Postnatal steroids for chronic lung disease

Postnatal steroids for chronic lung disease
Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Steroidsgiven either soon after birth to prevent CLD, or later to reduce its severity, are effective, but thereare acute and long-term adverse effects. When steroids are given early (first 4 days) there is anincreased risk of cerebral palsy in surviving infants which precludes their use at this time.
Dexamethasone may be effective in far lower doses than used in most of the randomised trialsto date. There are probably situations where its use is associated with more benefit than harm.
There is no convincing evidence that inhaled steroids alter the course of CLD. More research isneeded into ways of preventing or reducing CLD in at risk preterm infants.
Henry L Halliday
Chronic lung disease
arrested development, also known as ‘the respiratory distress syndrome (RDS) in the 1990s, survival rates of preterm babies have Department of Child HealthQueen’s University Belfast modest effect on reducing the incidence of translates into an increased overall number dysplasia (BPD) are used interchangeably, academic difficulties, delayed speech and until recently there has been no consistent definition of these conditions5. The best CLD persist into adolescence with reduced Keywords
corrected age of 36 weeks after efforts have been made to ensure that oxygen is indeed significantly different from very preterm dysplasia; corticosteroids; dexamethasone; 88%; the so called ‘physiologic definition’6.
sequelae are important it is not surprising Key points
weight and gestational age, with rates of less than 5% in infants weighing more than Halliday, H.L. (2007) Postnatal steroids for
1500 grams, increasing to 85% in those of chronic lung disease Infant 3(2): 78-81.
less than 700 grams7. Overall at least 20% 1. Chronic lung disease is associated with respiratory outcomes would be expected.
described by Bill Northway and colleagues History of postnatal steroids
in 1967 as a severe sequela of mechanical There is a long history of use of postnatal ventilation – the so called ventilator lung disease8 (FIGURE 1). Pathologically in classic
was first reported in 1956 in the US as a BPD there is severe alveolar fibrosis and potential treatment for respiratory distress 3. Inhaled steroids have little effect on the in infants of diabetic mothers15. Later in strategies of mechanical ventilation, the RDS16, but the first randomised controlled infants with significant chronic lungdisease or at high risk of developing it.
trial was not reported until 197217. This V O L U M E 3 I S S U E 2 2 0 0 7 infant
RR (95%CI)
NNT (95%CI)
and perforation. Some of these arepotentially reversible after corticosteroid treatment has been discontinued.
However, the long term adverse increased risk of cerebral palsy after early
treatment with postnatal steroids (TABLE 2).
It appears that this increased risk in earlytreated infants is due to their lower risk of steroids is weighted towards harm ratherthan benefit. With risks of CLD below 35% corticosteroid treatment significantlyincreases the chance of death or cerebral RR=relative risk, CI=confidence interval, NNT=number needed to treat, CLD=chronic lung disease, PDA=persistent ductus arteriosus. Data derived from Cochrane 65%, it reduces the chance of these adverse TABLE 1 Beneficial effects of systemic postnatal steroids.
used dexamethasone but the dose andduration varied considerably23. The most Systematic reviews of systemic
reducing course over two to six weeks.
increased risk of severe intraventricular postnatal steroids were first published in results of these systematic reviews is the problems20. As a result of these concerns cross over effect of the use of open label about serious long term adverse effects of reviews are classified according to postnatal corticosteroids in the control groups.
age at the start of treatment: early (<96 high dose dexamethasone was used to treat delayed (>3 weeks). Postnatal steroids, babies and this had the effect of reducing ventilator-dependent infants with CLD 21,22.
whether started early, moderately early or late, facilitate earlier extubation and reduce the risk of developing CLD at 36 weeks’ corrected age (TABLE 1). Neonatal mortality
studies with less than 30% cross over (or significant long term benfits. Few adverse effects were reported in these early studies about the safety of postnatal steroids and steroids was first shaken in 1998 with thepublication of a large multicentre follow- up study from Taiwan25. This study showed infants (TABLE 1).
lems and a doubling of the risk of cerebral palsy at two years in infants who had been treated with a 4 week course of dexametha- sone, started within 12 hours of birth. This study and others that followed in 1999 and steroids (TABLE 2).
postnatal corticosteroids to prevent CLD.
