This lecture was conducted during the Nephrology Unit Grand Ground by Nephrology Registrar under Nephrology Division, Department of Medicine in King Saud University. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

Diabetic Ketoacidosis Overview & Management Protocol Hanan Mal Sub-intern

Objectives Understand the action of insulin on the body Understand the mechanism of DKA and why it happens Understand the management protocol for DKA Understand the complications of DKA management

What is it? Ketonemia Acidemia An acute complication of Diabetes Hyperglycemia >250 mg/dl Ketonemia >54 mg/dl Acidemia pH<7.35 An acute complication of Diabetes A state of absolute or relative insulin deficiency Diagnostic Criteria: Glucose >14mmol/L Ketonuria(2+) & Ketonemia (>3mmol/L) pH <7.35 and HCO-3 <15mEqu/L

Pathophysiology Insulin is anabolic Stores glucose (as glycogen) Protein formation Stores fats (as TG) Lack of insulin leads to increased counter-regulatory hormones (catabolic) Increased insulin resistance Glycogenolysis Proteolysis and gluconeogenesis Lipolysis into FFA and Ketone bodies

Pathophysiology

Precipitating Factors STRESS Non-Compliance Infections (pneumonia & UTI) New Onset DM Co-morbidities Drug abuse Emotional/psych stress Recent Surgeries/ Trauma Drugs that affect carb metabolism

Reduced consciousness Presentation S&S Urinary system Polyuria Ketonuria glycosuria Gastric N&V Abdominal Pain Anorexia Central Reduced consciousness Respiratory Tachypnea Cardiac Tachycardia Other Dehydration Ketotic Breath

Investigations Cardiac monitor Input/output chart Vital signs q 2hr for 24 hrs CBC w/ differentials Glucose levels q 1hr Renal function VBG & U&E q 2hr (if K+ >6 or <3 q 1hr) CxR (r/o pneumonia) ECG & cardiac enzymes (ACS?) Calculate anion gap (Na+-(Cl- +HCO3-)) (8-14) Urinalysis and Ketones

Management Remember this is an EMERGENCY ABC Insert 2 IV cannula & give NS bolus We focus on 3 areas of management Fluid Insulin Electrolyte

FLUID Adults may lose up to 6L Aim to replace fluid over 48hrs and replace any urine output The main aims for the first few liters of fluid replacement correct hypotension by restoration of circulatory volume clear ketones correct electrolyte imbalance

FLUID 1L of NS as a bolus over the first 30min 1L over 1hr > 1L over 2hr > 1L over 4hr … If glucose is <14mmol/L we give D5 NS EXCEPT: Signs of heart failure or renal failure we give small boluses of IV fluids or a slower infusion rate Hyernatremia (Na+>150mmol/L) we give ½ NS instead If patient is <60Kg we consider less fluid

INSULIN Only start insulin once… the first bolus of fluid is given to avoid vascular collapse secondary to sudden fluid shift into ICS K+ levels are greater than 3.3mEq/L, otherwise insulin will mediate the movement of K+ intracellularly and worsen hypokalemia Insulin therapy improves hyperglycemia (inhibits gluconeogenesis) & ketosis & acidosis (inhibits ketone production and lipolysis)

INSULIN The standard regimen is 0.1 U/Kg/Hr Our goal is: Achieving a rate of decline of 3-4 mmol/hr Maintain glucose between 10-15 mmol/L in the first 24hrs Glucose level <5mmol/L  Infusion rate by 2U/Hr Give D50 DO NOT STOP INSULIN (Ketones must be cleared first) >15mmol/L Adjust insulin infusion 15-18 (1U) 18-20 (2U) >20 (0.1U/Kg bolus + 2U)

INSULIN Discontinue IV insulin only when the patient meets the following criteria: Anion gap is <12mEq/L HCO3- >19mEq/L Patient is tolerating oral feed Subcutaneous insulin has been initiated for 2hrs or more

POTASSIUM Potassium levels should be monitored Q 2hrs <3mEq/L add 60mEq KCl/h 3-4mEq/L add 40mEq KCl/h 4-5.9mEq/L add 20mEq KCl/h K+ Level > 5.9 or Renal Failure DO NOT START K+ REPLACEMENT <3 Hold insulin replacement

BICARBONATE & PHOSPHATE No evidence to support If pH <6.9 & patient is shocked give 1mEq/Kg IV over 2hr HCO3- can precipitate hypokalemia thus we add 20mEq KCl to infusion Phosphate No evidence shows clinical benefit May lead to hypocalemia Indicated to avoid cardiac dysfunction, skeletal muscle weakness & respiratory depression

Complications of Management Treatment for DKA has to be done by a trained specialist Constant monitoring of the patient is required to avoid development of complications Transfer patients to resuscitation if, Patient develops coma or impaired consciousness Hemodynamic instability pH <7.1 and HCO3- <5 K+ >6.5 or <3

Complication Cause Hypoglycemia Over administration of insulin (High dose regimen 1U/Kg) Hypokalemia Secondary to high dose regimen insulin (1U/Kg) and HCO3- Hyperglycemia Discontinuation/ interruption to insulin treatment Hyperchloremia Excessive saline administration Cerebral Edema Most fatal Possible contributors: hypoxia movement of water into the CNS with rapid fall in plasma osmolality effect of insulin on the plasma membrane of brain cells, which may promote cellular edema Fluid Overload Patients with cardiac failure or renal insufficiency may develop CHF ARDS Due to Pulmonary edema Thromboembolism Enhancement of the hypercoagulable state of a DM patient

Summery DKA is a common complication that will be met in any ER DKA can be easily diagnosed by asking the right questions and catching the right signs DKA can be easily managed if the protocol for management is followed correctly Complications can be avoided by making sure a trained specialist is present and monitoring is done correctly.

References Michelle A. Charfen, MD, Madonna Fernandez-Frackelton, MD, FACEP. Diabetic Ketoacidosis. Emerg Med Clin N Am 23 (2005) 609–628 Faiza A. Qari, FRCP, ABIM. Precipitating Factors for Diabetic Ketoacidosis. Saudi Med J 2002; Vol. 23 (2). M. W. Savage, et al. Diabetes UK Position Statements and Care Recommendations, Joint British Diabetes Societies guideline for the Management of Diabetic Ketoacidosis. Diabetic Medicine, 2011. Dr, Hani Ibrahim, Dr. Anwar Jammah. DKA Protocol. KKUH department of Emergency Medicine.