Background Although lactate clearance is affected by hepatic function, it is unclear whether the hepatic dysfunction is associated with lactate clearance as a prognostic marker of clinical outcomes in septic shock. We aimed to evaluate association between the lactate clearance and mortality divided by hepatic dysfunction based on total bilirubin level using two cohort of septic shock patients. Methods Lactate clearance, delta base excess and delta anion gap in 24 hours from septic shock onset

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... re analyzed using two cohorts of septic shock patients (derivation cohort, n = 230; validation cohort, n = 396) categorized into two groups by total bilirubin levels (TBIL) < 2 mg/dL and ≥ 2 mg/dL on day 1. The primary analysis was association between lactate clearance and 28-day mortality by total bilirubin category. Results In derivation cohort, lactate clearance was lower in non-survivors compared to survivors in the patients with TBIL ≥ 2 mg/dL (P = 0.0035), while there was a no significant difference in those with TBIL < 2 mg/dL. There were no significant differences in delta base excess and delta anion gap between non-survivors and survivors both in the patients with TBIL ≥ 2 mg/dL and < 2 mg/dL. In the multivariate logistic regression analysis, increased lactate clearance was significantly associated with decreased 28-day mortality in TBIL ≥ 2 mg/d group (10% lactate clearance, adjusted odds ratio 0.88, 95%CI; 0.80–0.97, P = 0.0075), whereas there was no significant association in TBIL < 2 mg/d group. We next tested for lactate clearance in TBIL ≥ 2 mg/dL using the validation cohort; lactate clearance was lower in non-survivors compared to survivors in the TBIL ≥ 2 mg/dL group (P = 0.0006), while no significant difference was observed in TBIL < 2 mg/dL. Increased lactate clearance was significantly associated with decreased 28-day mortality in the TBIL ≥ 2 mg/dL group (10% lactate clearance, adjusted odds ratio 0.89, 95%CI; 0.83–0.96, P = 0.0038); while no significant difference was observed in TBIL < 2 mg/dL in the validation cohort. Conclusions Patients with increased lactate clearance had decreased 28-day mortality when patients had hepatic dysfunction (TBIL ≥ 2 mg/dL) in septic shock.