1. Paediatric metabolic emergencies

2. To be covered 1. Recognition 1. Recognition 2. Investigations 2. Investigations 3. Hypoglycaemia 3. Hypoglycaemia 4. Hyperammonia 4. Hyperammonia 4. Hyperglycaemia 4. Hyperglycaemia

3. Recognition of metabolic disease Inborn errors of metabolism may have chronic and acute presentations Inborn errors of metabolism may have chronic and acute presentationsChronic Developmental delay or regression Developmental delay or regression Failure to thrive Failure to thrive Dysmorphic Dysmorphic Organomegaly – heart, liver Organomegaly – heart, liver Peripheral neuropathy, visual impairment Peripheral neuropathy, visual impairment

4. Acute presentations Vomiting leading to dehydration, shock Vomiting leading to dehydration, shock Lethargy, coma Lethargy, coma Tachypnoea without recession Tachypnoea without recession Hypoglycaemia Hypoglycaemia Rhabdomyolysis Rhabdomyolysis These can be life-threatening

5. Decompensation precipitants Common stressors: Fasting eg gastro, pre-operative Fasting eg gastro, pre-operative Increased catabolism eg infection, surgery Increased catabolism eg infection, surgery Eating a food rich in the component that cannot be processed Eating a food rich in the component that cannot be processed

6. Management ABC+DEFG AB – provide ventilatory support as required AB – provide ventilatory support as required C – IV access C – IV access –BSL, ketostix, VBG, EUC, LFT +/- coags –FBC, cultures, CRP if infection a possible trigger –Apply urine bag Call Paeds! Call Paeds!

7. 1. Hypoglycaemia (BSL<2.5) Formal glucose Formal glucose Ketostix – if negative, work fast! Ketostix – if negative, work fast! Take as much blood as you can (up to 15ml). Long list of the investigations (attached to Paeds IV trolley) Take as much blood as you can (up to 15ml). Long list of the investigations (attached to Paeds IV trolley) –Cortisol, insulin, GH –VBG for lactate; pyruvate if tube and ice available –Free fatty acids –Urine metabolic screen Correct with IV 2ml/Kg 10% dextrose Correct with IV 2ml/Kg 10% dextrose If BSL still < 3mmol, start 10% dextrose infusion If BSL still < 3mmol, start 10% dextrose infusion

8. Tachypnoea + recession = pneumonic process + recession = pneumonic process No recession – consider metabolic acidosis/ alkalosis No recession – consider metabolic acidosis/ alkalosis –Glucose, VBG –If pH normal/alkalosis, check Ammonia (green tube on ice)

9. 2. Raised Ammonia NB. Newborns have different diagnostic levels As a general rule, < 500µmol/L = liver failure < 500µmol/L = liver failure > 1000µmol/L = urea cycle defects > 1000µmol/L = urea cycle defects

10. Urea cycle defects Commonest is OTC deficiency – X linked so boys affected; but partially dominant so girls can present, too Commonest is OTC deficiency – X linked so boys affected; but partially dominant so girls can present, too Clinical manifestations depend on duration of exposure to NH3, not the degree of hyperammonaemia Clinical manifestations depend on duration of exposure to NH3, not the degree of hyperammonaemia May have DD and a big liver, but may present in crisis with vomiting, irritability progressing to coma May have DD and a big liver, but may present in crisis with vomiting, irritability progressing to coma

11. Hyperammonia crisis ABC – intubate if low GCS ABC – intubate if low GCS IV 10% glucose IV 10% glucose –If diagnosis not known, blood for amino acids –Urine metabolic screen IV benzoate +/- IV intralipid IV benzoate +/- IV intralipid

12. 3. Hyperglycaemia (BSL >11 if not fasting) Differentials: Stress response – steroids, inotropes Stress response – steroids, inotropes Pancreatitis Pancreatitis Hyperadrenalism (Cushings) Hyperadrenalism (Cushings) Hyperthyroidism Hyperthyroidism DKA DKA

13. Paediatric DKA If shocked, fluid resuscitate and then calculate fluids carefully! If shocked, fluid resuscitate and then calculate fluids carefully! –Children susceptible to cerebral oedema 2 IV – one for insulin infusion, one in big vein for blood sampling 2 IV – one for insulin infusion, one in big vein for blood sampling –Blood for BSL, VBG, EUC, HbA1C –If possibility of sepsis – FBC, CRP, Blood culture

14. Cerebral oedema In first 24hrs of DKA treatment In first 24hrs of DKA treatment Headache, Reduced LOC, progressing to herniation (pulse, BP ie/ Cushings triad) Headache, Reduced LOC, progressing to herniation (pulse, BP ie/ Cushings triad) Risk factors < 5 years < 5 years Severe dehydration Severe dehydration Severe acidosis with low CO2 Severe acidosis with low CO2 Hyponatremia HyponatremiaTreatment Call NETS Hypertonic saline (5ml/Kg 3% saline over 20 mins) or Mannitol 0.5mg/Kg over 20 minutes

15. 6 year old boy Adopted from Columbia aged 2 Adopted from Columbia aged 2 Recurrent presentations with vomiting +/- abdo pain or diarrhoea, usually settled with Ondansetron and oral fluids Recurrent presentations with vomiting +/- abdo pain or diarrhoea, usually settled with Ondansetron and oral fluids 3 episodes required IV fluids; EUC – Na 132-135, K normal 3 episodes required IV fluids; EUC – Na 132-135, K normal First year at school not successful academically – cultural differences? First year at school not successful academically – cultural differences? Odd behaviour eg falling off chairs - Attention seeking? Odd behaviour eg falling off chairs - Attention seeking?

16. 7 th presentation with vomiting No diarrhoea or fever, no-one unwell at home No diarrhoea or fever, no-one unwell at home O/E Suntanned – recent holiday Looks dry and is sleepy Pulse 140 RR 26 Sats 98% RA Cap refill < 2s Chest NAD Abdo soft, no masses, no organomegaly What do you do next?

17. Glucose 1.9 Hypoglycaemia screen performed Hypoglycaemia screen performed IV 10% dextrose started with rapid improvement IV 10% dextrose started with rapid improvement Na 128 K 5.3 Na 128 K 5.3 ?adrenal crisis BP normal BP normal

18. Summary Inborn errors of metabolism are rare, but may be devastating if missed Inborn errors of metabolism are rare, but may be devastating if missed If a child looks sicker than they should be, do a BSL and start to think! If a child looks sicker than they should be, do a BSL and start to think!