1. Diabetic Ketoacidosis Management
Heidi Chamberlain Shea, MD
Endocrine Associates of Dallas

2. Goals of Discussion Pathophysiology of DKA
Biochemical criteria for DKA
Treatment of DKA
Prevention of DKA
Hyperosmolar Nonketoic Syndrome

3. Epidemiology Annual incidence in U.S.
5-8 per 1000 diabetic subjects
2.8% of all diabetic admissions are due to DKA
Overall mortality rate ranges from 2-10%
Higher is older patients

4. DKA Precipitating Factors
Failure to take insulin
Failure to increase insulin
Illness/Infection
Pneumonia MI
Stroke
Acute stress
Trauma
Emotional
Medical Stress
Counterregulatory hormones
Oppose insulin
Stimulate glucagon release
Hypovolmemia
Increases glucagon and catecholamines
Decreased renal blood flow
Decreases glucagon degradation by the kidney

5. Diabetic Ketoacidosis
Due to:
Severe insulin deficiency
Excess counterregulatory hormones
Glucagon
Epinephrine
Cortisol
Growth hormone

6. Role of Insulin Required for transport of glucose into
Muscle
Adipose
Liver
Inhibits lipolysis
Absence of insulin
Glucose accumulates in the blood
Uses amino acids for gluconeogenesis
Converts fatty acids into ketone bodies
Acetone, Acetoacetate, β-hydroxybutyrate
Increased counterregulatory hormones

7. Counterregulatory Hormones - DKA
Increases insulin resistance
Activates glycogenolysis and gluconeogenesis
Activates lipolysis
Inhibits insulin secretion
Epinephrine X
Glucagon
Cortisol
Growth Hormone

8. Insulin Deficiency Hyperglycemia Dehydration Acidosis Glucose uptake
Lipolysis
Proteolysis
Free Fatty Acids
Glycerol
Amino Acids
Gluconeogenesis
Glycogenolysis
Hyperglycemia
Ketogenesis
Osmotic diuresis
Dehydration
Acidosis

9. Signs and Symptoms of DKA
Polyuria, polydipsia
Enuresis
Dehydration
Tachycardia
Orthostasis
Abdominal pain
Nausea
Vomiting
Fruity breath
Acetone
Kussmaul breathing
Mental status changes
Combative
Drunk
Coma

10. Lab Findings Hyperglycemia Anion gap acidosis
(Na + K) – (Cl + Bicarb) >12
Bicarbonate <15 mEq/L
pH <7.3
Urine ketones and serum ketones
Hyperosmolarity

11. Differential Diagnosis Anion Gap Acidosis
Alcoholic ketoacidosis
Lactic acidosis
Renal failure
Ethylene glycol or methyl alcohol poisoning
Starvation in late pregnancy or lactation (rare)

12. Atypical Presentations
DKA can be present with BS <300
Impaired gluconeogenesis
Liver disease
Acute alcohol ingestion
Prolonged fasting
Insulin-independent glucose is high (pregnancy)
Chronic poor control but taking insulin
Bedside urine ketones false negatives
Measure acetoacetate not β-hydroxybutyrate
Send blood to lab

13. Treatment of DKA Initial hospital management Once resolved
Replace fluid and electrolytes
IV Insulin therapy
Glucose administration
Watch for complications
Disconnect insulin pump
Once resolved
Convert to home insulin regimen
Prevent recurrence

14. Treatment of DKA Fluids and Electrolytes
Fluid replacement
Restores perfusion of the tissues
Lowers counterregulatory hormones
Average fluid deficit 3-5 liters
Initial resuscitation
1-2 liters of normal saline over the first 2 hours
Slower rates of 500cc/hr x 4 hrs or 250 cc/hr x 4 hours
When fluid overload is a concern
If hypernatremia develops ½ NS can be used

15. Treatment of DKA Fluids and Electrolytes
Hyperkalemia initially present
Resolves quickly with insulin drip
Once urine output is present and K<5.0, add meq KCL per liter.
Phosphate deficit
May want to use Kphos
Bicarbonate not given unless pH <7 or bicarbonate <5 mmol/L

16. Treatment of DKA Insulin Therapy
IV bolus of units/kg (~ 10 units) regular insulin
Follow with hourly regular insulin infusion
Glucose levels
Decrease mg/dl hour
Minimize rapid fluid shifts
Continue IV insulin until urine is free of ketones

