How to manage lactic acidosis in liver failure?

From the Guidelines

Managing lactic acidosis in liver failure requires a multifaceted approach targeting both the underlying liver dysfunction and the metabolic derangement, with the most recent guidelines suggesting early recognition and prompt management of liver failure and its complications may improve outcomes 1. Initial management should focus on hemodynamic stabilization with intravenous fluids, typically crystalloids like normal saline at 10-20 ml/kg, to improve tissue perfusion. Vasopressors such as norepinephrine (starting at 0.05-0.1 mcg/kg/min) may be necessary if fluid resuscitation alone is insufficient. Addressing the underlying liver failure is crucial, which may involve treating precipitating factors like infections with appropriate antibiotics, stopping hepatotoxic medications, or managing acute viral hepatitis. Some key considerations include:

• Continuous renal replacement therapy (CRRT) should be considered for severe acidosis (pH < 7.2) or when conventional measures fail, with bicarbonate preferred over lactate in patients with lactic acidosis and/or liver failure 1.
• Sodium bicarbonate administration (1-2 mEq/kg IV over 1-2 hours) may be used cautiously for severe acidosis, but its benefit is controversial as it can increase lactate production.
• Thiamine supplementation (100 mg IV daily for 3-5 days) is important as deficiency can contribute to lactic acidosis.
• Avoid medications metabolized by the liver that may worsen acidosis, such as metformin. Regular monitoring of arterial blood gases, lactate levels, and liver function tests is essential to guide therapy, as the liver normally clears lactate from the bloodstream, so when liver function is compromised, lactate accumulates, making management particularly challenging and often requiring intensive care support 1. In cases of acute liver failure, the use of N-acetylcysteine (NAC) is recommended, especially in patients with acetaminophen overdose 1. Overall, the management of lactic acidosis in liver failure should prioritize early intervention, careful monitoring, and a multidisciplinary approach to address the complex pathophysiology and improve patient outcomes.

From the FDA Drug Label

Sodium Bicarbonate Injection, USP is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis Vigorous bicarbonate therapy is required in any form of metabolic acidosis where a rapid increase in plasma total CO2 content is crucial - e. g., cardiac arrest, circulatory insufficiency due to shock or severe dehydration, and in severe primary lactic acidosis or severe diabetic acidosis. In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm.

Management of Lactic Acidosis in Liver Failure:

• The treatment of lactic acidosis, including in the context of liver failure, involves addressing the underlying cause of the acidosis.
• Sodium bicarbonate therapy may be indicated in severe primary lactic acidosis.
• The dosage and administration of sodium bicarbonate should be tailored to the individual patient's needs, with careful monitoring of blood gases, plasma osmolarity, arterial blood lactate, hemodynamics, and cardiac rhythm.
• A stepwise approach to therapy is recommended, with initial doses of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours, and subsequent adjustments based on clinical response 2, 2.

From the Research

Management of Lactic Acidosis in Liver Failure

• The management of lactic acidosis in liver failure involves addressing the underlying cause of the condition, ensuring adequate oxygen delivery to tissues, and reducing oxygen demand through sedation and mechanical ventilation 3.
• The use of sodium bicarbonate to correct severe acidemia is controversial, with some studies suggesting that it may not improve patient outcomes and can even have negative side effects such as decreasing vasomotor tone, decreasing myocardial contractility, and inducing intracellular acidosis 4, 5, 6.
• However, a randomized control trial found a survival benefit in a subgroup of critically ill patients with serum pH levels <7.2 with concomitant acute kidney injury, suggesting that bicarbonate use may be beneficial in certain cases 6.
• If bicarbonate is used, it is recommended to administer it as a slow IV infusion in the setting of adequate ventilation and calcium replacement to mitigate its untoward effects 5, 6.
• Other potential therapies for lactic acidosis include the use of other buffers such as THAM or Carbicarb, or dialysis, which may provide base with fewer untoward effects 7.
• The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger, and selective NHE1 inhibitors may improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality 7.
• Targeting the mechanisms that contribute to lactic acid accumulation, such as tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis, could allow for more specific therapy 7.