Neonatal Intensive Care Drug Manual

Caution – Increased risk of GI perforation particularly with simultaneous treatment with indomethacin. If hydrocortisone is required, delay treatment with indomethacin for at least 72 hours if possible.

For management of cortisol deficiency, change to oral preparation when possible.

Treatment of hypotension:

For primary treatment of hypotension: Hydrocortisone has not been shown to change clinical outcome and may not be as effective as dopamine. (LOE II, GOR D). [7]

For treatment of refractory hypotension: Hydrocortisone was effective in preventing persistent hypotension. (LOE I, GOR C). Dose range used in trials: 1 to 2.5 mg/kg every 6 to 12 hours weaned over 48 hours to 6 days. [7] There were no statistically significant effects on any other short or long-term outcome but analyses are underpowered to detect differences in clinical and safety outcomes.

Prevention of bronchopulmonary dysplasia:

Trials in ventilated preterm infants at risk of BPD started hydrocortisone from 2 hours to < 7 days, used various regimens ranging from 0.5 mg/kg/dose 12 hourly for 7 days and 24 hourly for 3 days [1, 2], 1 to 2 mg/kg every 8 to 24 hours for a duration 2 to 6 days [3, 8], up to 15 mg/kg x 2 doses [3, 8]. Subgroup analysis of trials of hydrocortisone found hydrocortisone was associated with reduced rates of patent ductus arteriosus, mortality, and the combined outcome of mortality or chronic lung disease, but with increased occurrence of intestinal perforation. Results showed that hydrocortisone was not associated with obvious longer-term problems [3]. Conclusion: Short-term and longer-term effects of early hydrocortisone to prevent bronchopulmonary dysplasia require further evaluation. (LOE I, GOR B)

Endocrine Society Clinical Practice Guidelines recommend treatment of primary adrenal insufficiency: [9]

Maintenance treatment of primary adrenal insufficiency in children: Hydrocortisone 8 mg/m²/ day in 3 or 4 divided doses.

Management of adrenal crisis: Hydrocortisone 50–100 mg/m² IV or IM, then 50–100 mg/m² every 24 hours.

Home management of illness with fever: Hydrocortisone replacement doses doubled (> 38°C) or tripled (> 39°C) until recovery.

Unable to tolerate oral medication due to gastroenteritis or trauma: Hydrocortisone 50 mg/m² IM.

Minor to moderate surgical stress: Hydrocortisone 50 mg/m² IM or hydrocortisone replacement doses doubled or tripled.

Major surgery: Hydrocortisone 50 mg/m2 IV followed by hydrocortisone 50–100 mg/m²/day divided 6 hourly.

Acute adrenal crisis: Rapid bolus of normal saline 0.9% 20 mL/kg. Can repeat up to a total of 60 mL/kg within 1 hour for shock. Hydrocortisone 50–100 mg/m² bolus followed by hydrocortisone 50–100 mg/m²/day divided 6 hourly.

Treatment of neonatal hypoglycaemia:

There are case reports of short term use of hydrocortisone for neonatal hyperinsulinaemic hypoglycaemia.[10, 11] Use of corticosteroids is not addressed in guidelines for management.

Safety:

Use of hydrocortisone in preterm infants in the first week is associated with intestinal perforation. [3, 8] (LOE I) The risk may be increased with concomitant treatment with indomethacin.[12, 13] (LOE II)

Use of hydrocortisone increased risk of hyperglycaemia in hypotensive preterm infants treated with adrenaline. (LOE II) [14]

Pharmacokinetics and pharmacodynamics:

The half-life of hydrocortisone is reported to be < 3 hours in newborn and premature infants. An increase in unbound hydrocortisone clearance was observed at 35 weeks postmenstrual age. [15, 16]

The pharmacodynamics effect of hydrocortisone on blood pressure in hypotensive preterm infants has been reported to have an onset by 2 hours and persist for at least 12 hours. [17, 18]