Paeds - Altered Conciousness

Question 1

To what extent is T1DM genetic?

Answer 1

Twin studies have shown concordance of 30-40%

Thus there is a notable genetic component but not a significant as T2DM (~ 80% concordance)

Question 2

What causes T1DM?

Answer 2

Often molecular mimicry between an environmental trigger and an antigen on the surface of pancreatic β­-cells

Environmental triggers:

• Enteroviral infections
• Cow’s milk proteins

Question 3

T1DM has 2 peaks in the age of presentation, what are they?

Answer 3

1) Pre-school
2) Teenagers

Question 4

How do children often present with T1DM?

Answer 4

Hx of a few weeks of:

• Classic triad:
  
  1. Polyuria
  2. Polydipsia
  3. Weight loss or excessive tiredness
• Hyperglycaemia (random plasma glucose > 11.1 mmol/L)
• Secondary nocturnal enuresis (young children)
• Candida infection (mouth, genitalia, feet)
• DKA:
  
  • Acetone breath
  • Abdominal pain
  • Hyperventilation due to acidosis (Kussmaul breathing)
  • Vomiting
  • Dehydration
  • Hypovolaemic shock
  • Drowsiness
  • Coma / Death

Question 5

How does diabetic ketoacidosis present?

Answer 5

• Polyuria
• Polydipsia
• Acetone breath
• Abdominal pain - correlates with degree of acidosis
• Hyperventilation due to acidosis (Kussmaul breathing)
• Vomiting
• Dehydration - dry mucous membranes, poor skin turgor, sunken eyes, ↑ HR, ↓ BP
• Hypovolaemic shock
• Drowsiness
• Coma / Death

Question 6

Define Diabetes Mellitus

Answer 6

Diabetes Mellitus = a reduction in insulin action sufficient to cause a level of hyperglycaemia that, over time, will result in diabetes specific microvascular pathology and macrovascular pathologies

Microvascular pathologies:

• Retinopathy
• Nephropathy
• Neuropathy

Macrovascular pathologies:

• Stroke
• MI
• Renovascular disease
• Limb ischaemia

Question 7

What are the 3 mechanisms by which ↓ insulin action occurs in Diabetes Mellitus?

Answer 7

1. ↓ insulin production
2. ↓ insulin sensitivity of target organs
3. Overwhelming ↑ in catabolic hormones
   
   • The anabolic effect of insulin is balanced against 4 main ‘catabolic hormones’ e.g. catecholamines, cortisol, glucagon and growth hormone

Question 8

Describe Non-diabetic hyperglycaemia (NDH) also called pre-diabetes (for patients) and impaired glucose regulation (for healthcare staff).

Answer 8

NDH = insulin action ↓ is sufficient to cause hyperglycaemia but not sufficient enough to cause microvascular damage

There are 2 main types of impaired glucose regulation:

1. Impaired fasting glucose (IFG) - due to hepatic insulin resistance
   
   • Fasting glucose 6.1 - 6.9 mmol/L
   • Pts with IFG should have an OGTT to rule out diabetes - if ≥ 7.8 but < 11.1 then pt has IGT
2. Impaired glucose tolerance (IGT) - due to muslce insulin resistance
   
   • Fasting glucose < 7.0 mmol/L + OGTT 2-hour ≥ 7.8 but < 11.1

Question 9

What is HbA1c?

Answer 9

HbA1c = glycated haemoglobin

• It is an indication of the previous 3-month average plasma [glucose]
• Test is limited to 3-month average as lifespan of RBCs is 120 days i.e. 4 months

Question 10

What is DKA (Diabetic Ketoacidosis)?

Answer 10

DKA = acute metabolic complicationof T1DM

it is characterised by the triad of:

1. Hyperglycaemia
2. Ketonaemia
3. Acidaemia

Question 11

What are the 3 most common events precipitating DKA?