FIGURE 1 Ventilator-dependent baby with chronic lung disease.
infant VO L U M E 3 I S S U E 2 2 0 0 7
prevent CLD and later to treat babies with inhaled and systemic corticosteroids, again cerebral palsy was as high as one for every both early (<2 weeks)38 and late (>2 four treated infants30. It seems likely that included five randomised controlled trials that outweigh its benefits. Its initial choice but did not show any reduction in CLD36.
suggesting that either the doses used were risk of hyperglycaemia. In summary, there safe, or alternatively were ineffective. A second systematic review also included five physiological secretion rate of cortisol in effective for prevention and treatment of corticosteroids have been used infrequently dexamethasone in reducing ventilation and Other systemic corticosteroids
Methylprednisolone has been compared
with dexamethasone in a non-randomised
RR (95%CI)
NNH (95%CI)
preterm infants at risk31. Although therewere no differences in oxygen requirements or in the rate of weaning from ventilation, the methylprednisolone-treated infantshad better weight gain, less hyperglycaemia than those treated with dexamethasone.
However, there have been no randomisedtrials with methylprednisolone, nor withbetamethasone, a drug commonly used antenatally to mature the fetal lungs.
Hydrocortisone, prescribed in a
relatively low dose as prophylaxis againstadrenal insufficiency, appeared to reduce the risk of CLD in a small pilotrandomised trial32. However, two larger early because of an excess ofgastrointestinal perforations in the cause of these perforations may have beenan interaction between early hydro- cortisone treatment and prophylacticindomethacin. Hydrocortisone has also been compared with dexamethasone fortreatment of CLD in non-randomised outcome may be better with hydro-cortisone. These findings need to be confirmed in randomised comparativetrials before alternative steroids can be Inhaled steroids
RR = relative risk, CI = confidence interval, NNH = number needed to harm. HCM = These should have direct beneficial effects hypertrophic cardiomyopathy, GI = gastrointestinal, CP = cerebral palsy. Data derived from Cochrane systematic reviews26-28.
systemic effects of dexamethasone. Inhaledsteroids have been used early to try to TABLE 2 Adverse effects of systemic postnatal steroids.
V O L U M E 3 I S S U E 2 2 0 0 7 infant
membrane disease: Bronchopulmonary dysplasia.
29. Doyle L.W., Halliday H.L., Ehrenkranz R.A., Davis
Overall conclusions
N Engl J Med 1967; 276: 357-68.
P.G., Sinclair J.C. Impact of postnatal systemic
Following the publication of guidelines for 9. Coalson J.J. Pathology of new bronchopulmonary
corticosteroids on mortality and cerebral palsy in postnatal steroid treatment in Europe40 and dysplasia. Semin Neonatol 2003; 8: 73-81.
preterm infants: Effect modification by risk of 10. Jobe A.H. The new BPD: An arrest of lung
chronic lung disease. Pediatrics 2005; 115: 655-61.
development. Pediatr Res 1999; 46: 641-43.
30. Barrington K.J. The adverse neuro-developmental
11. Speer C.P. New insights into the pathogenesis of
effects of postnatal steroids in the preterm infant: A Israel steroid use in very low birthweight pulmonary inflammation in preterm infants. Biol systematic review of RCTs. BMC Pediatrics 2001; 1.
infants fell from 23% in 1997-8 to 11% in Neonate 2001; 79: 205-09.
31. Andre P, Thebaud B, Odievre MH et al. Methylpred-
2003-442. However, this was associated with 12. Saugstad O.D. Bronchopulmonary dysplasia-
nisolone, an alternative to dexamethasone in very oxidative stress and antioxidants. Semin Neonatol premature infants at risk of chronic lung disease.
2003; 8: 39-49.
and 36 weeks’ corrected age, together with Intensive Care Med 2000; 26: 1496-500.
13. Anderson P.J., Doyle L.W. Neurodevelopmental
32. Watterberg K.L., Gerdes J.S., Gilford K.L., Lin H.M.
outcome of bronchopulmonary dysplasia. Semin Prophylaxis against early adrenal insufficiency to postnatal steroids should be avoided if at Perinatol 2006; 30: 227-32.
prevent chronic lung disease in premature infants.
all possible there are still occasions when 14. Doyle L.W., Faber B., Callanan C., Freezer N., Ford
Pediatrics 1999; 104: 1258-63.
their use may provide benefits in excess of G.W., Davis N.M. Bronchopulmonary dysplasia in
33. Watterberg K.L., Gerdes J.S., Cole C.H. et al.
very low birthweight subjects and lung function in Prophylaxis of early adrenal insufficiency to prevent late adolescence. Pediatrics 2006; 118: 108-13.
bronchopulmonary dysplasia: A multicenter trial.
