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
6. Role of Insulin
• Required for transport of glucose into
– Muscle
– Adipose
– Liver
• Inhibits lipolysis
• Absence of insulin
– Glucose accumulates in the blood
– Liver
• 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 X X X
Glucagon
X
Cortisol
X X
Growth
Hormone X X X
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
– 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
20-40 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 0.1-0.2 units/kg (~ 10 units)
regular insulin
• Follow with hourly regular insulin infusion
• Glucose levels
– Decrease 75-100 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
19. Complications of DKA
• Infection
– 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 0.5-0.6 units/kg/day
• Pubertal or highly insulin resistant patients
– 0.8-1.0 units/kg/day
• Long acting insulin
– 1/2-2/3 daily requirement
– NPH, Lente, Ultralente or Lantus
• Short acting insulin
– 1/3-1/2 given at meals
– Regular, Humalog, Novolog
• 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
300-500 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
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
– 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
