Can lactic acidosis be a cause of death?

Can Lactic Acidosis Be a Cause of Death?

Yes, lactic acidosis can absolutely be fatal and is associated with strikingly high mortality rates, particularly when severe (lactate >5 mmol/L) or when treatment is delayed beyond the first 6 hours of recognition. 1, 2, 3

Mortality Risk and Prognostic Factors

The mortality rate from lactic acidosis varies by severity and underlying cause, ranging from 30% to over 80% in severe cases:

• Patients with lactate levels ≥4 mmol/L have a mortality rate of 46.1%, comparable to overt septic shock 4
• When lactic acidosis is not properly treated within the first 6 hours of hospitalization, mortality increases significantly 3
• The FDA explicitly warns that metformin-associated lactic acidosis can cause death, with cases characterized by hypotension and resistant bradyarrhythmias occurring with severe acidosis 2
• Three maternal deaths from lactic acidosis were reported in HIV-infected pregnant women receiving stavudine and didanosine, with progression to death in the immediate postpartum period 1

Mechanisms Leading to Fatal Outcomes

Lactic acidosis causes death through cardiovascular collapse and multi-organ failure:

• Severe acidemia (pH <7.15) can lead to cardiovascular collapse, though the oft-cited rationale that bicarbonate might ameliorate hemodynamic depression has been convincingly disproved 5
• The condition causes hypotension and resistant bradyarrhythmias that can be refractory to treatment 2
• In cyanide poisoning, lactic acidosis is a sensitive and specific finding that accompanies life-threatening toxicity, with symptoms including arrhythmias, apnea, hypotension with bradycardia, seizures, and cardiovascular collapse 1

High-Risk Clinical Scenarios

Certain situations carry particularly high mortality risk:

• Medication-induced lactic acidosis: The combination of stavudine and didanosine in HIV-infected pregnant women resulted in maternal deaths, with two cases also associated with fetal demise 1
• Metformin-associated lactic acidosis: The FDA mandates that this is a rare but serious condition that can cause death, particularly in patients with renal impairment (eGFR <30 mL/min/1.73 m²) 2
• Septic shock with lactic acidosis: Mortality reaches 46.1% when lactate ≥4 mmol/L, even with aggressive treatment 4
• Acute mesenteric ischemia: Lactate >2 mmol/L indicates irreversible intestinal ischemia with a hazard ratio of 4.1 for mortality 4

Prognostic Indicators of Fatal Outcomes

Failure to normalize lactate predicts death:

• Normalization within 24 hours is associated with 100% survival in trauma patients 4
• If lactate remains elevated for 24-48 hours, survival drops to 77.8% 4
• If lactate remains elevated beyond 48 hours, survival plummets to only 13.6% 4
• The time to lactate clearance is a significant predictor of survival across all shock states 4

Critical Warning Signs of Impending Death

The FDA identifies specific symptoms that signal potentially fatal lactic acidosis requiring immediate hospital treatment:

• Hypotension and resistant bradyarrhythmias with severe acidosis 2
• Hypothermia (feeling cold in hands or feet) 2
• Resistant bradyarrhythmias (slow or irregular heartbeat) 2
• Severe respiratory distress or trouble breathing 2
• Increased somnolence or unusual sleepiness 2

Treatment Implications for Preventing Death

Prompt hemodialysis is recommended for metformin-associated lactic acidosis and has often resulted in reversal of symptoms and recovery, preventing death:

• The FDA states that in patients with suspected metformin-associated lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (clearance up to 170 mL/min) 2
• Hemodialysis has often resulted in reversal of symptoms and recovery 2
• General supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of the offending medication 2

Common Pitfall

Do not delay treatment waiting for lactate levels to worsen—early recognition and aggressive treatment of the underlying cause within the first 6 hours is critical to preventing death. 3 The mortality rate is strikingly high when treatment is delayed, and certain presentations (particularly medication-induced cases in vulnerable populations like pregnant women) can progress rapidly to death despite intervention 1.