Reduced Indocyanine Green Clearance Is Associated with Enteral Feeding Intolerance in Septic Patients Without Overt Liver Injury

Background/Objectives: The gut–liver axis is central to sepsis, but assessing mesenteric perfusion remains challenging. Indocyanine green (ICG) clearance reflects hepatic blood flow. Since portal flow is derived from mesenteric circulation and supplies most of the liver, reduced ICG clearance may indicate mesenteric hypoperfusion, which can lead to enteral feeding intolerance (EFI). This study examines whether reduced ICG clearance in septic patients without overt liver injury is associated with EFI. Methods: This study is a secondary analysis of a prospective cohort study (March–May 2024, 20-bed ICU). Septic patients without sepsis-related liver injury or recent abdominal surgery were included. ICG plasma disappearance rate (ICG-PDR) was measured at admission; patients were grouped by ICG-PDR (≤18%/min vs. >18%/min). The primary outcome was EFI within 7 days. Multivariate logistic regression and correlation analyses were performed. Results: Among 77 patients (44 with ICG-PDR > 18%/min, 33 with ≤18%/min), the decreased ICG-PDR group had higher SOFA scores (8.4 ± 4.2 vs. 5.4 ± 3.5, p = 0.001) and higher EFI rates (66.7% vs. 43.1%, p = 0.041). Univariate analysis showed ICG-PDR ≤ 18%/min associated with EFI (OR = 2.632, p = 0.043), but this was attenuated after SOFA adjustment (OR = 2.247, p = 0.171). Reduced ICG-PDR correlated with central venous pressure (CVP) (r = 0.626, p < 0.001) but not with mean arterial pressure (r = −0.175, p = 0.129). Conclusions: In septic patients with preserved hepatocyte function, reduced ICG clearance is associated with EFI, but this relationship is largely explained by disease severity (SOFA). Reduced ICG clearance correlates with CVP; however, ICG-PDR cannot distinguish between portal venous and arterial inflow components. The exact mechanism remains speculative.