Emergency management of metabolic crisis
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Emergency management of metabolic crisis

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Emergency management of metabolic crisis Presentation Transcript

  • 1. Emergency management ofMetabolic CrisisDr. Vidyut BhatiaPediatric GastroenterologistIndraprastha Apollo Hospital, New DelhiEditor: Celiac Focus
  • 2. Inborn Errors of MetabolismIndividually rare, together they are 1:800-5000 incidenceMost difficult task for clinician is to know when to considerIEM and which tests to order for evaluationDon’t be fooled--other diagnoses like sepsis, ICH, pulm. hem.may accompany IEMClues to presence of IEM may often be found in FH
  • 3. PROTEIN GLYCOGEN FAT FRUCTOSE AMINO ACIDS GALACTOSE GLUCOSE FREE FATTY ACIDS ORGANIC ACIDS AMMONIA PYRUVATE LACTATE ACETYL CoA UREA CYCLE KETONES UREA KREBS CYCLE NADH ATP An integrated view of the metabolic pathways
  • 4. Metabolic Diseases Which Can Present in CrisisDefects of glucose homeostasis (20)Defects of amino acids (10)Defects of fatty or organic acids (20)Defects of Lactate/Pyruvate (20)Defects of PeroxisomesOthers
  • 5. IEM- Index of SuspicionRapid deterioration in an Dietary aversionotherwise well infant Family historySeptic appearing infant Severe hyperammonemia,Failure to thrive metabolic acidosisRegression in milestones abnl urine/body smellRecurrent emesis or feedingdifficulty,alterations in respirations,lethargy, jaundice, sz,intractable hiccups
  • 6. “Waiting until sepsis and othermore common causes of illnessare ruled out before initiating aspecific diagnostic evaluation isinadvisable, as is indiscriminate study of all ill newborns for metabolic disorders.”
  • 7. History and Antecedent EventsCatabolic state induction (sepsis, fasting,dehydration)Protein intakeChange or addition of PO proteins, carbs, etc… informulaConsanguinityFHx of SIDS, autism, devl delay
  • 8. Assessment:VitalsLevel of alertnessAbnl activity/mvmtsCV- perfusionDysmorphology, hair, eyes-corneaAbdo- HS megalyNeuro- DTRs, tone, etcSkin- bruise, pigment, color
  • 9. Recognize that SmellMusty or Mousy: Sweaty feet:PKU isovaleric acidemia or glutaric acidemia type IIBoiled Cabbage Cat urineTyrosinemia orhypermethioninemia multiple carboxylase deficiencies (BiotinMaple Syrup deficiency)maple syrup urinedisease
  • 10. Laboratory Assessment of NeonatesSuspected of Having anInborn Error of MetabolismRoutine Studies Special StudiesBlood lactate and pyruvateComplete blood count and differential Plasma amino acidsPlasma ammonia Plasma carnitinePlasma glucose Urine amino acidsPlasma electrolytes and blood pH Urine organic acidsUrine ketonesUrine-reducing substances
  • 11. Emergency Management:Can be life threatening event requiringrapid assessment and managementTwo primary goals removal of accumulating metabolites prevention of catabolism
  • 12. Treatment of the Acutely Sick ChildMaintain ABC Oxygenation Hydration Acid/Base balanceSTRIVE TO IDENTIFY PRIMARY METABOLIC DISORDER
  • 13. Emergency ManagementNPOD5-D10 1-1.5 x maintCorrect hypoglycemiaCorrect hypoglycemia IV dextrose bolus, 25%, 0.25-0.5 g/kg/dose (1-2 mL/kg); not to exceed 25 g/doseDextrose 10-15% IV @ 8-10 mg/kg/minAdd insulin, 0.2-0.3 IU/kg, as needed
  • 14. Acidosis and electrolyte abnormalitiesThe pH and dose at which bicarbonate should beadministered are controversialpH <7.0-7.2, dose 0.35-0.5 mEq/kg/h up to 1-2mEq/kg/hFor intractable acidosis, consider hemodialysisDialysis, lactulose if High/toxic NH4 (nl is <35µmol/L)
  • 15. Some quick supplements:Carnitine: IV/PO 100 mg/kg/dSodium Benzoate, Phenylacetate for HyperammonemiaIV: 0.25 g/kg bolus over 24 h, then infusion of 0.25 g/kg over 24 hMega-vitamin therapy: Vitamin B12 (1 mg) should be given im (B12 responsiveform of methylmalonic academia) Biotin (10 mg) should be given orally or by nasogastric tube,(multiple carboxylase deficiency)
  • 16. Patient is stabilized Now what?Broad DDxYou can group into KEY featuresCan focus on initial labs = Hyperammonia,hypoglycemia, metabolic acidosis.Can focus on Prominent neurologic featuresCan focus on Dysmorphic featuresIf these don’t exactly fit, resort back to categories ofIEMs and Neurodegenerative Disorders.
