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

Summary

In a prospective ICU cohort of 93 septic patients, nearly half exhibited augmented hepatic clearance by ICG testing. ICG plasma disappearance rate strongly predicted subtherapeutic troughs of hepatically or partially cleared agents (e.g., voriconazole, linezolid), with excellent discrimination (AUC 0.853) and actionable cut-offs (~20.65%/min). Findings support dynamic liver function monitoring to personalize antibiotic dosing in sepsis.

Key Findings

• Augmented hepatic clearance phenotype was present in 49.5% of septic ICU patients (ICG-R15 < 6%).
• ICG-PDR and ICG-R15 strongly correlated with trough levels of hepatically/partially cleared antibiotics (voriconazole, linezolid), but not renally cleared agents.
• ICG-PDR independently predicted subtherapeutic concentrations with excellent performance (AUC 0.853; optimal cut-off ~20.65%/min).

Clinical Implications

In septic patients, consider ICG-PDR testing to identify augmented hepatic clearance and proactively adjust dosing of hepatically cleared drugs (e.g., linezolid, voriconazole), alongside therapeutic drug monitoring. Integrate dynamic liver function into PK models and dosing protocols.

Limitations

• Single-center study with modest sample size; external validity requires confirmation.
• No interventional arm to test ICG-guided dosing on clinical outcomes; correlations limited to selected antibiotics.

Future Directions

Conduct multicenter, interventional trials testing ICG-guided dosing strategies and integrate dynamic hepatic function into population PK models for precision antibiotic therapy.