What causes elevated lactic acid levels in patients, particularly those with conditions like diabetes or sepsis?

Why Lactic Acid Gets So High

Lactic acid becomes elevated primarily due to tissue hypoperfusion and hypoxia, which forces cells to switch from aerobic to anaerobic metabolism, producing lactate as a byproduct when oxygen delivery cannot meet metabolic demands. 1

Primary Mechanisms of Lactate Elevation

Type A: Tissue Hypoperfusion (Most Common)

Tissue hypoperfusion and hypoxia is the most common cause of elevated lactate, resulting from inadequate oxygen delivery to tissues causing anaerobic metabolism. 1 This occurs when your body cannot deliver enough oxygen to cells, forcing them to produce energy without oxygen—a much less efficient process that generates lactic acid as waste. 2

The major causes include:

• Shock states (hypovolemic, cardiogenic, distributive, obstructive) all lead to impaired tissue perfusion and force anaerobic metabolism 1, 3
• Sepsis and septic shock causes lactic acidosis through both tissue hypoperfusion and inflammatory mediators that directly affect cellular metabolism 1
• Trauma and hemorrhagic shock following major blood loss leads to elevated lactate levels that directly correlate with mortality 1
• Cardiac failure decreases cardiac output, reducing tissue perfusion and oxygen delivery 3
• Myocardial infarction causes regional hypoperfusion and triggers systemic inflammatory responses 3

Type B: Non-Hypoperfusion Causes

Lactate can elevate without tissue hypoxia through several distinct mechanisms. 1

Medication-Induced Elevation

• Metformin causes lactic acidosis in patients with impaired clearance (eGFR <30 mL/min/1.73 m²), impaired lactate clearance (liver failure), or conditions causing anaerobic metabolism (sepsis, hypoxia) 1, 4
• Epinephrine causes elevated lactate through beta-2-adrenergic receptor stimulation in skeletal muscle, activating glycogenolysis and glycolysis, leading to increased lactate production independent of tissue perfusion 1
• High-dose vasopressors can cause non-occlusive mesenteric ischemia (NOMI) leading to lactic acidosis 3

Metabolic and Organ Dysfunction

• Liver disease impairs lactate clearance since the liver is responsible for up to 70% of lactate metabolism 3, 5
• Accelerated aerobic glycolysis, driven by excess beta-adrenergic stimulation, can increase lactate without tissue hypoxia 1
• Thiamine deficiency causes impaired pyruvate metabolism, leading to lactate accumulation 3, 5
• Diabetic ketoacidosis (DKA) often presents with elevated lactate levels alongside ketoacidosis 3, 6

Ischemic Conditions

• Mesenteric ischemia (arterial embolism, arterial thrombosis, venous thrombosis, non-occlusive) produces marked lactate elevation; levels >2 mmol/L with abdominal pain carry a 4.1-fold increased risk of irreversible intestinal ischemia 1, 3
• Compartment syndrome restricts blood flow to tissues 3

Clinical Significance and Thresholds

Understanding lactate levels helps guide urgency of intervention:

• Normal: <2 mmol/L 1, 3
• Lactate 2-4 mmol/L: Indicates potential tissue hypoperfusion with ~30% mortality, warrants aggressive fluid resuscitation with at least 30 mL/kg IV crystalloid within first 3 hours 1
• Lactate ≥4 mmol/L: Medical emergency with 46.1% mortality, requires immediate protocolized resuscitation 1
• Lactate >5 mmol/L: Abnormal and indicates serious, possibly life-threatening situations 1

Prognostic Importance of Lactate Clearance

The duration of lactate elevation matters more than the initial value. 1

• Normalization within 24 hours is associated with 100% survival in trauma patients 1
• Normalization within 48 hours drops survival to 77.8% 1
• Elevated beyond 48 hours drops survival to 13.6% 1
• Lactate clearance time is a significant predictor of survival, with decreased survival if lactate levels remain elevated for >24-48 hours 1

Critical Clinical Pitfalls

• Don't ignore elevated lactate in seemingly stable patients, as it may indicate occult tissue hypoperfusion—patients can maintain normal blood pressure through compensatory mechanisms while experiencing significant tissue hypoperfusion 1
• Don't assume all elevated lactate indicates infection; consider non-infectious causes like medications (metformin, epinephrine), mesenteric ischemia, liver disease, and thiamine deficiency 3
• Don't delay imaging in suspected mesenteric ischemia—lactic acidosis with abdominal pain warrants immediate CT angiography even when the patient appears clinically stable 1
• Don't rely on blood pressure alone as an adequate marker of tissue perfusion in sepsis 1

The "Cryptic Shock" Phenomenon

Up to 23% of septic patients have lactate ≥2 mmol/L with central venous oxygen saturation (ScvO2) >70%, representing "cryptic shock" that doesn't fit traditional shock definitions. 1 This occurs because:

• Low oxygen extraction ratio is characteristic of severe sepsis, making ScvO2 unreliable for directing therapy 1
• Normal or high ScvO2 values do not rule out persistent tissue hypoxia in septic patients due to impaired oxygen extraction 1
• Abnormally high ScvO2 values can paradoxically associate with increased lactate and mortality, reflecting mitochondrial dysfunction rather than adequate perfusion 1

Management Approach

The primary treatment for elevated lactate is identifying and aggressively treating the underlying cause—tissue hypoperfusion requires immediate fluid resuscitation and hemodynamic support. 1

• Serial lactate measurements every 2-6 hours during acute resuscitation are essential to objectively evaluate response to therapy 1
• Target lactate clearance of at least 10% every 2 hours during the first 8 hours 1
• Sodium bicarbonate should NOT be used for pH ≥7.15 as it does not improve outcomes and may cause harm 1
• Consider medication effects such as those caused by epinephrine or metformin when interpreting elevated lactate levels 1, 4