Postnatal Corticosteroids to treat or prevent CLD in preterm infants

Question 1

Define Chronic Lung Disease

Answer 1

• Need for oxygen at 36 weeks postmenstrual age with respiratory symptoms and compatible changes on chest radiograph

Question 2

What is the incidence of CLD in Canada?

Answer 2

21% surviving infants born at less than 33 weeks GA and admitted to special care nurseries required oxygen at 36 weeks PMA

Question 3

What were the results of the meta-analysis done by Shinwell and Eventov-Friedman?

Answer 3

• Dexamethasone treatment associated with increased risk of CP (OR 1.63)
• Dexamethasone treatment associated with increased risk of neurdevelopmental impairment (OR 1.40)

Question 4

What were the beneficial effects of early corticosteroids demonstrated by the 2010 Cochrane review?

Answer 4

• Earlier extubation
• Reduced need for oxygen at 36 weeks PMA

Question 5

What are the short term adverse effects of dexamethasone in the preterm population?

Answer 5

• Hyperglycemia
• Hypertension
• Gastrointestinal hemorrhage
• Gastrointestinal perforation

Question 6

What was the overall conclusion about the use of dexamethasone for prevention of CLD in the 2010 Cochrane review?

Answer 6

• Increased rates of CP and CP or death (RR 1.17)
• Impact of dexamethasone greater than hydrocortisone both for decreasing CLD and increasing adverse neurodevelopmental outcomes
• Benefits of early corticosteroid did not outweigh the risk

Question 7

What were the effects of late dexamethasone as analyzed in the 2009 Cochrane review?

Answer 7

• Decreased mortality at 28 days
• Decreased rate of CLD at 36 weeks
• Decreased combined outcome of death or CLD at 36 weeks (RR 0.72)
• Decreased failure to extubate within 7 days
• Decreased amount of infants discharged home on O2

Question 8

What short-term adverse effects were associated with late dexamethasone?

Answer 8

• Hyperglycemia
• Hypertension
• Higher incidence hypertrophoc cardiomyopathy
• Higher incidence severe ROP

Question 9

What long term outcomes were associated with late dexamethasone?

Answer 9

• No increased incidence of blindness
• No differences in major neurosensory disability, CP or combined rates of death or CP
• Incerased rate of abnormal neurological examination noted in 4 studies, implications of this is unclear

Question 10

What ultimate recommendation was made about late dexamethasone?

Answer 10

• Because it had both beneficial and harmful effects, it should be reserved for infants who could not be weaned from mechanical ventilation

Question 11

What evidence is there to demonstrate safety of routine low dose dexamethasone use?

Answer 11

• Insufficienct evidence!
• DART study showed low dose dex facilitated extubation and shortened duration of extubation for ventilator dependent infants
  
  • Study terminated early due to declining enrollment
  • Not powered to detect differences in long term outcomes

Question 12

What is the evidence for dexamethasone use in infants at high risk of CLD?

Answer 12

• When the rate of CLD is > 65% dexamethasone decreases the rate of death or CP
• This effect has not yet been studied in clinical trials

Question 13

Why has hydrocortisone been proposed as an alternative to dexamethasone?

Answer 13

• Less potent glucocorticoid
• ? fewer side effects
• May mitigate against adrenal insufficiency to decrease CLD

Question 14

What are the effects of hydrocortisone therapy started in the first week of life?

Answer 14

• No decrease in mortality
• No decrease in need for oxygen at 36 weeks PMA
• No decrease in combined outcome of death or CLD
• No decrease in percent of survivors discharged home on O2
• No decrease in rate of failure to extubate
• No significant difference in rate of CP or combined mortality and CP

Question 15

What is the evidence for using hydrocortisone instead of dexamethasone to treat infants with prolonged ventilator dependence?

Answer 15

No evidence to show it is effective or safe

Question 16

What is the evidence for inhaled corticosteroids for preventing CLD?

Answer 16

• Meta-analysis (V. Shah): Looked at ICS used in the first two weeks of life for ventilated prems to prevent CLDCompared to placebo, no difference in CLD at 36 weeks, death by 36 weeks, death or CLD at 36 weeks or side effects including hyperglycemia, HTN, infection
• Meta-analysis (S. Shah): Looked at ICS use in infants who remained O2/ventilator dependent. Neither budesonide or beclomethasone was more effective than dex at decreasing death, CLD or death + CLD at 36 weeks. No differences in duration of mechanical ventilation or side effects
• Little evidence to support routine use of ICS for prevention or treatment of CLD/ ICS don’t offer significant benefits over systemic steroids for treating ventilator dependent infants