(Besides new presentation of T1DM as DKA)

Answer 11

1. Inadequate insulin therapy (e.g. missed insulin dose)
2. Infection (causes ↑ in bodies metabolic demands, for which there is insufficient insulin to accommodate for i.e. not enough to move enough glucose into cells)
   
   • Pneumonia and UTI are most common
3. MI - cardiovascular events can stim release of counter-regulatory hormones that precipitate DKA (catecholamines, cortisol, glucagon, growth hormone)

The following are other known risk factors for precipitating DKA:

• Pancreatitis
• Acromegaly (↑ GH production due to benign pituitary adenoma)
• Hyperthyroidism
• Cushing’s Syndrome
• Drugs affecting carbohydrate metabolism e.g. corticosteroids, thiazides, anitipsychotics

Question 12

What is the mechanism underpinning the development of DKA?

Answer 12

• Foundation is a combination of:
  
  • ↓ net effective insulin
  • ↑ counter-regulatory hormones (e.g. glucagon, catecholamines, cortisol and growth hormone)
• ↓ net effective insulin –> hyperglycaemia (as body is unable to move glucose into cells)
• The ↑ plasma [glucose] results in ↑ glucose in kidney nephrons –> this increases osmotic pressure (lowers H₂O potential) causing solutes and H₂O to move into the nephrons –> this is called osmotic diuresis
• ​Osmotic diuresis causes:
  
  • Polyuria
  • Dehydration
  • Polydipsia
  • Electrolyte loss/disturbances
• ↓ glucose moving into cells also causes ↑ lipolysis –> releasing fatty acids, which are converted by beta-oxidation (in the liver) into ketone bodies; acetoacetate and β-hydroxybutyrate
• Ketone bodies are used as an energy source in starvation (i.e. absence of carbohydrate energy sources fat stores are used) –> however they turn blood acidic
• The body initially buffers the ketoacidosis with bicarbonate (HCO₃^-), but is overwhelmed
• The body hyperventilates (respiratory compensation) to lower blood CO₂ (reduce acidity)
  
  • Kussmaul Breathing – is a form of hyperventilation involving deep + laboured breathing and associated with metabolic acidosis

Question 13

How is DKA diagnosed from tests (excluding examination)?

Answer 13

1. Hyperglycaemia - blood glucose > 11.0 mmol/L or known diabetes mellitus
2. Ketonaemia - > 3.0 mmol/L
   
   • Urinary ketones NOT used anymore (worse predictor of DKA)
3. Acidaemia:
   
   • Bicarbonate (HCO₃^-) < 15.0 mmol/L and/or
   • Venous pH < 7.3

Question 14

What tests/investigations might be useful in a patient suspected of DKA?

Answer 14

• Blood glucose > 11.1 mmol/L
  
  • 5-10% of DKA patients present as being euglycaemic
• Blood ketones - > 3.0 mmol/L
• Lactate - taken to exclude lactic acidosis (result should be normal in DKA)
• Blood glucose
  
  • 5-10% of DKA patients present as being euglycaemic
• VBG / ABG - severe metabolic acidosis
  
  • Generally VBG is easier, lower risk, and can be used to diagnose and determine response to treatment
  • VBGs can also provide glucose + potassium
  • ABG (gold standard for metabolic disturbances) is more accurate for determining hypercapnia and hypoxia
• U+Es:
  
  • Serum K⁺ often ↑ but total body K⁺ ↓
  • Na⁺, Cl^-, Mg²⁺ and Ca²⁺ are normally ↓
• Urine Dipstick:
  
  • +ve for leucocytes in UTI (can precipitate DKA)
  • +ve nitrites (infection)
  • +ve for glucose
  • +ve for ketones
• FBC:
  
  • Leucocytosis (↑ WBC) occurs during hyperglycaemic state and in infection
• Blood culture - looking for infective pathogen
• ECG - to identify MI as precipitant or examine cardiac effects of electrolytes disturbances (Hyperkalaemia = tall-tented T-waves and widened QRS, hypokalaemia = U-waves)
• CXR - if pneumonia thought to be precipitant of DKA

Question 15

What 3 things are done to mange DKA?

