Nicola Trevelyan Consultant Paediatrician Nov 2007
• Case history
– Diagnosis – Diabetic ketoacidosis – Treatment regimens – Insulin analogues
• 9 year old Hannah is brought to A&E by her mum with a 2 week history of increased thirst, increased weeing & being very tired. Over the last 2 days she has been very thirsty, breathing fast & vomiting. • O/E – Weight 26kg Alert co-operative afebrile • 5% dehydrated
• Blood gas – pH 7.16, pCO2 2.4, Bicarb 5, BE –24 • Glucose 28mmol/L • Urine 4+ ketones, 4+ glucose
What is the diagnosis?
• Newly diagnosed type 1 diabetes mellitus with diabetic ketoacidosis
Types of diabetes
sugar lack of useful insulin
insulin produced by pancreas
tissues resistant to insulin & pancreas unable to produce enough insulin
What are the abnormal results & what do they signify?
• High glucose = diabetes • Ketones in urine = ketosis (in absence of glycosuria may be starvation ketones) • Low pH = acidosis • Low Bicarbonate & negative base excess = metabolic acidosis • Low pCO2 = compensatory respiratory alkalosis
The role of insulin
• Uptake of glucose from blood into muscle & fat cells • Stops hepatic gluconeogenesis • Increases glycogen production in liver & muscle • Stimulates fat & protein synthesis
Decrease in glucose uptake from blood
What are the 2 problems which need treating?
Gluconeogenesis Decrease intracell glucose for metabolism Counter regulatory hormones Lipolysis Ketones Vomiting Rise in blood glucose
Treatment of DKA
– To slowly restore metabolic homeostasis – To correct lack of insulin – Correct dehydration over 48 hours – Switch off lipolysis and hence acidosis – Reduce hyperglycaemia
Treatment of DKA – IV fluids
• Start IV fluids before insulin • 0.9% saline with 40mmol/L KCl (if the child is PUing) • Once sugar drops to ~12mmol/L change to 0.45/5 dextrose saline with KCl added
What rate should Hannah’s fluids be given?
• Deficit = weight (kg) x % dehydn x 10 = 1300ml or 5% of 26kg = 0.05 x 26 = 1.3L or 5 x 26000 = 1300ml Given over 48hrs 100 • Maintenance = (100 x 10)+(50 x 10)+(20 x 6) = 1620ml per 24 hours • Hourly rate = (1300/2) + 1620 = 2270 = 94.6ml/hr 24 24
• Actrapid or any fast acting analogue available (Humulin S, Humalog, Novorapid) • 50 units in 50ml Normal saline • Run at 0.1ml/kg/hour – only dose proven in literature to be effective at switching off ketosis.
Complications of DKA
• Cerebral oedema • Other complication
– Gastric stasis – Pancreatitis
• Complications of treatment
– Hypoglycaemia – Hypokalaemia
• Typically occurs 4 -12 hrs after starting treatment • Risk 7 / 1000 episodes of DKA • 12 / 1000 episodes of DKA in new IDDM
• 24% morbidity • 35% left with significant morbidity
What we do know about cerebral oedema…
• We don’t seem to be getting any better at preventing it - overall risk stable over last 20 years • The sicker you are at presentation the more likely you seem to be to get it
• Not related to type of fluid
– HAS vs 0.9% saline
• Not always related to treatment
– Some develop it prior to reaching hospital
Why does it happen?
• No one really knows! • Numerous mechanisms proposed
– – – – – – Cerebral hypoxia Drop in plasma osmolality Generation of inflammatory mediators Disruption of cell membrane ion transport Aquaporin channels Generation of intracellular organic osmolytes causing influx water into brain cells
Risk factors for cerebral oedema
• Younger child • Newly diagnosed Diabetes • Lower pH • High urea at highest risk
• Administration of insulin within 1st hour (OR 4.7) • Administration of bicarbonate
• Administration of large volumes of fluid in the 1st 4 hours of treatment
– – – – Headache Drowsiness Incontinence Vomiting recurrence
– – – – – – Decreased LOC Bradycardia Rising BP Decreasing O2 sats Neurological signs Abnormal pupil responses – Abnormal posturing
Treatment of cerebral oedema
• Mannitol 0.5g to 1.5g / kg (= 2.5 to 7.5ml / kg 20% Mannitol) over 30mins • 3% saline
24 hours later Hannah is feeling much better.
What are the different SC treatments regimens available to Hannah and what are their pros & cons? How are you going to change her from IV to SC insulin?
