From the Guidelines
To differentiate between mixed respiratory alkalosis with increased anion gap metabolic acidosis versus increased anion gap metabolic acidosis with respiratory compensation, focus on the pH and the degree of respiratory response, as the most recent and highest quality study 1 emphasizes the importance of acid-base balance in determining the underlying cause of the disorder. In mixed disorders, the respiratory alkalosis is primary and excessive beyond what would be expected for compensation, while in compensated metabolic acidosis, the respiratory response is proportional to the metabolic derangement. For mixed disorders, the pH may be near normal or even alkalemic despite the metabolic acidosis, and the PCO2 will be lower than predicted by Winter's formula (PCO2 = 1.5 × HCO3 + 8 ± 2), as discussed in the context of hyperglycemic crises in diabetes 1. Common causes include sepsis, liver failure, or salicylate toxicity where both primary respiratory alkalosis and metabolic acidosis occur simultaneously, and can be identified through diagnostic criteria such as those outlined for DKA and HHS 1. In compensated metabolic acidosis, the pH remains acidemic, and the PCO2 decreases proportionally according to Winter's formula, representing a normal physiologic response where the respiratory system attempts to normalize pH by increasing ventilation to blow off CO2. Key laboratory findings that suggest a mixed disorder include:
- a PCO2 that is significantly lower than predicted by Winter's formula
- clinical scenarios that commonly cause both disorders
- arterial blood gases
- anion gap calculation
- clinical context, all of which are essential for accurate diagnosis and appropriate management of the underlying causes, as emphasized by the importance of monitoring and managing acid-base disorders in patients with diabetes 1 and other conditions 1.
From the Research
Mixed Respiratory Alkalosis and Increased Anion Gap (IAG) Metabolic Acidosis
- Mixed metabolic-respiratory acid-base disorders may be diagnosed when the respiratory compensation for a primary metabolic acidosis or alkalosis is inappropriate or when there is inappropriate metabolic compensation for a primary respiratory disorder 2
- The magnitude of the primary change in HCO3 concentration (in metabolic disorders) defines the limits of compensation
- When the delta HCO3 is less than the delta AG, a mixed metabolic alkalosis and metabolic acidosis is likely to be present 2
Increased Anion Gap Metabolic Acidosis with Respiratory Compensation
- Anion gap calculation distinguishes between anion gap metabolic acidosis and non-anion gap metabolic acidosis 3
- The evaluation for anion gap metabolic acidosis includes calculating the osmolal gap and conducting a gap-gap analysis 3
- Treatment of an anion gap acidosis is aimed at the underlying disease or removal of the toxin 4
Key Differences
- Mixed Respiratory Alkalosis and Increased Anion Gap (IAG) Metabolic Acidosis involves a combination of respiratory alkalosis and metabolic acidosis, whereas Increased Anion Gap Metabolic Acidosis with Respiratory Compensation involves a primary metabolic acidosis with a compensatory respiratory response
- The presence of mixed acid-base disorders can make diagnosis and treatment more complex, and requires a systematic approach to evaluation 3, 4
- The use of delta AG and delta HCO3 can help diagnose and manage mixed metabolic acid-base disorders 2