Guidelines for the Early Management of Diabetic Ketoacidosis in Children

1. Guidelines for the Early Management of Diabetic Ketoacidosis in Children Michael Bressack, MD

2. DEFINITION • Hyperglycemia (serum glucose >300 mg/dl) with glycosuria • Metabolic acidosis (serum bicarbonate <15, elevated anion gap, pH <7.30) • Ketonemia with ketonuria

3. CLINICAL PRESENTATION - HYPERGLYCEMIA • Polyuria • Polydipsia • Weight loss • Dehydration/shock • Decreased level of consciousness

4. CLINICAL PRESENTATION - METABOLIC ACIDOSIS • Kussmaul breathing • Fruity breath (acetone) • ? decreased level of consciousness • ? depressed cardiac function • ? intestinal ileus (vomiting, pain)

5. LABORATORY DATA • Hyperglycemia • Metabolic acidosis (anion gap) • [Na+]-([Cl-]+[HCO3-]) • OH butyrate • Low [Na+]

6. [Nac+] = [Nam+] + 1.6(blood glucose-100) 100

7. LABORATORY DATA • Hyperglycemia • Metabolic acidosis (anion gap) • [Na+]-([Cl-]+[HCO3-]) • OH butyrate • Low [Na+] • Abnormal [K+] • Pre-renal azotemia

8. MONITORING • Blood glucose q 1 h -q 4 h • Electrolytes q 1 h -q 4 h • Anion gap q 1 h -q 4 h • Renal function q 4 h – q 6 h • Cardiac monitor/EKG

9. CLINICAL MONITORING • Cardiovascular • Intake/urinary output • Neurologic status (Glasgow Coma Scale)

10. CARDIOVASCULAR TREATMENT • Treat shock immediately • 10-20 ml/kg doses of NS or LR • Slow rehydration for 5-15% deficit over 48 hours

11. SLOW REHYDRATION • Maintenance, deficit, excessive urine (because of the risks of cerebral edema, infuse fluid at a maximal rate of 1.5 to 2 times maintenance) • Normal saline is usually the best initial fluid (avoid hypotonic fluid) • Follow [Na+] closely (keep [Na+corrected] 135meq/l)

12. TREATMENT FOR HYPER- GLYCEMIA / KETOACIDOSIS • Rehydration lowers blood glucose • Low-dose continuous insulin • (.05 - 0.1 u/kg/hr) • IV bolus of insulin is not necessary

13. CONTINUOUS INSULIN DRIP • Decrease blood glucose 50-100 mg/dl/hr (after the initial drop due to rehydration) • Add glucose to intravenous fluid when blood glucose <250-300 mg/dl • add glucose to maintenance fluids only • Increases bicarbonate and decreases anion gap (takes longer to correct ketoacidosis than hyperglycemia) • use enough insulin to correct the anion gap acidosis, and add enough glucose to the intravenous fluid to tolerate the insulin

14. TREATMENT FOR K+ • Usually hyperkalemia on presentation • Total body K+ deficit • Monitor EKG • Initiate K+ replacement when serum level <5.5meq/l and adequate urine output • In the rare situation of hypokalemia at presentation, immediately treat with K+ replacement and fluid therapy, but delay insulin treatment until K+ >3.3meq/l

15. INDICATION FOR BICARBONATE • Life-threatening hyperkalemia • Bicarbonate has no place in the management of DKA

16. Cerebral edema is a medical emergency (major cause of death in pediatric DKA)

17. Causes of Morbidity/Mortality in DKA • Cerebral edema/dysfunction (80-90% of deaths) • Shock/ischemia • Hyper/hypokalemia • Hypoglycemia • Sepsis • ARDS • Thrombosis • Central venous catheters are particularly prone to thrombosis. If used, prophylaxis with low-dose heparin should be considered.

18. Cerebral Edema/CNS Dysfunction • Clinical cerebral edema occurs in 0.5-0.9% of all episodes of DKA and accounts for 57-87% of all DKA deaths • A clinical, not a radiological, diagnosis (e.g. CNS dysfunction does not correlate with CT changes) • Mortality ~25% (respiratory arrest on presentation has the worst prognosis) • Significant morbidity in survivors (~25%) • Morbidity/mortality from herniation • Major cause of death in DKA • Occurs nearly exclusively in patients <20 years old • More common in: • younger children • children who have a longer duration of DKA before treatment • children with newly diagnosed diabetes • elevated initial BUN • low initial pCO2 • rapid administration of hypotonic fluids • failure of corrected serum sodium to rise during treatment • treatment with bicarbonate • Occurs within first 24 hours after starting Rx (usually 4-12hrs)

19. Signs and Symptoms of Cerebral Edema • Headache, emesis • Lethargy, incoherence, agitation, incontinence, coma • Seizures • Sudden, persistent bradycardia (decline >20bpm) not attributable to improved intravascular volume or sleep state • Abnormal neurogenic respiratory pattern (e.g. tachypnea, Cheyne-Stokes respiration, apneusis) • Decreasing Glasgow Coma Scale • Cranial nerve palsy (e.g. III, IV, VI) • Cushing’s reflex (e.g. hypertension) • Decorticate / decerebrate posturing • Cardiopulmonary arrest

20. Etiology of Cerebral Edema • Cerebral edema due to osmotic shift of fluid • Primary ischemia/hypoxia with secondary cerebral edema

21. Prevention and Treatment of Cerebral Edema • Cardioplumonary stabilization on presentation • fluid boluses of isotonic crystalloids for shock • intubation/ventilation for respiratory failure • After acute therapy for shock, avoid excessive fluid or hypotonic fluid (use only 0.45%saline or normal saline) • Avoid medications that can mask intracranial hypertension e.g. phenergan, benzodiazepines • Promptly give intravenous mannitol (0.5-1.0gm/kg) or 3% saline (5-10ml/kg) for clinical signs of elevated ICP • Consider intubation for neurologic deterioration- risks include pCO2, which can elevate ICP, and pCO2, which causes cerebral ischemia