1. Slides current until 2008 Diabetic ketoacidosis and hyperosmolar hyperglycaemic state Abdulrahman Al shaikh.Asso professor, consultant endo. Al shaikh

2. DKA and HHS Curriculum Module III-6 Slide 2 of 55 Slides current until 2008 What is DKA? Absolute or relative insulin deficiency Increase in counter-regulatory hormones Breakdown of fat and muscle Biochemical triad –hyperglycaemia –ketoacids –metabolic acidosis High blood glucose, ketones, acidosis and dehydration Al shaikh

3. DKA and HHS Curriculum Module III-6 Slide 3 of 55 Slides current until 2008 Incidence of DKA Varies Death mainly from cerebral oedema Most common at onset in type 1 diabetes Recurrent episodes Can occur in type 2 diabetes Kitabchi et al 2001, Joslin 2005 Al shaikh

4. DKA and HHS Curriculum Module III-6 Slide 4 of 55 Slides current until 2008 DKA – cause or trigger Incidence New-onset diabetes5-40% Acute illness10-20% Insulin omission/non-adherence33% Infection20-38% Heart attack, stroke, pancreatitis <10% Booth 2001, Joslin 2005 Al shaikh

5. DKA and HHS Curriculum Module III-6 Slide 5 of 55 Slides current until 2008 Insulin deficiency Glucose uptake Lipolysis HyperglycaemiaGluconeogenesis GlycerolFree fatty acids Ketogenesis Ketonemia Ketonuria Osmotic diuresis Urinary water losses Electrolyte depletion Dehydration Acidosis Diabetic ketoacidosis Adapted from Davidson 2001 Glucosuria Al shaikh

6. DKA and HHS Curriculum Module III-6 Slide 6 of 55 Slides current until 2008 Ketones Used as fuel when calories are restricted Physiological ketosis when fasting or with prolonged exercise Insulin deficiency  lypolysis and ketone production  acidosis –beta-hydroxybutyrate –acetoacetate –acetone Al shaikh

7. DKA and HHS Curriculum Module III-6 Slide 7 of 55 Slides current until 2008 Ketones Beta-hydroxybutyrate predominant – not detected by test strips or acetone tablets Ketoacidosis may be present without detectable urinary ketones Blood ketone testing may enable early identification of DKA Al shaikh

8. DKA and HHS Curriculum Module III-6 Slide 8 of 55 Slides current until 2008 Earlier clinical symptoms and signs of DKA Polyuria Polydipsia Polyphagia Tiredness Muscle cramps Flushed facial appearance Al shaikh

9. DKA and HHS Curriculum Module III-6 Slide 9 of 55 Slides current until 2008 Later clinical symptoms and signs of DKA Weight loss Nausea and vomiting Abdominal pain Dehydration Acidotic breath Hypotension Shock Altered consciousness Coma Al shaikh

10. DKA and HHS Curriculum Module III-6 Slide 10 of 55 Slides current until 2008 DKA – investigations Immediate for diagnosis Capillary blood glucose, urinary glucose and ketones Urgent for assessment and treatment Blood glucose Blood gases Electrolytes, urea, creatinine WBC Consider Cardiac monitor Blood culture, urine culture Chest X-ray Al shaikh

11. DKA and HHS Curriculum Module III-6 Slide 11 of 55 Slides current until 2008 DKA – laboratory findings Blood glucose>14mmol/L (252mg/dL) KetonesUrine: moderate to large Blood: >3mmol/L OsmolalityIncreased – high blood glucose and urea/creatinine, dehydration Electrolytes Low/normal Na+ and Cl- Low/normal/high K+ (often misleading) Low HCO 3 (normal 23-31) Anion gap>10 mild >12 moderate to severe Blood gases pH <7.30, HCO 3 <15 (mild) pH <7.00, HCO 3 <10 (severe) Al shaikh

12. DKA and HHS Curriculum Module III-6 Slide 12 of 55 Slides current until 2008 DKA – treatment Rehydration1. Correct shock with bolus saline 2. Rehydration rate depends on clinical status, age and kidney function Normal saline (0.9%) for resuscitation and rehydration initially Glucose/saline solution when glucose around 14 mmol/L (252mg/dL) Rehydrate steadily over 48 hours 3. Consider NG tube PotassiumEssential after resuscitation and when urine output confirmed Kitabchi et al 1976 Al shaikh

