From the Guidelines
Lactic acidosis should be managed by addressing the underlying cause, fluid resuscitation, oxygen supplementation, and hemodynamic support, with consideration of discontinuing metformin in medication-induced cases, as evidenced by a recent study 1. The condition occurs when there is inadequate oxygen delivery to tissues or when the body cannot properly utilize oxygen, causing cells to switch to anaerobic metabolism. Common causes include:
- Shock
- Severe infections
- Heart failure
- Liver disease
- Certain medications (metformin, nucleoside reverse transcriptase inhibitors)
- Excessive exercise
- Seizures
- Certain inherited metabolic disorders Initial management includes:
- Fluid resuscitation with isotonic crystalloids to improve tissue perfusion
- Oxygen supplementation
- Hemodynamic support with vasopressors if needed Sodium bicarbonate may be considered for severe acidosis (pH < 7.1), though its use remains controversial, as suggested by guidelines 1. In medication-induced cases, the offending drug should be discontinued. For metformin-associated lactic acidosis, hemodialysis may be necessary to remove both metformin and excess lactate, particularly in patients with significant renal impairment or liver failure 1. Continuous renal replacement therapy or hemodialysis may be required in severe cases unresponsive to conventional treatment. Blood glucose monitoring is essential during treatment, as correction of acidosis can affect glucose metabolism. The prognosis depends largely on the underlying cause and the severity of acidosis at presentation, with prompt identification and treatment being crucial for improved outcomes. Discontinuation of metformin is recommended in patients at risk for lactic acidosis, such as those with anaerobic metabolism, impaired metformin clearance, or impaired lactic acid clearance 1.
From the FDA Drug Label
There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypotension and resistant bradyarrhythmias have occurred with severe acidosis Metformin associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride tablets In metformin hydrochloride tablets treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions).
Causes of Lactic Acidosis:
- Renal impairment
- Drug interactions that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation
- Age 65 or greater
- Radiologic studies with contrast
- Surgery and other procedures that may increase the risk for volume depletion, hypotension, and renal impairment
- Hypoxic states, such as acute congestive heart failure, cardiovascular collapse, acute myocardial infarction, sepsis
- Excessive alcohol intake
- Hepatic impairment
Treatment of Lactic Acidosis:
- Immediate discontinuation of metformin hydrochloride tablets
- General supportive measures in a hospital setting
- Prompt hemodialysis to correct the acidosis and remove accumulated metformin 2
From the Research
Causes of Lactic Acidosis
- Lactic acidosis is common in severely ill patients, often combined with other acid-base disturbances 3
- Metformin use in treatment of type 2 diabetes mellitus is associated with a rare but important complication of lactic acidosis, with an overall mortality of approximately 50% 4
- However, evidence suggests that diabetes rather than metformin therapy is the major risk factor for the development of lactic acidosis 5
- Acute cardiorespiratory illness, acute renal impairment, and sepsis are common precipitating factors for lactic acidosis 5
Treatment of Lactic Acidosis
- Treating the underlying causes of the acid-base disturbances is the only warranted intervention, as there is no specific treatment for lactic acidosis 3
- Eliminating the triggering conditions remains the most effective therapy for lactic acidosis 6
- Administration of sodium bicarbonate does not improve cardiovascular function or reduce mortality, and may even have negative effects such as reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification 6
- Other buffers, such as THAM or Carbicarb, or dialysis might provide base with fewer untoward effects 6
- Aggressive treatment strategies, including hemodialysis, peritoneal dialysis, continuous bicarbonate infusion, and tight glucose control, have been recommended for metformin-associated lactic acidosis 4