Diabetic ketoacidosis and hyperosmolar hyperglycaemic state

Slides current until 2008

Diabetic ketoacidosis andhyperosmolar hyperglycaemic state

Abdulrahman Al shaikh.Asso professor, consultant endo.Abdulrahman Al shaikh.Asso professor, consultant endo.

Al shaikh

DKA and HHSCurriculum Module III-6

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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


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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


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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 <10%

Booth 2001, Joslin 2005

Al shaikh


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Insulin deficiency

Glucose uptake Lipolysis

Hyperglycaemia Gluconeogenesis

Glycerol Free fatty acids

Ketogenesis

Ketonemia

KetonuriaOsmotic diuresis

Urinary water losses

Electrolyte depletion

Dehydration

Acidosis

Diabetic ketoacidosis

Adapted from Davidson 2001

Glucosuria

Al shaikh


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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– acetoneAl

shaikh


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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


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Earlier clinical symptoms and signs of DKA

• Polyuria

• Polydipsia

• Polyphagia

• Tiredness

• Muscle cramps

• Flushed facial appearance Al shaikh


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Later clinical symptoms and signs of DKA

• Weight loss• Nausea and vomiting• Abdominal pain• Dehydration • Acidotic breath• Hypotension • Shock• Altered consciousness • Coma

Al shaikh


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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-rayAl

shaikh


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DKA – laboratory findings

Blood glucose >14mmol/L (252mg/dL)

Ketones Urine: moderate to large

Blood: >3mmol/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 >10 mild

>12 moderate to severe

Blood gases pH <7.30, HCO3 <15 (mild)

pH <7.00, HCO3 <10 (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

Kitabchi et al 1976

Al shaikh


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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


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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


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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 potassiumAl

shaikh


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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


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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

Kitabchi et al 2001

Al shaikh


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HHS – key features

• Marked hyperglycaemia

• Hyperosmolarity

• Absence of severe ketosis

• Altered mental awareness

Joslin 2005

Al shaikh


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HHS – causes or triggers

Booth 2001

Incidence

Infection 40-60%

New-onset diabetes 33%

Acute illness 10-15%

Medicines, steroids <10%

Insulin omission 5-15%

Al shaikh


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Signs and symptoms of HHS

• Initially polyuria and polydipsia

• Altered mental status

• Profound dehydration

• Precipitating factors

Al shaikh


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HHS – biochemical findings

Jones 2001

Blood glucose >33mmol/L (600mg/dl)

Ketones Urine: negative – small

Blood: <0.6 mmol/L

Osmolality >320mOsm/kg - (raised Na, BG, urea)

Electrolytes Raised Na, BG, urea creatinine

Anion gap <12

Blood gases pH >7.30

normal or raised HCO3Al shaikh


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Treatment

Rehydration Caution!

Normal saline 1 l per hour initially

Consider ½ strength normal saline

Potassium Only if hypokalaemic and renal function adequate – give before insulin

Insulin May be needed as slow infusion0.1 unit/kg/hour to be increased with care if BG is slow to fall

Monitoring BG, BP, neurological function hourly until stableElectrolytes 2-hourlyCardiac or CVP monitoringAl

shaikh


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HHS – complications

Complication Prevention

Hypoglycaemia Prevent by adding glucose infusion when glucose <14mmol/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 <4mmol/L (72mg/dL) per hour; aggressive Mannitol treatment if any early signs of cerebral oedema

Meltzer 2004

Al shaikh


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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


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


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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

<4 (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

>18.1 (325) + 10 units + 8 units + 12 units


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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)


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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 1–2 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


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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


Slide 37 of 55ACTIVITY


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


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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


Slide 40 of 55ACTIVITY


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?


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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


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Type 2 diabetes

Metformin

• Cease 24 hours before

surgery

• Restart!


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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


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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


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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


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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


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Summary – diabetes and illness

• Call for help in case of

– persistent or severe vomiting

– exhaustion or confusion

– rapid breathing

– worsening abdominal pain

– uncertainty


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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


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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


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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?

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


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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?

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


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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. Joslin’s 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 Joslin’s Textbook Diabetes. Publ Lippincott Williams & Wilkins, Philadelphia, 2005.

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Diabetic ketoacidosis and hyperosmolar hyperglycaemic state