From the Research
High anion gap respiratory alkalosis is typically caused by a combination of conditions that simultaneously produce both metabolic acidosis and respiratory alkalosis, with salicylate poisoning being a notable cause, as evidenced by a recent case report 1. The most common causes of this mixed disorder include:
- Salicylate poisoning (aspirin overdose), which directly stimulates the respiratory center in the brain while also causing metabolic acidosis through various mechanisms including inhibition of the Krebs cycle, as seen in a case report where the patient presented with a normal anion gap metabolic acidosis due to laboratory interference 1.
- Sepsis, which can lead to this mixed disorder as inflammatory mediators trigger hyperventilation while tissue hypoperfusion causes lactic acidosis.
- Liver failure, which may present with this pattern due to hyperventilation from encephalopathy alongside metabolic acidosis from lactate accumulation and other organic acids.
- Stimulant overdose (such as cocaine, amphetamines, or caffeine), which can cause respiratory alkalosis through central stimulation while simultaneously causing metabolic acidosis through increased lactate production.
- Pulmonary embolism with hypoxemia, which may trigger hyperventilation while tissue hypoxia leads to lactic acidosis.
It is essential to note that the diagnosis of high anion gap respiratory alkalosis can be challenging, and the anion gap may not always be elevated, as seen in cases of salicylate poisoning where laboratory interference can cause a falsely normal anion gap 1, 2. The use of urine anion gap can help differentiate between chronic respiratory alkalosis and metabolic acidosis, especially when arterial blood gas is not obtained, as shown in a recent study 3. In clinical practice, it is crucial to consider the possibility of high anion gap respiratory alkalosis in patients presenting with hyperventilation and low serum bicarbonate concentration, and to use a combination of clinical assessment, laboratory tests, and imaging studies to establish the underlying cause of this mixed disorder.