From the Guidelines
High anion gap metabolic acidosis (HAGMA) should be managed by treating the underlying cause, providing supportive care, and considering hemodialysis for severe poisonings, significant renal failure, or profound acidemia unresponsive to conventional therapy, as recommended by the EXTRIP workgroup 1.
Causes and Diagnosis
High anion gap metabolic acidosis is characterized by an elevated anion gap, typically greater than 12 mEq/L. Common causes can be remembered using the mnemonic MUDPILES: Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, and Salicylates. Initial diagnosis involves calculating the anion gap and identifying the underlying cause.
Treatment Approach
Initial treatment includes:
- Fluid resuscitation with isotonic saline at 10-20 mL/kg/hr
- Correcting electrolyte imbalances (particularly potassium)
- Addressing the specific etiology For diabetic ketoacidosis, insulin therapy (0.1 units/kg/hr) is essential. In toxic alcohol ingestions, fomepizole (15 mg/kg loading dose, then 10 mg/kg every 12 hours) or ethanol may be administered to block alcohol metabolism.
Indications for Hemodialysis
Hemodialysis is indicated for:
- Severe poisonings
- Significant renal failure
- Profound acidemia unresponsive to conventional therapy
- Anion gap > 27 mmol/L in the context of ethylene glycol exposure, as recommended by the EXTRIP workgroup 1
Important Considerations
Prompt identification and treatment are crucial as severe acidosis can lead to cardiac dysfunction, altered mental status, and multiorgan failure. The underlying pathophysiology involves accumulation of unmeasured anions from various processes, including ketone production, lactic acid accumulation, or ingested toxins, which disrupt the body's acid-base balance.
Key Recommendations
- Hemodialysis should be considered for patients with an anion gap > 27 mmol/L in the context of ethylene glycol exposure 1
- Fomepizole or ethanol should be administered to block alcohol metabolism in toxic alcohol ingestions 1
- Insulin therapy is essential for diabetic ketoacidosis 1
- Sodium bicarbonate may be considered for severe cases with pH below 7.1, although this remains controversial 1
From the FDA Drug Label
The diagnosis of these poisonings may be difficult because ethylene glycol and methanol concentrations diminish in the blood as they are metabolized to their respective metabolites Hence, both ethylene glycol and methanol concentrations and acid base balance, as determined by serum electrolyte (anion gap) and/or arterial blood gas analysis, should be frequently monitored and used to guide treatment Treatment consists of blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection, and correction of metabolic abnormalities Begin fomepizole injection treatment immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis, increased osmolar gap, visual disturbances, or oxalate crystals in the urine, OR a documented serum ethylene glycol or methanol concentration greater than 20 mg/dL
High anion gap metabolic acidosis is a condition that can be caused by ethylene glycol or methanol poisoning.
- The treatment of high anion gap metabolic acidosis caused by ethylene glycol or methanol poisoning involves blocking the formation of toxic metabolites using inhibitors of alcohol dehydrogenase, such as fomepizole injection, and correction of metabolic abnormalities.
- Fomepizole injection should be started immediately upon suspicion of ethylene glycol or methanol ingestion based on patient history and/or anion gap metabolic acidosis.
- Hemodialysis should be considered in addition to fomepizole injection in the case of renal failure, significant or worsening metabolic acidosis, or a measured ethylene glycol or methanol concentration of greater than or equal to 50 mg/dL 2
From the Research
Definition and Causes of High Anion Gap Metabolic Acidosis
- High anion gap metabolic acidosis is a condition characterized by an increase in the anion gap, which represents the difference between unmeasured cations and unmeasured anions 3.
- The most common causes of high anion gap metabolic acidosis include renal failure, diabetic ketoacidosis, and lactic acidosis 3, 4.
- Other causes of high anion gap metabolic acidosis include intoxication with ethylene glycol, methanol, salicylate, and less commonly with pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean (gjenkolism) 4.
- Severe increases in concentration of phosphorus can also cause hyperphosphatemic acidosis 3.
Diagnosis and Treatment of High Anion Gap Metabolic Acidosis
- The diagnosis of high anion gap metabolic acidosis is established by identifying a decrease in pH, decrease in HCO3- or base excess, and an increased anion gap 3.
- The therapeutic approach should be first aimed at early correction of concurrent clinical problems, such as fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, and hemodialysis for acute intoxications 5.
- In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy 5.
- The treatment of acute organic acidosis, such as lactic acidosis, has been very controversial, and the only effective treatment is cessation of acid production via improvement of tissue oxygenation 4.
Clinical Disorders Causing Metabolic Acidosis
- Metabolic acidosis can be categorized both by mechanism and by the presence or absence of an increased anion gap 6.
- When a diagnosis of metabolic acidosis is established, it becomes imperative to identify the primary causative etiology as quickly as possible, often readily apparent from the history and physical exam 6.
- A stepwise consideration of each of the potential causative etiologies will usually direct the clinician to order the appropriate diagnostic studies 6.
- High anion gap metabolic acidosis can be induced by a variety of underlying conditions, including sepsis, hyperglycaemia, prior gastric bypass surgery, decreased renal perfusion, and paracetamol intake 7.