Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department

Abstract

DKA is a severe metabolic derangement characterized by dehydration, loss of electrolytes, hyperglycemia, hyperketonemia, acidosis and progressive loss of consciousness that results from severe insulin deficiency combined with the effects of increased levels of counterregulatory hormones (catecholamines, glucagon, cortisol, growth hormone). The biochemical criteria for diagnosis are: blood glucose > 200 mg/dl, venous pH <7.3 or bicarbonate <15 mEq/L, ketonemia >3 mmol/L and presence of ketonuria. A patient with DKA must be managed in an emergency ward by an experienced staff or in an intensive care unit (ICU), in order to provide an intensive monitoring of the vital and neurological signs, and of the patient's clinical and biochemical response to treatment. DKA treatment guidelines include: restoration of circulating volume and electrolyte replacement; correction of insulin deficiency aiming at the resolution of metabolic acidosis and ketosis; reduction of risk of cerebral edema; avoidance of other complications of therapy (hypoglycemia, hypokalemia, hyperkalemia, hyperchloremic acidosis); identification and treatment of precipitating events. In Brazil, there are few pediatric ICU beds in public hospitals, so an alternative protocol was designed to abbreviate the time on intravenous infusion lines in order to facilitate DKA management in general emergency wards. The main differences between this protocol and the international guidelines are: intravenous fluid will be stopped when oral fluids are well tolerated and total deficit will be replaced orally; if potassium analysis still indicate need for replacement, it will be given orally; subcutaneous rapid-acting insulin analog is administered at 0.15 U/kg dose every 2-3 hours until resolution of metabolic acidosis; approximately 12 hours after treatment initiation, intermediate-acting (NPH) insulin is initiated at the dose of 0.6-1 U/kg/day, and it will be lowered to 0.4-0.7 U/kg/day at discharge from hospital.

ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state

“…Thereafter, and after commencing insulin therapy, the plasma glucose concentration typically decreases at a rate of 2 to 5 mmol/L/h, depending on the timing and amount of glucose administration To prevent an unduly rapid decrease in plasma glucose concentration and hypoglycemia, 5% glucose, initially, should be added to the IV fluid when the plasma glucose falls to approximately 14 to 17 mmol/L (250‐300 mg/dL), or sooner if the rate of fall is precipitous. It may be necessary to use 10% or even 12.5% dextrose to prevent hypoglycemia while continuing to infuse insulin to correct the metabolic acidosis. These glucose concentrations are often necessary to prevent hypoglycemia when insulin is infused at a rate of 0.1 unit/kg/h. If BG falls very rapidly (>5 mmol/L/h) after initial fluid expansion, consider adding glucose even before plasma glucose has decreased to 17 mmol/L (300 mg/dL). If biochemical parameters of DKA (venous pH, anion gap, BOHB concentration) do not improve, reassess the patient, review insulin therapy, and consider other possible causes of impaired response to insulin; for example, infection, errors in insulin preparation or route of administration. In circumstances where continuous IV administration is not possible and in patients with uncomplicated DKA, hourly or 2‐hourly SC rapid‐acting insulin analog (insulin lispro or insulin aspart) is safe and may be as effective as IV regular insulin infusion, but, ideally, should not be used in patients whose peripheral circulation is impaired. Initial dose SC: 0.3 unit/kg, followed 1 hour later by SC insulin lispro or aspart at 0.1 unit/kg every hour, or 0.15 to 0.20 units/kg every 2 to 3 hours …”

“…These glucose concentrations are often necessary to prevent hypoglycemia when insulin is infused at a rate of 0.1 unit/kg/h. If BG falls very rapidly (>5 mmol/L/h) after initial fluid expansion, consider adding glucose even before plasma glucose has decreased to 17 mmol/L (300 mg/dL). If biochemical parameters of DKA (venous pH, anion gap, BOHB concentration) do not improve, reassess the patient, review insulin therapy, and consider other possible causes of impaired response to insulin; for example, infection, errors in insulin preparation or route of administration. In circumstances where continuous IV administration is not possible and in patients with uncomplicated DKA, hourly or 2‐hourly SC rapid‐acting insulin analog (insulin lispro or insulin aspart) is safe and may be as effective as IV regular insulin infusion, but, ideally, should not be used in patients whose peripheral circulation is impaired. Initial dose SC: 0.3 unit/kg, followed 1 hour later by SC insulin lispro or aspart at 0.1 unit/kg every hour, or 0.15 to 0.20 units/kg every 2 to 3 hours If blood glucose falls to <14 mmol/L (250 mg/dL) before DKA has resolved, reduce SC insulin lispro or aspart to 0.05 unit/kg/h to keep BG ≈11 mmol/L (200 mg/dL) until resolution of DKA. Subcutaneous administration of short‐acting insulin (regular) every 4 hours is also a safe and effective alternative to IV insulin infusion in children with pH ≥7.0 …”

“…If biochemical parameters of DKA (venous pH, anion gap, BOHB concentration) do not improve, reassess the patient, review insulin therapy, and consider other possible causes of impaired response to insulin; for example, infection, errors in insulin preparation or route of administration. In circumstances where continuous IV administration is not possible and in patients with uncomplicated DKA, hourly or 2‐hourly SC rapid‐acting insulin analog (insulin lispro or insulin aspart) is safe and may be as effective as IV regular insulin infusion, but, ideally, should not be used in patients whose peripheral circulation is impaired. Initial dose SC: 0.3 unit/kg, followed 1 hour later by SC insulin lispro or aspart at 0.1 unit/kg every hour, or 0.15 to 0.20 units/kg every 2 to 3 hours …”

“…• When ketoacidosis has resolved, oral intake is tolerated, and the change to SC insulin is planned, a dose of basal (long-or intermediate-acting) insulin should be administered in addition to rapid-or short-acting insulin. 158 The most convenient time to change to SC insulin is just before a mealtime. There may, also, be benefits to earlier administration of a dose of basal insulin while the patient is still receiving IV insulin infusion.…”

“… Oral fluids should be introduced only when substantial clinical improvement has occurred (mild acidosis/ketosis may still be present). Persistent ketonuria (measurement of urine ketones with test strips is based on the nitroprusside reaction, which measures acetoacetate and acetone) characteristically occurs for several hours after serum BOHB levels have returned to normal Absence of ketonuria should not be used as an end‐point for determining resolution of DKA. When ketoacidosis has resolved, oral intake is tolerated, and the change to SC insulin is planned, a dose of basal (long‐ or intermediate‐acting) insulin should be administered in addition to rapid‐ or short‐acting insulin . The most convenient time to change to SC insulin is just before a mealtime.…”