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Hypoglycemia Vandana Nayal, MD Edited May 2005 Definition  Plasma glucose less than 40 mg/dl  Immediate questions 1. Has a plasma blood sugar been sent to the laboratory? 2. Is the baby symptomatic? 3. Is the mother a diabetic? 4. How much glucose is the infant receiving? Measurement of glucose  Bedside glucose strips can give incorrect values if the test is not done properly, if the strips used are too old, if the hematocrit is very high, or the glucose level is very low  There is a wide variation when compared to laboratory determined plasma levels – Glucose concentration in whole blood is 10-15% lower than in plasma  ALWAYS confirm your measurement in the lab Symptoms of hypoglycemia  Apnea, hypotonia, irritability, irregular respirations, poor sucking or feeding, exaggerated Moro reflex, cyanosis, tremors, eye rolling, pallor, seizures, lethargy, temperature instability and coma  Rarely bradycardia, tachycardia, high pitched cry, tachypnea, and vomiting  Some have no symptoms despite documented hypoglycemia Glucose requirement How much glucose is the infant receiving in IV fluids? Normal glucose requirement is 4-10 mg/kg/min Check to be sure that calculations were correct Causes of transient hypoglycemia  Perinatal stress  Sepsis, esp. Gram-negative  Asphyxia or HIE  Hypothermia  Polycythemia  Shock  Infant of diabetic mother  Decreased glycogen stores  Insufficient amount of glucose administered  Maternal meds: terbutaline, propranolol Infants of diabetic mothers 40% of infants of diabetic mothers have documented hypoglycemia Diabetic mothers have fluctuating hyperglycemia that results in fetal hyperglycemia – induces pancreatic B-cell hyperplasia = hyperinsulism – after delivery, hyperinsulism persists and hypoglycemia results Decreased glycogen stores  Intrauterine growth retardation or small for gestational age  Premature infants  Post-mature infants Causes of persistent hypoglycemia Hormone excess - hyperinsulism – – – – Beckwith-Wiedemann syndrome Islet cell adenoma Beta cell hyperplasia, dysplasia Nesidioblastosis Beckwith-Wiedemann syndrome (because it is on the boards)  Macroglossia,  Hepatomegaly, Omphalocele, macrosomia, ear creases, mild to mod mental deficiency  Large kidneys with renal medullary dysplasia, pancreatic hyperplasia  Neonatal polycythemia,cryptorchid ism, hypoglycemia(1/2 to 1/3 of cases) which is responsive to HC hemihypertrophy, (increased malignancy) hepatoblastoma, immunodeficiency  US and serial alpha feto protein every 6 months till the patient is 6 years of age to r/o Wilms’s and hepatoblastoma  Duplication of 11p15.5 causes BWS. IGF-2 gene localization to 11p causes BWS Persistent hypoglycemia hormone deficiencies  Growth hormone deficiency  ACTH unresponsiveness  Thyroid deficiency  Epinephrine deficiency  Glucagon deficiency  Cortisol deficiency  Hypoplastic pituitary  Hypothalamic hormone deficiencies  Midline CNS malformation Defects in carbohydrate metabolism Glycogen storage disease type 1 Fructose intolerance Galactosemia Glycogen sythase deficiency Fructose 1,6 diphosphatase deficiency Defects in amino acid metabolism Maple syrup urine disease Propionic acidemia Methylmalonic acidemia Tyrosinosis 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency Defects in fatty acid metabolism Medium and long chain deficiency Approach to hypoglycemia History and physical Evaluate infant for symptoms of hypoglycemia Look for signs of shock, sepsis, midline defects, or Beckwith-Wiedemann syndrome Laboratory studies for transient hypoglycemia Serum glucose level should be sent to the lab to confirm the paper strip result CBC with differential to evaluate for sepsis and to rule out polycythemia Persistent Hypoglycemia  Initial studies – Serum glucose, insulin, cortisol, growth hormone at the time of hypoglycemic event; serum ketones  Ratio of insulin to glucose is obtained – level of >0.3 indicates a non hyperinsulinemic cause of hypoglycemia  Serum ketones are low or absent in the presence of hyperinsulinemia Follow-up studies for persistent hypoglycemia  GH, Free Fatty acids, T3, T4, TSH  Glucagon, uric acid, lactate, Alanine  Ketone levels before and 15 min after administration of glucagon- 0.3mg/kg/dose  Urine collection for AA, OA, catecholamines, specific reducing sugars  Somatomedins (IGF-1, IGF-2, IGF binding proteins)  Ultrasound or CT scan of the pancreas Management Overall plan to maintain normoglycemia (level > 45 mg/dL) Screen those at risk or those with symptoms suspicious for hypoglycemia – glucose check every 1-2 hr before feeds until glucose levels are stable, then every 4 hours Determine why the baby is hypoglycemic – obvious reasons or need further work up? At risk?  Premature  SGA, LGA  BW < 2500 g  Smaller of discordant twins (wt. Diff. > 25%)  Asphyxiated infant (5 min Apgar < 5)  Infants of massively obese mothers  Infants of diabetic mothers  Infants with polycythemia, infection, microphallus/midline defects, anomalies associated with low glucose (BWS) Asymptomatic hypoglycemia  Treatment is controversial  Term infants, first 6-12 hrs, not high risk – give early feeding  Level < 25mg/dl is a medical emergency – give parenteral glucose - 2-3 ml/kg D10W IV over 2-3 minutes  Check glucose q 15-30 minutes until stable  Always follow your institution guidelines Symptomatic, persistent, or severe (< 25) hypoglycemia  If chemstrip values persist < 40 mg/dL or initial < 25 mg/dl (confirmed by stat lab level) – Give bolus and start a glucose infusion of 6mg/kg/min even if the infant is asymptomatic  Increase level of infusion until normoglycemia is achieved (> 45 mg/dL) – Peripheral IV can take up to D13 otherwise will need central access  Check glucose levels q 15-30 minutes until stable  Document improvement in symptoms Glucagon If an intravenous line cannot be started, glucagon can be given to infants with adequate glycogen stores – Infants of diabetic mothers have good stores – less effective in IUGR or SGA Dose is 300mcg/kg not to exceed1mg total dose subcutaneously or IM while vascular access is attempted Other treatments  Trial of corticosteroids – Hydrocortisone sodium succinate mg/kg/day given intravenously or orally every 12 hours – prednisone 2mg/kg/day  If hypoglycemia persists – Diazoxide (inhibits pancreatic insulin release)m815mg/kg/day PO in 2-3 divided doses or IV 35mg/kg/dose repeat in 20 min if no effect  Somatostatin analog – Octreotide 2-10mcg/kg/day sc divided every 6-8h or continuous IV  HGH 0.1unit/day