Paeds - Altered Conciousness Flashcards
To what extent is T1DM genetic?
Twin studies have shown concordance of 30-40%
Thus there is a notable genetic component but not a significant as T2DM (~ 80% concordance)
What causes T1DM?
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
T1DM has 2 peaks in the age of presentation, what are they?
1) Pre-school
2) Teenagers
How do children often present with T1DM?
Hx of a few weeks of:
- Classic triad:
- Polyuria
- Polydipsia
- 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
How does diabetic ketoacidosis present?
- 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
Define Diabetes Mellitus
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
What are the 3 mechanisms by which ↓ insulin action occurs in Diabetes Mellitus?
- ↓ insulin production
- ↓ insulin sensitivity of target organs
- Overwhelming ↑ in catabolic hormones
- The anabolic effect of insulin is balanced against 4 main ‘catabolic hormones’ e.g. catecholamines, cortisol, glucagon and growth hormone
Describe Non-diabetic hyperglycaemia (NDH) also called pre-diabetes (for patients) and impaired glucose regulation (for healthcare staff).
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:
-
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
-
Impaired glucose tolerance (IGT) - due to muslce insulin resistance
- Fasting glucose < 7.0 mmol/L + OGTT 2-hour ≥ 7.8 but < 11.1
What is HbA1c?
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
What is DKA (Diabetic Ketoacidosis)?
DKA = acute metabolic complicationof T1DM
it is characterised by the triad of:
- Hyperglycaemia
- Ketonaemia
- Acidaemia
What are the 3 most common events precipitating DKA?
(Besides new presentation of T1DM as DKA)
- Inadequate insulin therapy (e.g. missed insulin dose)
-
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
- 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
What is the mechanism underpinning the development of DKA?
- 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
How is DKA diagnosed from tests (excluding examination)?
- Hyperglycaemia - blood glucose > 11.0 mmol/L or known diabetes mellitus
-
Ketonaemia - > 3.0 mmol/L
- Urinary ketones NOT used anymore (worse predictor of DKA)
-
Acidaemia:
- Bicarbonate (HCO3-) < 15.0 mmol/L and/or
- Venous pH < 7.3
What tests/investigations might be useful in a patient suspected of DKA?
-
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
What 3 things are done to mange DKA?
-
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
-
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
- K+ replacement - correction of hypokalaemia (caused by insulin)
What is the fluid replacement regime for DKA?
Fluid replacement
- Insert 2 large-bore cannula (one in each arm ideally)
- 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
- If/once systolic BP > 90 mmHg:
- See image
What are the potassium cut-offs which dictate potassium replacement during DKA?
Hypokalaemia and hyperkalaemia can occur in DKA:
- K+ is normally ↑ on admission (even though the total body K+ is ↓)
- But will ↓ post insulin treatment
How is T1DM diagnosed in children?
- Symptoms of DKA:
- Hyperglycaemia
- Ketonaemia - > 3.0 mmol/L or significant ketonuria (more than ++ on urine dipstick)
- Acidaemia
- Symptoms typical of T1DM in children:
- Polyuria
- Polydipsia
- Weight loss
- Hyperglycaemia:
- Random blood glucose > 11.1 mmol/L
- Fasting blood glucose > 7 mmol/L
- Raised HbA1c > 6.5% or 48 mmol/mol
- Glycosuria
What features of a Hx might indicate a child has T2DM as opposed to T1DM?
- 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
What are the classifcations / types of insulin - based on their profile of action/duration?
-
Rapid-acting insulin analogues
- Onset = 5 mins
- Peak = 1 hour
- Duration = 3-5 hours
-
Short-acting insulin (also called soluable insulin)
- Onset = 30 mins
- Peak = 3 hours
- Duration = 6-8 hours
-
Intermediate-acting insulin
- Onset = 2 hours
- Peak = 5-8 hours
- Duration = 12-18 hours
-
Long-acting insulin analogues
- Onset = 1-2 hours
- Peak = flat profile
- Duration = 24 hours
What is a basal-bolus regime for Insulin?
It is the combination of:
- Rapid/short-acting ‘bolus’ insulin before meals
- Intermediate/long-acting ‘basal’ insulin once or twice daily
Name some examples of the following Insulin types:
- Rapid-acting insulin analogues
- Short-acting insulins
- Intermidate-acting insulins
- Long-acting insulin analogues
-
Rapid-acting insulin analogues:
- Insulin Aspart (Novorapid)
- Insulin Lispro (Humalog)
-
Short-acting insulins:
- Actrapid
- Humulin S
-
Intermidate-acting insulins:
- Isophane insulin
-
Long-acting insulin analogues:
- Insulin determir (Levemir) - once or twice daily
- Insulin glargine (Lantus) - once daily
What are ‘Premixed’ preparations of Insulin composed of?
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
Is Insulin typically administered; subcutaneously, intramuscularly, IV or oral?
Subcutaneously
What localised side effect can insulin injection cause?
Lipohypertrophy
small lump under skin due to fat accumulation at injection sites (insulin causes fat hypertrophy)
What factors can cause blood glucose to go up vs down?
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
How is DKA in a child managed?
This regimen is initiated IF the child is:
- vomiting or
- has reduced conciousness level or
- clinically dehydrated
(otherwise only subcut insulin is required)
-
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
-
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
-
Potassium
- Initially hyperkalaemia but will fall with insulin
- Start K+ replacement as soon as urine is passed
- Continuous ECG monitoring (to avoid hyperkalaemia)
-
Acidosis
- This will correct with fluids + insulin
- Only give bicarbonate if in shock and note responding to therapy
Which human leukocyte antigens (HLA) are associated with T1DM?
