Diabetic ketoacidosis and hyperosmolar hyperglycaemic state

1
Diabetic ketoacidosis andhyperosmolar
hyperglycaemic state
Al shaikh
Abdulrahman Al shaikh.Asso professor, consultant
endo.
2
What is DKA?
High blood glucose, ketones, acidosis and
dehydration

• Absolute or relative insulin deficiency
• Increase in counter-regulatory hormones
• Breakdown of fat and muscle
• Biochemical triad
• hyperglycaemia
• ketoacids
• metabolic acidosis

Al shaikh
3
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
• 
  

Al shaikh
Kitabchi et al 2001, Joslin 2005
4
DKA cause or trigger
Incidence
New-onset diabetes 5-40
Acute illness 10-20
Insulin omission/non-adherence 33
Infection 20-38
Heart attack, stroke, pancreatitis lt10
Al shaikh
Booth 2001, Joslin 2005
5
Diabetic ketoacidosis
Insulin deficiency
Lipolysis
Glucose uptake
Glycerol
Free fatty acids
Hyperglycaemia
Gluconeogenesis
Ketogenesis
Glucosuria
Ketonemia
Ketonuria
Electrolyte depletion
Osmotic diuresis
Dehydration
Urinary water losses
Acidosis
Al shaikh
Adapted from Davidson 2001
6
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
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
Earlier clinical symptoms and signs of DKA

• Polyuria
• Polydipsia
• Polyphagia
• Tiredness
• Muscle cramps
• Flushed facial appearance

Al shaikh
9
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 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 laboratory findings
Blood glucose gt14mmol/L (252mg/dL)
Ketones Urine moderate to large Blood gt3mmol/L
Osmolality Increased high blood glucose and urea/creatinine, dehydration
Electrolytes Low/normal Na and Cl- Low/normal/high K (often misleading) Low HCO3 (normal 23-31)
Anion gap gt10 mild gt12 moderate to severe
Blood gases pH lt7.30, HCO3 lt15 (mild) pH lt7.00, HCO3 lt10 (severe)
Al shaikh
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DKA treatment
Rehydration 1. 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
Potassium Essential after resuscitation and when urine output confirmed
Al shaikh
Kitabchi et al 1976
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DKA treatment
Insulin Infusion 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
Monitoring BG, BP, urine output and hourly neurological status Blood gases and electrolytes 2-hourly initially
Al shaikh
14
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

Al shaikh
Joslin 2005
15
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
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

Al shaikh
Kitabchi et al 2001
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HHS incidence and features

• 0.5 of primary diabetes hospital admissions
• 15 mortality rate
• Can occur in type 1 diabetes and younger people

Al shaikh
Kitabchi et al 2001
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HHS key features

• Marked hyperglycaemia
• Hyperosmolarity
• Absence of severe ketosis
• Altered mental awareness

Al shaikh
Joslin 2005
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HHS causes or triggers
Incidence
Infection 40-60
New-onset diabetes 33
Acute illness 10-15
Medicines, steroids lt10
Insulin omission 5-15
Al shaikh
Booth 2001
20
Signs and symptoms of HHS

• Initially polyuria and polydipsia
• Altered mental status
• Profound dehydration
• Precipitating factors

Al shaikh
21
HHS biochemical findings
Blood glucose gt33mmol/L (600mg/dl)
Ketones Urine negative small Blood lt0.6 mmol/L
Osmolality gt320mOsm/kg - (raised Na, BG, urea)
Electrolytes Raised Na, BG, urea creatinine
Anion gap lt12
Blood gases pH gt7.30 normal or raised HCO3
Al shaikh
Jones 2001
22
Treatment
Rehydration Caution!
Rehydration Normal saline 1 l per hour initially
Rehydration Consider ½ strength normal saline
Potassium Only if hypokalaemic and renal function adequate give before insulin
Insulin May be needed as slow infusion 0.1 unit/kg/hour to be increased with care if BG is slow to fall
Monitoring BG, BP, neurological function hourly until stable Electrolytes 2-hourly Cardiac or CVP monitoring
Al shaikh
23
HHS complications
Complication Prevention
Hypoglycaemia Prevent by adding glucose infusion when glucose lt14mmol/L (250 mg/dL)
Hypokalaemia Early potassium replacement and monitoring
Fluid overload Careful clinical monitoring and central line as needed
Vomiting/aspiration NG tube and may be nursed on side
Cerebral oedema Avoid fast blood glucose falls (should be lt4mmol/L (72mg/dL) per hour aggressive Mannitol treatment if any early signs of cerebral oedema
Al shaikh
Meltzer 2004
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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
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Managing diabetes during illness
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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

