Elevated Lactate: Indicators and Clinical Significance
Elevated lactate levels primarily indicate tissue hypoperfusion and hypoxia, causing cells to shift to anaerobic metabolism when oxygen delivery is inadequate. 1
Primary Causes of Elevated Lactate
Tissue hypoperfusion and hypoxia is the most common cause of elevated lactate, resulting from inadequate oxygen delivery to tissues which forces cells to produce energy through anaerobic metabolism 1
Sepsis and septic shock are major causes of lactic acidosis due to both tissue hypoperfusion and inflammatory mediators affecting cellular metabolism 1, 2
Various shock states including hypovolemic, cardiogenic, and distributive shock lead to impaired tissue perfusion and subsequent lactate elevation 1
Trauma, particularly hemorrhagic shock following major trauma, leads to elevated lactate levels that correlate with mortality 1
Other Important Mechanisms of Lactate Elevation
Accelerated aerobic glycolysis driven by excess beta-adrenergic stimulation can increase lactate production without tissue hypoxia 1, 3
Medication-induced lactate elevation, particularly from epinephrine through beta-2-adrenergic receptor stimulation in skeletal muscle, can activate glycogenolysis and glycolysis 1
Mitochondrial dysfunction rather than tissue hypoxia may explain lactate elevation in sepsis 4
Clinical Significance
Marker of tissue hypoperfusion: In sepsis, lactate ≥4 mmol/L is defined as sepsis-induced tissue hypoperfusion according to the Surviving Sepsis Campaign guidelines 2
Prognostic indicator: Elevated lactate levels are strongly associated with increased mortality in various shock states 1, 5
Resuscitation target: Normalization of lactate levels is associated with improved survival, with the Surviving Sepsis Campaign suggesting guiding resuscitation to normalize lactate in patients with elevated levels 2
Serial measurements: Lactate clearance time is a significant predictor of survival, with decreased survival if lactate levels remain elevated for >24-48 hours 1
Important Clinical Considerations
While traditionally viewed as a marker of anaerobic metabolism, elevated lactate doesn't always indicate tissue hypoxia - it may reflect increased aerobic glycolysis or adrenergic stimulation 3, 4
The 2016 Surviving Sepsis Campaign guidelines suggest "guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion" (weak recommendation, low quality of evidence) 2
Lactate levels should be interpreted in clinical context, as multiple mechanisms can contribute to elevation beyond just tissue hypoxia 6
Serial lactate measurements provide an objective evaluation of response to therapy and should be used to assess treatment efficacy 1
Clinical Approach to Elevated Lactate
Identify and treat the underlying cause of elevated lactate, focusing on improving tissue perfusion in shock states 1
In sepsis-induced hypoperfusion, administer at least 30 mL/kg of IV crystalloid fluid within the first 3 hours 2
Consider medication effects, such as those caused by epinephrine, when interpreting elevated lactate levels 1
Target an initial mean arterial pressure of 65 mmHg in patients with septic shock requiring vasopressors 2