HLA-DR3 and HLA-DR4
What kidney condition is diabetes
the commonest cause of?
End Stage Renal Disease (ESRD)
What conditions can cause diabetes?
- 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)
How would you rule out cerebral oedema due to iatrogenic treatment of DKA?
CT head + senior review
Which population are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA management?
Children and young adults
When does cerebral oedema usually occur in the treatment of DKA?
4-12 hours after treatment
but can present at any time
Under what conditions / circumstances is DKA likely to occur?
- At diagnosis (pts with T1DM can not present to doctors until DKA)
- Illness e.g. viral / bacterial infection
- Growth spurt / puberty
- Insulin omission (for any reason)
- Malfunctioning insulin pump (pump doesn’t give any long-acting insulin, so without short-acting supply, DKA can develop)
If a child presents with:
- polydipsia
- polyuria
- 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?
Caillary blood glucose
> 11 mmol/L + symptoms of DKA = suspect DKA & send to hospital
When DKA is suspected in a child with known T1DM
what blood test should be done?
Blood ketones
If elevated –> send to hospital
What should your initial actions be when you suspect / diagnose a child with DKA?
- Inform responsible senior clinician
- Explain to child / young person / family what DKA is and the care required
-
Record:
- consciousness level
- vital signs; HR, BP, temp, RR (Kussmaul)
- Hx of nausea or vomiting
- clinical evidence of dehydration
- body weight
If a child has DKA and is NOT:
- vomiting or
- has reduced conciousness level or
- clinically dehydrated
how are they managed?
- Oral fluids
- Subcut insulin
- Monitor ketonaemia + acidosis via blood ketones & blood gases
What 3 things (that are normal in adult DKA management) are not normally given in child DKA management?
- Fluid bolus
- Insulin bolus
- IV sodium bicarbonate (or any bicarbonate for that matter)
When giving IV fluids for DKA in a child how is their total fluid requirement for the first 48hrs calculated?
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
What monitoring is needed during treatment of DKA in children?
- Hourly - capillary glucose, ketones, vitals and fluid balance
- Every 30 mins - level of conciousness (modified GCS) and HR (to detect bradycardia) - because children are are greater risk of cerebral oedema
- Continuous ECG - monitor for hypokalaemia (ST depression and prominent U-waves)
-
At 2 hours post start of treatment then every 4 hrs:
- blood glucose
- blood gas (pH, pCO2)
- U+Es
- Face-to-face review
What are the early manifestations of Cerebral Oedema in children?
- Headache
- Agitation
- Irritability
- Unexpected drop in HR & increased BP
- Deterioration in level of consciousness
- Respiratory pauses
- Ocullomotor palsies
- Pupil inequality or dilation
How do you treat cerebral oedema in children?
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
What messages should be given to diabetic patients regdarding
Sick Days, so called ‘Sick Day Rules’?
- Increase frequency of blood glucose monitoring to 4-hourly or more
- Encourage fluid intake - aim for at > 3L in 24hrs
- If unable/struggling to eat –> keep sugary drinks to maintain blood glucose
- Advise pts to keep a box of ‘sick day supplies’ for if they become unwell
- Continue to take oral hypoglycaemic medication even if not eating - bodies response to stress is ↑ cortisol –> ↑ glucose
- 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)
- Advise pt to keep access to a mobile phone –> has been shown to reduce progression of ketosis to diabetic ketoacidosis
What are the diagnostic criteria for T2DM for each of the following investigations, with symptoms and then without symptoms:
- Random plasma glucose
- Fasting glucose
- Oral glucose tolerance test (OGTT)
- HbA1c
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)
What is the risk that gestational diabetes poses?
How can it be diagnosed via fasting glucose or OGTT?
↑ foetal morbidity/mortality
- Fasting glucose ≥ 5.6 mmol/L
- OGTT ≥ 7.8 mmol/L
What test can be done to help confirm T1DM in an ambiguous clinical picture?
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)
How often should children with T1DM test their blood sugar?
~ 5 times per day
(more during illness / symptomatic / physical activity etc)
How many times per year should children with T1DM be offered HbA1c measurement?
4 times per year
(more frequent if concern about blood glucose control)
How is hypoglycaemia in children / young people with T1DM managed?
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
In the treatment of severe hypoglycaemia in children without IV access what do you give and how much?
- Child < 8-yrs or weigh < 25 kg –> 500 micograms of IM glucagon
- Child > 8-yrs or weigh > 25 kg –> 1 mg of IM glucagon
When can IM glucagon be ineffective in treating hypoglycaemia?
In T1DM patients whose hypoglycaemia is due to alcohol consumption
Diabetes can involve various complications, what monitoring is done for these?
- Thyroid disease - TFTs at diagnosis + annually
- Diabetic retinopathy - opthalmoscopy annually from 12-yrs
-
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
- Hypertension - BP annually from 12-yrs
What are some rare complications of T1DM?
- Juvenile cataracts
- Necrobiosis lipoidica - a necrotising skin condition associated with diabetes and RA
- Addison’s disease
What does this image show?
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)
What blood glucose level indicates hypoglycaemia?
< 4.0 mmol/L
