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What determines the outcome of children with diabetic ketoacidosis admitted to the pediatric intensive care unit of a developing country?

Recently, a number of studies and reviews have focused on diabetic ketoacidosis (DKA) in children, causes of mortality and morbidity (1–3), and optimization of management (4). Although diabetes mellitus in children does not appear to be particularly uncommon in the developing world, there are few reports on DKA in this context, with mortality rates ranging from 3% (of 72 episodes) (5) to 18.2% (of 93 episodes) (6). In this issue of Pediatric Critical Care Medicine, Drs. Jayashree and Singhi (7) present their experience with 68 patients who were admitted to their pediatric intensive care unit over a period of 8 yrs. Nine (13%) of these patients died, and complications such as hypokalemia, hypoglycemia, and cerebral edema were seen in 41%, 15%, and 13.2%, respectively. The causes of death were septic shock (four of nine), cerebral edema (four of nine) with associated pulmonary edema in two patients, and cardiac arrhythmia (related to hypokalemia). Although the authors do not provide information about how many patients with DKA were seen in the hospital over this time period and therefore how their patients were selected, the incidence of cerebral edema is very high. In several studies (1, 2, 8), the incidence of cerebral edema in children with DKA in the United States and United Kingdom was 1%, although it may be marginally higher in newly diagnosed children (1). No factors were identified in this study to explain the high incidence of cerebral edema. Sepsis in this study is common, including infections such as hepatitis, which would be rare in the developed world and is the cause of death in four patients with septic shock (7). Septic shock has not been a feature of recent reviews of death in DKA, and a recent study suggested that 69% of children ( 21 yrs of age) with DKA had no evidence of infection, 17.8% had presumed viral infection, and only 12.9% had bacterial infection (9). Even in earlier reports of DKA, sepsis was not a major factor. In the era 1950–1985, a review of 55 deaths related to childhood diabetes mellitus, at the Children’s Hospital of Pittsburgh, showed that in new-onset patients, one of 20 deaths was related to sepsis with DKA, whereas in 35 previously diagnosed diabetics four deaths occurred from sepsis related to DKA (10). Patients who died were shown to be older (median of 11 vs. 6 yrs) and sicker at the time of admission, with lower pH (median, 6.98 vs. 7.07), lower PCO2 (median, 13.7 vs. 21 mm Hg), and higher osmolality (median, 315 vs. 303 mOsm/ L). Over the next 6–12 hrs, the patients who subsequently died had significantly lower pH, bicarbonate, and PCO2, whereas glucose remained higher. This suggests that protocols for management of DKA should include options for intervention when expected improvements do not occur. The majority of protocols for management of DKA are based on the assumption of normal renal function and absence of severe underlying pathology. In regions with high sepsis or with malnutrition, this may not be appropriate. The complication rates with hypoglycemia and hypokalemia seem high. The authors were using management protocols similar to those used throughout the developed world, and they present evidence that nutritional status may affect complication rate. No patient with normal nutritional grade became hypoglycemic vs. five (31%) of those with severe protein energy malnutrition, and only two patients (15.3%) with normal nutrition vs. 11 (68.7%) of those with severe protein energy malnutrition developed hypokalemia. There are some concerns about the use of weight for age as the sole measure of nutritional status, particularly if admission weight (in the presence of dehydration) is used for the assessment. However, it is possible that malnourished children with DKA may need earlier and larger supplements of glucose and potassium. Other trace element deficiencies (e.g., magnesium and phosphate) may also contribute to the severity of DKA in the setting of malnutrition and should be considered, particularly as Dr. Singhi and colleagues have previously demonstrated a high frequency of hypocalcemia (11), hypomagnesemia (12), and hypokalemia (13) in patients admitted to their pediatric intensive care unit. Malnutrition has been associated with the development of forms of diabetes mellitus, and the pathophysiology of DKA in malnourished children may be more complex. The first step required to decrease mortality rates from diabetes in children is to increase the early diagnosis of the condition. However, this is unlikely to carry high priority in the developing world. Under 5 mortality rates in the areas around Chandigarh ranged from 73 (Punjab) to 110 (Haryana) per 1,000 live births (14), and appropriate focus on immunization and nutrition is more important to saving the lives of children Appropriate provision of services for management of DKA is required, but the services available at Chandigarh (24-hr intensivist cover, 1:1 nursing for ventilated patients and 1:2 for other patients, all the equipment associated with modern intensive care, and 24-hr availability of radiology and laboratory services) are more than adequate for the management of DKA and considerably better than most hospitals within the developing world. *See also p. 427.