15. Haddad H.M., Hsia D.Y., Gellis S.S. Studies on
Pediatrics 2004; 114: 1649-57.
respiratory rate in the newborn: Its use in the 34. Peltoniemi O., Kari M.A., Heinonen K. et al.
evaluation of respiratory distress in infants of Pretreatment cortisol values may predict responses diabetic mothers. Pediatrics 1956; 17: 204-13.
to hydrocortisone administration for the prevention 16. Altman H. The respiratory distress syndrome of the
of bronchopulmonary dysplasia in high risk infants.
J Pediatr 2005; 146: 632-37.
conservatively. S Afr Med J 1965; 39: 746-48.
respiratory function with a starting dose 35. Karemaker R., Heijnen C.J., Veen S. et al. Differences
17. Baden M., Bauer C.R., Colle E., Klein G., Taeusch
in behavioural outcome and motor development at H.W. Jr., Stern L. A controlled trial of hydrocortisone
school age after neonatal treatment for chronic there is also anecdotal evidence that doses therapy in infants with respiratory distress syndrome. Pediatrics 1972; 50: 526-34.
hydrocortisone. Pediatr Res 2006; 60: 745-50.
18. Ewerbeck H., Helwig H., Reynolds J.W., Provenzano
36. Shah V., Ohlsson A., Halliday H.L., Dunn M.S. Early
R.W. Treatment of idiopathic respiratory distress
administration of inhaled corticosteroids for with large doses of corticoids. Pediatrics 1972; 49:
needed to determine the best corticosteroid preventing chronic lung disease in ventilated very low birth weight preterm neonates. Cochrane 19. Taeusch H.W. Jr., Wang N.S., Baden M., Bauer C.R.,
Database Sys Rev 2000; (2): CD001969.
Stern L. A controlled trial of hydrocortisone therapy
37. Lister P., Iles R., Shaw B., Ducharme F. Inhaled
in infants with respiratory distress syndrome: II.
steroids for neonatal chronic lung disease.
Pathology. Pediatrics 1973; 52: 850-54.
Cochrane Database Syst Rev 2000; (3): CD002311.
20. Fitzhardinge P.M., Eisen A., Lejtenyi C., Metrakos K.,
38. Shah S.S., Ohlsson A., Halliday H.L., Shah V.S.
Ramsay M. Sequelae of early steroid administration
Inhaled versus systemic corticosteroids for References
to the newborn infant. Pediatrics 1974; 53: 877-83.
preventing chronic lung disease in ventilated very 21. Mammel M.C., Green T.P., Johnson D.E., Thompson
1. Schwartz R.M., Luby A.M., Scanlon J.W., Kellogg R.J.
low birth weight preterm neonates. Cochrane T.R. Controlled trial of dexamethasone therapy in
Effect of surfactant on morbidity, mortality, and Database Syst Rev 2003; (1): CD002058.
infants with bronchopulmonary dysplasia. Lancet resource use in newborn infants weighing 500 to 39. Shah S.S., Ohlsson A., Halliday H.L., Shah V.S.
1983; 1(8338): 1356-58.
1500 g. N Engl J Med 1994; 330: 1476-80.
Inhaled versus systemic corticosteroids for the 22. Avery G.B., Fletcher A.B., Kaplan M., Brudno D.S.
2. Corcoran J.D., Patterson C.C., Thomas P.S., Halliday
treatment of chronic lung disease in ventilated very Controlled trial of dexamethasone in respirator- H.L. Reduction in the risk of bronchopulmonary
low birth weight preterm infants. Cochrane dysplasia from 1980-1990: Results of a multivariate dysplasia. Pediatrics 1985; 75: 106-11.
Database Syst Rev 2003; (2): CD002057.
logistic regression analysis. Eur J Pediatr 1993; 152:
23. Grier D.G., Halliday H.L. Management of
40. Halliday H.L. Guidelines on neonatal steroids.
bronchopulmonary dysplasia in infants: Guidelines Prenat Neonatal Med 2001; 6: 371-73.
