Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Lily - - PowerPoint PPT Presentation

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Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State

Lily Lin Pharmacy Resident Preceptor: Katherin Badke

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Learning Objectives

• Be able to summarize the pathophysiology of

diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)

• Be able to list at least 4 causes of DKA and HHS
• Be able to list key interventions for patients with

DKA/HHS

• Create a monitoring plan for a patient presenting

with DKA/HHS

Background

• Diabetic ketoacidosis (DKA) and hyperosmolar

hyperglycemic state (HHS) are common diabetic emergencies

• Estimated 5000-10000 hospital admissions for

DKA per year in Canada

• Mortality rate: estimated up to 4-10% per year

for DKA and 10-50% per year for HHS

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Background: Physiology

Glucose: primary molecule used for energy source in plants and animals

Insulin Mechanism of Action

Glucagon Mechanism of Action

Question time!

• Where are insulin and glucagon produced?
• What molecule helps facilitate the transport
• f glucose into cells?

Type 1 Diabetes Mellitus

• Body does not produce insulin due to destruction of beta-cells
• Insulin required for glucose uptake into adipose tissue and

skeletal muscle

• Glucose transport impaired → no energy production
• Overall: increased serum glucose levels

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Type 1 Diabetes Mellitus

• Patients can still respond to insulin – therefore

requires lifelong insulin therapy

Diabetic Ketoacidosis

Occurs predominantly in Type I Diabetes, can occur in Type II diabetes under conditions of extreme stress

Diabetic Ketoacidosis

Diabetic Ketoacidosis

Acetone: breakdown product of acetoacetic acid and beta-hydroxybutyric acid

Diabetic Ketoacidosis

• Increased lipolysis (release of free fatty acids (FFA) from

adipose tissues)

• FFA transported to liver, undergoes ketogenesis (beta-
• xidation) to make ketone bodies
• Ketone bodies: acetone, acetoacetate, beta-hydroxybutyrate

(can serve as energy source)

• Ketones are acidic, reduce pH in blood and urine (pH < 7.35,

metabolic acidosis)

Serum Potassium Levels in DKA

Upon presentation

• Overall potassium deficit 2-5 mmol/kg (urinary losses)
• HOWEVER, serum potassium usually normal or elevated
• n admission
• Causes of elevated serum K:
• Insulin deficiency (potassium shifted out of cells)
• Hyperosmolality (shift from ICF to ECF)

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Causes of DKA

• Undiagnosed diabetes
• Body needs more insulin: illness, stress,

infection

• Non-adherent to insulin use (uncontrolled

hyperglycemia)

• Myocardial infarction

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Euglycemic DKA (Normal serum glucose)

• Carbohydrate/fluid restriction
• Medications

– SGLT2 Inhibitors (empagliflozin, dapagliflozin, canagliflozin) – Antipsychotic agents – Corticosteroids – Sympathomimmetic agents – Thiazide diuretics – Illicit drugs (e.g. cocaine)

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Diagnosis of DKA

• Serum glucose generally between 19.4-27.8mmol/L
• Plasma osmolality usually ≤ 320 mosmol/kg
• Arterial pH ≤ 7.3
• Anion gap > 12 mmol/L (Na - (Cl + HCO3))
• Serum bicarbonate ≤ 15 mmol/L
• Positive serum and/or urine ketones (greater than 2+ standard

urine sticks) – Acetoacetic acid – Beta-hydroxybutyric acid (≥ 1.5 mmol/L) – Acetone

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Metabolic Acidosis and Anion Gap

Ketones raise level of acid (decreasing pH) CO2 + H2O → ← H2CO3 → ← H + HCO3 Anion Gap: Na - (Cl + HCO3) Overall: decreased pH (metabolic acidosis) and elevated anion gap

Head to Toe Assessment: DKA

Vitals: tachycardia, hypotension, tachypnea CNS: varying from alertness to lethargy/coma RESP: Kussmaul breathing; rapid, deep breathing HEENT: acetone “fruity” breath, polydipsia GI: abdominal pain, N/V/D, increased bowel sounds GU: polyuria (osmotic diuresis) DERM: dry mucous membranes, flushed face, decreased skin turgor, dry axillae

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Question Time!

• What electrolyte may be elevated in the

blood but depleted in the body?

• What process in the body induces the

formation of ketone bodies?

Hyperosmolar Hyperglycemic State

• Occurs predominantly in Type II Diabetes
• Insulin resistance or absence of insulin →

significant hyperglycemia and increased serum osmolality → excessive urination

• Sufficient amount of insulin to prevent

lipolysis → no ketone bodies

Diagnosis of HHS

• Serum glucose ≥ 44mmol/L
• Minimal or no serum ketone/ketonuria
• Arterial pH > 7.3
• Serum bicarbonate greater than 18mmol/L
• Plasma osmolality > 320 mOsm/kg

Head to Toe Assessment: HHS

Vitals: tachycardia, hypotension, tachypnea CNS: mental obtundation and coma, hemiparesis/hemianopsia, seizures DERM: dry mucous membranes, flushed face, decreased skin turgor GI: N/V/D GU: polyuria

Question Time!

