Postnatal corticosteroids

Question 1

What is chronic lung disease?

Answer 1

Definition:

1. Persistent oxygen requirement after 36 wks post-menstrual age
2. Respiratory symptoms
3. CXR compatible

Question 2

When and why did the use of steroids change from liberal to restrictive?

Answer 2

In 2002, CPS and AAP published recommendations regarding their use - saying not to use in very low birthweight infants.
There were concerns regarding the short and long term effects of corticosteroids including poor neurodevelopment outcome

Question 3

Was the decrease use of steroids in VLBW infants associated with bad outcomes?

Answer 3

No. There was no increased risk in mortality or major short term morbidities, such as O2 need > 36 wks PMA.
There may be increased rates of CLD, but the full understanding of this is still pending.

Question 4

What are the short and long term adverse effects of early (1-7 days) dexamethasone?

Answer 4

Long term: Increased risk of CP, neurodevelopmental impairment and death
Short term: hyperglycaemia, HTN, GI haemorrhage, GI perforation.

Question 5

What are the proven benefits of early dexamethasone?

Answer 5

Earlier extubation

Decreased O2 need at 36 weeks PMA

Question 6

Which is better/worse: early dexamethasone or early hydrocortisone?

Answer 6

Dexamentasone treated groups had lower rates of CLD but higher rates of CP

Question 7

What are the benefits of late dexamethasone?

Answer 7

Decreased mortality at 28 days
Decreased CLD
Decreased CLD and death at 28 days
Decreased failure to extubatne within seven days
Decreased number of infants discharged with home oxygen

Question 8

What are the short term adverse effects of late dexamethasone therapy?

Answer 8

Hyperglycaemia
HTN
Hypertrophic cardiomyopathy
Severe ROP - no increased risk of blindness

Question 9

Did late dexamethasone therapy affect neurodevelopment outcomes (as compared to placebo)?

Is this data awesome?

Answer 9

There was no differences in major neurosensory disability, cerebral palsy or combined rates of death or CP

Four studies shoed increased rates of abnormal neurological examination but unclear significant

The data is not awesome: some of the studies were not powered to detect increased rates of adverse neurodevelopental outcomes

Question 10

What are the current recommendations for late dexamethasone?

Answer 10

Because there are both positive and harmful effects, late dexamethasone is supposed to be used only for infants who you cannot wean from mechanical ventilation. It can be considered for infants very high risk for CLD with parental agreement.

IE it is not routinely recommended of infants still on mechanical ventilation at 7 days

Question 11

What dosing do you use for dexamethasone?

Answer 11

traditional dosing: 0.5mg/kg/day - 1mg/kg/day - variable taper. Better at decreasing mortality and CLD
Low does: 0.15 mg/kg/day - taper over 10 days. Fewer side effects

There is insufficient evidence to conclude which dosing is superior.

Question 12

Apart from QoL, why is oxygen dependency at 36 weeks PMA bad?
Why is this important?

Answer 12

Because it is one of three independent predictors of poor neurodevelopmental outcome at 18-24 months

–> it makes clinicians wonder if using steroids is justified, because both steroids and CLD affect neurodevelopmental outcomes, and the latter has more evidence. So treating bad CLD (or kids very high risk for CLD) might actually improve neurodevelopmental outcomes.
NB this is not evidence based yet

Question 13

Why have people suggested using hydrocortisone?

Answer 13

It is less potent, so may have fewer side effects.

It might mitigate against adrenal insufficiency experienced by some preterm infants (which might affect CLD)

Question 14

What is the evidence for the use of hydrocortisone?

Answer 14

The studies all used early hydrocortisone and had variable dosing regimes.

Evidence: did not decrease mortality, CLD, combined outcome of death or CLD, % of survivors on home O2, or the rate of extubation failure.
There was no significant difference in the rate of CP or CP/mortality

Question 15

Have people looked at late hydrocortisone?

Answer 15

very few. There is one study that looked that this, and found that you may be able to wean from ventilation, but unlikely to affect oxygen need. Long term follow p of these kids found that they had not observable difference in neurodevelopmental outcome as compared to their peers also born preterm.

Question 16

What are the recommendations re hydrocortisone?

Answer 16

Although it may be a promising alternative, there is insufficient evidence to recommend it over dexamethasone for CLD

Question 17

Can inhaled corticosteroids, early, prevent CLD?

Answer 17

There are trials investigating this, and the evidence shows that inhaled corticosteroids do not prevent CLD/death

Question 18

Can late inhaled corticosteroids provide benefit?

Answer 18

There is very little evidence. There is no study comparing inhaled to placebo. Inhaled corticosteroids were inferior to dexamethasone. They did not affect growth. It may provide some benefit for short term ventilatory mechanics, but not long term.

Question 19

So what are the recommendations for inhaled corticosteroids?

Answer 19

There is insufficient evidence to support their use.
They do not appear to offer significant benefit over systemic corticosteroids for the treatment of infants on ventilators.

Question 20

What is the most important short term side effect of corticosteroid therapy

Answer 20

Adrenal insufficiency - especially important to think about if the infant is experience a stressor : surgery, NEC, sepsis.

Question 21

What is the bottom line?

Answer 21

• Early steroids = NO
• High dose (0.5 mg/kg/day) = NO
• Late steroids a routine = NO
• Inhaled steroids = NO
• Hydrocortisone = NO
• Can consider late low dose dexamethasone if the infant is high risk and parents agree. In this situation you can consider inhaled steroids as an alternative (but no clear dosing recommendations)