Diagnosis of mixed acid-base disorders in diabetic ketoacidosis

In diabetic ketoacidosis, a mixed acid-base disorder is suggested when the anion gap increase (delta AG) does not equal the bicarbonate decrease (delta HCO3), or when the delta AG/delta HCO3 ratio does not equal 1.0. It is widely assumed that delta AG/delta HCO3 is significantly different from 1.0 when it is less than 0.8 or greater than 1.2. The validity of these ratio limits were examined by analyzing a normal control group of 68 subjects and 27 diabetic ketoacidosis admissions that had no evidence of mixed disorders. In the 27 ketoacidosis admissions, regression analysis showed that delta AG was predicted to equal delta HCO3, as expected in pure anion gap acidosis: delta AG = 1.0 delta HCO3 (r = 0.744, p < 0.001). It was found that delta AG is significantly different from delta HCO3 when they differ by more than 8 mEq/L, and equivalently, delta AG/delta HCO3 is significantly different from 1.0 when it is less than (1.0 - 8/delta HCO3) or greater than (1.0 + 8/delta HCO3). These criteria from regression analysis suggested that 4% of the 27 pure anion gap acidoses, and 3% of the control group, had mixed disorders. In contrast, the ratio limits of 0.8 and 1.2 suggested 56% of the pure anion gap acidoses, and 94% of the control group, had mixed disorders. It was concluded that mixed disorders are overdiagnosed by the ratio limits of 0.8 and 1.2. Mixed disorders are more accurately detected by noting whether delta AG and delta HCO3 differ by more than 8 mEq/L.