Answer 15

1. Fluid replacement:
   
   • Typical fluid deficit in DKA ~100ml/Kg e.g. 70kg = 7 litres
   • Always consider age, gender and concomitant medication and co-morbidites when replacing fluid
   • Caution when replacing fluid in following; Young adults (18-25yrs), elderly, pregnant, HF or kidney failure or if taking mediation for BP
2. Fixed rate Insulin infusion:
   
   • IV fixed rate infusion pump - made of up of 50 units insulin made up to 50ml with 0.9% saline –> infuse at rate of 0.1 unit/kg/hr
   • When blood glucose < 15 mmol/l an infusion of 5% dextrose should be started
   • Continue pts long-acting insulin at usual dose + times in diabetic patients
   • Only give bolus (stat) dose of IM insulin (0.1 unit/kg) if there is delay in setting up infusion
3. K⁺ replacement - correction of hypokalaemia (caused by insulin)

Question 16

What is the fluid replacement regime for DKA?

Answer 16

Fluid replacement

1. Insert 2 large-bore cannula (one in each arm ideally)
2. If systolic BP < 90 mmHg (and no concomitant HF or sepsis):
   
   • 500ml 0.9% sodium chloride (Saline) over 10-15 mins
   • If BP doesn’t improve then another 500ml over 10-15 mins + contact senior
   • If BP remains low –> contact ICU
3. If/once systolic BP > 90 mmHg:
   
   • See image

Question 17

What are the potassium cut-offs which dictate potassium replacement during DKA?

Answer 17

Hypokalaemia and hyperkalaemia can occur in DKA:

• K+ is normally ↑ on admission (even though the total body K+ is ↓)
• But will ↓ post insulin treatment

Question 18

How is T1DM diagnosed in children?

Answer 18

1. Symptoms of DKA:
   
   • Hyperglycaemia
   • Ketonaemia - > 3.0 mmol/L or significant ketonuria (more than ++ on urine dipstick)
   • Acidaemia
2. Symptoms typical of T1DM in children:
   
   • Polyuria
   • Polydipsia
   • Weight loss
3. Hyperglycaemia:
   
   • Random blood glucose > 11.1 mmol/L
   • Fasting blood glucose > 7 mmol/L
   • Raised HbA1c > 6.5% or 48 mmol/mol
4. Glycosuria

Question 19

What features of a Hx might indicate a child has T2DM as opposed to T1DM?

Answer 19

• Family history of T2DM
• Child is black or from indian subcontinent
• Severly obese
• Signs of insulin resistance:
  
  • Acanthosis nigricans - velvety dark skin on the neck or armpits
  • Skin tags
  • Polycystic ovaries in females

Question 20

What are the classifcations / types of insulin - based on their profile of action/duration?

Answer 20

1. Rapid-acting insulin analogues
   
   • Onset = 5 mins
   • Peak = 1 hour
   • Duration = 3-5 hours
2. Short-acting insulin (also called soluable insulin)
   
   • Onset = 30 mins
   • Peak = 3 hours
   • Duration = 6-8 hours
3. Intermediate-acting insulin
   
   1. Onset = 2 hours
   2. Peak = 5-8 hours
   3. Duration = 12-18 hours
4. Long-acting insulin analogues
   
   1. Onset = 1-2 hours
   2. Peak = flat profile
   3. Duration = 24 hours

Question 21

What is a basal-bolus regime for Insulin?

Answer 21

It is the combination of:

1. Rapid/short-acting ‘bolus’ insulin before meals
2. Intermediate/long-acting ‘basal’ insulin once or twice daily

Question 22

Name some examples of the following Insulin types:

1. Rapid-acting insulin analogues
2. Short-acting insulins
3. Intermidate-acting insulins
4. Long-acting insulin analogues

Answer 22

1. Rapid-acting insulin analogues:
   
   • Insulin Aspart (Novorapid)
   • Insulin Lispro (Humalog)
2. Short-acting insulins:
   
   • Actrapid
   • Humulin S
3. Intermidate-acting insulins:
   
   • Isophane insulin
4. Long-acting insulin analogues:
   
   • Insulin determir (Levemir) - once or twice daily
   • Insulin glargine (Lantus) - once daily

Question 23

What are ‘Premixed’ preparations of Insulin composed of?

Answer 23

Combinations of intermediate acting insulin + either a rapid-acting insulin analogue or short-acting insulin e.g.

• Novomix 30:
  
  • 30% insulin aspart (rapid-acting)
  • 70% insulin aspart protamine (intermediate-acting)
• Humalog Mix 25:
  
  • 25% insulin lispro (rapid-acting)
  • 75% insulin lispro protamine (intermediate-acting)
• Humalog Mix 50:
  
  • 50% insulin lispro
  • 50% insulin lispro protamine

Question 24

Is Insulin typically administered; subcutaneously, intramuscularly, IV or oral?