17. Treatment of DKA Glucose Administration
Supplemental glucose
Hypoglycemia occurs
Insulin has restored glucose uptake
Suppressed glucagon
Prevents rapid decline in plasma osmolality
Rapid decrease in insulin could lead to cerebral edema
Glucose decreases before ketone levels decrease
Start glucose when plasma glucose <300 mg/dl

18. Insulin-Glucose Infusion for DKA
Blood glucose
Insulin Infusion
D5W Infusion
<70
0.5 units/hr
150 cc/hr
70-100
1.0
125
2.0
100
3.0
4.0 75
6.0 50
8.0
10.0
12.0
15.0
>500
20.0

19. Complications of DKA Infection Shock Vascular thrombosis
Precipitates DKA
Fever
Leukocytosis can be secondary to acidosis
Shock
If not improving with fluids r/o MI
Vascular thrombosis
Severe dehydration
Cerebral vessels
Occurs hours to days after DKA
Pulmonary Edema
Result of aggressive fluid resuscitation
Cerebral Edema
First 24 hours
Mental status changes
Tx: Mannitol
May require intubation with hyperventilation

20. Once DKA Resolved Treatment
Most patients require units/kg/day
Pubertal or highly insulin resistant patients
units/kg/day
Long acting insulin
1/2-2/3 daily requirement
NPH, Levemir or Lantus
Short acting insulin
1/3-1/2 given at meals
Regular, Humalog, Novolog or Apidra
Give insulin at least 2 hours prior to weaning insulin infusion.

21. Prevention of DKA Sick Day Rules
Never omit insulin
Cut long acting in half
Prevent dehydration and hypoglycemia
Monitor blood sugars frequently
Monitor for ketosis
Provide supplemental fast acting insulin
Treat underlying triggers
Maintain contact with medical team

22. Goals of Discussion Pathophysiology of DKA
Biochemical criteria for DKA
Treatment of DKA
Prevention of DKA
Hyperosmolar Nonketoic Syndrome

23. Hyperosmolar Nonketotic Syndrome
Extreme hyperglycemia and dehydration
Unable to excrete glucose as quickly as it enters the extracellular space
Maximum hepatic glucose output results in a plateau of plasma glucose no higher than mg/dl
When sum of glucose excretion plus metabolism is less than the rate which glucose enters extracellular space.

24. Hyperosmolar Nonketotic Syndrome
Extreme hyperglycemia and hyperosmolarity
High mortality (12-46%)
At risk
Older patients with intercurrent illness
Impaired ability to ingest fluids
Urine volume falls
Decreased glucose excretion
Elevated glucose causes CNS dysfunction and fluid intake impaired
No ketones
Some insulin may be present
Extreme hyperglycemia inhibits lipolysis

25. Hyperosmolar Nonketotic Syndrome Presentation
Extreme dehydration
Supine or orthostatic hypotension
Confusion coma
Neurological findings
Seizures
Transient hemiparesis
Hyperreflexia
Generalized areflexia

26. Hyperosmolar Nonketotic Syndrome Presentation
Glucose >600 mg/dl
Sodium
Normal, elevated or low
Potassium
Normal or elevated
Bicarbonate >15 mEq/L
Osmolality >320 mOsm/L

27. Hyperosmolar Nonketotic Syndrome Treatment
Fluid repletion
NS 2-3 liters rapidly
Total deficit = 10 liters
Replete ½ in first 6 hours
Insulin
Make sure perfusion is adequate
Insulin drip 0.1U/kg/hr
Treat underlying precipitating illness

28. Clinical Errors Fluid shift and shock Hyperkalemia Hypokalemia
Giving insulin without sufficient fluids
Using hypertonic glucose solutions
Hyperkalemia
Premature potassium administration before insulin has begun to act
Hypokalemia
Failure to administer potassium once levels falling
Recurrent ketoacidosis
Premature discontinuation of insulin and fluids when ketones still present
Hypoglycemia
Insufficient glucose administration

29. Conclusion Successful management requires
Judicious use of fluids
Establish good perfusion
Insulin drip
Steady decline
Complete resolution of ketosis
Electrolyte replacement
Frequent neurological evaluations
High suspicion for complications
Determine etiology to avoid recurrent episodes