The Prognostic Value of a Liver Function Test Using Indocyanine Green (ICG) Clearance in Patients with Multiple Organ Dysfunction Syndrome (MODS)

Background: Multiple organ dysfunction syndrome (MODS) is common in intensive care units (ICUs) and is associated with high mortality. Although there have been multiple investigations into a multitude of organ dysfunctions, little is known about the role of liver dysfunction. In addition, clinical and laboratory findings of liver dysfunction may occur with a significant delay. Therefore, the aim of this study was to investigate whether a liver function test, based on indocyanine green (ICG)-clearance, contains prognostic information for patients in the early phase of MODS. Methods: The data of this analysis were based on the MODIFY study, which included 70 critically ill patients of a tertiary medical ICU in the early phase of MODS (<= 24 h after diagnosis by an APACHE II score >= 20 and a sinus rhythm >= 90 beats per minute, with the following subgroups: cardiogenic (cMODS) and septic MODS (sMODS)) over a period of 18 months. ICG clearance was characterized by plasma disappearance rate = PDR (%/min); it was measured non-invasively by using the LiMON system (PULSION Medical Systems, Feldkirchen, Germany). The PDR was determined on the day of study inclusion (baseline) and after 96 h. The primary endpoint of this analysis was 28-day mortality. Results: ICG clearance was measured in 44 patients of the MODIFY trial cohort, of which 9 patients had cMODS (20%) and 35 patients had sMODS (80%). Mean age: 59.7 +/- 16.5 years; 31 patients were men; mean APACHE II score: 33.6 +/- 6.3; 28-day mortality was 47.7%. Liver function was reduced in the total cohort as measured by a PDR of 13.4 +/- 6.3%/min At baseline, there were no relevant differences between survivors and non-survivors regarding ICG clearance (PDR: 14.6 +/- 6.1%/min vs. 12.1 +/- 6.5%/min; p = 0.21). However, survivors showed better liver function than non-survivors after 96 h (PDR: 21.9 +/- 6.3%/min vs. 9.2 +/- 6.3%/min, p < 0.05). Consistent with these findings, survivors but not non-survivors show a significant improvement in the PDR (7.3 +/- 6.3%/min vs. -2.9 +/- 2.6%/min; p < 0.01) within 96 h. In accordance, receiver-operating characteristic curves (ROCs) at 96 h but not at baseline show a link between the PDR and 28-day mortality (PDR at 96 h: AUC: 0.87, 95% CI: 0.76-0.98; p < 0.01. Conclusions: In our study, we found that ICG clearance at baseline did not provide prognostic information in patients in the early stages of MODS despite being reduced in the total cohort. However, improvement of ICG clearance 96 h after ICU admission is associated with reduced 28-day mortality.