Diabetic Ketoacidosis Management

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Diabetic Ketoacidosis Management

• Heidi Chamberlain Shea, MD
• Endocrine Associates of Dallas

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Goals of Discussion

• Pathophysiology of DKA
• Biochemical criteria for DKA
• Treatment of DKA
• Prevention of DKA
• Hyperosmolar Nonketoic Syndrome

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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

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DKAPrecipitating 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

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Diabetic Ketoacidosis

• Due to
• Severe insulin deficiency
• Excess counterregulatory hormones
• Glucagon
• Epinephrine
• Cortisol
• Growth hormone

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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, ß-hydroxybutyrate
• Increased counterregulatory hormones

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

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Lab Findings

• Hyperglycemia
• Anion gap acidosis
• (Na K) (Cl Bicarb) gt12
• Bicarbonate lt15 mEq/L
• pH lt7.3
• Urine ketones and serum ketones
• Hyperosmolarity

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Differential Diagnosis Anion Gap Acidosis

• Alcoholic ketoacidosis
• Lactic acidosis
• Renal failure
• Ethylene glycol or methyl alcohol poisoning
• Starvation in late pregnancy or lactation (rare)

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Atypical Presentations

• DKA can be present with BS lt300
• 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 ß-hydroxybutyrate
• Send blood to lab

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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

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Treatment of DKAFluids 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

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Treatment of DKAFluids and Electrolytes

• Hyperkalemia initially present
• Resolves quickly with insulin drip
• Once urine output is present and Klt5.0, add 20-40
  meq KCL per liter.
• Phosphate deficit
• May want to use Kphos
• Bicarbonate not given unless pH lt7 or bicarbonate
  lt5 mmol/L

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Treatment of DKAInsulin 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

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Treatment of DKAGlucose 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 lt300 mg/dl

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Insulin-Glucose Infusion for DKA
Blood glucose Insulin Infusion D5W Infusion
lt70 0.5 units/hr 150 cc/hr
70-100 1.0 125
101-150 2.0 100
151-200 3.0 100
201-250 4.0 75
251-300 6.0 50
301-350 8.0 0
351-400 10.0 0
401-450 12.0 0
451-500 15.0 0
gt500 20.0 0
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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

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Once DKA ResolvedTreatment

• 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, 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.

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Prevention of DKASick 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

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Goals of Discussion

• Pathophysiology of DKA
• Biochemical criteria for DKA
• Treatment of DKA
• Prevention of DKA
• Hyperosmolar Nonketoic Syndrome

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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.

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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

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Hyperosmolar Nonketotic Syndrome Presentation

• Extreme dehydration
• Supine or orthostatic hypotension
• Confusion coma
• Neurological findings
• Seizures
• Transient hemiparesis
• Hyperreflexia
• Generalized areflexia

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Hyperosmolar Nonketotic Syndrome Presentation

• Glucose gt600 mg/dl
• Sodium
• Normal, elevated or low
• Potassium
• Normal or elevated
• Bicarbonate gt15 mEq/L
• Osmolality gt320 mOsm/L

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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

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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

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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