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Lactate Cut-offs for 28-Day Mortality in Septic Shock

Wanka, S.-T.; Zilberszac, R.; Hermann, A.; Lenz, M.; Hengstenberg, C.; Schellongowski, P.; Staudinger, T.

2026-02-10 intensive care and critical care medicine
10.64898/2026.02.08.26345840 medRxiv
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BackgroundEarly lactate is widely used to risk-stratify septic shock, yet clinically actionable cut-offs for 28-day mortality remain uncertain. MethodsIn a single-centre study conducted across two intensive care units, we analysed 84 adults with septic shock identified within 24 hours of intensive care unit admission. The primary endpoint was 28-day mortality. Four lactate metrics obtained during the first 24 hours were evaluated: first (admission) lactate, last lactate, peak lactate, and lactate clearance from first to last. Associations were tested using logistic regression with and without adjustment for the Simplified Acute Physiology Score 3; discrimination was assessed by area under the receiver-operating characteristic curve (AUROC), and optimal cut-offs were defined by the Youden index. ResultsThirty-nine of 84 patients (46.4%) died by day 28. Higher absolute lactate values were independently associated with death (adjusted odds ratio (OR) per 1 mmol/L increase: First 1.47, p<0.001; Last 1.41, p=0.002; Peak 1.39, p<0.001), whereas Lactate clearance was not (OR 0.65, p=0.202). Discrimination was moderate to good for peak (AUROC 0.817), first (0.791), and last (0.757) lactate, and poor for clearance (0.577). Youden-derived thresholds provided pragmatic trade-offs: First 3.55 mmol/L (sensitivity 0.821, specificity 0.689), Last 3.15 mmol/L (0.567, 0.864), and Peak 3.55 mmol/L (0.973, 0.556). Kaplan-Meier curves using these cut-offs showed early and sustained separation. ConclusionsIn adults with septic shock, simple early lactate thresholds around 3.3- 3.6 mmol/L (first/peak) and approximately 3.15 mmol/L (last) identify 28-day mortality risk and outperform lactate clearance.

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