13. DKA and HHS Curriculum Module III-6 Slide 13 of 55 Slides current until 2008 DKA – treatment InsulinInfusion: 0.1 units/kg/hour after resuscitation, saline established and BG falling Rate should be increased by 10-20% if glucose not fallen by 2-3 mmol/L (45- 54mg/dL) over first hour MonitoringBG, BP, urine output and hourly neurological status Blood gases and electrolytes 2-hourly initially Al shaikh

14. DKA and HHS Curriculum Module III-6 Slide 14 of 55 Slides current until 2008 DKA – complications Hypoglycaemia +/- hypokalaemia Acidosis not improving – consider continuing dehydration or infection Aspiration pneumonia Headache +/- falling level of awareness – consider cerebral oedema and urgent treatment with Mannitol Joslin 2005 Al shaikh

15. DKA and HHS Curriculum Module III-6 Slide 15 of 55 Slides current until 2008 DKA – recovery Rapid improvement Continue IV insulin while ketosis present Oral intake when possible Rapid-acting insulin 30-60 minutes before discontinuing IV insulin Usual insulin regimen Consider drinks and food containing potassium Al shaikh

16. DKA and HHS Curriculum Module III-6 Slide 16 of 55 Slides current until 2008 What is HHS? Ketosis may be present Coma not always present Primarily in older people with/without history of type 2 diabetes Always associated with severe dehydration and hyperosmolar state Develops over weeks Kitabchi et al 2001 Al shaikh

17. DKA and HHS Curriculum Module III-6 Slide 17 of 55 Slides current until 2008 HHS – incidence and features 0.5% of primary diabetes hospital admissions ~15% mortality rate Can occur in type 1 diabetes and younger people Kitabchi et al 2001 Al shaikh

18. DKA and HHS Curriculum Module III-6 Slide 18 of 55 Slides current until 2008 HHS – key features Marked hyperglycaemia Hyperosmolarity Absence of severe ketosis Altered mental awareness Joslin 2005 Al shaikh

19. DKA and HHS Curriculum Module III-6 Slide 19 of 55 Slides current until 2008 HHS – causes or triggers Booth 2001 Incidence Infection40-60% New-onset diabetes33% Acute illness10-15% Medicines, steroids<10% Insulin omission5-15% Al shaikh

20. DKA and HHS Curriculum Module III-6 Slide 20 of 55 Slides current until 2008 Signs and symptoms of HHS Initially polyuria and polydipsia Altered mental status Profound dehydration Precipitating factors Al shaikh

21. DKA and HHS Curriculum Module III-6 Slide 21 of 55 Slides current until 2008 HHS – biochemical findings Jones 2001 Blood glucose>33mmol/L (600mg/dl) KetonesUrine: negative – small Blood: <0.6 mmol/L Osmolality>320mOsm/kg - (raised Na, BG, urea) ElectrolytesRaised Na, BG, urea creatinine Anion gap<12 Blood gasespH >7.30 normal or raised HCO 3 Al shaikh

22. DKA and HHS Curriculum Module III-6 Slide 22 of 55 Slides current until 2008 Treatment RehydrationCaution! Normal saline 1 l per hour initially Consider ½ strength normal saline PotassiumOnly if hypokalaemic and renal function adequate – give before insulin InsulinMay be needed as slow infusion 0.1 unit/kg/hour to be increased with care if BG is slow to fall MonitoringBG, BP, neurological function hourly until stable Electrolytes 2-hourly Cardiac or CVP monitoring Al shaikh

23. DKA and HHS Curriculum Module III-6 Slide 23 of 55 Slides current until 2008 HHS – complications ComplicationPrevention HypoglycaemiaPrevent by adding glucose infusion when glucose <14mmol/L (250 mg/dL) HypokalaemiaEarly potassium replacement and monitoring Fluid overloadCareful clinical monitoring and central line as needed Vomiting/aspirationNG tube and may be nursed on side Cerebral oedemaAvoid fast blood glucose falls (should be <4mmol/L (72mg/dL) per hour; aggressive Mannitol treatment if any early signs of cerebral oedema Meltzer 2004 Al shaikh

