Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs

Nieman, Gary F.; Gatto, Louis A.; Paskanik, Andrew M.; Yang, Bennett; Fluck, R. R.; Picone, Anthony

doi:10.1097/00003246-199606000-00024

Cited by 40 publications

(23 citation statements)

References 29 publications

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“…Injury from oleic acid infusion via the pulmonary artery shows almost no improvement with surfactant, 150 although many would argue that this is a lethal injury with substantial cellular disruption 151 that is unlikely to respond to any therapy. A porcine sepsis model that used intravenous lipopolysaccharide infusion showed some oxygenation improvement following surfactant administration, 152,153 but the response was less striking than in the surfactant-treated animals injured with intratracheal lipopolysaccharide above. 146,147 It is notable that the different responses to surfactant between direct and indirect lung injury in animals resemble the response pattern seen in humans; analysis of 2 trials found that direct pulmonary ALI/ARDS is impacted most beneficially by surfactant therapy.…”

Section: Animal Studies Of Surfactantmentioning

confidence: 96%

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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Section: Animal Studies Of Surfactantmentioning

confidence: 96%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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“…in, such as Salmonella enteritidis [42] , are also used occasionally. In pigs and sheep, a dosage of 1-100 g/kg of LPS is diluted in normal saline and infused intravenously over a half hour to several hours [39][40][41][43][44][45][46][47] . In dogs, due to their tolerance to endotoxin, extremely high doses of endotoxin ( 1 1 mg/kg) are routinely needed to induce this model [48,49] .…”

Section: Oai Modelmentioning

confidence: 99%

Overview of the Pathology of Three Widely Used Animal Models of Acute Lung Injury

Wang

Bodenstein²,

Markstaller³

2008

Eur Surg Res

152

140

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Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute diffuse damage to the pulmonary parenchyma by a variety of local or systemic insults. Increased alveolar capillary membrane permeability was recognized as the common end organ injury and a central feature in all forms of ALI/ARDS. Although great strides have been made in understanding the pathogenesis of ALI/ARDS and in intensive care medicine, the treatment approach to ARDS is still relying on ventilatory and cardiovascular support based on the recognition of the clinical picture. In the course of evaluating novel treatment approaches to ARDS, 3 models of ALI induced in different species, i.e. the surfactant washout lavage model, the oleic acid intravenous injection model and the endotoxin injection model, were widely used. This review gives an overview of the pathological characteristics of these models from studies in pigs, dogs or sheep. We believe that a good morphological description of these models, both spatially and temporally, will help us gain a better understanding of the real pathophysiological picture and apply these models more accurately and liberally in evaluating novel treatment approaches to ARDS.

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“…Aspiration of acid [82][83][84]or meconium [85][86][87][88] Anti-lung serum infusion [89] Bacterial or endotoxin-induced injury [90][91][92][93][94][95] Bilateral vagotomy [96] Hyperoxic lung injury [97][98][99][100][101] In vivo lung lavage with mechanical ventilation [102][103][104][105][106][107] NNNMU-induced lung injury [108][109][110] Viral pneumonia [111,112] NNNMU is N-nitroso-N-methylurethane. See text for discussion.…”

Section: Summary and Future Prospects For Surfactant Therapy In Amentioning

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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Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs

Cited by 40 publications

References 29 publications

The Future of Exogenous Surfactant Therapy

The Future of Exogenous Surfactant Therapy

Overview of the Pathology of Three Widely Used Animal Models of Acute Lung Injury

Surfactant for Pediatric Acute Lung Injury

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