Cerebral edema in diabetic ketoacidosis with serum sodium below 135 mEq/L

J Pediatr. 2008 Jan;152(1):145-6;

Sema A, Puliyel JM.

Cerebral edema in diabetic ketoacidosis with serum sodium below 135 mEq/L

Hooran et al1 have studied a group of patients with diabetic ketoacidosis (DKA) and cerebral edema (CE) against 2 control groups without CE, one with and the other without hypernatraemia. They suggest that a gradual decrease in plasma glucose and a concomitant increase in serum sodium, decrease the likelihood of CE. This finding takes us a little closer to understanding CE in DKA.

However our analysis of their data shows that there is a characteristic of the CE group that has not been highlighted by the authors which may be crucial. The CE group had significantly lower levels of serum sodium at the start of therapy, than even the ‘low sodium control group’ (LSCG). The 95% confidence intervals (CI) lies below the normal serum sodium threshold (135 mEqL), while the CI in the LSCG lies above this threshold.

We have previously shown that DKA patients have raised osmolality (measured osmolality evaluated by depression of freezing point) and that they have a large osmolar gap (Osmolar gap = Measured osmolality (-) Calculated osmolality); (Calculated osmolality = 2 ×PNa + P Glucose (in mmol/l)2. Unmeasured substances like ketoacids are responsible for the osmolar gap. Using a modified red-blood-cell saline fragility test, we have previously shown that ketoacids are osmotonic in nature, and that they cause fluid shifts across cell membranes3. Ketoacids are also responsible for the effective osmolality like glucose in DKA.

The finding of significant hyponatraemia before the onset of treatment, in patients with CE by Hooran and colleagues, ties in with our observations. Patients with DKA and a high serum osmolality [due to high levels of glucose (a measured substance) and high ketoacid levels (unmeasured)], will respond with reduced serum sodium levels in an effort to maintain serum osmolality as close to normal as possible. Treatment of DKA results in a fall in glucose and ketoacid levels. Physicians know to be careful to bring down levels of glucose gradually but they are not aware how quickly ketoacid levels are changing.

We believe that Hoorn et al have shown that a serum sodium level below 135mEq/L before treatment, is a risk factor for development of CE and this may be a pointer to the high levels of unmeasured osmotic substances in the blood. Further we reiterate that patients with DKA should have serum osmolality measured objectively by techniques like the depression of freezing point as this provides a clearer index of the changes being brought about during the treatment of DKA 4.

Akatoli Sema DCH
Jacob M Puliyel MD MRCP M Phil
Department of Pediatrics
St Stephens Hospital, Delhi 110054 India

1. Hoorn EJ, Carlotti AP, Costa LA, MacMohan B, Bohn G, Zietse R, Halperin ML, Bohn D. Preventing a drop in effective plasma osmolality to minimize the likelihood of cerebral edema during treatment of children with diabetic ketoacidosis. J Pediatr. 2007;150:467-73.

2. Puliyel J, Puliyel M, Hincliff R. Hypertonicity in diabetic ketoacidosis: Unexpected biochemical correlates and clinical implications. Joint Meeting of International Symposium on Diabetes and Endocrine disorders of the young and 4th Asian Symposium of Childhood and Juvenile Diabetes: Chaing Mai Thailand Jan 26-9 1997

3. Puliyel JM. Osmotonicity of acetoacetate: possible implications for cerebral edema in diabetic ketoacidosis. Med Sci Monit. 2003;9:BR130-3.

4. Puliyel JM, Bhambhani V. Ketoacid levels may alter osmotonicity in diabetic ketoacidosis and precipitate cerebral edema. (Letter) Arch Dis Child. 2003; 88:366.