Understanding Diabetic Coma: Causes and Complications

1. بـه نـام خـدا

2. Coma in diabetics Abnormal glycaemia (a) Hypoglycaemic (b) Hyperglycaemic: (i) ketoacidotic, (ii) non-ketoacidotic Other metabolic, consequent upon the diabetic state (a) Uraemic coma, with or without glycaemic upset (b) Lactic acidosis, with or without glycaemic upset (c) Alcoholic coma, with possible abnormalities in ‘ketone bodies’, lactate, or glucose Non-metabolic coma For example, subarachnoid haemorrhage

3. Diabetes mellitus Differential diagnosis of coma in diabetics

4. MAJOR ACUTE COMPLICATIONS Metabolic problems ■Nonketotic hyperosmolar hyperglycemic coma ■ Hypoglycemia ■ Diabetic Ketoacidosis (unlikely in type II diabetes mellitus except during periods of stress such as those caused by trauma and intercurrent infection or disease) ■ Lactic acidosis Infection

5. Hyperglycemic crises DKA, NKHHC Acute complications of DM DKA ► Acute complication of type 1 DM ► Occasionally occurs in type 2 DM ► An Endocrine Emergency ► With a mortality rate of 5 – 10% ► Life threatening condition but preventable in many cases ► Results form absolute insulin deficiency or relative insulin deficiency combined with counter-regulatory hormones excess (mainly glucagon excess)

6. Physiologic Effects of High-Versus Low-Insulin States

7. Major physiologic effects of glucagon I. Carbohydrate metabolism A. Increases hepatic glucose output 1. Increases gluconeogenolysis 2. Increases gluconeogenesis B. Decreases glycogen synthesis II. Lipid metabolism A. Increases lipolysis B. Increases ketogenesis C. Decreases lipogenesis III. Protein metabolism A. Decreases protein synthesis

8. Contribution of Hormonal Abnormalities to Metabolic Derangements of Severe Diabetes

9. INSULIN DIFICIENCY (DECREASED SECRETION, RESISTANCE OR BOTH) LIVER INCREASED GLUCONEOGENESIS PERIPHERY DECREASED GLUCOSE UTILIZATION ADIPOSE TISSUE INCREASED LIPOLYSIS LIVER INCREASED KETOGENESIS HYPERGLYCEMIA KETOACIDOSIS The pathophysiologic basis of diabetic ketoacidosis

10. HYPERGLYCEMIA GLYCOSURIA HYPEROSMOLARITY OSMOTIC DIURESIS H2O LOSS > Na SHIFT OF H2O OUT OF CELL HYPOVOLEMIC SHOCK CELLULAR DEHYDRATION PRERENAL AZOTEMIA COMA DEATH Osmotic effects of hyperglycemia

11. Decreased Insulin and Increased Counterregulatory Hormones (Glucagon, Catecholemines, and Cortisol) INCREASED LIPOLYSIS AND TG BREAKDOWN INCREASED GLUCOSE PRODUCTION AND DECREASED GLUCOSE UPTAKE INCREASED PROTEOLYSIS Increased FFA in Plasma Increased Plasma Amino Acids Stimulate Precursors for Increased Amino Acids to Liver Increased FFA to Liver HYPERGLYCEMIA Gluconecgenesis Gluconecgenesis Glycosuria Increased Ketogenesis Osmotic Diuresis Ketonemia and ketonuria Loss of Electrolytes Volume Depletion Decreased Alkali Reserve Volume Depletion Acidosis Impaired Renal Function

12. PURE KETOACIDOSIS KETOACIDOSIS-HYPEROSMOLAR COMA PURE HYPEROSMOLAR COMA SLOW ONSET MILD INSULIN LACK RAPID ONSET MARKED INSULIN LACK INTERMEDIATE Clinical spectrum of diabetic ketoacidosis and hyperosmolar coma

