Increase in counter regulatory hormones including glucagon, catecholamines, cortisol, and growth hormone
Hyperglycemia owing to:
Decreased peripheral glucose utilization
Increased hepatic gluconeogenesis
Hyperosmolality and osmotic diuresis due to hyperglycemia
Ketoacidosis produced by increased lipolysis, with ketone body (β-hydroxybutyrate, acetoacetate) production, causes ketonemia and metabolic acidosis, which is augmented with lactic acidosis from poor tissue perfusion
Potassium deficit:
Intracellular shifts into extracellular space owing to hydrogen ion exchange
The overall incidence has been increased worldwide by 2-5% over the past 20 yr.
Precipitating events leading to diabetic ketoacidosis (DKA):
Infection, often minor acute illness such as virus, group A streptococcal pharyngitis, or UTI
Stress
Endocrine: Pregnancy, puberty, hyperthyroidism
Psychiatric disorders, including eating disorders
Medication noncompliance, inappropriate interruption of insulin pump therapy, or treatment error
Risk factors for cerebral edema:
Attenuated rise in measured serum sodium during DKA therapy (unrelated to the volume or sodium content of IV fluid or rate of change in serum glucose)
Bicarbonate treatment for acidosis correction
Hypocapnia
Increased serum urea nitrogen
No association with degree of hyperglycemia
Demographic factors that have been associated with an increased risk of cerebral edema include younger age, longer duration of symptoms, and new onset diabetes mellitus. These factors are also associated with increased risk of severe DKA.
Diagnosis
Signs and Symptoms
Polydipsia
Polyuria (may have good urine output despite dehydration)
Nocturia
Polyphagia
Malaise, weight loss
DKA:
Initial presentation in 20-40% of patients
Often associated with tachypnea (Kussmaul respiration), tachycardia, orthostatic BP changes
Nausea
Vomiting
Abdominal pain, often resolving with reduction in ketosis/acidosis
Hyperpnea
Fruity breath secondary to ketones
Rapid onset of DKA can occur within 7-8 hr with the use of insulin pump therapy if there is an infusion set or insulin delivery malfunction. This is due secondary to lack of long acting insulin to provide a safety net (more commonly seen in female >10 yr of age).
Findings with more advanced disease
Dehydration, drowsiness, altered mental status, and ultimately, late stage coma and shock
Cerebral edema:
The incidence ranges from 0.87-1.1%.
Cerebral edema accounts for 57-87% of all DKA deaths.
It typically occurs 4-12 hr after treatment is initiated, but can be presenting (subclinical) before treatment has started.
Headache
Change in neurologic status, such as drowsiness, irritability, or specific neurologic deficit, such as pupillary responses or cranial nerve palsies
Inappropriate slowing in pulse rate
Increase in BP
Hyperglycemic hyperosmolar nonketotic coma:
Glucose level of 800-1,200 mg/dL
Rare in children; more common in adults
Essential Workup
For DKA:
The International Society for Pediatric and Adolescent Diabetes (ISPAD) defines DKA as blood bicarbonate level <15 mmol/L or venous pH <7.3 and hyperglycemia (>200 mg/dL) with related ketonemia or ketonuria.
DKA classification:
Mild DKA: Venous pH <7.2-7.3 or HCO3 <10-15 mmol/L
Moderate DKA: Venous pH <7.1-7.2 or HCO3 <5-10 mmol/L
Severe DKA: Venous pH <7.1 or HCO3 <5 mmol/L
Hourly vital signs and neurologic checks
Frequent blood chemistries
ECG monitoring (in severe DKA) to assess T-waves for evidence of hyperkalemia or hypokalemia
Accurate fluid input and output. Consider urinary catheterization in patients with impaired level of consciousness.
Diagnosis Tests & Interpretation
Lab
For DKA:
Glucose, serum: Hyperglycemia
Urinalysis:
Glycosuria
Ketonuria
Exclude UTI
Blood chemistries every 2-4 hr until acidosis has resolved (more frequent as clinically indicated in the more severe cases)
Electrolytes and venous pH
Anion gap metabolic acidosis:
Potassium-high or normal (artifactual owing to extracellular shift)
Serum potassium rises 0.5 mEqL for each 0.1 decrease in pH
Sodium-low or normal (may be artifactual owing to hyperglycemia)
Corrected Na (mEq/L) = [measured serum Na (mEqL) + plasma glucose (mg/dL) - 100] — 0.016
Bicarbonate-low
Calculation: Na - (Cl + HCO3)
Serum ketones-elevated. β-hydroxybutyrate (BHOB) is a quantitative test that is available to replace the classic nitroprusside test for serum ketones
Serum osmolality
CBC:
WBC often elevated owing to stress or infection
Calcium
Phosphate
Cultures as indicated: Group A streptococcal pharyngeal swab, urine, etc.
Pregnancy test if indicated
ECG if potassium markedly abnormal
Imaging
CXR if any suggestion of pneumonia
Head CT if there are concerns about cerebral edema
Differential Diagnosis
Infection (may precipitate):
UTI
Gastroenteritis
Appendicitis
Sepsis
Ingestion (salicylates, alcohols, glycols)
Diabetes insipidus
Treatment
Pre-Hospital
For DKA:
ABCs
Airway protection
Establish IV access and initiate fluid therapy.
Initial Stabilization/Therapy
For DKA:
Oxygen
Cardiac monitor
IV access and volume resuscitation
Ed Treatment/Procedures
For DKA:
Fluid replacement:
Assume fluid deficit of 10% of body weight.
Initial volume expansion with 10-20 mL/kg of 0.9% NaCl or lactated Ringer; may repeat to achieve hemodynamic stability
Correct 50% of fluid deficit over 1st 8 hr, remainder over 24-48 hr.