Answer 24

Subcutaneously

Question 25

What localised side effect can insulin injection cause?

Answer 25

Lipohypertrophy

small lump under skin due to fat accumulation at injection sites (insulin causes fat hypertrophy)

Question 26

What factors can cause blood glucose to go up vs down?

Answer 26

Raise blood glucose:

• Omission of insulin
• Food (especially refined carbs e.g. white bread, white pasta, white rice, sweets etc)
• Illness - but lack of eating during illness can cause varied blood glucose (best to monitor BMs closely and respond appropriately)
• Menstruation (shortly before onset)
• Growth hormone
• Corticosteroids
• Sex hormones at puberty
• Surgery

Lower blood glucose:

• Insulin
• Exercise
• Alcohol
• Anxiety / excitement
• Medication

Question 27

How is DKA in a child managed?

Answer 27

This regimen is initiated IF the child is:

1. vomiting or
2. has reduced conciousness level or
3. clinically dehydrated

(otherwise only subcut insulin is required)

1. Fluids
   
   • If in shock –> resus with 0.9% saline, insert central venous line + urinary catheter
   • If vomiting or reduced conciousness –> NG tube (to reduce risk of aspiration)
   • Rehydrate over 48-72h (rapid rehydration can cause cerebral oedema)
   • 40 mmol/L of potassium - ensure all fluids given to children /w DKA contain 40 mmol/L of K⁺
   • Don’t stop IV fluid therapy until ketosis is resolving + alert + oral fluids without vomiting
   • Monitor:
     
     • Fluid input + output
     • U+Es, creatinine and blood gas
     • Neurological state
2. Insulin
   
   • Do not give bolus
   • Insulin infusion 0.05-0.1 U/kg/hr - start 1-2hr after IV fluid therapy
   • Monitor BMs regularly - aim for gradual reduction of 2 mmol/hr
   • Change to 0.9% saline with 5% dextrose and 40 mmol/L potassium chloride (KCl) when blood glucose < 14 mmol/L to avoid hypoglycaemia
   • Don’t change IV insulin to subcut insulin until ketosis is resolving + alert + oral fluids without vomiting
   • Start subcut insulin 30-60 mins before stopping IV insulin
3. Potassium
   
   • Initially hyperkalaemia but will fall with insulin
   • Start K⁺ replacement as soon as urine is passed
   • Continuous ECG monitoring (to avoid hyperkalaemia)
4. Acidosis
   
   • This will correct with fluids + insulin
   • Only give bicarbonate if in shock and note responding to therapy

Question 28

Which human leukocyte antigens (HLA) are associated with T1DM?

Answer 28

HLA-DR3 and HLA-DR4

Question 29

What kidney condition is diabetes

the commonest cause of?

Answer 29

End Stage Renal Disease (ESRD)

Question 30

What conditions can cause diabetes?

Answer 30

• Cushing’s syndrome
• Acromegaly (GH excess)
• Gestational diabetes
• Chronic pancreatitis
• Cystic fibrosis (features of both T1DM / T2DM in that it exhibits reduced insulin production but reduced insulin sensitivity)

Question 31

How would you rule out cerebral oedema due to iatrogenic treatment of DKA?

Answer 31

CT head + senior review

Question 32

Which population are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA management?

Answer 32

Children and young adults

Question 33

When does cerebral oedema usually occur in the treatment of DKA?

Answer 33

4-12 hours after treatment

but can present at any time

Question 34

Under what conditions / circumstances is DKA likely to occur?

Answer 34

1. At diagnosis (pts with T1DM can not present to doctors until DKA)
2. Illness e.g. viral / bacterial infection
3. Growth spurt / puberty
4. Insulin omission (for any reason)
5. Malfunctioning insulin pump (pump doesn’t give any long-acting insulin, so without short-acting supply, DKA can develop)

Question 35

If a child presents with:

1. polydipsia
2. polyuria
3. and unexplained weight loss or excessive tiredness

• and any of the following:
  
  • nausea / vomiting
  • abdo pain
  • hyperventilation
  • dehydration
  • reduced level of consciousness

What investigation should be done immediately?