24. DKA and HHS Curriculum Module III-6 Slide 24 of 55 Slides current until 2008 DKA and HHS – prevention is key Identify and treat underlying cause Can be prevented by –better public awareness –improved access to medical care –improved education in treating hyperglycaemia during illness –emergency communication with healthcare provider Al shaikh

25. Slides current until 2008 Managing diabetes during illness

26. DKA and HHS Curriculum Module III-6 Slide 26 of 55 Slides current until 2008 Diabetes and illnesses People with adequate glycaemic control not at increased risk of infection Poor metabolic control increases risk - decreases immunity - leads to persistent glycosuria and dehydration

27. DKA and HHS Curriculum Module III-6 Slide 27 of 55 Slides current until 2008 Impact of illness Infective illness –increased stress hormones  gluconeogenesis + insulin insensitivity  hyperglycaemia + ketones Nausea, vomiting, diarrhoea –poor gastric emptying + rapid intestinal transit + poor food absorption  hypoglycaemia Milder illnesses –little or no effect

28. DKA and HHS Curriculum Module III-6 Slide 28 of 55 Slides current until 2008 Mismanagement of illness Mismanagement of illness a common cause of increasing hyperglycaemia and ketoacidosis Omission of insulin because food not taken or vomiting Inadequate hydration during hyperglycaemia, polyuria and fever Poor glucose intake during gastroenteritis causing hypoglycaemia Inadequate education and written guidelines for management

29. DKA and HHS Curriculum Module III-6 Slide 29 of 55 Slides current until 2008 Illnesses and hyperglycaemia General management Identify and treat cause of illness Treat symptoms such as fever with paracetamol Adequate fluids – frequent diet drinks More frequent blood glucose tests Check urine for ketones Blood ketone tests if available Laffel et al 2005

30. DKA and HHS Curriculum Module III-6 Slide 30 of 55 Slides current until 2008 Insulin management Never stop insulin (fever and stress increase insulin needs) Continue intermediate- or long- acting insulin Shorter-acting insulin (soluble or rapid acting) should be adjusted according to blood glucose values People with type 2 diabetes may need short-term insulin treatment if illness severe Hanas 2004

31. DKA and HHS Curriculum Module III-6 Slide 31 of 55 Slides current until 2008 Algorithm for guidance BreakfastLunchSupperBedtime Usual dose (example)Soluble 10Soluble 8Soluble 12NPH 24 If blood glucose is... Units of insulin reduced (-) or added (+) to usual dose <4 (72)- 5 units- 4 units- 6 unitscontinue 4.1-6.0 (73-108)- 2 units 6.1-10.0 (109-180)Usual dose 10.1-12.0 (181-216)+ 2 units 12.1-14.0 (217-252)+ 4 units 14.1- 18.0 (253-324)+ 8 units+ 6 units+ 10 units >18.1 (325)+ 10 units+ 8 units+ 12 units

32. DKA and HHS Curriculum Module III-6 Slide 32 of 55 Slides current until 2008 Insulin correction doses Blood glucose >15mmol/L (270 mg/dL), ketones present Usual insulin PLUS Short- or rapid-acting insulin 10-20% of total daily dose every 2-4 hours (short-acting insulin) or every 1-2 hours (rapid-acting insulin) Glucose tests every 1-2 hours Eg: blood glucose 20 mmol (360 mg/dL) normal doses insulin Rapid acting =10 + 8 + 12 NPH = 22 Total = 52 units/day Give 20% ~10 units of rapid acting Give additional doses every 1 to 4 hours until blood glucose <12mmol/L (216mg/dL) and ketones reduced (urine or blood <1.0mmol/L)

33. DKA and HHS Curriculum Module III-6 Slide 33 of 55 Slides current until 2008 Sick days and pump therapy Rapid-acting insulin; no long- acting If pump problem, no insulin after 3 hours Become sick very quickly Need to carry or able to access a new infusion set and insulin pen at all times Need to be able to test ketones