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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

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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

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Illnesses and hyperglycaemiaGeneral 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
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
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Algorithm for guidance
Breakfast Lunch Supper Bedtime
Usual dose (example) Soluble 10 Soluble 8 Soluble 12 NPH 24
If blood glucose is... Units of insulin reduced (-) or added () to usual dose Units of insulin reduced (-) or added () to usual dose Units of insulin reduced (-) or added () to usual dose Units of insulin reduced (-) or added () to usual dose
lt4 (72) - 5 units - 4 units - 6 units continue
4.1-6.0 (73-108) - 2 units - 2 units - 2 units
6.1-10.0 (109-180) Usual dose Usual dose Usual dose
10.1-12.0 (181-216) 2 units 2 units 2 units
12.1-14.0 (217-252) 4 units 4 units 4 units
14.1- 18.0 (253-324) 8 units 6 units 10 units
gt18.1 (325) 10 units 8 units 12 units
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Insulin correction doses

• Blood glucose gt15mmol/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 lt12mmol/L (216mg/dL) and ketones
reduced (urine or blood lt1.0mmol/L)
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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

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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 12 hourly thereafter
• If no change suspect site problem
• Use pen
• Re-site cannula

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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
Food tolerance

• If unable to tolerate food
• Eg blood glucose gt15mmol/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

37

• 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.

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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
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

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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
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
Type 2 diabetes

• Metformin
• Cease 24 hours before surgery
• Restart!

43
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
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
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
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
Summary diabetes and illness

• Call for help in case of
• persistent or severe vomiting
• exhaustion or confusion
• rapid breathing
• worsening abdominal pain
• uncertainty

48
Review question

• Which of the following is the most important
  ketone body in DKA?
• Acetone
• Acetoacetate
• Beta-hydroxybutyrate
• None of the above

49
Review question

• Which feature is more indicative of HHS than DKA?
• Extreme hyperglycaemia
• Extreme insulin deficiency
• Large anion gap
• Acetone breath

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Review question


   

• 3. Which of the following strategies should
  always be a part of the treatment plan for a
  person with DKA?
• Insulin therapy and magnesium replacement
• Possible insulin therapy and re-hydration
• Insulin therapy and re-hydration
• Possible insulin therapy and sodium bicarbonate
  replacement
•  

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Review question

• 4. Which of the following strategies should
  always be a part of the treatment plan for a
  person with HHS?
• Insulin therapy and magnesium replacement
• Insulin therapy and re-hydration
• Possible insulin therapy and sodium bicarbonate
  replacement
• Possible insulin therapy and re-hydration

52
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

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Answers

1. c
2. a
3. c
4. d
5. b

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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 5th ed. Canadian
   Diabetes Association, Canada, 2004.
7. Davidson MB. Hyperglycemia. In Franz MJ, ed. A
   Core Curriculum for Diabetes Education Diabetes
   and Complications. 4th ed. Chicago American
   Association of Diabetes Educators 2001 23.
8. Joslins Diabetes Mellitus. Eds Kahn CR,Weir GC
   et al. Publ Lippincott Williams Wilkins,
   Philadelphia, 2005 53.

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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 Joslins Textbook Diabetes. Publ Lippincott
   Williams Wilkins, Philadelphia, 2005.