Nebulisation of surfactants in an animal model of neonatal respiratory distress

Fok, Tai Fai; Al-Essa, Mazen; Dolovich, Myrna; Rasid, Farid; Kirpalani, Haresh

doi:10.1136/fn.78.1.f3

Cited by 47 publications

(26 citation statements)

References 31 publications

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“…Despite many experimental studies of nebulized surfactant, using various animal models of surfactant deficiency or depletion, the results have been inconsistent and often disappointing. In some studies, there was no benefit from nebulized surfactant (10,12,13), whereas in others a significant improvement in gas exchange and lung mechanics was observed (9,11). A possible explanation of these findings is the low rates of surfactant deposition within the lung.…”

Section: Discussionmentioning

confidence: 99%

“…Nebulization of surfactant offers an attractive alternative. Unfortunately, studies of nebulized surfactant have shown inconsistent clinical response and surfactant distribution (9)(10)(11)(12)(13)(14)(15)(16). Moreover, most of the studies, even those in which a lung function improvement was observed, reported very low (<10%) fractions of surfactant deposition into the lung (9,12,(17)(18)(19)(20).…”

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confidence: 99%

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Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome

et al. 2016

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Background: Aerosolization of exogenous surfactant remains a challenge. This study is aimed to evaluate the efficacy of atomized poractant alfa (Curosurf ) administered with a novel atomizer in preterm lambs with respiratory distress syndrome. Methods: Twenty anaesthetized lambs, 127 ± 1 d gestational age, (mean ± SD) were instrumented before birth and randomized to receive either (i) positive pressure ventilation without surfactant (Control group), (ii) 200 mg/kg of bolus instilled surfactant (Bolus group) at 10 min of life or (iii) 200 mg/kg of atomized surfactant (Atomizer group) over 60 min from 10 min of life. All lambs were ventilated for 180 min with a standardized protocol. Lung mechanics, regional lung compliance (electrical impedance tomography), and carotid blood flow (CBF) were measured with arterial blood gas analysis. results: Dynamic compliance and oxygenation responses were similar in the Bolus and Atomizer groups, and both better than Control by 180 min (all P < 0.05; two-way ANOVA). Both surfactant groups demonstrated more homogeneous regional lung compliance throughout the study period. There were no differences in CBF conclusion: In a preterm lamb model, atomized surfactant resulted in similar gas exchange and mechanics as bolus administration. This study suggests evaluation of supraglottic atomization with this system when noninvasive support is warranted. s urfactant replacement therapy is a well-established standard of care for the treatment and prevention of neonatal respiratory distress syndrome (RDS), significantly reducing mortality and morbidity (1). Currently, endotracheal instillation is the only approved method of administration. However, over the last decade, the management of mild to moderate RDS has dramatically changed, endotracheal tube (ETT) intubation is often avoided and infants were managed with noninvasive modalities, such as continuous positive airway pressure whilst spontaneously breathing. In this population, surfactant administration is generally only provided when oxygen requirement increases and intubation is necessary (2,3).The increase in noninvasive ventilation use has led to less invasive methods of surfactant delivery during continuous positive airway pressure being developed (4,5). All reported methods require technical skills, some degree of invasive intervention, and still involve instillation of liquid surfactant directly into the trachea via a process that is not dissimilar to intubation (6-8). Nebulization of surfactant offers an attractive alternative. Unfortunately, studies of nebulized surfactant have shown inconsistent clinical response and surfactant distribution (9-16). Moreover, most of the studies, even those in which a lung function improvement was observed, reported very low (<10%) fractions of surfactant deposition into the lung (9,12,(17)(18)(19)(20). Notwithstanding differences in nebulizer design, and thus particle size production, such modest deposition is likely due to the fact that most studies used aerosols generated extracorporeally by ...

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Section: Discussionmentioning

confidence: 99%

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Intratracheal atomized surfactant provides similar outcomes as bolus surfactant in preterm lambs with respiratory distress syndrome

et al. 2016

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“…Multiple studies have reported respiratory improvement with surfactant aerosol in animals with surfactant deficiency or dysfunction, 131,135,153,[155][156][157][158][159][160][161][162][163] although other aerosol studies have been less positive. [164][165][166][167] Several animal studies have directly compared aerosolization to tracheal instillation, and reported that aerosolization can have equal or greater effectiveness, 131,155,159 whereas others have found that instillation is more effective than aerosolization. 131,165,168 An example illustrating the need for further clarity on this issue is the study by Lewis et al 131 In lung-lavaged sheep, exogenous bovine lung extract surfactant was effective when instilled but ineffective when aerosolized, whereas beractant in the same animal model was more effective when aerosolized than when instilled.…”

Section: Animal Studies Of Surfactantmentioning

confidence: 99%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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Since the identification of surfactant deficiency as the putative cause of the infant respiratory distress syndrome (RDS) by Avery and Mead in 1959, our understanding of the role of pulmonary surfactant in respiratory physiology and the pathophysiology of acute lung injury (ALI) has advanced substantially. Surfactant replacement has become routine for the prevention and treatment of infant RDS and other causes of neonatal lung injury. The role of surfactant in lung injury beyond the neonatal period, however, has proven more complex. Relative surfactant deficiency, dysfunction, and inhibition all contribute to the disturbed physiology seen in ALI and acute respiratory distress syndrome (ARDS). Consequently, exogenous surfactant, while a plausible therapy, has proven to be less effective in ALI/ ARDS than in RDS, where simple deficiency is causative. This failure may relate to a number of factors, among them inadequacy of pharmaceutical surfactants, insufficient dosing or drug delivery, poor drug distribution, or simply an inability of the drug to substantially impact the underlying pathophysiology of ALI/ARDS. Both animal and human studies suggest that direct types of ALI (eg, aspiration, pneumonia) may be more responsive to surfactant therapy than indirect lung injury (eg, sepsis, pancreatitis). Animal studies are needed, however, to further clarify aspects of drug composition, timing, delivery, and dosing before additional human trials are pursued, as the results of human trials to date have been inconsistent and largely disappointing. Further study and perhaps the development of more robust pharmaceutical surfactants offer promise that exogenous surfactant will find a place in our armamentarium of treatment of ALI/ARDS in the future. Key words: surfactant; infant respiratory distress syndrome; RDS; acute lung injury; ALI; acute respiratory distress syndrome; ARDS; neonatal. [Respir Care 2011;56(9):1369 -1386.

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“…Delivery of aerosolized SF (SF-aero) might be a useful alternative to tracheal instillation for the treatment of RDS, but experimental and clinical results with this technique remain inconsistent (6)(7)(8)(9)(10)(11)(12)(13). Discrepancies in the results can be attributed to the use of different animal models of lung injury (neonatal RDS vs. adult RDS), aerosol devices (jet vs. ultrasonic), sites for the placement of the aerosol devices (endotracheal tube vs. nasal prong), and SF preparations (natural vs. synthetic), as well as variations in the doses used.…”

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confidence: 99%