Early Recognition and Treatment of Sepsis After the Addition of Lactate to the Laboratory’s Critical Result Call List

Kuttab, Hani I.; Sterk, Ethan; Rech, Megan A.; Nghiem, Trac; Bahar, Burhanuddin; Kahn, Stephen E.

doi:10.1177/0885066616668148

Cited by 4 publications

(6 citation statements)

References 17 publications

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“…In BMMC and PMC, physiologically relevant lactic acid concentrations suppressed the LPS-induced production of several cytokines and chemokines. We observed significant effects between 6 and 12 mM, which are relevant to wound tissue lactate concentrations (5-20 mM; maximum 80 mM) (56, 57) and blood lactate concentrations (2-10 mM; maximum 20 mM) (15,17,54,58). Importantly, many studies define high lactate as blood concentrations .4 mM (13,14,59).…”

Section: Discussionmentioning

confidence: 73%

“…Because of these associations, lactate clearance has been added as a treatment guideline for sepsis to improve diagnosis and initial treatment for patients (1). This has reduced mortality in at least one study (17). Although these data suggest lactate and mortality are related, it is not known whether elevated lactate is a cause or consequence of the infection.…”

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confidence: 99%

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Lactic Acid Inhibits Lipopolysaccharide-Induced Mast Cell Function by Limiting Glycolysis and ATP Availability

Caslin

Abebayehu

Qayum

et al. 2019

The Journal of Immunology

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Sepsis has a well-studied inflammatory phase, with a less-understood secondary immunosuppressive phase. Elevated blood lactate and slow lactate clearance are associated with mortality; however, regulatory roles are unknown. We hypothesized that lactic acid (LA) contributes to the late phase and is not solely a consequence of bacterial infection. No studies have examined LA effects in sepsis models in vivo or a mechanism by which it suppresses LPS-induced activation in vitro. Because mast cells can be activated systemically and contribute to sepsis, we examined LA effects on the mast cell response to LPS. LA significantly suppressed LPS-induced cytokine production and NF-kB transcriptional activity in mouse bone marrow-derived mast cells and cytokine production in peritoneal mast cells. Suppression was MCT-1 dependent and reproducible with sodium lactate or formic acid. Further, LA significantly suppressed cytokine induction following LPS-induced endotoxemia in mice. Because glycolysis is linked to inflammation and LA is a byproduct of this process, we examined changes in glucose metabolism. LA treatment reduced glucose uptake and lactate export during LPS stimulation. LA effects were mimicked by glycolytic inhibitors and reversed by increasing ATP availability. These results indicate that glycolytic suppression and ATP production are necessary and sufficient for LA effects. Our work suggests that enhancing glycolysis and ATP production could improve immune function, counteracting LA suppressive effects in the immunosuppressive phase of sepsis.

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Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

Lactic Acid Inhibits Lipopolysaccharide-Induced Mast Cell Function by Limiting Glycolysis and ATP Availability

Caslin

Abebayehu

Qayum

et al. 2019

The Journal of Immunology

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“…One hallmark is elevated lactate levels due to tissue hypoperfusion, impaired pyruvate dehydrogenase activity, elevated catecholamine secretion, and increased immune cell activation ( Vary, 1996 ; Haji-Michael et al, 1999 ; McCarter et al, 2001 ). Blood lactate concentrations in sepsis are often between 2 and 10 mM; however, concentrations have been reported as high as 20mM due to the timing of measurement and severity of disease ( Filho et al, 2016 ; Kuttab et al, 2018 ; Theerawit et al, 2018 ). Many studies show that elevated blood lactate (≥4mM) and impaired clearance are independently associated with increased mortality in septic patients ( Nguyen et al, 2004 ; Trzeciak et al, 2007 ; Arnold et al, 2009 ; Nichol et al, 2011 ; Marty et al, 2013 ).…”

Section: Implications For Diseasementioning

confidence: 99%

“…Many studies show that elevated blood lactate (≥4mM) and impaired clearance are independently associated with increased mortality in septic patients ( Nguyen et al, 2004 ; Trzeciak et al, 2007 ; Arnold et al, 2009 ; Nichol et al, 2011 ; Marty et al, 2013 ). Thus, the use of lactate clearance as a treatment guideline for sepsis has gained traction in adult and pediatric patients alike ( Rhodes et al, 2017 ; Kuttab et al, 2018 ; Nazir et al, 2019 ). It is not fully understood if lactate is a cause or a consequence of sepsis.…”

