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StuNews By Students, for Students StuNews 2012 Summer Issue Clinical Case Submitted by: Danielle Smidt, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Pharm.D. Candidate 2013 [email protected] Reviewed by: Tyree H. Kiser, Pharm.D., BCPS, Assistant Professor, Department of Clinical Pharmacy [email protected] A 33-year-old white man is brought to the emergency department by ambulance after being found minimally responsive with Kussmaul-type respirations and hyperglycemia. He is transferred to the intensive care unit with chief concerns of abdominal pain, nausea/vomiting, and thirst. PMH: Type 1 diabetes Allergies: NKDA Current Medications: Insulin glargine 20 units subcutaneously daily Insulin lispro 10 units subcutaneously with meals Vital signs: BP 88/48 mm Hg, HR 125 beats/minute, RR 15 breaths/minute Laboratory values: Glucose 593 mg/dL, serum sodium 136 mmol/L, serum ketones positive, urine ketones positive The patient is given a diagnosis of diabetic ketoacidosis (DKA). Test your knowledge: 1. What are differences in diagnostic criteria and severity classification for DKA and hyperosmolar hyperglycemic state (HHS)? 2. What is optimal fluid therapy for patients with DKA? 3. What are the most efficacious route and dose of insulin in the treatment of patients with DKA? Answers: 1. What are differences in diagnostic criteria and severity classification for DKA and HHS? Diabetic Ketoacidosis (DKA) Blood glucose concentrations (mg/dL) Arterial pH – acidosis Serum bicarbonate (mEq/L) Anion gap Serum and/or urine ketones Mental status Serum osmolality (mOsm/kg) Hyperglycemic Hyperosmolar State (HHS) Mild Moderate Severe > 250 > 250 > 250 > 600 7.25–7.3 7.0–7.24 < 7.0 > 7.3 15–18 10–14 < 10 > 15 > 10 > 12 > 12 Positive Positive Positive Negative – small Alert Alert/drowsy Stupor/coma Variable Variable > 320 Although not diagnostic criteria, DKA occurs most commonly in patients with type 1 diabetes mellitus, whereas HHS occurs most frequently in patients with type 2 diabetes mellitus. In addition, patients with HHS will typically have greater total body water and electrolyte deficits than other patients with DKA. Adapted from Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011;94:340–51. Page 1 StuNews StuNews 2012 Summer Issue Clinical Case 2. What is the optimal fluid therapy in patients with DKA? Three-step fluid strategy: 1. Initial bolus fluid of isotonic saline (0.9% sodium chloride [NaCl]) infused at the rate of 15–20 mL/kg/hour over the first hour. 2. Then, give continuous-infusion maintenance fluid of either 0.9% NaCl or 0.45% NaCl. The choice of maintenance fluid is based on corrected sodium* concentrations: Eunatraemic or hypernatraemic patients: 0.45% saline at 250–500 mL/hour Hyponatraemic patients: 0.9% NaCl at 250–500 mL/hour *Serum sodium should be calculated to correct for the level of hyperglycemia by adding 1.6 mmol/L of sodium for every 100 mg/dL of glucose above 100 mg/dL. The rate of hydration should be guided by hemodynamic status, the state of hydration, serum electrolyte levels, and urinary output. 3. When blood glucose concentrations are less than 200 mg/dL, 5% dextrose should be added to maintenance fluid to prevent hypoglycemia while continuing insulin administration until ketonemia is resolved. 3. What is the most efficacious route and dose of insulin in the treatment of patients with DKA? Intravenous regular insulin 0.14 unit/kg/hour as continuous infusion or a bolus of 0.1 unit/kg followed by 0.1 unit/kg/hour. Insulin infusion protocols should decrease blood glucose concentrations at a rate of 50–75 mg/dL/hour. If blood glucose does not fall by 10% in the first hour, it is recommended to give 0.14 unit/kg as a bolus, followed by continuous infusion at the previous rate. When blood glucose concentrations are less than 200 mg/dL, the insulin infusion rate should be reduced to 0.02–0.05 unit/kg/hour, and dextrose should be added to intravenous fluids. The rate of insulin and dextrose administration should be titrated to keep blood glucose concentrations between 150 and 200 mg/dL until DKA resolution. Once DKA is resolved (blood glucose less than 200 mg/dL and at least two of the following: serum bicarbonate of 15 mEq/L or greater, pH greater than 7.3, and normal anion gap) and the patient is able to eat, several dose insulins can be initiated with a long-acting subcutaneous insulin to cover basal insulin requirements and short/rapid-acting subcutaneous insulin given before meals as needed to control blood glucose. The intravenous insulin infusion should be continued for 1–2 hours after the subcutaneous insulin is given to ensure adequate blood insulin concentrations. References: 1. American Diabetes Association. Hyperglycemic crisis in diabetes. Diabetes Care 2009;32:1335–43. 2. Nyenwe EA, Kitabchi AE. Evidence-based management of hyperglycemic emergencies in diabetes mellitus. Diabetes Res Clin Pract 2011;94:340–51. 3. Chiasson JL, Aris-Jilwan N, Bélanger R, et al. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. CMAJ 2003;168:859–66. Page 2