Do not give >3 L/m2 over 1st 24 hr.
Begin IV insulin infusion after ketoacidosis confirmed:
Initial rate of continuous infusion (regular insulin) 0.1 U/kg/h IV
Adjust rate to drop serum glucose 50-100 mg/dL/h.
Add dextrose to infusion fluid when serum glucose <300 mg/dL.
Change to SC insulin when no longer significantly acidotic and able to eat.
Some clinicians prefer IM route, commonly initially using regular insulin at a dose of 0.1-0.2 U/kg/h.
Replace potassium and phosphate losses:
Verify adequate urine output.
Add to fluids as K-acetate (or KCl if acetate not available) and K3PO4 in equal amounts.
Large doses of K+ may be necessary; guide therapy by frequent monitoring of K+.
Monitor serum sodium:
Risk for cerebral edema if Na+ fails to rise as glucose falls
Bicarbonate therapy:
Not recommended in most cases since generally it does not alter outcome and it increases risk for cerebral edema with its use
Use it with caution in patients with severe acidosis (pH <6.9) in whom peripheral vasodilation and decreased cardiac contractility may further impair tissue perfusion and in potentially life-threatening hyperkalemia.
Cerebral edema:
Treat cerebral edema as soon as the condition is suspected due to its high mortality and morbidity rates: 21-25% and 10-26%, respectively.
Decrease fluid administration rate.
Mannitol (0.25-1 g/kg over 20 min): No large studies to date demonstrate definitive beneficial or detrimental effects. Consider its use in patients with signs of cerebral edema before impeding respiratory failure. Dose can be repeated in 2 hr if there is no initial response.
Endotracheal intubation and ventilation: Avoid aggressive hyperventilation since it has been associated with poor outcome in DKA-related cerebral edema (similar to that found in head trauma).
Medication
Insulin drip: Start regular insulin 0.1 U/kg/h IV (some clinicians prefer the IM dosing and route).
Mannitol: 0.25-1 g/kg IV
Follow-Up
Disposition
Admission Criteria
For DKA:
ICU:
Altered mental status
Shock or cardiac dysrhythmia
Initial glucose >700 mg/dL
Initial pH <7
Risk factors for cerebral edema (age <5 yr, prolonged symptoms, high BUN)
Patients with ketoacidosis not meeting requirements for ICU care
Compliance concerns or other social issues
Discharge Criteria
Known diabetic patients who respond well to therapy with normalization of glucose, pH, and ketosis
Tolerating oral fluids
Reliable parents
Reliable follow-up within 24 hr including appropriate education
Issues for Referral
Critically ill
Persistent abnormal mental status
Poorly controlled diabetes
Follow-Up Recommendations
Close follow-up with the primary care physician is important even after the resolution of DKA to ensure appropriate management of the patients diabetes to prevent further occurrence of DKA.
Many children with diabetes are followed at comprehensive diabetes centers in collaboration with primary care physician.
Pearls and Pitfalls
Mortality from DKA is predominately related to the occurrence of cerebral edema. Therefore, early and appropriate treatment is of most importance in managing children with DKA.
In children, avoid using an insulin bolus since it increase the risk of cerebral edema. Recently, some data suggest that starting insulin drip at 0.05 U/kg/h may reduce the risk for rapid fluid shifts and theoretically for cerebral edema.
Additional Reading
Al Hanshi S, Shann F. Insulin infused at 0.05 versus 0.1 units/kg/hr in children admitted to intensive care with diabetic ketoacidosis. Pediatr Crit Care Med. 2011;12:137-140.
Cebeci AN, Guven A, Kirmizibekmez H, et al. Clinical features and management of diabetic ketoacidosis in different age groups of children: Children less than 5 years of age are at higher risk of metabolic decompensation. J Pediatr Endocrinol Metab. 2012;25(9-10):917-925. doi:10.1515/jpem-2012-0110.
de Vries L, Grushka Y, Lebenthal Y, et al. Factors associated with increased risk of insulin pump discontinuation in pediatric patients with type 1 diabetes. Pediatr Diabetes. 2011;12(5):506-512. doi:10.1111/j.
Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001;344:264-269.
Kamat P, Vats A, Gross M, et al. Use of hypertonic saline for the treatment of altered mental status associated with diabetic ketoacidosis. Pediatr Crit Care Med. 2003;4:239-242.
Roberts JS, Vavilala MS, Schenkman KA, et al. Cerebral hyperemia and impaired cerebral autoregulation associated with diabetic ketoacidosis in critically ill children. Crit Care Med. 2006;34:2217-2223.
Toledo JD, Modesto V, Peinador M, et al. Sodium concentration in rehydration fluids for children with ketoacidotic diabetes: Effect on serum sodium concentration. J Pediatr. 2009;154:895-900.
Wolfsdorf J, Craig ME, Daneman D, et al. Diabetic ketoacidosis in children and adolescents with diabetes. Pediatr Diabetes. 2009;10(suppl 12):118-133.
Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:1150-1159.
Codes
ICD9
250.01 type I diabetes mellitus [insulin dependent type] [IDDM] [juvenile type], not stated as uncontrolled, without mention of complication
250.03 Diabetes mellitus without mention of complication, type I [juvenile type], uncontrolled
250.11 type I diabetes mellitus [insulin dependent type] [IDDM] [juvenile type], not stated as uncontrolled, with ketoacidosis
ICD10
E10.9 Type 1 diabetes mellitus without complications
E10.10 Type 1 diabetes mellitus with ketoacidosis without coma
E10.65 Type 1 diabetes mellitus with hyperglycemia
SNOMED
46635009 Diabetes mellitus type 1 (disorder)
420270002 Ketoacidosis in type I diabetes mellitus (disorder)
441656006 Hyperglycemic crisis in diabetes mellitus (disorder)