34. DKA and HHS Curriculum Module III-6 Slide 34 of 55 Slides current until 2008 Insulin pump therapy  basal (25% to 100%) Know effect of a unit of insulin on blood glucose Correction dose for ketones up to double usual correction Test in 1 hour and 1–2 hourly thereafter If no change suspect site problem Use pen Re-site cannula

35. DKA and HHS Curriculum Module III-6 Slide 35 of 55 Slides current until 2008 Food tolerance Insulin must be given but may be reduced Eg: blood glucose 10-12mmol/L (180-216mg/dL) About 150 ml sweetened fluids each hour to hydrate and avoid hypoglycaemia If feverish, additional 150 ml low- calorie fluid each hour may be needed for re-hydration

36. DKA and HHS Curriculum Module III-6 Slide 36 of 55 Slides current until 2008 If unable to tolerate food Eg: blood glucose >15mmol/L (270mg/dL) (additional insulin needed as above) Give 150 ml to 300 ml of low-calorie fluid each hour for hydration and to help blood glucose to fall Monitor blood glucose every 1-2 hours Food tolerance

37. DKA and HHS Curriculum Module III-6 Slide 37 of 55 ACTIVITY Slides current until 2008 Provide a list of drinks easily available in your community that are suitable for an ill person with diabetes who is nauseated and unable to eat food.

38. DKA and HHS Curriculum Module III-6 Slide 38 of 55 Slides current until 2008 When to seek professional help Advise to call the physician or nurse if... Uncertain of diagnosis Persistent vomiting or diarrhoea (3 episodes or more within 6 hours) Unwell for 2 days and not getting better Blood glucose remains above 15 mmol/L (270 mg/dL) despite extra fluid and insulin Moderate to large ketones persist, despite extra fluid and insulin

39. DKA and HHS Curriculum Module III-6 Slide 39 of 55 Slides current until 2008 Hospital transfer Transfer to hospital if... Abdominal pain worsening Breathing difficulty or hyperventilation Co-existing serious diseases Person looking increasingly unwell/exhausted Care-givers exhausted or uncertain of diagnosis

40. DKA and HHS Curriculum Module III-6 Slide 40 of 55 ACTIVITY Slides current until 2008 Type 2 diabetes Mr M: 20 years, type 2 diabetes –maximal sulphonylureas and metformin –twice a day intermediate acting insulin Presented with 12 hours diarrhoea, nausea, no appetite What do you do? Stop tablets, remain on insulin, or stop insulin and remain on tablets?

41. DKA and HHS Curriculum Module III-6 Slide 41 of 55 Slides current until 2008 Type 2 diabetes Metformin can aggravate gut problems Often easier to cease medication and continue insulin Easier to control glucose levels with insulin; may need reduced dose Re-introduce oral medication when food intake normal and symptoms subside

42. DKA and HHS Curriculum Module III-6 Slide 42 of 55 Slides current until 2008 Type 2 diabetes Metformin Cease 24 hours before surgery Restart!

43. DKA and HHS Curriculum Module III-6 Slide 43 of 55 Slides current until 2008 Develop clear plans for sick days Make written guideline available and review plans with all people with diabetes regularly Determine when healthcare provider should be contacted or alerted Establish blood glucose goals for sick days Adapted from: Diab Care 2004; 27 Suppl 1

44. DKA and HHS Curriculum Module III-6 Slide 44 of 55 Slides current until 2008 Develop clear plans for sick days Define how to use supplemental short-acting insulin Explain how to use a fluid diet when unable to eat Explain what equipment is required

45. DKA and HHS Curriculum Module III-6 Slide 45 of 55 Slides current until 2008 Education tips Under-treated sick days are a common cause of diabetic ketoacidosis and hospitalization At each annual complication assessment, ask your patient to solve a sick-day scenario Access a 24-hour hotline

46. DKA and HHS Curriculum Module III-6 Slide 46 of 55 Slides current until 2008 Summary – diabetes and illness Never stop insulin Do more blood glucose tests –high blood glucose levels means more insulin In case of loss of appetite, eat foods that are easy to digest and drink more sugar-free fluids In case of vomiting, drink frequent small volumes of carb-containing fluids

