Lactic Acidosis in Sepsis: It’s Not All Anaerobic: Implications for Diagnosis and Management

doi:10.1378/chest.15-1703

Chest

Volume 149, Issue 1, January 2016, Pages 252-261

https://doi.org/10.1378/chest.15-1703 Get rights and content

Increased blood lactate concentration (hyperlactatemia) and lactic acidosis (hyperlactatemia and serum pH < 7.35) are common in patients with severe sepsis or septic shock and are associated with significant morbidity and mortality. In some patients, most of the lactate that is produced in shock states is due to inadequate oxygen delivery resulting in tissue hypoxia and causing anaerobic glycolysis. However, lactate formation during sepsis is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery. In this review, we initially outline the metabolism of lactate and etiology of lactic acidosis; we then address the pathophysiology of lactic acidosis in sepsis. We discuss the clinical implications of serum lactate measurement in diagnosis, monitoring, and prognostication in acute and intensive care settings. Finally, we explore treatment of lactic acidosis and its impact on clinical outcome.

Section snippets

Lactate Production

Under normal conditions, lactate is produced at the remarkably high rate of approximately 1.5 mol per day; thus, lactate is not simply a waste product indicating anaerobic metabolism. Rather, the “lactate shuttle” theory highlights the role of lactate in the distribution of oxidative and gluconeogenic substrates as well as in cell signalling.8, 9 Lactate produced in one location can be used as a preprocessed fuel for mitochondrial respiration by numerous distant tissues or can be used by the

Lactate Clearance

Lactate is a transportable metabolite that then can be metabolized for energy production by local or distant mitochondria (pyruvate and then the Krebs cycle) or as a substrate for gluconeogeneses (the Cori cycle). Lactate is metabolized primarily by the liver and, to some extent, by the kidneys. Cardiac myocytes use lactate as fuel in some circumstances, such as during exercise, β-adrenergic stimulation, and shock.17, 18 The brain also consumes lactate when metabolic requirements are increased.

Where Does the Acid Come From?

Note that glycolytic flux from glucose to pyruvate generates H⁺, but conversion of pyruvate to lactate consumes the molar equivalent H⁺ flux; therefore, increased generation of lactate resulting in hyperlactatemia is not, by itself, acidosis. Where does the acid come from? ATP hydrolysis is the major generator of H⁺ (protons = acid). This acid is avidly consumed by the Krebs cycle; therefore, acid builds up during tissue-hypoxic conditions when the Krebs cycle consumption of H⁺ is reduced by a

Etiologies of Lactic Acidosis

From a clinical perspective, hyperlactatemia develops when lactate production is augmented, lactate utilization and clearance are diminished, or both. Sepsis and shock are common causes of hyperlactatemia.²⁰ In patients with vasopressor-dependent septic shock, Dugas and colleagues²¹ demonstrated that more than half of the patients had elevated lactate concentrations. This finding was confirmed by the recent Surviving Sepsis Campaign Database that illustrated approximately two-thirds of patients

Inadequate Whole-Body Oxygen Delivery

Lactic acidosis in sepsis and septic shock has traditionally been explained as a result of tissue hypoxia when whole-body oxygen delivery fails to meet whole-body oxygen requirements (Fig 2).⁶ Early studies in patients with septic shock, which found a sloped relationship between measurements of whole-body oxygen delivery and consumption, suggested that this was evidence of tissue hypoxia because the slope in an oxygen consumption-delivery relationship was found below the critical oxygen

How and When Lactate Should Be Measured

Although an increased anion gap can be considered a screening tool for the diagnosis of lactic acidosis,⁵⁵ a normal anion gap does not exclude the possibility of lactic acidosis, which can present with a normal anion gap up to 50% of the time.⁵⁶ Even in the setting of lactic acidosis, other causes of an increased anion gap should be considered.⁵⁷ Therefore, measurement of blood lactate concentration is necessary. In most circumstances, venous blood lactate concentrations are modestly higher

Conclusion

Lactic acidosis is common in patients with severe sepsis or septic shock and strongly correlates with illness severity and prognosis. However, it does not exclusively represent tissue hypoxia. It may indicate an adaptive response to metabolic processes of severe infection and response to therapies. Physicians should understand the complexity of lactate metabolism and the limitations of lactate measurements in patient management. Use of lactate clearance as a target of septic shock treatment

Acknowledgments

Financial/nonfinancial disclosures: None declared.

