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, 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  Hepatomegaly, 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)m8 15mg/kg/day PO in 2-3 divided doses or IV 3 5mg/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