47. DKA and HHS Curriculum Module III-6 Slide 47 of 55 Slides current until 2008 Summary – diabetes and illness Call for help in case of –persistent or severe vomiting –exhaustion or confusion –rapid breathing –worsening abdominal pain –uncertainty

48. DKA and HHS Curriculum Module III-6 Slide 48 of 55 Slides current until 2008 Review question 1.Which of the following is the most important ketone body in DKA? a.Acetone b.Acetoacetate c.Beta-hydroxybutyrate d.None of the above

49. DKA and HHS Curriculum Module III-6 Slide 49 of 55 Slides current until 2008 Review question 2.Which feature is more indicative of HHS than DKA? a.Extreme hyperglycaemia b.Extreme insulin deficiency c.Large anion gap d.Acetone breath

50. DKA and HHS Curriculum Module III-6 Slide 50 of 55 Slides current until 2008 Review question 3. Which of the following strategies should always be a part of the treatment plan for a person with DKA? a.Insulin therapy and magnesium replacement b.Possible insulin therapy and re- hydration c.Insulin therapy and re-hydration d.Possible insulin therapy and sodium bicarbonate replacement

51. DKA and HHS Curriculum Module III-6 Slide 51 of 55 Slides current until 2008 Review question 4. Which of the following strategies should always be a part of the treatment plan for a person with HHS? a.Insulin therapy and magnesium replacement b.Insulin therapy and re-hydration c.Possible insulin therapy and sodium bicarbonate replacement d.Possible insulin therapy and re- hydration

52. DKA and HHS Curriculum Module III-6 Slide 52 of 55 Slides current until 2008 Review question 5. Which electrolyte is critical to monitor during DKA as correction of the metabolic acidosis can possibly result in cardiac arrythmias and muscle weakness? a. Sodium b. Potassium c. Acetoacetate d. Beta-hydroxybutyrate

53. DKA and HHS Curriculum Module III-6 Slide 53 of 55 Slides current until 2008 Answers 1.c 2.a 3.c 4.d 5.b

54. DKA and HHS Curriculum Module III-6 Slide 54 of 55 Slides current until 2008 References – DKA and HHS 1.Booth GL. Short-Term Clinical Consequences of diabetes. In H. Gerstein & RB Haynes (EDs.), Hamilton: BC Decker. Evidence-Based Diabetes Care 2001; 75-90. 2.Jones H, Cleave B, Fredericks C, Hamilton C, Opsteen C. Building Competency in Diabetes education: the essentials. Canadian Diabetes Association, Canada, 2001. 3.Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001; 24(1): 131-53. 4.Kitabchi AE, Ayyagari V, Guerra SMO. The efficacy of low dose versus conventional therapy of insulin for treament of DKA. Ann Int Med 1976; 84: 633-8. 5.American Diabetes Association. Hyperglycemic crisis in patients with diabetes. Diabetes Care 2001; 26(S1): S109-17. 6.Meltzer S, Yale JF, Belton AB, Clement M. Eds. Practical Diabetes Management; Clinical support for primary care physicians 5 th ed. Canadian Diabetes Association, Canada, 2004. 7.Davidson MB. Hyperglycemia. In: Franz MJ, ed. A Core Curriculum for Diabetes Education: Diabetes and Complications. 4 th ed. Chicago: American Association of Diabetes Educators 2001; 23. 8.Joslin’s Diabetes Mellitus. Eds Kahn CR,Weir GC et al. Publ Lippincott Williams & Wilkins, Philadelphia, 2005; 53.

55. DKA and HHS Curriculum Module III-6 Slide 55 of 55 Slides current until 2008 References – managing illness 1.Hyperglycemic crises in diabetes. ADA position statement. Diab Care 2004; 27 (Suppl 1). 2.Hanas R. Type 1 diabetes in children, adolescents and young adults. 2nd edition 2004. Publ Class Publishing, London 3.Laffel L, Pasquarello C, Lawlor M. Treatment of the child and adolescent with diabetes. Chap 35 in Joslin’s Textbook Diabetes. Publ Lippincott Williams & Wilkins, Philadelphia, 2005.