Treatment options – Type 1
• Insulin sub cut injection
– Fast acting – Insulin mixes – Long acting
• Pump (CSII) • ? Inhaled insulin • ? Stem cell transplant
Fast acting insulin
• Soluble insulin
– Actrapid – Onset of action 30 mins Peak 1-2 hours – Lasts around 6 to 8 hours
• Insulin analogues
– Humalog, novorapid – Onset of action within 15 minutes peak 3070 mins – Last around 2 to 5 hours
• Until recently most commonly used insulin in children • Convenient
• Mixtard 30 or M3– 30% fast, 70% intermed • Mixtard 20 or M2 – 20% fast, 80% intermed • Humalog 25 – 25% fast 75% intermed Etc.
Long acting insulin
• Isophane insulin (intermediate)
– Insulatard, Humulin I – onset of action 2 hours – Peak 4 to 6 hours – lasts 12 hours
• Insulin analogue
– Glargine (Lantus) – lasts 24 hours – Detemir (Levemir) – lasts around 20 hrs
Glargine vs Detemir
• Once daily • Lasts 24hrs • Acidic injection which stings 5-10% • Poor pen device
• Once / twice daily • Lasts 20-24 hrs • Evidence of reductn in nocturnal hypos • Good pen
Insulin regimes – BD insulin mixes
Insulin regimes – BD insulin mixes
Advantages • Convenient • Well understood • Lots of pens / mixes available • Only 2 injections a day Disadvantages • Lack of flexibility • Have to be up & injected by 9am at latest • Have to have 3 snacks a day & 3 meals a day
Insulin regimes – Basal Bolus with Glargine (Lantus)
Insulin regimes – Basal Bolus
Advantages • Much more flexibility • Can alter doses according to size of meal • Less need to have between meal snacks • If child unwell & not eating can omit doses of fast insulin
• 4 injections a day • Need injection at school • Easier to manipulate insulin • Need to have clear understanding of diabetes
Theory of Insulin Pump Therapy
• Low rate insulin pumped in 24 hr/day • Background rate can be preprogrammed to change at different times during the 24 hours • Extra insulin bolus given when anything is eaten
Is a insulin pump better than multiple injections of insulin?
• Control of sugars - Generally better on an insulin
• Incidence of severe hypoglycaemia (low sugars) - Much lower on an insulin pump
– Up to 50% reduction in severe hypos compared to having multiple injections of insulin (Bolland et al
Diabetes Care 1999)
• Weight - No increase in weight on an insulin pump • Quality of life - Increased flexibility in lifestyle
Advantages of CSII
• • • • • More flexible lifestyle & eating pattern Delivers insulin in more physiological way Can improve diabetes control Lessens the risk of hypoglycaemia Multiple injections a day replaced by insertion of cannula every 2 to 4 days • Positive effects on quality of life
Disadvantages of CSII
• It is an intensive therapy and this can = hard work • Pump is intelligent but still needs to be told what to do • Not everyone wants to visible sign of their diabetes • Concerns about wearing a pump during sport & sex • Risk of skin infection at the cannula site • Expensive (pump cost £2400 + ~£1500/yr consumables)
Are pumps safe?
• Modern pumps much more reliable • Lots of alarms, safety checks & warning systems • Can be programmed to have a maximum amount of insulin they’ll deliver in one go • Pump can be locked • Line blockages can cause problems
Are pumps safe?
• Risk of diabetic ketoacidosis (insufficient insulin
leading to high sugars, ketones and acid in the blood)
– Higher in some clinical trials – No deposits of long acting insulin under the skin – Switching off insulin supply from the pump can lead to trouble within 1 or 2 hours – Risk decreases with increased experience using the pump – Need to measure sugars at least 3 or 4 times / day
Who is eligible for an insulin pump?
• N.I.C.E. 2004
– Type 1 diabetes on multiple daily injections of insulin including Glargine or similar AND – HbA1c above 7.5% – Recurrent unpredictable hypoglycaemia (low blood sugars) or hypoglycaemia unawareness or night time hypoglycaemia – Patient willing and able to use therapy safely & effectively
The future CSII…
Changing from IV to SC insulin
• Ensure the child is tolerating oral intake • Give SC insulin prior to stopping IV insulin • If starting a basal bolus regimen try to ensure the basal insulin (glargine / detemir) is given the night before stopping the IV
What other education will Hannah’s family need prior to discharge?
• Able to do injections & blood glucose monitoring • Basic dietary advice • Hypoglycaemia management • Ketone monitoring if sugar levels high
Hypoglycaemia symptoms & signs
anxiety abdominal pain palpitations nausea & vomiting blurred vision confusion apnoea headache weakness tremor fainting dizziness abnormal convulsions cry irritability hypotonia
pins & needles
Conscious – 10g fast carbohydrate followed by starchy snack • Conscious but unco-operative – Glucogel followed by starchy snack • Unconscious – Glucagon then starchy snack if possible & hospital