Lactic acidosis: Clinical implications and management strategies

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ABSTRACTIn hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment.


  • Serum lactate levels can become elevated by a variety of underlying processes, categorized as increased production in conditions of hypoperfusion and hypoxia (type A lactic acidosis), or as increased production or decreased clearance not due to hypoperfusion and hypoxia (type B).
  • The higher the lactate level and the slower the rate of normalization (lactate clearance), the higher the risk of death.
  • Treatments differ depending on the underlying mechanism of the lactate elevation. Thus, identifying the reason for hyperlactatemia and differentiating between type A and B lactic acidosis are of the utmost importance.
  • Treatment of type A lactic acidosis aims to improve perfusion and match oxygen consumption with oxygen delivery by giving fluids, packed red blood cells, and vasopressors or inotropic agents, or both.
  • Treatment of type B involves more specific management, such as discontinuing offending medications or supplementing key cofactors for anaerobic metabolism.



Physicians are paying more attention to serum lactate levels in hospitalized patients than in the past, especially with the advent of point-of-care testing. Elevated lactate levels are associated with tissue hypoxia and hypoperfusion but can also be found in a number of other conditions. Therefore, confusion can arise as to how to interpret elevated levels and subsequently manage these patients in a variety of settings.

In this review, we discuss the mechanisms underlying lactic acidosis, its prognostic implications, and its use as a therapeutic target in treating patients in septic shock and other serious disorders.


Figure 1.

Lactate, or lactic acid, is produced from pyruvate as an end product of glycolysis under anaerobic conditions (Figure 1). It is produced in most tissues in the body, but primarily in skeletal muscle, brain, intestine, and red blood cells. During times of stress, lactate is also produced in the lungs, white blood cells, and splanchnic organs.

Most lactate in the blood is cleared by the liver, where it is the substrate for gluconeogenesis, and a small amount is cleared by the kidneys.1,2 The entire pathway by which lactate is produced and converted back to glucose is called the Cori cycle.


In this review, we will present lactate levels in the SI units of mmol/L (1 mmol/L = 9 mg/dL).

Basal lactate production is approximately 0.8 mmol/kg body weight/hour. The average normal arterial blood lactate level is approximately 0.620 mmol/L and the venous level is slightly higher at 0.997 mmol/L,3 but overall, arterial and venous lactate levels correlate well.

Normal lactate levels are less than 2 mmol/L,4 intermediate levels range from 2 to less than 4 mmol/L, and high levels are 4 mmol/L or higher.5

To minimize variations in measurement, blood samples should be drawn without a tourniquet into tubes containing fluoride, placed on ice, and processed quickly (ideally within 15 minutes).


An elevated lactate level can be the result of increased production, decreased clearance, or both (as in liver dysfunction).

Type A lactic acidosis—due to hypoperfusion and hypoxia—occurs when there is a mismatch between oxygen delivery and consumption, with resultant anaerobic glycolysis.

The guidelines from the Surviving Sepsis Campaign6 emphasize using lactate levels to diagnose patients with sepsis-induced hypoperfusion. However, hyperlactatemia can indicate inadequate oxygen delivery due to any type of shock (Table 1).

Type B lactic acidosis—not due to hypoperfusion—occurs in a variety of conditions (Table 1), including liver disease, malignancy, use of certain medications (eg, metformin, epinephrine), total parenteral nutrition, human immunodeficiency virus infection, thiamine deficiency, mitochondrial myopathies, and congenital lactic acidosis.1–3,7 Yet other causes include trauma, excessive exercise, diabetic ketoacidosis, ethanol intoxication, dysfunction of the enzyme pyruvate dehydrogenase, and increased muscle degradation leading to increased production of pyruvate. In these latter scenarios, glucose metabolism exceeds the oxidation capacity of the mitochondria, and the rise in pyruvate concentration drives lactate production.8,9 Mitochondrial dysfunction and subsequent deficits in cellular oxygen use can also result in persistently high lactate levels.10

In some situations, patients with mildly elevated lactic acid levels in type B lactic acidosis can be monitored to ensure stability, rather than be treated aggressively.


The higher the lactate level and the slower the rate of normalization (lactate clearance), the higher the risk of death.

Lactate levels and mortality rate

Shapiro et al11 showed that increases in lactate level are associated with proportional increases in the mortality rate. Mikkelsen et al12 showed that intermediate levels (2.0–3.9 mmol/L) and high levels (≥ 4 mmol/L) of serum lactate are associated with increased risk of death independent of organ failure and shock. Patients with mildly elevated and intermediate lactate levels and sepsis have higher rates of in-hospital and 30-day mortality, which correlate with the baseline lactate level.13

In a post hoc analysis of a randomized controlled trial, patients with septic shock who presented to the emergency department with hypotension and a lactate level higher than 2 mmol/L had a significantly higher in-hospital mortality rate than those who presented with hypotension and a lactate level of 2 mmol/L or less (26% vs 9%, P < .0001).14 These data suggest that elevated lactate levels may have a significant prognostic role, independent of blood pressure.

Slower clearance

The prognostic implications of lactate clearance (reductions in lactate levels over time, as opposed to a single value in time), have also been evaluated.

Lactate clearance of at least 10% at 6 hours after presentation has been associated with a lower mortality rate than nonclearance (19% vs 60%) in patients with sepsis or septic shock with elevated levels.15–17 Similar findings have been reported in a general intensive care unit population,18 as well as a surgical intensive care population.sup>19

Puskarich et al20 have also shown that lactate normalization to less than 2 mmol/L during early sepsis resuscitation is the strongest predictor of survival (odds ratio [OR] 5.2), followed by lactate clearance of 50% (OR 4.0) within the first 6 hours of presentation. Not only is lactate clearance associated with improved outcomes, but a faster rate of clearance after initial presentation is also beneficial.15,16,18

Lactate clearance over a longer period (> 6 hours) has not been studied in patients with septic shock. However, in the general intensive care unit population, therapy guided by lactate clearance for the first 8 hours after presentation has shown a reduction in mortality rate.18 There are no data available on outcomes of lactate-directed therapy beyond 8 hours, but lactate concentration and lactate clearance at 24 hours correlate with the 28-day mortality rate.21

Cryptic shock

Cryptic shock describes a state in a subgroup of patients who have elevated lactate levels and global tissue hypoxia despite being normotensive or even hypertensive. These patients have a higher mortality rate independent of blood pressure. Jansen et al18 found that patients with a lactate level higher than 4 mmol/L and preserved blood pressure had a mortality rate of 15%, while those without shock or hyperlactatemia had a mortality rate of 2.5%. In addition, patients with an elevated lactate level in the absence of hypotension have mortality rates similar to those in patients with high lactate levels and hypotension refractory to fluid boluses, suggesting the presence of tissue hypoxia even in these normotensive patients.6

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