Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Lily - PowerPoint PPT Presentation

Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State Lily Lin Pharmacy Resident Preceptor: Katherin Badke 1

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 2

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 3

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 of 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 10

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- oxidation) 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 on admission • Causes of elevated serum K: • Insulin deficiency (potassium shifted out of cells) • Hyperosmolality (shift from ICF to ECF) 17

Causes of DKA • Undiagnosed diabetes • Body needs more insulin: illness, stress, infection • Non-adherent to insulin use (uncontrolled hyperglycemia) • Myocardial infarction 18

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) 19

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 20

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 22

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 31

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 33

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 37

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) 39

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 41

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) 42

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 osmolality < 315 mOsmol/kg • Patient able to tolerate PO feeds 44

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 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- Daily x 2 days hydroxybuytrate 47

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.