Prognostic value of lactate levels and lactate clearance in sepsis and septic shock with initial hyperlactatemia

Lee, Seung-Geun; Song, Jae-Ju; Park, Dae Won; Moon, Sung Woo; Cho, Han Jin; Kim, Joo Yeong; Park, Jong Hak; Hyung, Jae

doi:10.1097/md.0000000000024835

Cited by 39 publications

(43 citation statements)

References 25 publications

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“…Based on the results from the KEGG analysis regarding the upregulated acetylome, the acetylation increased in four proteins-ALDOA, PGK1, ENO1, and PKM2-in the glycolysis pathways. The sepsis metabolism is associated with various metabolic changes, including insulin resistance, hyperlactatemia, hypoglutaminemia, hypercatabolism, and muscle wasting [33][34][35][36]. In particular, an increase in lactate concentration, a diagnostic marker in the early stages of sepsis, is thought to be a sign of acute organ dysfunction [37].…”

Section: Discussionmentioning

confidence: 99%

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Paudel

Choi

et al. 2021

IJMS

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Sepsis-induced liver dysfunction (SILD) is a common event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification and diseases is challenging. We studied the relationship among lysine acetylation (Kac), sirtuin (SIRTs), and the factors involved in SILD, which was induced in LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1449 Kac sites based on comparative acetylome analysis and quantified 1086 Kac sites on 410 proteins for acetylation. Interestingly, the upregulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed at three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, consequently increasing the lactate concentration. In conclusion, this study is the first to conduct global profiling of Kac, suggesting that the Kac mechanism of PKM2 in glycolysis is associated with sepsis. Moreover, it helps to further understand the systematic information regarding hyperacetylation during the sepsis process.

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Section: Discussionmentioning

confidence: 99%

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Paudel

Choi

et al. 2021

IJMS

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“…S.G. Lee и соавт. в исследовании показали, что 6-часовой уровень лактата имеет лучшую прогностическую ценность, чем исходный уровень лактата и его клиренс [38]. Оценка уровня провоспалительных цитокинов также не является специфичным методом диагностики септического шока.…”

Section: развитие полиорганной недостаточности при септическом шокеunclassified

Topical issues of clinical symptoms and diagnostics of septic shock

Гоманова

Fokina

2022

Russian Journal of Infection and Immunity

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Currently, septic shock remains an unresolved public health problem that leads to serious epidemiological, economic and social problems. Septic shock is a common hemodynamic disorder caused by the interaction between pathogenic microbes and host cells, resulting in developing hypoxia, severe metabolic disorders and multiple organ failure. By now, no unified concept for pathophysiology of septic shock are available. However, the aforementioned data prove that one of the key arms in the pathogenesis is endothelial dysfunction and associated ischemic disorders. In the clinical course of septic shock, three stages are distinguished: the stage of compensation, decompensation as well as the stage of irreversible disorders. The initial stage, or the stage of compensation, is characterized by the activated inflammatory response against infectious agents. Clinically, this stage is characterized by the development of warm shock: fever, dermal hyperemia, hyperventilation, increased cardiac output, and tachycardia. The second stage in developing septic shock is characterized by arising cold shock as a consequence of escalating heart and respiratory failure. The final stage is the development of multiple organ failure manifested by emerging shock organs. Multiple organ failure occurs due to microthrombosis and increasing ischemia, which leads to hypoxia and development of mitochondrial dysfunction in immune cells. At this stage patients are characterized by the progressive cyanosis, developing anuria and intestinal obstruction, as well as altered mental status. Laboratory and instrumental diagnostics of septic shock is a promising approach to examine septic shock. The level of serum C-reactive protein, lactate, and proinflammatory cytokines are not highly specific diagnostic parameters of septic shock, because they can be found in any inflammatory process. Today, the promising diagnostic markers are pentraxin-3, high-density lipoproteins, and phosphatidylcholine. The severity of septic shock can be assessed by determining blood schistocytes, central venous pressure, and the ratio of venous-arterial CO2 and arterial-venous O2 pressure. The following diagnostic methods can be used to determine multiple organ failure: level of serum proenkephalin A119159 and heparin-binding protein; echocardiography, troponin I concentration and N-terminal pro-b-type natriuretic peptides; measuring activity of the renin-angiotensin-aldosterone system. Here we discuss the key aspects of pathogenesis, clinical picture and morphological changes of septic shock. The promising methods for diagnosing the disease and its complications have been studied.

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“…Elevated blood lactate is common among patients with sepsis and is associated with significantly greater mortality[ 12 ]. Toxic levels of H 2 O 2 can inhibit enzymes in the Krebs cycle and electron transport chain leading to hyperlactatemia and bioenergetic failure characteristic of advanced sepsis[ 54 - 59 ].…”

Section: Clinical Manifestations Of H2o2 Induced Oxidative Stressmentioning

confidence: 99%

Sepsis: Evidence-based pathogenesis and treatment

Pravda¹

2021

WJCCM

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Sepsis can develop during the body’s response to a critical illness leading to multiple organ failure, irreversible shock, and death. Sepsis has been vexing health care providers for centuries due to its insidious onset, generalized metabolic dysfunction, and lack of specific therapy. A common factor underlying sepsis is the characteristic hypermetabolic response as the body ramps up every physiological system in its fight against the underlying critical illness. A hypermetabolic response requires supraphysiological amounts of energy, which is mostly supplied via oxidative phosphorylation generated ATP. A by-product of oxidative phosphorylation is hydrogen peroxide (H 2 O 2 ), a toxic, membrane-permeable oxidizing agent that is produced in far greater amounts during a hypermetabolic state. Continued production of mitochondrial H 2 O 2 can overwhelm cellular reductive (antioxidant) capacity leading to a build-up within cells and eventual diffusion into the bloodstream. H 2 O 2 is a metabolic poison that can inhibit enzyme systems leading to organ failure, microangiopathic dysfunction, and irreversible septic shock. The toxic effects of H 2 O 2 mirror the clinical and laboratory abnormalities observed in sepsis, and toxic levels of blood H 2 O 2 have been reported in patients with septic shock. This review provides evidence to support a causal role for H 2 O 2 in the pathogenesis of sepsis, and an evidence-based therapeutic intervention to reduce H 2 O 2 levels in the body and restore redox homeostasis, which is necessary for normal organ function and vascular responsiveness.

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Prognostic value of lactate levels and lactate clearance in sepsis and septic shock with initial hyperlactatemia

Cited by 39 publications

References 25 publications

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

Topical issues of clinical symptoms and diagnostics of septic shock

Sepsis: Evidence-based pathogenesis and treatment

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