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ARTICLES: Elena Gastiasoro-Cuesta, Francisco J. Alvarez-Diaz, Carmen Rey-Santano, Arantxa Arnaiz-Renedo, Begoña Loureiro-Gonzalez, and Adolf Valls-i-Soler Acute and Sustained Effects of Lucinactant Versus Poractant- on Pulmonary Gas Exchange and Mechanics in Premature Lambs With Respiratory Distress Syndrome Pediatrics 2006; 117: 295-303 [Abstract] [Full text] [PDF]

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Synthetic Surfactants

Satyan Lakshminrusimha, James J. Cummings, MD, Professor of Pediatrics and Physiology, East Carolina University   (8 March 2006)

Synthetic Surfactants 8 March 2006
Satyan Lakshminrusimha, Assistant Professor of Pediatrics State University of New York, Buffalo NY, James J. Cummings, MD, Professor of Pediatrics and Physiology, East Carolina University Send letter to journal: Re: Synthetic Surfactants slakshmi{at}buffalo.edu Satyan Lakshminrusimha, et al.	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

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