatory signaling markers within patient-derived mucosal biopsies and blood samples were detected by targeted transcriptomics and enzyme-linked Immunosorbent Assay (ELISA). Infiltration of pro-inflammatory (M1) macrophages was analyzed by immunohistochemistry. Levels of pro-inflammatory markers and perioperative blood gas parameters were correlated with surgical outcome.

Results Increased mucosal protein levels of pro-inflammatory makers, such as the chemoattractant CCL2, were associated with AL development. In all patients, intraoperative CO₂ levels increased over time and correlated with the length of operation. Patients with subsequent AL showed significantly enhanced CO₂kinetics during surgery and lower postoperative CO₂levels. Preliminary subgroup analysis suggested, that high levels of CO₂ and low pH were associated with lower mucosal CCL2 levels and macrophage infiltration. Importantly, perioperative oxygen levels did not correlate with any of the afore-mentioned findings.

Conclusion Carbon dioxide is highly immuno-modulatory and (short-term) perioperative CO₂ elevations might be beneficial for healing of intestinal anastomoses – especially in patients with inflammation-driven co-morbidities.

Publication History

Article published online:
19 August 2022