Dose and Administration

The use of Dexamethasone may be considered in infants who are:

• Requiring mechanical ventilation between 7 and 21 days of age, 
• In supplemental oxygen, and
• At high risk of neonatal Chronic Lung Disease (CLD)

The recommended course for use in National Women's Health is the course used in the DART trial.¹  Parental consent after explanation of the potential benefits and risks of treatment will be documented in the clinical notes.

• Some individuals may receive subsequent doses of 0.01mg/kg/day every 2-3 days if there is significant deterioration after the tapering of the dose on day 10.
• Repeat courses may be indicated in selected infants with severe CLD.

1. 0.25 mg/kg/dose IV, PO 8 hourly for 3 doses.
   First dose administered approximately 4 hours before the scheduled extubation.

Indications

1. To improve lung function and facilitate extubation in infants requiring prolonged mechanical ventilation or supplementary oxygen.
2. Subglottic oedema.

Contraindications and Precautions

1. Known hypersensitivity to corticosteroids and/or dexamethasone.
2. Caution in acute infection, especially systemic fungal infections.
3. Caution with positive sputum cultures for Candida albicans.
4. Caution in gastrointestinal ulceration and renal disease.

Interactions

1. Barbiturates, phenytoin and rifampin decrease corticosteroid effect.
2. Indomethacin increases the risk of GI bleeding.
3. May decrease the antibody response to vaccines.

Clinical Pharmacology

Dexamethasone is a synthetic adrenocortical steroid possessing basic glucocorticoid actions and effects. It is among the most active members of its class, being about 25-30 times as potent as hydrocortisone. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium retaining property of hydrocortisone and closely related derivatives of hydrocortisone. Dexamethasone is readily absorbed from the gastrointestinal tract. The plasma half-life is 3-4 hours but the biological half-life is 36-54 hours. The metabolic clearance of dexamethasone is enhanced by the concurrent administration of phenobarbitone, phenytoin, and other drugs that induce hepatic enzyme function. Elimination in urine and bile.

Pharmacological effects of dexamethasone are numerous and predominantly affect metabolism, including glucose homeostasis, promoting catabolism, suppression of the hypothalamus-pituitary-adrenal axis, suppression of growth. The potential benefits of dexamethasone on respiratory function may be mediated through a reduction of bronchial and pulmonary oedema, bronchospasm, reduced inflammation (through inhibition of prostaglandin and leukotriene synthesis, increased antioxidant activity, and cell membrane stabilisation).

Possible Adverse Effects

1. Increased susceptibility to and suppression of the usual symptoms and signs of infection.
2. Glucose metabolism: hyperglycaemia, glycosuria.
3. Cardiovascular: hypertension, myocardial hypertrophy.
4. Electrolyte disturbances: sodium and water retention, hypokalaemia and hypocalcaemia.
5. Gastrointestinal: haemorrhage, gastric ulceration and duodenal perforation.
6. Haematological: Leukocytosis, neutrophilia, monocytopaenia, lymphopaenia, eosinopaenia
7. Skin: Thin fragile skin, impaired wound healing
8. Renal: Nephrocalcinosis, nephrolithiasis
9. Musculo-skeletal: myopathy, osteopenia.
10. Posterior subcapsular cataracts
11. Cessation of linear growth
12. Benign raised intracranial pressure
13. Suppression of adrenal glands (HPA axis)

Special Consideration

1. Several regimens for the use of dexamethasone in chronic lung disease have been described in the literature. They may be classified as short, intermediate or long. At present there are few comparative data recording the efficacy and safety of these regimens.
2. Biochemical and haematological disturbances are common. Urea, electrolytes, glucose and WBC should be monitored frequently.
3. Use cautiously with potassium-depleting diuretic therapy.
4. Suppression of the HPA axis occurs if dexamethasone is used for longer than one week. Acute adrenal insufficiency may occur if dexamethasone is abruptly discontinued. Infants who have received dexamethasone for more than one week must be weaned over a period of several days.
   1. Infants who deteriorate during the weaning phase of their course of dexamethasone, or shortly after discontinuing dexamethasone, may benefit from additional dexamethasone.
   2. Infants undergoing surgery while receiving dexamethasone must have their dose increased during the perioperative period.
5. There have been recent concerns about potential long-term adverse neurodevelopmental effects in preterm infants exposed to postnatal steroids for treatment or prevention of chronic lung disease.⁷  The DART study ceased early due to slow recruitment but did not show a significant differences in the primary outcome of survival without disability between the dexamethasone and placebo groups. 
6. Systematic reviews have demonstrated that moderately early (7-14 days) steroid use is associated with a reduction in mortality and in the incidence of CLD.⁸  Similar reductions in these outcomes are seen with early (<96 hours of age) steroids.⁹  Delayed (>21 days) steroid use is not associated with increased survival but there may be a reduction in CLD.¹⁰
7. The reviews of early ⁹ and delayed ¹⁰ steroids have also raised concerns about long-term outcomes, which are more common in steroid treated infants.  There are insufficient data regarding the long-term outcomes with moderately early steroid use.  However, there may be a decreased risk of neurodevelopmental problems when steroids are used in infants at high risk of CLD.¹²