Answer 35

Caillary blood glucose

> 11 mmol/L + symptoms of DKA = suspect DKA & send to hospital

Question 36

When DKA is suspected in a child with known T1DM

what blood test should be done?

Answer 36

Blood ketones

If elevated –> send to hospital

Question 37

What should your initial actions be when you suspect / diagnose a child with DKA?

Answer 37

1. Inform responsible senior clinician
2. Explain to child / young person / family what DKA is and the care required
3. Record:
   
   • consciousness level
   • vital signs; HR, BP, temp, RR (Kussmaul)
   • Hx of nausea or vomiting
   • clinical evidence of dehydration
   • body weight

Question 38

If a child has DKA and is NOT:

1. vomiting or
2. has reduced conciousness level or
3. clinically dehydrated

how are they managed?

Answer 38

1. Oral fluids
2. Subcut insulin
3. Monitor ketonaemia + acidosis via blood ketones & blood gases

Question 39

What 3 things (that are normal in adult DKA management) are not normally given in child DKA management?

Answer 39

1. Fluid bolus
2. Insulin bolus
3. IV sodium bicarbonate (or any bicarbonate for that matter)

Question 40

When giving IV fluids for DKA in a child how is their total fluid requirement for the first 48hrs calculated?

Answer 40

Estimated fluid deficit + fluid maintenance

Estimated fluid deficit:

• Mild - moderate DKA (pH of 7.1 or above) = 5%
• Severe DKA (pH of below 7.1 ) = 10%

Maintenance fluids ‘reduced volume’ rules:

• < 10 kg = 2 ml/kg/hr
• 10 - 40 kg = 1 ml/kg/hr
• > 40 kg = fixed volume of 40 ml/hr

Question 41

What monitoring is needed during treatment of DKA in children?

Answer 41

1. Hourly - capillary glucose, ketones, vitals and fluid balance
2. Every 30 mins - level of conciousness (modified GCS) and HR (to detect bradycardia) - because children are are greater risk of cerebral oedema
3. Continuous ECG - monitor for hypokalaemia (ST depression and prominent U-waves)
4. At 2 hours post start of treatment then every 4 hrs:
   
   • blood glucose
   • blood gas (pH, pCO2)
   • U+Es
   • Face-to-face review

Question 42

What are the early manifestations of Cerebral Oedema in children?

Answer 42

1. Headache
2. Agitation
3. Irritability
4. Unexpected drop in HR & increased BP
5. Deterioration in level of consciousness
6. Respiratory pauses
7. Ocullomotor palsies
8. Pupil inequality or dilation

Question 43

How do you treat cerebral oedema in children?

Answer 43

Mannitol 20%, 0.5–1 g/kg over 10–15 minutes

OR

Hypertonic sodium chloride 2.7% or 3%, 2.5–5 ml/kg over 10–15 minutes

Question 44

What messages should be given to diabetic patients regdarding

Sick Days, so called ‘Sick Day Rules’?

Answer 44

1. Increase frequency of blood glucose monitoring to 4-hourly or more
2. Encourage fluid intake - aim for at > 3L in 24hrs
3. If unable/struggling to eat –> keep sugary drinks to maintain blood glucose
4. Advise pts to keep a box of ‘sick day supplies’ for if they become unwell
5. Continue to take oral hypoglycaemic medication even if not eating - bodies response to stress is ↑ cortisol –> ↑ glucose
6. If on insulin –> take doses as normal - if blood glucose + ketones are high –> give corrective insulin dose
   
   • Rule of thumb: total daily insulin / 6 (max 15 units)
7. Advise pt to keep access to a mobile phone –> has been shown to reduce progression of ketosis to diabetic ketoacidosis

Question 45

What are the diagnostic criteria for T2DM for each of the following investigations, with symptoms and then without symptoms:

1. Random plasma glucose
2. Fasting glucose
3. Oral glucose tolerance test (OGTT)
4. HbA1c

Answer 45

If patient is SYMPTOMATIC + ONE of:

• Fasting glucose ≥ 7.0 mmol/L
• Random plasma gucose ​≥ 11.1 mmol/L
• Oral glucose tolerance test (OGTT) - ≥ 11.1 mmol/L (2h after 75g glucose given orally)

If patient is ASYMPTOMATIC the above criteria apply BUT must be demonstrated on two seperate occasions!

