Lactic Acidosis

Obtain a blood gas, serum lactate, basic metabolic panel, glucose, and renal and hepatic indices when hyperlactatemia accompanies suspected metabolic acidosis. Lactic acidosis is characterized by acidemia with elevated lactate; one commonly used definition is pH below 7.35 with lactate greater than 2 mmol/L, whereas metformin-associated lactic acidosis uses lactate greater than 5 mmol/L with pH below 7.35 in the setting of metformin exposure. ScienceDirect+2ScienceDirectMetformin-associated lactic acidosis: Bridging pharmacokinetic ...WileyMetformin‐Associated Lactic Acidosis Following Acute Overdose ...WileySevere Metformin‐Associated Lactic Acidosis—A Case Report

Prioritize conditions in which lactate reflects inadequate oxygen delivery or regional ischemia: septic, cardiogenic, and hypovolemic shock; post-cardiac-arrest states; and limb or mesenteric ischemia. These type A processes require correction of the underlying perfusion or oxygenation deficit rather than treatment directed at lactate alone. ScienceDirect+2ScienceDirectMetformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm - ScienceDirectWolters KluwerA Case of Metformin Associated Lactic Acidosis : Bangladesh Journal of Endocrinology and MetabolismWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library

A serum bicarbonate below 10 mEq/L should broaden the immediate differential beyond isolated lactate elevation to severe ketoacidosis, toxic alcohol ingestion, severe limb or mesenteric ischemia, renal or hepatic failure, metformin-related acidemia, and multifactorial shock. Measure glucose and ketones and review toxicologic and medication exposures in parallel with resuscitation. ScienceDirectScienceDirectMetformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm - ScienceDirect

Calculate the anion gap to recognize unmeasured anions, but directly measure lactate whenever lactic acidosis is suspected. Ketoacidosis and lactic acidosis are common causes of an increased anion gap, yet serum anion gap has poor sensitivity for hyperlactatemia in critically ill patients. Nature+1NatureSignificance of lactate clearance in septic shock patients with high bilirubin levels | Scientific ReportsOxford AcademicLaboratory Recognition and Testing in Acid-Base Disorders

Interpret a falling anion gap cautiously during resuscitation. Chloride-rich fluid administration and hypoalbuminemia can make the apparent anion gap improve even when the patient is clinically worsening or lactate metabolism remains impaired. WileyWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library

Trend lactate with the same attention given to perfusion, hemodynamics, oxygenation, and organ function. In septic shock cohorts, lactate clearance correlated with change in anion gap and was associated with 28-day mortality; this supports serial physiologic reassessment rather than a single lactate-based etiologic conclusion. NatureNatureSignificance of lactate clearance in septic shock patients with high bilirubin levels | Scientific Reports

Type A lactic acidosis is associated with tissue ischemia and anaerobic metabolism. Septic, cardiogenic, and hypovolemic shock, severe hypoxemia, and limb or mesenteric ischemia are high-priority causes because failure to reverse the underlying process can permit continued lactate generation. Wolters Kluwer+1Wolters KluwerA Case of Metformin Associated Lactic Acidosis : Bangladesh Journal of Endocrinology and MetabolismWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library

Type B lactic acidosis occurs without overt tissue hypoperfusion or hypoxia and includes liver disease, malignancy, medications such as metformin and epinephrine, total parenteral nutrition, HIV, thiamine deficiency, trauma, excessive exercise, and ethanol intoxication. Liver and kidney dysfunction also matter because these organs normally contribute to lactate clearance. Nature+1NatureExercise-induced lactic acidemia associated with a SLC16A13 biallelic variant | npj Genomic MedicineWolters KluwerA Case of Metformin Associated Lactic Acidosis : Bangladesh Journal of Endocrinology and Metabolism

Avoid treating type A and type B as mutually exclusive in an unstable patient. Critical illness can combine cellular ischemia, enhanced glycolysis, hepatic or renal impairment, and catecholamine infusion; the resulting lactate level may reflect several active mechanisms. WileyWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library