Section: Implications For Diseasementioning

confidence: 99%

Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function

et al. 2021

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Lactate and the associated H+ ions are still introduced in many biochemistry and general biology textbooks and courses as a metabolic by-product within fast or oxygen-independent glycolysis. However, the role of lactate as a fuel source has been well-appreciated in the field of physiology, and the role of lactate as a metabolic feedback regulator and distinct signaling molecule is beginning to gain traction in the field of immunology. We now know that while lactate and the associated H+ ions are generally immunosuppressive negative regulators, there are cell, receptor, mediator, and microenvironment-specific effects that augment T helper (Th)17, macrophage (M)2, tumor-associated macrophage, and neutrophil functions. Moreover, we are beginning to uncover how lactate and H+ utilize different transporters and signaling cascades in various immune cell types. These immunomodulatory effects may have a substantial impact in cancer, sepsis, autoimmunity, wound healing, and other immunomodulatory conditions with elevated lactate levels. In this article, we summarize the known effects of lactate and H+ on immune cells to hypothesize potential explanations for the divergent inflammatory vs. anti-inflammatory effects.

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“…Although progress has been made in the treatment of primary injuries after severe trauma, the incidence and mortality of posttraumatic sepsis have not been controlled well [ 1 – 4 ]. According to statistics, infection, second only to shock, is one of the main causes of sepsis and death after trauma, which can lead to multiple organ dysfunction syndrome (MODS) and even death in severe cases if not properly treated [ 3 , 5 – 7 ]. Early goal-directed therapy (EGDT) can improve the condition and prognosis of patients with sepsis, and clinical nursing is a key link to ensure the continuity of treatment, with an extremely important role.…”

Section: Introductionmentioning

confidence: 99%

Retrospective Analysis of the Clinical Efficacy of Early Goal-Directed Therapy Combined with Meticulous Nursing Intervention in Patients with Posttraumatic Sepsis

Yuan

Yang

Zhang

et al. 2021

Journal of Healthcare Engineering

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Objective. To explore the intervention effect of early goal-directed therapy (EGDT) combined with meticulous nursing on patients with posttraumatic sepsis. Methods. The data of 50 patients with posttraumatic sepsis undergoing EGDT in the emergency department of our hospital from January 2020 to December 2020 were retrospectively analyzed. According to different nursing methods, they were divided into control group (n = 25) with routine nursing measures and observation group (n = 25) with meticulous nursing measures. The application effect of the two nursing modes was scientifically evaluated. Results. No statistical differences in general data were found between the two groups ( P > 0.05 ). After 6 h of intervention, the circulatory function, oxygenation function, and renal function of both groups were better than those before intervention, and central venous pressure (CVP), mean arterial pressure (MAP), blood oxygen (PaO2), oxygenation index (PaO2/FiO2), central venous oxygen saturation (ScvO2), and urine volume in the observation group were notably higher than those in the control group ( P < 0.05 ). The heart rate (HR), serum creatinine (SCr), and blood lactic acid in the observation group were notably lower than those in the control group ( P < 0.05 ). The 28-day survival rate and quality of life after intervention in the observation group were notably higher than those in the control group, with obvious differences between the two groups ( P < 0.05 ). Conclusion. Meticulous nursing intervention for patients with posttraumatic sepsis undergoing EGDT can effectively improve the body’s functional indexes, which is superior to the routine nursing in controlling the patients’ condition, improving the survival rate and quality of life after intervention, and ensuring the clinical treatment effect. Therefore, it is worthy of promotion.

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Early Recognition and Treatment of Sepsis After the Addition of Lactate to the Laboratory’s Critical Result Call List

Cited by 4 publications

References 17 publications

Lactic Acid Inhibits Lipopolysaccharide-Induced Mast Cell Function by Limiting Glycolysis and ATP Availability

Lactic Acid Inhibits Lipopolysaccharide-Induced Mast Cell Function by Limiting Glycolysis and ATP Availability

Lactate Is a Metabolic Mediator That Shapes Immune Cell Fate and Function

Retrospective Analysis of the Clinical Efficacy of Early Goal-Directed Therapy Combined with Meticulous Nursing Intervention in Patients with Posttraumatic Sepsis

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