3. Egberts J., Brand R., Walti H., Bevilacqua G., Breart
for corticosteroid use. Drugs 2005; 66: 15-29.
41. American Academy of Pediatrics Committee on
G., Gardini F. Mortality, severe respiratory distress
24. Hack M., Fanaroff A.A. Outcomes of children of
Fetus and Newborn, Canadian Paediatric Society
syndrome and chronic lung disease of the newborn extremely low birthweight and gestational age in Fetus and Newborn Committee. Postnatal
are reduced more after prophylactic than after the 1990s. Early Hum Dev 1999; 53: 193-218.
corticosteroids to treat or prevent chronic lung therapeutic administration of the surfactant 25. Yeh T.F., Lin Y.J., Huang C.C. et al. Early
disease in preterm infants. Pediatrics 2002; 109:
Curosurf. Pediatrics 1997; 100: e4.
dexamethasone therapy in preterm infants: A 4. Halliday H.L. Postnatal steroids and chronic lung
follow-up study. Pediatrics 1998; 101: e7.
42. Shinwell E.S., Lerner-Geva L., Lusky A., Reichman B.,
disease in the newborn. Paediatr Resp Rev 2004; 26. Halliday H.L., Ehrenkranz R.A., Doyle L.W. Early
in collaboration with the Israel Neonatal Network.
5(Suppl A): S245-8.
5. Jobe A.H., Bancalari E. Bronchopulmonary dysplasia.
postnatal (<96 hours) corticosteroids for preventing Less postnatal steroids, more bronchopulmonary Am J Respir Crit Care Med 2001; 163: 1723-29.
chronic lung disease in preterm infants. Cochrane dysplasia: A population-based study in very low 6. Walsh M.C., Wilson-Costello D., Zadell A., Newman
Database Syst Rev 2003; (1): CD001146.
birthweight infants. Arch Dis Child Fetal Neonatal Ed N., Fanaroff A. Safety, reliability, and validity of a
27. Halliday H.L., Ehrenkranz R.A., Doyle L.W.
2007; 92: F30-33.
physiologic definition of bronchopulmonary 43. Doyle L.W., Davis P.G., Morley C.J., McPhee A., Carlin
dysplasia. J Perinatol 2003; 23: 451-56.
corticosteroids for preventing chronic lung disease J.B.; DART Study Investigators. Low-dose
7. Parker R.A., Lindstrom D.P., Cotton R.B. Improved
in preterm infants. Cochrane Database Syst Rev dexamethasone facilitates extubation among survival accounts for most, but not all, of the 2003; (1): CD001144.
chronically ventilator-dependent infants: A increase in bronchopulmonary dysplasia. Pediatrics 28. Halliday H.L., Ehrenkranz R.A., Doyle L.W. Delayed
multicenter, international, randomised, controlled 1992; 90: 663-68.
(>3 weeks) postnatal corticosteroids for chronic lung trial. Pediatrics 2006; 117: 75-83.
8. Northway W.H. Jr., Rosan R.C., Porter D.Y. Pulmonary
disease in preterm infants. Cochrane Database Syst 44. Halliday H.L. Postnatal steroids: A dilemma for the
disease following respirator therapy of hyaline Rev 2003; (1): CD001145.
neonatologist. Acta Paediatr 2001; 90: 116-18.
infant VO L U M E 3 I S S U E 2 2 0 0 7


Mania: a short history of bipolar disorder, 2008, 296 pages, david healy, jhu press, 2008, ebook

Mania: A Short History of Bipolar Disorder, David Healy, JHU Press, 2008, 0801888220, 9780801888229,296 pages. This provocative history of bipolar disorder illuminates how perceptions of illness, if not theillnesses themselves, are mutable over time. Beginning with the origins of the concept of maniaвЂ―andthe term maniacвЂ―in ancient Greek and Roman civilizations, ren

timothy alikakos, md, facc

Timothy J. Alikakos, MD, FACC Robert B Johnson, MD, FACC Board Certified Board Certified Cardiovascular Disease Cardiovascular Disease Interventional Cardiology Interventional Vascular Medicine C a r d i o v a s c u l a r S p e c i a l i s t s , S C Patient Instructions for Nuclear Stress Testing: Please follow Instructions carefully

Copyright © 2018 Medical Abstracts