Partial Liquid Ventilation with Perflubron in Premature Infants with Severe Respiratory Distress Syndrome

Leach, Corinne L.; Greenspan, Jay S.; Rubenstein, S. David; Shaffer, Thomas H.; Wolfson, Marla R.; Jackson, J. Craig; deLemos, Robert A.; Fuhrman, Bradley P.

doi:10.1056/nejm199609123351101

Cited by 431 publications

(239 citation statements)

References 22 publications

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“…For example, studies indicate that the distribution and/or efficacy of instilled exogenous surfactant can be improved by jet ventilation [161,162] and partial liquid ventilation [163][164][165]. Additional mechanism-based research on the impact of specific ventilation methods and strategies on the delivery, distribution, and efficacy of exogenous surfactants may be important for optimizing this therapy in ALI/ARDS.…”

Section: Delivery Methods and Dosages For Exogenous Surfactant Therapmentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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Section: Delivery Methods and Dosages For Exogenous Surfactant Therapmentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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“…PFC liquids are inert fluorinated hydrocarbon compounds, one of which, perflubron, has been extensively investigated for use in clinical trials of partial liquid ventilation (Leach et al, 1996;Hirschl et al, 2002;Kacmarek et al, 2006). Even though randomized clinical trials of liquid ventilation using perflubron versus conventional gas ventilation did not show significant improvement in survival (and as such, liquid ventilation has largely fallen out of clinical use), a strong safety record for intratracheal administration of perflubron has been established.…”

Section: Discussionmentioning

confidence: 99%

“…Perfluorochemical (PFC) liquids are inert, nontoxic liquids that had been extensively investigated for use in preclinical models of lung injury and in clinical application of partial liquid ventilation (PLV) for diseased lungs (Leach et al, 1996;Hirschl et al, 2002;Kacmarek et al, 2006). Although liquid ventilation has generally fallen from clinical use, administration of perflubron (LiquiVent; Alliance Pharmaceutical, San Diego, CA) and other PFC liquids in PLV was safe and could improve oxygenation and lung mechanics while also decreasing histopathological injury and inflammation in injured lungs (Hirschl et al, 1995(Hirschl et al, , 2002Leach et al, 1996;Rotta et al, 1999;Kacmarek et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…Although liquid ventilation has generally fallen from clinical use, administration of perflubron (LiquiVent; Alliance Pharmaceutical, San Diego, CA) and other PFC liquids in PLV was safe and could improve oxygenation and lung mechanics while also decreasing histopathological injury and inflammation in injured lungs (Hirschl et al, 1995(Hirschl et al, , 2002Leach et al, 1996;Rotta et al, 1999;Kacmarek et al, 2006). More recently it has been found that inhalation of nebulized perflubron and other PFC compounds comparably enhances oxygenation and improves lung mechanics in preclinical models of lung injury (Bleyl et al, 1999;Kandler et al, 2001Kandler et al, , 2004Ragaller et al, 2001;von der Hardt et al, 2004;Gama de Abreu et al, 2005;Meinhardt et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

Beckett

Bonneau

Howard

et al. 2012

Human Gene Therapy Methods

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Use of perfluorochemical liquids during intratracheal vector administration enhances recombinant adenovirus and adeno-associated virus (AAV)-mediated lung epithelial gene expression. We hypothesized that inhalation of nebulized perfluorochemical vapor would also enhance epithelial gene expression after subsequent intratracheal vector administration. Freely breathing adult C57BL/6 mice were exposed for selected times to nebulized perflubron or sterile saline in a sealed Plexiglas chamber. Recombinant adenoviral vector was administered by transtracheal puncture at selected times afterward and mice were killed 3 days after vector administration to assess transgene expression. Mice tolerated the nebulized perflubron without obvious ill effects. Vector administration 6 hr after nebulized perflubron exposure resulted in an average 540% increase in gene expression in airway and alveolar epithelium, compared with that with vector alone or saline plus vector control ( p < 0.05). However, vector administration 1 hr, 1 day, or 3 days after perflubron exposure was not different from either nebulized saline with vector or vector alone and a 60-min exposure to nebulized perflubron is required. In parallel pilot studies in macaques, inhalation of nebulized perflubron enhanced recombinant AAV2/5 vector expression throughout the lung. Serial chest radiographs, bronchoalveolar lavages, and results of complete blood counts and serum biochemistries demonstrated no obvious adverse effects of nebulized perflubron. Further, one macaque receiving nebulized perflubron only was monitored for 1 year with no obvious adverse effects of exposure. These results demonstrate that inhalation of nebulized perflubron, a simple, clinically more feasible technique than intratracheal administration of liquid perflubron, safely enhances lung gene expression.

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“…Several researchers have explored how these properties might be exploited to assist with ventilation and have demonstrated that intrapulmonary delivery of PFC is beneficial for the treatment of various pulmonary diseases (2-4) including neonatal respiratory distress syndrome (RDS) (5,6).…”

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confidence: 99%

Aerosolized perfluorocarbon improves gas exchange and pulmonary mechanics in preterm lambs with severe respiratory distress syndrome

et al. 2012

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Background: aerosolized perfluorocarbon (PFc) has been proposed as an alternative method of PFc administration; however, the efficacy of aerosolized PFc in a preterm animal model has not yet been demonstrated. Methods: Twelve preterm lambs were randomized to two groups: a perfluorodecalin (PFD) aerosol group (n = 6) receiving 10 ml/kg/h of PFD delivered by an intratracheal inhalation catheter followed by 4 h of mechanical ventilation (MV) or the control group, in which animals (n = 6) were managed for 6 h with MV. Gas exchange, pulmonary mechanics, cardiovascular parameters, and cerebral blood flow (cBF) were measured. results: Both groups developed hypoxia, hypercarbia, and acidosis at baseline. aerosolized PFD improved oxygenation (P < 0.0001) and pulmonary mechanics (P < 0.0001) and changed carbon dioxide values to normal physiological levels, unlike the treatment given to the controls (P < 0.0003). The time course of mean arterial blood pressure and cBF were significantly affected by PFD aerosolization, especially during the first hour of life. cBF gradually decreased during the first hour in the PFD aerosol group and remained stable until the end of the follow-up, whereas cBF remained higher in the control group (P < 0.0028). conclusion: aerosolized PFD improves pulmonary function in preterm lambs and should be further investigated as an alternative mode of PFc administration.

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Partial Liquid Ventilation with Perflubron in Premature Infants with Severe Respiratory Distress Syndrome

Abstract: Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.

Cited by 431 publications

References 22 publications

Surfactant for Pediatric Acute Lung Injury

Surfactant for Pediatric Acute Lung Injury

Inhalation of Nebulized Perfluorochemical Enhances Recombinant Adenovirus and Adeno-Associated Virus-Mediated Gene Expression in Lung Epithelium

Aerosolized perfluorocarbon improves gas exchange and pulmonary mechanics in preterm lambs with severe respiratory distress syndrome

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