in whom complications could be more severe, such as
increase in IVH. Several randomized, controlled trials are
currently underway, which, it is hoped, will address some
of the important currently unresolved issues. The potential
benefits of inhaled nitric oxide for the prevention of chronic
lung disease is another area of intense research. The cur-
rently available evidence is insufficient to recommend the
use of inhaled nitric oxide outside randomized, controlled
trials in this population, although we have used it in ex-
ceptional circumstances, under a compassionate care pro-
tocol, with parental informed consent.
Summary
Despite the tremendous advances in the management of
RDS, substantial respiratory morbidity in the form of BPD
remains a major problem. Prenatal corticosteroids for lung
maturation and postnatal surfactant replacement therapy
significantly reduce the incidence, severity, and mortality
associated with RDS and are currently considered standard
of care. Only natural surfactants are currently available for
use in the United States, and there are no significant dif-
ferences in clinically important outcomes among prepara-
tions.
The ventilatory management of babies suffering RDS
may require further refinement. The new generation of
ventilators may allow us to better monitor and control tidal
volume delivery to minimize volutrauma while preventing
unwanted atelectasis. Based on the currently available clin-
ical data, there is no significant difference in outcomes
between conventional and high-frequency ventilation for
the management of RDS, although there is considerable
center-to-center variation in outcomes. Recent data sug-
gest that HFOV, when used properly, does not seem to
increase the incidence of intracranial hemorrhage. Nasal
CPAP may reduce the damaging effects of mechanical
ventilation on the developing lung. Finally, the general
principles of neonatal care and a team approach should be
applied to maximize the occurrence of good short-term
and long-term outcomes.
REFERENCES
1. Avery ME, Mead J. Surface properties in relation to atelectasis and
hyaline membrane disease. Am J Dis Child 1959;97:517–523.
2. Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T. Artifi-
cial surfactant therapy in hyaline-membrane disease. Lancet 1980;
1(8159):55–59.
3. Jobe AH, Mitchell BR, Gunkel JH. Beneficial effects of the com-
bined use of prenatal corticosteroids and postnatal surfactant on pre-
term infants. Am J Obstet Gynecol 1993;168(2):508–513.
4. Kari MA, Hallman M, Eronen M, Teramo K, Virtanen M, Koivisto
M, Ikonen RS. Prenatal dexamethasone treatment in conjunction
with rescue therapy of human surfactant: a randomized placebo-
controlled multicenter study. Pediatrics 1994;93(5):730–736.
5. Liggins GC, Howie RN. A controlled trial of anterpartum glucocor-
ticoid treatment for prevention of the respiratory distress syndrome
in premature infant. Pediatrics 1972;50(4):515–525.
6. Ballard PL, Ballard RA. Scientific basis and therapeutic regimens for
use of antenatal glucocorticoids. Am J Obstet Gynecol 1995;173(1):
254–262.
7. Rodriguez RJ, Martin RJ, Fanaroff AA. The respiratory distress syn-
drome and its management. In: Fanaroff AA, Martin RJ, editors. Neo-
natal-perinatal medicine, 7th ed. St Louis: Mosby-Year Book; 2002.
8. Hack M, Wright LL, Shankaran S, Tyson JE, Horbar JD, Bauer CR,
Younes N. Very-low-birth-weight outcomes of the National Institute
of Child Health and Human Development Neonatal Network, No-
vember 1989 to October 1990. Am J Obstet Gynecol 1995;172(2 Pt
1):457–464.
9. Clements JA. Surface tension of lung extracts. Proc Soc Exp Biol
Med 1957;95:170–172.
10. Pattle RE. Properties, function and origin of the alveolar lining layer.
Nature 1995;175:1125–1126.
11. Rodriguez RJ, Martin RJ. Exogenous surfactant therapy in new-
borns. Respir Care Clin N Am 1999;5(4):595–616
12. Jobe AH, Ikegami M, Seidner SR, Pettenazzo A, Ruffini L. Surfac-
tant phosphatidylcholine metabolism and surfactant function in pre-
term, ventilated lambs. Am Rev Respir Dis 1989;139(2):352–359.
13. Hawgood S, Clements JA. Pulmonary surfactant and its apoproteins.
J Clin Invest 190;86(1):1–6.
14. Benson B. Genetically engineered human pulmonary surfactant. Clin
Perinatol 1993;20(4):791–811.
15. Ballard PL, Nogee LM, Beers MF, Ballard RA, Planer BC, Polk L,
et al. Partial deficiency of surfactant protein B in an infant with
chronic lung disease. Pediatrics 1995;96(6):1046–1052.
16. Chida S, Phelps DS, Cordle C, Soll R, Floros J, Taeusch HW. Sur-
factant-associated proteins in tracheal aspirates of infants with re-
spiratory distress syndrome after surfactant therapy. Am Rev Respir
Dis 1988;137(4):943–947.
17. Hall SB, Venkitaraman AR, Whitsett JA, Holm BA, Notter RH.
Importance of hydrophobic apoproteins as constituents of clinical
exogenous surfactants. Am Rev Respir Dis 1992;145(1):24–30.
18. Klein JM, Thompson MW, Snyder JM, George TN, Whitsett JA, Bell
EF, et al. Transient surfactant protein B deficiency in a term infant with
severe respiratory failure. J Pediatr 1998;132(2):244–248.
19. Nogee LM, de Mello DE, Dehner LP, Colten HR. Brief report:
deficiency of pulmonary surfactant protein B in congenital alveolar
proteinosis. N Engl J Med 1993;328(6):406–410.
20. Kala P, Ten Have HT, Nielsen H, Dunn M, Floros J. Association of
pulmonary surfactant protein A (SP-A) gene and respiratory distress
syndrome: interaction with SP-B. Pediatr Res 1998;43(2):169–177.
21. Moya FR, Montes HF, Thomas VL, Mouzinho AM, Smith JF, Rosen-
feld CR. Surfactant protein A and saturated phosphatidylcholine in
respiratory distress syndrome. Am J Respir Crit Care Med 1994;
150(6 Pt 1):1672–1677.
22. Collaborative European Multicenter Study Group. Surfactant replace-
ment therapy for severe neonatal respiratory distress syndrome: an
international randomized clinical trial. Pediatrics 1988;82(5):683–
691.
23. Dunn MS, Shennan AT, Possmayer F. Single- versus multiple-dose
surfactant replacement therapy in neonates at 30 to 36 weeks’-ges-
tation with respiratory distress syndrome. Pediatrics 1990;86(4):564–
571.
24. Egberts J, de Winter JP, Sedin G, de Kleine MJ, Broberger U, van
Bel F, et al. Comparison of prophylaxis and rescue treatment with
Curosurf in neonates less than 30 weeks’ gestation: a randomized
trial. Pediatrics 1993;92(6):768–774.
25. Fujiwara T, Konishi M, Chida S, Okuyama K, Ogawa Y, Takeuchi
Y, et al: Surfactant replacement therapy with a single postventilatory
M
ANAGEMENT OF
R
ESPIRATORY
D
ISTRESS
S
YNDROME
284
R
ESPIRATORY
C
ARE
•
M
ARCH
2003 V
OL
48 N
O
3