Persistent Hypoglycemia, Newborn, N/IICU — 5-Day Trial of Diazoxide — Clinical Pathway: ICU

Newborn Persistent Hypoglycemia Clinical Pathway — N/IICU

5-Day Trial of Diazoxide

Maintain Euglycemia

  • Titrate glucose infusion rates to achieve euglycemia.
  • For infants > 72 hours, try to maintain serum glucose > 70 mg/dl.
  • Dextrose concentrations of up to 50% may be required in order to deliver glucose infusion rates of 15-30 mg/kg/min.
  • Dextrose concentration greater than 12.5% must be administered through a central line.

After establishing the diagnosis of Hyperinsulinism, begin trial of diazoxide.

First Line Treatment: 5 Day Trial of Diazoxide

NOTE: All treatment should be done in consultation with Pediatric Endocrinology.

Day 1
(of treatment after diagnosis is established)		 Establish the diagnosis of HI (see diagnostic work up and differential diagnosis)
Obtain an ECHO prior to start of diazoxide therapy
Begin 5 day trial of diazoxide
If HI is less severe/perinatal-stress, start diazoxide at 5-8 mg/kg/DAY PO in two divided doses
If HI is severe begin diazoxide at a dose of 10-15 mg/kg/DAY PO in two divided doses (max dose 15 mg/kg/DAY)
  • Start a diuretic (chlorothiazide) with diazoxide
  • Chlorothiazide Dosing
    • Start chlorothiazide 10-20 mg/kg/DAY PO divided twice daily.
    • Can titrate up to a max of 40 mg/kg/DAY PO divided twice daily.
    • Conversion from enteral chlorothiazide to enteral hydrochlorothiazide
      • Chlorothiazide 10 mg PO = hydrochlorothiazide 1 mg PO
  • For infants on diuretics, monitor BMPs routinely to check for electrolyte disturbances
Day 2-5
of treatment
  • Wean GIR to maintain blood glucose between 70-100
  • Watch very closely for signs of fluid retention
  • May titrate diazoxide dose up after 72 hours
If HI is severe or GIR is > 10 mg/kg/min, send mutation analysis on HI genes for infants and parents
Day 6 +
of treatment		 Determine fasting tolerance on diazoxide, off IV fluids
  • Perform a 6-12 hour safety fast. In infants WITHOUT a history of perinatal stress, it is strongly recommended to perform a 9-12 hour fast
  • Failure to maintain BS > 70 mg/dL during the fast indicates diazoxide unresponsiveness
Fails Fast
Tolerates Fast
  • Diazoxide unresponsiveness suggests a KATP channel HI and potential surgical candidate
  • Send expedited genetic testing of ABCC8 and KCNJ11
  • Discontinue diazoxide
  • Maintain plasma glucose above 70 mg/dL with dextrose containing IVF
  • Consider central line placement to give higher dextrose concentration in IVF
  • Consider continuous glucagon infusion (1 mg/day) if concern fluid overload is a problem
  • Arrange transfer to CHOP for further care
    and potential 18F-DOPA PET
  • Continue diazoxide with glucose monitoring
  • Obtain ECHO, CBC with diff, and BMP 1 week after starting diazoxide or prior to discharge
  • Send comprehensive HI genetic testing
  • Discharge Planning with Endocrinology