• Type I diabetic patient presents with nausea and

vomiting, increased labored breathing and lethargy in context of missed insulin doses.

• Blood glucose 22 mmol/L, beta-hydroxybutyrate

level 19 mmol/L, pH < 7.3

• What medical condition is patient likely

experiencing?

Initial Evaluation

• ABC (IV access)
• Mental status
• Precipitating events
• Volume status

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Management: VCH DKA PPO

Fluid Management (VCH DKA PPO)

• Fluid (if blood glucose > 14 mmol/L)

– Correct hypovolemic state with IV normal saline (0.9% NaCl) – Severe dehydration: NS 2L/hr to correct shock, then step down to mild/moderate dosing – Mild/moderate dehydration: 500mL/hr x 4 hours, then 250mL/hr x 4h

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Fluid Management (VCH DKA PPO)

If blood glucose 10-14 mmol/L, add dextrose 5% to NaCl infusion

Fluid Management (VCH DKA PPO)

Change IV solution to 0.45% NaCl if:

• Euvolemic
• Serum Na normal (135-145 mmol/L) or elevated

Continue 0.9% NaCl if euvolemic but serum Na low

Potassium Repletion

Caution:

• Serum potassium may be elevated or normal

but overall low body stores

• Very important that serum potassium is

greater than 3.5 mmol/L before starting insulin infusion

Potassium Repletion: VCH DKA PPO

For patients with eGFR ≥ 30 mL/min: Note: Max rate (peripheral) 20 mmol/hour

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Potassium Repletion: VCH DKA PPO

Caution for patients with reduced kidney function!

Insulin

• Lowers serum glucose (drive glucose uptake into cells)
• Diminishes ketone production
• Wait until K+ ≥ 3.5mmol/L prior to starting infusion!
• Use IV regular insulin
• ? Bolus (0.1 units/kg body weight)?
• Continuous infusion (0.1 units/kg/hour)

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IV Insulin (VCH DKA PPO)

Continue infusion until ketosis resolves, defined by: Beta-hydroxybutyrate normalized AND either one of:

• 1. pH 7.3 or more or CALCULATED anion gap 13 or less

OR

• 2. Serum bicarbonate greater than 15 mmol/L or glucose less

than 11 mmol/L

Transition from IV to SC Insulin

• Consider conversion to SC when patient is

eating and drinking

• Overlap insulin IV and SC for 2 hours before

discontinuing IV insulin infusion

• Abrupt discontinuation → rebound

hyperglycemia and ketoacidosis

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Conversion to subcutaneous insulin (UptoDate)

• If previously treated with insulin, may initiate

pre-DKA regimen

• Insulin-naive patients: initiate at 0.5-0.8

units/kg/day (including basal and bolus)

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Treatment of HHS - UptoDate

• Similar fluid recommendations except: add dextrose

5% when serum glucose reaches 13.9-16.7 mmol/L

• Same potassium repletion recommendations
• Continue and adjust insulin infusion rate to

maintain serum glucose between 13.9 to 16 mmol/L

• Do not allow for glucose to fall lower → may

precipitate cerebral edema

Patient stabilized when...

• DKA: normalized anion gap and serum beta-

hydroxybutyrate levels

• HHS: patient mentally alert, plasma
• smolality < 315 mOsmol/kg
• Patient able to tolerate PO feeds

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Question Time!

• How long do we overlap IV insulin with SC insulin to

prevent rebound hyperglycemia?

• How do you manage a DKA patient (eGFR:

60mL/min) who presents with a serum potassium of 3.1 mmol/L?

Monitoring

What are some monitoring parameters for DKA?

Monitoring - DKA

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Vitals HR, RR, BP q1h x 6 hours, then reassess Blood glucose CBG Q1H, serum glucose Q2H Electrolytes Q2H Serum osmolality Q2H until anion gap less than 13 Serum beta- hydroxybuytrate Daily x 2 days

Head to Toe - DKA

Monitoring CNS Improved/normal mentation, intact level of consciousness, absence seizure activity RESP Absence of rapid, deep breathing (Kussmaul), RR WNL HEENT Absence of acetone “fruity” breath, decreased polydipsia GI Absence abdominal pain, N/V/D GU Decreased polyuria DERM Alleviation dry mucous membranes, increased skin turgor

Monitoring - HHS

• Similar monitoring and head-to-toe

assessment vs. DKA

• CNS: assess for mentation, LOC, absence of

seizure activity, absence headache/decreased arousal

Thank you!

lily.lin@fraserhealth.ca

References

• 1. Diabetes Mellitus Video. Osmosis.org
• 2. UptoDate - Diabetes Mellitus
• 3. VCH DKA PPO
• 4. Chiasson JL, Aris-Jilwan N, Bélanger R, et al. Diagnosis and treatment of diabetic ketoacidosis

and the hyperglycemic hyperosmolar state [published correction appears in CMAJ. 2003 May 13;168(10):1241]. CMAJ. 2003;168(7):859–866.