Page 1: Diabetic Ketoacidosis Management

Diabetic Ketoacidosis Management

Heidi Chamberlain Shea, MDEndocrine Associates of Dallas

Page 2: Diabetic Ketoacidosis Management

Goals of Discussion

• Pathophysiology of DKA

• Biochemical criteria for DKA

• Treatment of DKA

• Prevention of DKA

• Hyperosmolar Nonketoic Syndrome

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• Annual incidence in U.S. – 5-8 per 1000 diabetic


• 2.8% of all diabetic admissions are due to DKA

• Overall mortality rate ranges from 2-10%– Higher is older


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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


• Decreases glucagon degradation by the kidney

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Diabetic Ketoacidosis

Due to:

Severe insulin deficiency

Excess counterregulatory hormones




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, β-hydroxybutyrate

– Increased counterregulatory hormones

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Counterregulatory Hormones - DKAIncreases

insulin resistance

Activates glycogenolysis

and gluconeogenesis

Activates lipolysis

Inhibits insulin secretion

Epinephrine X X X XGlucagon XCortisol X XGrowth

Hormone X X X

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Insulin Deficiency

Glucose uptakeProteolysis


Amino Acids

Glycerol Free Fatty Acids

GluconeogenesisGlycogenolysisHyperglycemiaHyperglycemia Ketogenesis

AcidosisAcidosisOsmotic diuresis DehydrationDehydration

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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) >12

– Bicarbonate <15 mEq/L– pH <7.3

• 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 <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

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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 K<5.0, add 20-40

meq KCL per liter.• Normo/Hypokalemia

– Malnourished individuals (alcoholics)– Start K replacement and have K > 3.0 prior to start of

insulin– Remember to check magnesium

• Phosphate deficit– May want to use Kphos

• Bicarbonate not given unless pH <7 or bicarbonate <5 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


• Glucose decreases before ketone levels decrease

• Start glucose when plasma glucose <300 mg/dl

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Insulin-Glucose Infusion for DKABlood glucose Insulin Infusion D5W Infusion

<70 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

>500 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


• Pulmonary Edema– Result of aggressive fluid


• Cerebral Edema– First 24 hours– Mental status changes– Tx: Mannitol– May require intubation with


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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

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Once DKA ResolvedTreatment

• Give SQ insulin at least 2 hours prior to stopping insulin infusion.

• Lantus or Levemir– Steady state at 2-4 hrs

• Short acting analogs for meal times• If transitioning to the pump

– Restart the pump and after 30 minutes stop insulin infusion

• May still be more insulin resistant so will need more than usual dose

• Check blood sugars in 2 hrs – Offer supplemental

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Insulin Types and ActionINSULIN TYPE




Humalog Novolog Apidra





Glargine Detemir

1-2 hrs 24 hrs

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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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Preventing DKA• Education

– Sick days or NPO• Do not stop insulin but adjust• Continue basal insulin• NPH insulin- decrease by 30-50%• Use short acting

– Q2-3 hrs with Novolog, Humalog and Apidra– Q4 hrs with regular insulin

– Hyperglycemia• If > 300 mg/dl, then check urine ketones• If ketones positive

– Increase fluids– Take supplemental insulin Q2 hrs

– Insulin temperature sensitive• < 77 degrees• Teenagers, homeless, pen and pump users• Do not store insulin in the car• Traveling and summer outdoor activities• May need to replace more frequently

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Pump patients

• If blood sugars are increasing (>200 mg/dl)– Bolus– Check 2 hrs later, if

climbing– Give SQ correction– Change site– Make sure pump is working– Change insulin

• Pump patients need long acting back up at home and when traveling

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Pump patients

• If in DKA– Disconnect the pump

• Transitioning back to pump– Start pump with basal

x 2 hrs, then stop insulin drip

– Check blood sugars every 2 hrs to make sure they are in range

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Clinical Trials

• Immune modulating studies––

• Anti CD3- monoclonal AB– Phase 3 trials– Newly diagnosed Type 1 Diabetes

• Call Research Institute of Dallas 214-363-5535

• Immune modulating vaccines

• Stem cell and pancreas transplants

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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 >600 mg/dl

• Sodium– Normal, elevated or low

• Potassium– Normal or elevated

• Bicarbonate >15 mEq/L

• Osmolality >320 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


• 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