Which one is a better predictor of ICU mortality in septic patients? Comparison between serial serum lactate concentrations and its removal rate

Mahmoodpoor, Ata; Shadvar, Kamran; Saghaleini, Seied Hadi; Koleini, Evin; Hamishehkar, Hadi; Ostadi, Zohre; Nader, Nader D.

doi:10.1016/j.jcrc.2017.10.019

Cited by 20 publications

(18 citation statements)

References 37 publications

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“…Another case similar to our study is lactate which exhibits higher levels in septic shock patients [38]. It is well known that serum lactate levels are served as a clinical marker of sepsis severity [39]. Nonetheless, Colegio et al reported that lactate could promote macrophage M2 polarization and inhibit sepsisinduced inflammation [40].…”

Section: Discussionsupporting

confidence: 84%

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

Wang

et al. 2020

Cells

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Macrophages are critical for regulation of inflammatory response during endotoxemia and septic shock. However, the mediators underlying their regulatory function remain obscure. Growth differentiation factor 3 (GDF3), a member of transforming growth factor beta (TGF-β) superfamily, has been implicated in inflammatory response. Nonetheless, the role of GDF3 in macrophage-regulated endotoxemia/sepsis is unknown. Here, we show that serum GDF3 levels in septic patients are elevated and strongly correlate with severity of sepsis and 28-day mortality. Interestingly, macrophages treated with recombinant GDF3 protein (rGDF3) exhibit greatly reduced production of pro-inflammatory cytokines, comparing to controls upon endotoxin challenge. Moreover, acute administration of rGDF3 to endotoxin-treated mice suppresses macrophage infiltration to the heart, attenuates systemic and cardiac inflammation with less pro-inflammatory macrophages (M1) and more anti-inflammatory macrophages (M2), as well as prolongs mouse survival. Mechanistically, GDF3 is able to activate Smad2/Smad3 phosphorylation, and consequently inhibits the expression of nod-like receptor protein-3 (NLRP3) in macrophages. Accordingly, blockade of Smad2/Smad3 phosphorylation with SB431542 significantly offsets rGDF3-mediated anti-inflammatory effects. Taken together, this study uncovers that GDF3, as a novel sepsis-associated factor, may have a dual role in the pathophysiology of sepsis. Acute administration of rGDF3 into endotoxic shock mice could increase survival outcome and improve cardiac function through anti-inflammatory response by suppression of M1 macrophage phenotype. However, constitutive high levels of GDF3 in human sepsis patients are associated with lethality, suggesting that GDF3 may promote macrophage polarization toward M2 phenotype which could lead to immunosuppression.

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Section: Discussionsupporting

confidence: 84%

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

Wang

et al. 2020

Cells

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“…This demonstrates the importance of monitoring lactate beyond 6 hours after ICU admission. Several studies reported lactate at 24 hours as the strongest prognosticator; however, a quicker assessment would be preferable to determine successfulness of a treatment over shorter periods.…”

Section: Discussionmentioning

confidence: 99%

Optimal cut‐off for hourly lactate reduction in ICU‐treated patients with septic shock

Promsin

Grip

Norberg

et al. 2019

Acta Anaesthesiol Scand

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Background: A decrease in lactate concentration over time during septic shock is associated with favourable outcomes. However, if this applies to hourly intervals during the initial time period in the ICU is unknown. The aim of this study was to investigate whether there is an early hourly reduction rate of lactate that is related to clinical outcome in septic shock patients treated in the ICU. Methods:A cohort of adult septic shock patients admitted to the ICU with an initial lactate level >2 mmol/L and receiving vasopressor was retrospectively analysed.Mean hourly reduction rate of lactate (ΔLact/h) was calculated individually from all lactate concentrations measured from inclusion until normalization of lactate (≤1.5 mmol/L) within 24 hours. The mortality at 30 days following ICU admission was evaluated.Results: Among 1405 ICU admissions during 2 years, 104 patients were eligible.Mortality rate at 30 days was 34%. The optimal cut-off values of baseline lactate and ΔLact/h for 30-day mortality were 4 mmol/L and 2.5%/h. When stratifying the patients by these cut-points, those with baseline lactate > 4 mmol/L and ΔLact/h < 2.5%/h had lowest probability of survival (27%). Multivariable logistic regression showed that ΔLact/h <2.5%/h, baseline lactate >4 mmol/L and high Simplified Acute Physiology Score III were independent risk factors of 30-day mortality. Conclusions:In this retrospective pilot cohort, a mean reduction rate of lactate <2.5%/h within the first 24 hours of ICU stay was associated with an increased risk of 30-day mortality in septic shock patients.

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“…For lactate, prognostic significance of the course or clearance has been evaluated 3,13,[15][16][17] . In sepsis patients, lactate at 24 hours was found to be strongest predictor of mortality in serial lactate measurements 17 and early lactate clearance was associated with improved outcome 16 .…”

Section: Discussionmentioning

confidence: 99%

Course of Lactate, pH and Base Excess for Prediction of Mortality in Medical Intensive Care Patients

Schork

Moll

Haap

et al. 2021

Preprint

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Introduction: As base excess (BE) had shown superiority over lactate as a prognostic parameter in intensive care unit (ICU) surgical patients we aimed to evaluate course of lactate, base excess and pH for prediction of mortality of medical ICU patients. Materials and Methods: For lactate, pH and base excess, values at the admission to ICU, at 24 ± 4 hours, maximum / minimum in the first 24 hours and in 24 – 48 hours after admission were collected from all patients admitted to the Medical ICU of the University Hospital Tübingen between January 2016 until December 2018 and investigated for prediction of in-hospital-mortality. Results: Mortality in the cohort of 4067 patients was 22 % and significantly correlated with all evaluated parameters. Strongest predictors of mortality determined by ROC were maximum lactate in 24 h (AUROC 0.74, cut off 2.7 mmol/L, hazard ratio of risk group with value > cut off 3.20) and minimum pH in 24 h (AUROC 0.71, cut off 7.31, hazard ratio for risk group 2.94). Kaplan Meier Curves stratified across these cut offs showed early and clear separation. Hazard ratios per standard deviation increase were highest for maximum lactate in 24 h (HR 1.65), minimum base excess in 24 h (HR 1.56) and minimum pH in 24 h (HR 0.75). In multiple logistic regression analysis, age, minimum pH in 24 h, pH at 24 h after admission, maximum lactate in 24 h, maximum lactate in 24 – 48 h, minimum base excess in 24 h and minimum base excess in 24 – 48 h were independent predictors of mortality. Discussion: Lactate, pH and base excess were all suitable predictors of mortality in internal ICU patients, with maximum / minimum values in 24 and 24-48 h after admission altogether stronger predictors than values at admission. Base excess and pH were not superior to lactate for prediction of mortality.

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Which one is a better predictor of ICU mortality in septic patients? Comparison between serial serum lactate concentrations and its removal rate

Cited by 20 publications

References 37 publications

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

GDF3 Protects Mice against Sepsis-Induced Cardiac Dysfunction and Mortality by Suppression of Macrophage Pro-Inflammatory Phenotype

Optimal cut‐off for hourly lactate reduction in ICU‐treated patients with septic shock

Course of Lactate, pH and Base Excess for Prediction of Mortality in Medical Intensive Care Patients

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