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Contemporary Reviews in Critical Care MedicineLactic Acidosis in Sepsis: It’s Not All Anaerobic: Implications for Diagnosis and Management

Section snippets

Lactate Production

Lactate Clearance

Where Does the Acid Come From?

Etiologies of Lactic Acidosis

Inadequate Whole-Body Oxygen Delivery

How and When Lactate Should Be Measured

Conclusion

Acknowledgments

Lactic acidosis in critical illness

Crit Care Med

Lactate metabolism – a new paradigm for the third millennium

J Physiol

Lactate as a hemodynamic marker in the critically ill

Curr Opin Crit Care

The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814-1869) in January 1843

Intensive Care Med

Abnormal resting blood lactate. I. The significance of hyperlactatemia in hospitalized patients

Am J Med

Abnormal resting blood lactate. II. Lactic acidosis

Am J Med

Clinical and Biochemical Aspects of Lactic Acidosis

Cell–cell and intracellular lactate shuttles

J Physiol

Intra- and extra-cellular lactate shuttles

Med Sci Sports Exerc

Lactate: a key metabolite in the intercellular metabolic interplay

Crit Care

Lactate as a fuel for mitochondrial respiration

Acta Physiol Scand

Lactate and shock state: the metabolic view

Curr Opin Crit Care

Release of lactate by the lung in acute lung Injury

Chest

Bench-to-bedside review: lactate and the lung

Crit Care

Energy metabolism of human neutrophils during phagocytosis

J Clin Invest

Rethinking glycolysis: on the biochemical logic of metabolic pathways

Nat Chem Biol

Myocardial lactate metabolism during exercise

Med Sci Sports Exerc

Lactate improves cardiac efficiency after hemorrhagic shock

Shock

Blood lactate is an important energy source for the human brain

J Cerebr Blood Flow Metab

Admission hyperlactatemia: causes, incidence, and impact on outcome of patients admitted in a general medical intensive care unit

J Crit Care

Prevalence and characteristics of nonlactate and lactate expressors in septic shock

J Crit Care

Lactate measurements in sepsis-induced tissue hypoperfusion: results from the Surviving Sepsis Campaign Database

Crit Care Med

Identification of the critical oxygen delivery for anaerobic metabolism in critically ill septic and nonseptic humans

JAMA

Oxygen delivery and consumption in patients with hyperdynamic septic shock

Crit Care Med

Oxygen supply dependency can characterize septic shock

Intensive Care Med

Elevation of systemic oxygen delivery in the treatment of critically ill patients

N Engl J Med

Time-pattern of lactate and lactate to pyruvate ratio in the first 24 hours of intensive care emergency admissions

Shock

Evolution of lactate/pyruvate and arterial ketone body ratios in the early course of catecholamine-treated septic shock

Crit Care Med

Increased lactate/pyruvate ratio with normal beta-hydroxybutyrate/acetoacetate ratio and lack of oxygen supply dependency in a patient with fatal septic shock

Intensive Care Med

Markers of tissue hypoperfusion in pediatric septic shock

Intensive Care Med

Lactate/pyruvate ratio as a marker of tissue hypoxia in circulatory and septic shock

Anaesth Intensive Care

A randomized trial of protocol-based care for early septic shock

N Engl J Med

Goal-directed resuscitation for patients with early septic shock

N Engl J Med

Relationship of oxygen delivery and mixed venous oxygenation to lactic acidosis in patients with sepsis and acute myocardial infarction

Crit Care Med

Tissue oxygenation and perfusion in patients with systemic sepsis

Crit Care Med

Contemporary Reviews in Critical Care Medicine
Lactic Acidosis in Sepsis: It’s Not All Anaerobic: Implications for Diagnosis and Management