Suspect metformin-associated lactic acidosis when recent metformin exposure accompanies lactate greater than 5 mmol/L and pH below 7.35. A proposed more restrictive causal paradigm also requires a circulating metformin concentration above 5 mg/L, but metformin assays are often unavailable in emergency care and should not delay treatment. ScienceDirect+2ScienceDirectMetformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm - ScienceDirectScienceDirectMetformin-associated lactic acidosis: Bridging pharmacokinetic ...WileyMetformin‐Associated Lactic Acidosis Following Acute Overdose ...

Separate metformin-induced toxicity from metformin-associated acidemia due to another acute illness whenever possible. In a metformin user with sepsis, cardiac failure, hemorrhage, hypoxia, or renal failure, metformin may be an amplifier, a consequence of reduced clearance, or merely a concomitant medication; management must address all plausible contributors. ScienceDirect+1ScienceDirectMetformin-Induced Lactic Acidosis (MILA): Review of current diagnostic paradigm - ScienceDirectScienceDirectMetformin-Associated Lactic Acidosis - ScienceDirect

Immediately discontinue metformin and identify reversible precipitants: AKI or significant renal impairment, hypovolemia, hepatic dysfunction, tissue hypoxia, sepsis, heart failure, and heavy alcohol intake. Metformin inhibits mitochondrial complex I, reducing oxidative phosphorylation and shifting metabolism toward lactate production; renal dysfunction also impairs drug clearance. Nature+3NatureMetformin-Associated Lactic Acidosis in Clinical Diabetes Management | Clinical Pharmacology and Therapeutics | Pharmacology and Pharmaceutical Sciences | Health sciences | Topics | Nature IndexWolters KluwerMetformin-Associated Lactic Acidosis : Advanced Emergency Nursing JournalScienceDirectMetformin-Associated Lactic Acidosis - ScienceDirectWolters KluwerA Case of Metformin Associated Lactic Acidosis : Bangladesh Journal of Endocrinology and Metabolism

Direct treatment at the dominant cause of lactate generation or impaired clearance. In shock or ischemia, restore oxygen delivery and correct the precipitating process; in drug-associated hyperlactatemia, withdraw or reduce the contributing exposure when clinically feasible; in metformin-associated disease, stop metformin and correct circulatory, electrolyte, and acid-base abnormalities. Nature+3NatureMetformin-Associated Lactic Acidosis in Clinical Diabetes Management | Clinical Pharmacology and Therapeutics | Pharmacology and Pharmaceutical Sciences | Health sciences | Topics | Nature IndexNatureLactic Acidosis in Acute Severe Asthma | Respiratory Diseases | Cardiovascular Medicine and Haematology | Health sciences | Topics | Nature IndexWolters KluwerA Case of Metformin Associated Lactic Acidosis : Bangladesh Journal of Endocrinology and MetabolismWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library

Do not reflexively administer bicarbonate for every lactic acidosis. In diabetic ketoacidosis with metabolic acidosis, bicarbonate is described as unnecessary when hydration and reduction of blood glucose will correct the acidosis; by contrast, severe toxic or renal failure-associated metabolic acidosis may require alkali or renal replacement therapy. NEJM+1NEJM118 Readers' Comments - The New England Journal of MedicineNEJMNEJMra1503102_discussion_1

Use serial lactate, pH, bicarbonate, electrolytes, renal function, and clinical perfusion to determine whether the chosen intervention is working. A biochemical improvement in anion gap alone is insufficient when hyperchloremia, hypoalbuminemia, persistent ischemia, or impaired clearance may conceal ongoing physiologic deterioration. Nature+1NatureSignificance of lactate clearance in septic shock patients with high bilirubin levels | Scientific ReportsWileyMetabolic acidosis in the critically ill: Part 2. Causes and treatment - Morris - 2008 - Anaesthesia - Wiley Online Library