The relationship between hypercapnia, vasopressin and gastrointestinal dysfunction in critically ill patients

• Applicant: Dr. Carsten Marcus
• Subject Area: Anaesthesiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 560573584

Abdominal sepsis and anastomotic insufficiency are both medically and socially significant problems for which there are currently insufficient effective supportive or, in the case of anastomotic insufficiency, preventive measures. Abdominal sepsis disrupts the previously intact gastrointestinal barrier due to splanchnic hypoperfusion, which leads to the transmigration of local immune cells, the release of cytokines and the passage of endotoxins, ultimately aggravating the disease and leading to multi organ dysfunction syndrome. Enhancing the impaired intestinal microcirculation could potentially improve patient outcomes. Moreover, as anastomotic leakage is reduced in patients with adequate oxygen delivery, an intervention that improves the microcirculatory perfusion and oxygenation of the gastrointestinal tract may have a protective effect on anastomotic integrity. Experimental animal models suggest that hypercapnia and vasopressin offer promising avenues for developing preventive and supportive strategies to address impaired intestinal microcirculation. The hypothesis is that permissive hypercapnia and vasopressin use have a protective effect on the development of abdominal sepsis, anastomotic insufficiency, and other clinically relevant outcomes in intensive care patients. To test this hypothesis in a translational approach, data from the "Perioperative Outcomes Lab" at the Center for Anesthesia Research Excellence (CARE) at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School in Boston will be analyzed in two parts. Part I of the project will consist of a retrospective analysis of all ventilated intensive care patients from 2008 to 2024, aiming to assess the association between balanced hypercapnia and abdominal sepsis. In Part II, an analysis of all ICU patients receiving vasopressin therapy (as either single or adjunctive treatment) will be conducted to evaluate relevant abdominal-centered endpoints. The findings and hypotheses shall then be validated in a prospective study of intensive care patients at the University Hospital Düsseldorf. Based on the data collected, we hope to improve both the care of patients undergoing abdominal surgery and that of intensive care patients in general with regard to abdominal sepsis and anastomotic insufficiency.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Privatdozent Dr. Maximilian Schaefer, Ph.D.