To the editor,
We read the article on the acute and sustained effects of lucinactant
compared to poractant-alpha in preterm lambs by Gastiasoro-Cuesta et al
with great interest(1). The authors concluded that lucinactant produced
improvements in gas exchange and lung mechanics similar to those observed
with poractant, but the model chosen and differences in both pretreatment
characteristics and treatment responses may preclude such a sweeping
statement.
At 135 days of gestation, newborn lambs generally do not have severe
RDS, and can be quite variable in their endogenous surfactant sufficiency,
making clinical comparisons difficult. Jobe et al ventilated 134-136 day
gestation lambs without surfactant therapy and the mean PaO2 in most of
these lambs ranged from 250 – 300 mmHg (on 100% oxygen) after the first
hour of life; there was also other clear evidence that most of the
animals had significant endogenous surfactant.(2) In the study by
Gastiasoro-Cuesta et al, the authors used in-vivo compliance to estimate a
“functional” gestational age of 100 +/- 6 days in their 135-day gestation
lambs, but they measured compliance within the first five minutes of life,
before newborn lambs, delivered without the benefit of labor, generally
have established maximal surfactant concentrations within their alveolar
lining fluid.(3,4) For these reasons, a control arm with lambs of the same
strain receiving placebo and endogenous surfactant measurements might have
helped to properly interpret data and assess the efficacy of lucinactant
and to determine if the exogenous surfactant had any effect over the
endogenous surfactant present.
Baseline characteristics differed somewhat between the two groups.
Lambs in the poractant group were, on average, more than 10% smaller.
Basal mean oxygenation indices (OI) were quite different between the
poractant and lucinactant groups (67.7 and 30.4, respectively), suggesting
sicker animals in the poractant group.
The significantly higher mean airway pressures (and OI) required in
the lucinactant group and the lack of response to lucinactant in one-third
of the lambs in that group is very concerning. If those two animals had
little endogenous surfactant, this synthetic surfactant shares the same
characteristic that a previous synthetic surfactant, Exosurf, exhibited in
premature lambs, i.e. no biological activity without significant
endogenous material.(5)
Satyan Lakshminrusimha, MD
Assistant Professor of Pediatrics,
State University of New York
James J. Cummings, MD
Professor of Pediatrics and Physiology
East Carolina University
1. Gastiasoro-Cuesta E, Alvarez-Diaz FJ, Rey-Santano C, Arnaiz-Renedo
A, Loureiro-Gonzalez B, Valls-i-Soler A. Acute and sustained effects of
lucinactant versus poractant-alpha on pulmonary gas exchange and mechanics
in premature lambs with respiratory distress syndrome. Pediatrics
2006;117(2):295-303.
2. Jobe AH, Ikegami M, Jacobs HC, Jones SJ. Surfactant pool sizes and
severity of respiratory distress syndrome in prematurely delivered lambs.
Am Rev Respir Dis 1983;127(6):751-5.
3. Lawson EE, Brown ER, Torday JS, Madansky DL, Taeusch HW, Jr. The
effect of epinephrine on tracheal fluid flow and surfactant efflux in
fetal sheep. Am Rev Respir Dis 1978;118(6):1023-6.
4. Lawson EE, Birdwell RL, Huang PS, Taeusch HW, Jr. Augmentation of
pulmonary surfactant secretion by lung expansion at birth. Pediatr Res
1979;13(5 Pt 1):611-4.
5. Cummings JJ, Holm BA, Hudak ML, Hudak BB, Ferguson WH, Egan
EA.. A controlled clinical comparison of four different surfactant
preparations in surfactant deficient preterm lambs. Am Rev Respir Dis
1992; 145:999-1004
Conflict of Interest:
Dr. Cummings is a medical consultant for iNO Therapeutics, a member of the research grant committee for Forest Pharmaceuticals, and a site investigator for Discovery Labs
on Pulmonary Gas Exchange and Mechanics in Premature Lambs With Respiratory Distress Syndrome
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