  • 17. Diagnostic algorithm METABOLIC ACIDOSIS yes no Ketonuria Ketonuria yes no yes no Major hyperlactatemia Maple Syrup Urine Hyperlactatemia Maple Syrup Urine HYPERAMMONEMIA Disease (MSUD) Disease (MSUD) yes no yes no yes noMitochondrial Organic Hypoglycemia Organic aciduria Hypoglycemia Non-ketonic hyperglycinemia defect aciduria Pyroglutamic Sulfite oxydase deficiency - XO aciduria yes no yes no Fatty acid oxydation Respiratory Fatty acid oxydation Urea Cycle Glycogen storage disease chain Variant hyperinsulinism Disorders Glyconeogenesis defects (glutamate dehydrogenase)
  • 18. Quick References:MA:*metabolicacidosisNH4:Glu: *Non-ketotic *Urea Cycle *Fatty Acid *OAemia *OAemia *OAemia *Glycogen StrgDz: Hyperglycine defects Oxs dfc *OAemia *Amino Aciduris *Carb Metabolism dfc
  • 19. Organic Acidemias:*Acidotic with high Gap*Urine Ketones high*High to nl AmmoniaOften present first 2-7 days of life after dietary proteinintroduced.Drunk appearance in infant.*May have low WBC and Plts.Check serum AAs/OAs, Urine AAs/OAs, CSF OAs/AAs.
  • 20. Organic Acidemias Organic acids are intermediates in the catabolic pathways to break down amino acids, lipids and other compounds to acetyl CoA and succinyl CoA which are entry points into the Kreb cycleIsoleucineValine biotin B12Methionine Propionyl CoA Methylmalonyl CoA Succinyl CoACholesterolOdd chain fattyacids Krebs Cycleleucine Isovaleryl CoA 3MCC HMG CoA Acetyl CoA Lysine Acetyl Tryptophan Glutaryl CoA Crotonyl CoA CoA *Urine organic acid analysis will show elevation of organic acids proximal to the enzymatic block; the resulting pattern is interpreted by the metabolic laboratory
  • 21. Urea Cycle DefectsSymptom free period and then emesis->lethargy-->>COMAKey features: High Ammonia, low BUN Possible Lactic acidosis *Absence of ketonuria* Nl to mild low Glucose**Treat high ammonia, infuse glucose, send plasma AAs/OAs,urine orotic acid, and plasma citrulline.Infusion of 6ml/kg 10% Arginine HCl over 90 min may help
  • 22. ConsequencesOnce ammonia >150 µmol/L can lead topermanent neurological damageRequires prompt & aggressive treatment Withdraw dietary protein Sodium benzoate/ phenylbutyrate Haemofiltration/dialysis
  • 23. Urea cycle disease versus organic acidemias UCD OAlethargy/coma + +vomiting + +hyperammonemia ++ +/-metabolic - +ketoacidosisprimary respiratory + -alkalosis
  • 24. Fatty acid oxidation Brain CPT1/CPT2Fatty VLCAD LCHAD MCAD SCAD ketonesacids + fasting acetyl CoA Krebs cycleDistinguishing feature of FAOD is hypoketotic hypoglycemiaMCAD deficiency most common and has a 25% risk of death withfirst episodeLCHAD, VLCAD and carnitine uptake disorder are variablyassociated with, hepatomegaly, liver disease, hypertrophiccardiomyopathy and potential arrythmias
  • 25. Liver diseaseA metabolic liver disease should be suspected ifthere is one or more of the following: persistent unconjugated jaundice hepatocelluar dysfunction hypoglycemia without other liver dysfunction
  • 26. Liver diseaseHepatocellular dysfunction Disorders of amino acid metabolism Tyrosinemia I Disorders of carbohydrate metabolism Galactosemia Hereditary Fructose Intolerance Glycogen Storage Disease type IVLysosomal storage disorders Niemann Pick Disease
  • 27. Galactosemia Galactokinase deficiency--less common Galactose-1-P uridyl transferase (GALT) deficiency- causes classic galactosemia Gal-1- P is toxicClinical Presents classically as a sick newborn with vomiting diarrhea, jaundice, progressive liver and renal disease, E.coli sepsis, progressive bilateral cataracts
  • 28. GalactosemiaDx assisted by Non-glucose reducingsubstances in urineConfirmation by Galactose-1-PO uridyltransferase activity in RBCs
  • 29. Lastly: Non-ketotic HyperglycinemiaUnique entity in that Glucose, NH4, pH are allnormal4 types with varying ages of onset, however, classicform is Neonatal with onset in 1st week of life.Will present just like the other devastating IEMs.Lethargy, emesis, hypotonia, seizures, etc…Uncontrolled hiccups.Dx with no urine ketones, and Elevated Glycine.No effective Rx. Will require diet restriction
  • 30. The Metabolically ill Child If you Don’t know you Wont think If You Dont Think You Wont Look If You Dont Look You Wont Find If You Dont Find You Can’t Treat