The confounding effect of hyperchloraemia on the base deficit in diabetic ketoacidosis

Objectives

To test the hypotheses: (1) that chloride accounts for an increasing proportion of the base deficit with treatment in diabetic ketoacidosis (DKA), and (2) that the perceived discrepancy between changes in the anion gap and bicarbonate/base deficit during treatment is primarily due to the chloride effect.

Methods

A retrospective cohort study of children <16 years (n = 18) admitted for acute management of DKA to two paediatric ICUs. Stewart's physicochemical theory was used to calculate the independent effect of chloride on the bicarbonate and base deficit via a linear regression model. This model was then used to: (1) quantify the effect of chloride on the base deficit, and (2) evaluate the relationship between change in the anion gap and both bicarbonate and base deficit before and after correction for chloride.

Results

Eighteen children (median age 12.7 years, weight 43 kg) were followed for 20 hours after initiation of therapy (insulin and fluid resuscitation). There was a steady improvement in pH over this time (mean pH 6.97–7.31). However, at 20 hours a significant base deficit persisted (mean 10.1 mmol/l), despite the anion gap having normalised (mean 33.7 to 16.4 mmol/l). The base deficit at this time was almost exclusively due to hyperchloraemia (98%).

The relationship between changes in the anion gap and both bicarbonate and base deficit improved dramatically, approaching one-for-one after correction for chloride (slope 0.99, r² = 0.96 and slope 1.14, r² = 0.95, respectively).

Conclusions

Chloride has a confounding effect on the interpretation of the base deficit and bicarbonate during the treatment of DKA. This does not occur with the anion gap, which may be a better marker to track resolution of ketoacidosis and should therefore be incorporated into treatment guidelines.

Figure 1