A Multicenter, Randomized, Controlled Trial Comparing Surfaxin (Lucinactant) Lavage With Standard Care for Treatment of Meconium Aspiration Syndrome

Wiswell, Thomas E.; Knight, G. R.; Finer, Neil N.; Donn, Steven M.; Desai, Hemant; Walsh, William F.; Sekar, Krishnamurthy; Bernstein, Graham; Keszler, Martin; Visser, Valya E.; Merritt, T. Allen; Mannino, Frank L.; Mastrioianni, Lisa; Marcy, Brian; Revak, Susan D.; Tsai, Huei‐Ting; Cochrane, Charles G.

doi:10.1542/peds.109.6.1081

Cited by 176 publications

(113 citation statements)

References 26 publications

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“…In addition, there are two studies evaluating the use of surfactant lavage in newborn infants with MAS. Although, the techniques used in these studies were different, both the studies reported promising results [18,37].…”

Section: Discussionmentioning

confidence: 99%

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Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Meister

Balaraman

Ramirez

et al. 2004

Lung

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Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf® or Exosurf® by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4mg phospholipid/ ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO 2 were observed in the lavage groups compared to the bolus groups and the controls. PaO 2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 ± 54, E-LAVAGE =280 ± 57; I-BOLUS = 139 ± 31; E-BOLUS = 152 ± 29; C = 119 ± 73 (mean ± SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of nonhomogeneous lung injury.

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Section: Discussionmentioning

confidence: 99%

“…Despite prophylactic oropharyngeal suctioning of infants delivered with meconiumstained amniotic fluid, the incidence of MAS varies widely (1.7%-35.8%) [5,33,37]. In its severest form, MAS results in a vicious cycle of hypoxemia, hypercapnia, acidosis, and death [1,5,29].…”

Section: Introductionmentioning

confidence: 99%

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Meister

Balaraman

Ramirez

et al. 2004

Lung

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“…No adverse effects were reported. In a multicenter study, Wiswell et al 42 examined the use of surfactant lavage for MAS using lucinactant, a synthetic surfactant. Although it was potentially safe and effective, lucinactant failed to show a significant advantage with surfactant lavage.…”

Section: Surfactant Therapy and Nasal Continuous Positive Airway Presmentioning

confidence: 99%

Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS

Ramanathan

2006

J Perinatol

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Many different surfactant preparations derived from animal sources, as well as synthetic surfactants, are available for the treatment of preterm infants with respiratory distress syndrome (RDS). Natural, modified surfactants containing surfactant-associated proteins appear to be more effective than non-protein-containing synthetic surfactants. Comparative trials with poractant alfa at a higher initial dose of 200 mg/kg appear to be associated with rapid weaning of FiO 2 , less need for additional doses, and decreased mortality in infants <32 weeks gestation when compared with beractant. Early rescue (<30 min of age) surfactant therapy is an effective method to minimize over treatment of some preterm infants who may not develop RDS. Surfactant therapy followed by rapid extubation to nasal ventilation appears to be more beneficial than continued mechanical ventilation. In near-term or term newborns with acute RDS, surfactant therapy has been shown to be 70% effective in improving respiratory failure.

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“…Another peptide design strategy has used the Leu-Leu repeat sequence in the C-terminal helical region of SP-B (residues 57-63) as a molecular template for the synthetic peptide KL 4 (Surfaxin) (36). This peptide does not have the in Vitro and in ViVo efficacy observed for native and synthetic SP-B sequences (37) but has shown some promise as a bronchoalveolar lavage for improving lung function in meconium aspiration syndrome (38).…”

mentioning

confidence: 99%

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

et al. 2004

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Although the membrane-associated surfactant protein B (SP-B) is an essential component of lung surfactant, which is itself essential for life, the molecular basis for its activity is not understood. SP-B's biophysical functions can be partially mimicked by subfragments of the protein, including the C-terminus. We have used NMR to determine the structure of a C-terminal fragment of human SP-B that includes residues 63-78. Structure determination was performed both in the fluorinated alcohol hexafluoro-2-propanol (HFIP) and in sodium dodecyl sulfate (SDS) micelles. In both solvents, residues 68-78 take on an amphipathic helical structure, in agreement with predictions made by comparison to homologous saposin family proteins. In HFIP, the five N-terminal residues of the peptide are largely unstructured, while in SDS micelles, these residues take on a well-defined compact conformation. Differences in helical residue side chain positioning between the two solvents were also found, with better agreement between the structures for the hydrophobic face than the hydrophilic face. A paramagnetic probe was used to investigate the position of the peptide within the SDS micelles and indicated that the peptide is located at the water interface with the hydrophobic face of the helix oriented inward, the hydrophilic face of the helix oriented outward, and the N-terminal residues even farther from the micelle center than those on the hydrophilic face of the R-helix. Interactions of basic residues of SP-B with anionic lipid headgroups are known to have an impact on function, and these studies demonstrate structural ramifications of such interactions via the differences observed between the peptide structures determined in HFIP and SDS.

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A Multicenter, Randomized, Controlled Trial Comparing Surfaxin (Lucinactant) Lavage With Standard Care for Treatment of Meconium Aspiration Syndrome

Abstract: Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.

Cited by 176 publications

References 26 publications

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS

NMR Structures of the C-Terminal Segment of Surfactant Protein B in Detergent Micelles and Hexafluoro-2-propanol

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