13. Common Presenting Symptoms and Signs in Diabetic Ketoacidosis

14. MAJOR SIGNS AND SYMPTOMS OF DKA-HYPEROSMOLAR COMA 1.In 50% to 60% of hyperosmolar patients, hyperosmolar coma is the first sign of diabetes 2.Dehydration can be maqnifested by thirst, decreased turgor, soft eye balls, and orthostasis 3.Temperature is usually normal or low but if elevated, infection is present 4.Stupor, coma, and convulsions are present in hyperosmolar coma, but not in DKA 5.Kussmaul breathing indicating a pH < 7.2 6.Abdominal pain is present in at least 30% of patients 7.Vomiting is seen in 50% to 80% of patients causing further dehydration

15. LABORATORY STUDIES OBTAINED ON ADMISSION

16. LABORATORY CHARACTERISTICS OF DIABETIC KETOACIDOSIS VERSUS HYPERGLYCEMIC HYPEROSMOLAR NONKETOTIC STATE PATIENTS ON ADMISSION

17. PRECIPITATING FACTORS IN DKA-HYPEROSMOLAR COMA 1.Too little insulin 2. Infection (even minor) 3. Severe stress (physical or ? Emotional) 4. Hypokalemia, usually diuretic induced 5. Renal failure 6. Most important: inadequate fluid intake caused by: a.Old age (decreased sensitivity to thirst) b. Infancy (cannot get to or drink water) c. Incapacitation occurring at any age (cannot get to or drink water)

18. Other Hyperglycemic States Diabetes Mellitus Non-Ketotic Hyperosmolar Coma Impaired Glucose Tolerance Stress Hyperglycemia Acidosis Hyperglycemia DKA Other Metabolic Acidotic States Lactic Acidosis Hyperchloremic Acidosis Salicylism Uremic Acidosis Drug-Induced Acidosis Ketosis Other Ketotic States KetoticHypoglycemia Alcoholic Ketosis Starvation Ketosis

19. Points to Consider in Treating Diabetic Ketoacidosis ■A precipitating cause may be identified in 80% of patients ■An ECG is identified in all adult patients ■Isotonic saline is initially preferred to rehydrate patients ■Intravenous insulin is the preferred route of delivery ■DKA patients are deplete in total-body potassium regardless of plasma potassium concentration ■Bicarbonate should only be administered when specifically indicated ■Preventing DKA is the long-term goal of good diabetes management

20. Confusing clinical features of diabetic ketoacidosis Temperature may be normal or low despite infection • Leucocytosis is common and dose not confirm infection • Hepatic enzymes may be increased due to the ketoacidosis • Amylase may be raised, and not due to pancreatitis Urine keton es may be apparently low or absent if the major increase is in -hydroxybutyrate rather than acetoacetate

21. Management of Diabetic Ketoac idosis 1. Confirm diagnosis (↑ plasma glucose, positive serum ketones, metabolic acidosis). 2. Admit to hospital; intensive care setting may be necessary for frequent monitoring or if pH <7.00 or unconscious. 3. Assess: Serum electrolytes (K+, Na+, Mg2+, Cl−, bicarbonate, phosphate) Acid-base status—pH, HCO3 −, Pco2, β-hydroxybutyrate Renal function (creatinine, urine output)

22. Management of Diabetic Ketoac idosis 4. Replace fluids: 2–3 L of 0.9% saline over first 1–3 h (10–20 mL/kg per hour); subsequently, 0.45% saline at 250–500 mL/h; change to 5% glucose and 0.45% saline at 150–250 mL/h when plasma glucose reaches 250 mg/dL (13.9 mmol/L). 5. Administer short-acting insulin: IV (0.1 units/kg), then 0.1 units/kg per hour by continuous IV infusion; increase two- to threefold if no response by 2–4 h. If the initial serum potassium is <3.3 mmol/L (3.3 meq/L), do not administer insulin until the potassium is corrected. 6. Assess patient: What precipitated the episode (noncompliance, infection, trauma, pregnancy, infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures, CXR, ECG).

