Can steroids, such as prednisone, elevate lactic acid levels, particularly in patients with pre-existing metabolic or hepatic conditions, like diabetes or liver disease?

Can Steroids Elevate Lactic Acid Levels?

Steroids do not directly elevate lactic acid levels through their primary pharmacologic mechanisms, but they can indirectly contribute to lactic acidosis in specific high-risk clinical scenarios, particularly in patients with pre-existing liver disease, sepsis, or when combined with metformin in the setting of renal impairment.

Direct Effects of Steroids on Lactate

• Corticosteroids themselves are not recognized as direct causes of hyperlactatemia or lactic acidosis in the medical literature 1, 2.
• The primary metabolic effects of steroids—impaired insulin secretion, increased insulin resistance, and enhanced hepatic gluconeogenesis—lead to hyperglycemia, not lactate accumulation 3, 4.
• A systematic review of 286 cases of medication-induced lactate elevations involving 59 unique FDA-approved drugs did not identify corticosteroids as causative agents 1.

Indirect Mechanisms: High-Risk Clinical Scenarios

Liver Disease Context

Patients with hepatic insufficiency receiving steroids face compounded risk for lactic acidosis through multiple pathways:

• Acute or chronic liver disease impairs lactate clearance by reducing hepatic oxidation and gluconeogenesis, the two primary mechanisms for lactate removal 5, 6.
• Steroids are commonly used in severe alcoholic hepatitis (Maddrey score >32), where underlying liver dysfunction already compromises lactate metabolism 7.
• In patients with liver disease and hypoalbuminemia, decreased protein binding and delayed clearance of prednisolone can exacerbate metabolic complications 8.
• Acute precipitating events in chronic liver disease patients—particularly sepsis and gastrointestinal hemorrhage—trigger type A lactic acidosis, and steroid use in this context may worsen outcomes 6.

Diabetes and Metformin Interaction

The most clinically relevant concern involves the interaction between steroid-induced hyperglycemia and metformin use:

• Steroids cause severe hyperglycemia that can lead to acute kidney injury through hyperosmolar states, reducing metformin clearance 3, 4.
• Metformin accumulation in the setting of declining renal function (eGFR <45 mL/min/1.73 m²) significantly increases lactic acidosis risk 7.
• In hospitalized patients with COVID-19 and diabetes, metformin use was associated with increased lactic acidosis incidence (adjusted hazard ratio 4.46), particularly with higher doses, worse kidney function, and severe illness 7.
• Critical pitfall: Steroid-induced hyperglycemia can precipitate acute kidney injury, creating the exact conditions where metformin becomes dangerous 7, 9.

Sepsis and Tissue Hypoxia

• Steroids are frequently administered in septic patients, where type A lactic acidosis from tissue hypoxia is already present 5, 2.
• The combination of underlying circulatory failure, potential liver dysfunction from sepsis, and steroid administration creates a perfect storm for lactate accumulation 5, 6.

Clinical Management Algorithm

When evaluating a patient on steroids with elevated lactate:

1. Immediately assess for type A lactic acidosis causes (tissue hypoxia, sepsis, shock, circulatory failure) 5, 2.

2. Evaluate hepatic function comprehensively:

   • Check prothrombin time (prolongation is an early marker of acute hepatic failure) 6.
   • Assess for acute precipitating events: sepsis, GI bleeding, or acute liver decompensation 6.
   • Measure serum albumin (hypoalbuminemia increases steroid toxicity risk) 8.

3. Review all medications for drug-induced causes:

   • Discontinue metformin immediately if eGFR <30 mL/min/1.73 m² or if acute kidney injury, hypoxia, or shock is present 7, 9.
   • Check lactate levels in fragile patients on metformin, especially with declining renal function 7.
   • Assess for other medications known to cause hyperlactatemia (epinephrine, albuterol, nucleoside reverse transcriptase inhibitors) 1.

4. Monitor renal function closely:

   • Steroid-induced hyperglycemia can precipitate acute kidney injury 3, 4.
   • Check eGFR every 3-6 months in patients on metformin with baseline eGFR 30-45 mL/min/1.73 m² 9.

5. Manage steroid-induced hyperglycemia aggressively to prevent secondary complications:

   • Target blood glucose 100-180 mg/dL (5.6-10.0 mmol/L) 4.
   • Use NPH insulin for intermediate-acting steroids or long-acting basal insulin for dexamethasone 4.
   • Avoid relying on oral antidiabetic agents alone for high-dose steroid therapy 4.

Key Clinical Caveats

• Do not attribute lactic acidosis to steroids without excluding all other causes, as this represents a diagnosis of exclusion 1, 2.
• Patients with chronic liver disease receiving steroids for alcoholic hepatitis have no long-term survivors when lactic acidosis develops, making prevention critical 6.
• Hypoglycemia in acute hepatic failure can paradoxically worsen lactate levels; glucose administration alone can rapidly lower lactate in this specific context 6.
• The mortality rate for medication-induced lactic acidosis is 16%, with 6% of deaths directly attributed to the medication 1.
• Metformin must be temporarily discontinued during acute illness, contrast procedures, acute kidney injury, and hospitalization in patients receiving steroids 7, 9.