# ICG clearance as an indicator of augmented hepatic clearance and subtherapeutic drug concentrations in septic patients

## TL;DR

This study shows that ICG clearance can predict subtherapeutic antibiotic levels in septic patients with augmented hepatic clearance.

## Contribution

The study introduces ICG-PDR as a novel predictor of inadequate antibiotic exposure in septic patients.

## Key findings

- ICG-PDR is a strong predictor of subtherapeutic antibiotic concentrations in septic patients.
- AHC is common in sepsis and is linked to higher mortality in patients with impaired hepatic clearance.
- ICG clearance parameters correlate strongly with drug concentrations of hepatically cleared antibiotics.

## Abstract

To assess indocyanine green (ICG) clearance as a quantitative indicator of augmented hepatic clearance (AHC) in septic patients and to evaluate its impact on subtherapeutic antibiotic concentrations and 28-day mortality.

This prospective observational study enrolled 93 septic patients admitted to the intensive care unit (ICU), from whom 113 ICG clearance tests were obtained. Patients were stratified into three groups based on ICG retention rate at 15 min (ICG-R15): augmented (AHC, ICG-R15 < 6%), normal (NHC, 6% ≤ ICG-R15 ≤ 12%), and impaired hepatic clearance (IHC, ICG-R15 > 12%). Trough concentrations were measured for the following antibiotics: imipenem/cilastatin, piperacillin/tazobactam, voriconazole, linezolid, vancomycin, cefoperazone/sulbactam, and teicoplanin. Correlations between ICG clearance parameters (ICG-R15 and ICG plasma disappearance rate [PDR] ) and antibiotic concentrations were analyzed. Multivariate logistic regression and ROC analysis were performed to identify independent predictors of subtherapeutic concentrations.

Nearly half of the cohort (49.5%, 46/93) presented with AHC. The 28-day mortality rate was highest in the IHC group (48.4%), with no significant difference between the AHC (10.9%) and NHC (12.5%) groups. Trough concentrations of hepatically or partially cleared antibiotics (voriconazole and linezolid) showed strong correlations with ICG-R15 (r = 0.679 and r = 0.626, respectively) and ICG-PDR (r = -0.673 and r = -0.629, respectively; all p < 0.01). No significant correlations were found for renally cleared antibiotics (imipenem, piperacillin). Multivariate analysis identified ICG-PDR as the only independent predictor of subtherapeutic concentrations for hepatically or partially eliminated antibiotics (OR = 0.885, 95% CI: 0.807–0.970, p = 0.009). In ROC analysis, ICG-PDR demonstrated excellent predictive performance for the entire antibiotic cohort (AUC = 0.853, p < 0.001), with a sensitivity of 89.5% and specificity of 72.6% at the optimal cut-off of 20.65%/min. When specifically applied to hepatically cleared antibiotics, it remained a strong predictor (AUC = 0.791, p = 0.003), with a cut-off of 21.55%/min yielding a sensitivity of 81.8% and specificity of 71.1%.

AHC is a prevalent phenotype in sepsis and identifies a patient subgroup at high risk for subtherapeutic concentrations of hepatically or partially cleared antibiotics. ICG-derived parameters, particularly ICG-PDR, are robust predictors of inadequate drug exposure, supporting the use of dynamic liver function monitoring to optimize antibiotic dosing in septic patients.

The online version contains supplementary material available at 10.1186/s12871-025-03534-9.