HbA1c:

• Diabetes = HbA1c ≥ 48 mmol/mol (6.5%)
• Pre-diabetes = HbA1c 42-47 mmol/mol
• Not diabetic = HbA1c ≤ 41 mmol/mol (5.9%)
• If asymptomatic the test must be repeated to confirm
• Conditions that affects RBC turnover can produced misleading HbA1c - thus the it can’t be used in the following conditions:
  
  • Children
  • Pts with symptoms < 2 months
  • Haemoglobinopathies
  • Haemolytic anaemia
  • Untreated iron deficiency anaemia
  • Suspected gestational diabetes
  • HIV
  • CKD
  • Medication that may cause hyperglycaemia (e.g. corticosteroids)

Question 47

What is the risk that gestational diabetes poses?

How can it be diagnosed via fasting glucose or OGTT?

Answer 47

↑ foetal morbidity/mortality

• Fasting glucose ≥ 5.6 mmol/L
• OGTT ≥ 7.8 mmol/L

Question 48

What test can be done to help confirm T1DM in an ambiguous clinical picture?

Answer 48

GAD antibodies test

(Glutamic Acid Decarboxylase autoantibodies)

• GAD antibiodies +ve in autoimmune style diabetes e.g. T1DM
• Can be used to distinguish between LADA & T2DM in an adult with low BMI or weight loss (suggestive of autoimmune diabetes pattern)

Question 49

How often should children with T1DM test their blood sugar?

Answer 49

~ 5 times per day

(more during illness / symptomatic / physical activity etc)

Question 50

How many times per year should children with T1DM be offered HbA1c measurement?

Answer 50

4 times per year

(more frequent if concern about blood glucose control)

Question 51

How is hypoglycaemia in children / young people with T1DM managed?

Answer 51

Mild - moderate hypoglycaemia:

• Fast-acting glucose e.g. 10-20g PO
  
  • Raises blood glucose within 5-15 mins
  • Glucogel can be rubbed on lips
  • May need to be given in frequent small amounts as hypoglycaemia can cause vomiting
• Re-check blood glucose within 15 mins
• Oral complex long-acting carbohydrate - give when symptoms improve / normoglycaemia is achieved (unless about to have a snack)

Severe hypoglycaemia:

• IF rapid IV access –> 10% IV glucose, max dose of 500 mg/kg
• IF no rapid IV access –> IM glucagon or concentrated oral glucose solution (e.g. Glucogel)
  
  • Do not use oral glucose solution is level of consciousness is reduced

Question 52

In the treatment of severe hypoglycaemia in children without IV access what do you give and how much?

Answer 52

• Child < 8-yrs or weigh < 25 kg –> 500 micograms of IM glucagon
• Child > 8-yrs or weigh > 25 kg –> 1 mg of IM glucagon

Question 53

When can IM glucagon be ineffective in treating hypoglycaemia?

Answer 53

In T1DM patients whose hypoglycaemia is due to alcohol consumption

Question 54

Diabetes can involve various complications, what monitoring is done for these?

Answer 54

1. Thyroid disease - TFTs at diagnosis + annually
2. Diabetic retinopathy - opthalmoscopy annually from 12-yrs
3. Diabetic kidney disease - ACR of 3-30 mg/mmol (microalbuminuria) tested for annually from 12-yrs
   
   • Use ‘early morning urine’ sample (first urine sample of day) - reduces risk of false +ve results
4. Hypertension - BP annually from 12-yrs

Question 55

What are some rare complications of T1DM?

Answer 55

1. Juvenile cataracts
2. Necrobiosis lipoidica - a necrotising skin condition associated with diabetes and RA
3. Addison’s disease

Question 56

What does this image show?

Answer 56

Necrotising Lipoidica

(severity or control of diabetes does not affect who experiences it)

• Hardened, raised are under skin
• Yellow-ish tint to centre with dark pink surrounding
• Often appears on shins, both legs (can also be on forearms, trunk and hands)

Question 57

What blood glucose level indicates hypoglycaemia?

Answer 57

< 4.0 mmol/L