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