23. Fluid Replacement HOUR 1 15 ml/kg isotonic NaCl (500 ml/m2/h) ( if elderly patient or one with heart disease, administer fluid cautiously, e.g., according to central venous pressure). HOUR 2 Continue isotonic NaCl (15 ml/kg). However, if patient is hypernatremic, in congestive heart failure, or is a child, consider 0.5 isotonic sodium chloride. HOUR 3 Reduce fluid rate to 7.5 ml/kg/h. change fluid to 0.5 isotonic saline. HOUR 4 Adjust fluid rate to meet clinical need. Consider rate of urine output in fluid replacement calculation

24. Fluid Replacement ►When blood glucose approaches 300 mg/dL, change fluid to 5% dextrose in 0.5 isotonic saline. ►Continue intravenous fluids, including insulin, until acidosis is corrected and patient can ingest food without vomiting. ►Change to short-acting insulin subcutaneously every 4 – 6 h, giving first dose before discontinuing intravenous insulin.

25. INSULIN ADMINISTRATION IN DKA Initial Dose 0.1 U/kg body weight IV and 0.1 U/kg body weight IM Subsequent Doses 0.1 U/kg body weight IM or SC hourly

26. Guidelines for Potassium Replacement in Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State. Do not administer potassium if serum potassium >5.5 m\Eq/L or patient is anuric Use KCI but alternate with KPO4 if there is severe phosphate depletion and patient is unable to take phosphate by mouth Add i.v. potassium to each liter of fluid administered unless contraindicated Serum K (mEq/L)Additional K required <3.5 40 mEq/L 3.5-4.5 20 mEq/L 4.5-5.5 10mEq/L >5.5 Stop K infusion

27. Guidelines for Bicarbonate;Therapyin Diabetic Ketoacidosis Use clinical judgment in deciding if bicarbonate therapy is indicated If pH is < 7.0, give 100 mL NaHCO3 over 45 min Check acid-base status 30 min later and repeat if pH remains <7.0

28. Flow sheet for treatment of diabetic ketoacidosis

29. Prevention of DKA and HHC

30. Prevention of DKA and HHC • DKA and HHC are preventable disorders. • These conditions may be the first presentation of diabetes • The most common precipitating causes of DKA include: • Infection, • Intercurrent illness • Psychological stress • Noncompliance with therapy.

31. Prevention of DKA and HHC • Outpatient management is more cost- effective and can minimize missed days of school and work for patients with diabetes • Patient education and 24- hour access to advice and care, remain the cornerstone of preventative therapy. • With improved outpatient treatment programs and better adherence to self-care, nearly 50% to 75% of DKA admission may be preventable.

32. Prevention of DKA and HHC • The frequency of hospitalizations for DKA has been reduced following: • Diabetes education programs • Improved follow-up care • Access to medical advice. • Many patients with recurrent DKA are unaware of sick- day management or the consequences of skipping or discontinuing insulin therapy.

33. Prevention of DKA and HHC • An important feature of patient education is how to deal with illness. This includes: 1) Initiating early contact with health care providers 2) Emphasizing the importance of insulin therapy during illness and that insulin should never be discontinued 3) Initiating early management of fevers and infections 4) Ensuring adequate fluid intake.

34. Prevention of DKA and HHC • Patients should be taught how to manage their diabetes during periods of stress or intercurrent infection (sick –day rules) • Should understand the importance of frequent monitoring of: • Blood glucose • Urine ketones • Temperature

35. Prevention of DKA and HHC • Diabetes education and sick-day management should be reviewed periodically in patients with type 1 diabetes and should include: • Specific information on when to contact the health care provider • The use of supplemental short-or rapid-acting insulin during illness • Most imperative, the importance of never discontinuing insulin.

36. Prevention of DKA and HHC • The elderly patient living in a nursing home, who isunable to keep up with fluid losses or is unaware of fluid losses during intercurrent illness,is particularly at risk for the development of HHC. • Education of caregivers who should learn to recognize signs and symptoms of increasing hyperglycemia will reduce the incidence of severe HHC.

37. Thank you