Surfactant displacement by meconium free fatty acids: An alternative explanation for atelectasis in meconium aspiration syndrome

Clark, David A.; Nieman, Gary F.; Thompson, Jeffrey E.; Paskanik, Andrew M.; Rokhar, John E.; Bredenberg, Carl E.

doi:10.1016/s0022-3476(87)80021-5

Cited by 139 publications

(65 citation statements)

References 16 publications

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“…Meconium mechanically obstructs airways, causes inflammation, 206 and inhibits the biophysical activity of lung surfactant. 97,207 Auten et al, 196 Khammash et al, 66 and Findlay et al 67 have all reported significant lung-function improvement following exogenous surfactant administration (calfactant, beractant) to infants with meconium aspiration syndrome. The randomized controlled study by Findlay et al 67 also found significant reductions in the incidence of pneumothorax, duration of mechanical ventilation and oxygen therapy, time of hospitalization, and extracorporeal membrane oxygenation (ECMO) requirement in 20 term infants with meconium aspiration syndrome treated with beractant, compared to a similar number of controls.…”

Section: Human Studiesmentioning

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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Section: Human Studiesmentioning

confidence: 99%

The Future of Exogenous Surfactant Therapy

Willson

Notter

2011

Respir Care

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“…Meconium obstructs and injures the lungs when aspirated and is known to cause surfactant dysfunction [56,138]. Auten et al [129], Khammash et al [132], and Findlay et al [133] have all reported significant improvement from surfactant administration in infants with meconium aspiration.…”

Section: Current Studies On Surfactant Replacement Therapy In Patmentioning

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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“…In several in vivo 40,41,69 and in vitro 39 -41 studies, meconium has been shown to inhibit surfactant function in a dose-dependent manner. 41 This inhibition of surfactant function can be overcome with sufficiently high concentrations of surfactant, 39 suggesting that meconium may inhibit surfactant function by competing with surfactant molecules for space at the air-liquid interface.…”

Section: Mas and Surfactantmentioning

confidence: 99%

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

Fuloria

Wiswell

1999

J Perinatol

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The term meconium was originally coined by Aristotle who used the Greek word meconium-arion 1 meaning "opium-like," because he believed meconium induced fetal sleep. It is probable that he recognized the association between the presence of meconium in the amniotic fluid and the occurrence of fetal deaths and neonatal depression.Depending on the population studied, the frequency of meconium-stained amniotic fluid (MSAF) at the time of delivery is variable, ranging between approximately 8% and 19% of all term deliveries. [2][3][4][5][6][7][8] Alexander and colleagues 9 noted a 1.5-fold increased risk for MSAF in black women compared with white women. The authors recommended that maternal ethnicity be viewed as a risk indicator of, and not a causal factor for, MSAF. They also observed an increased likelihood of MSAF with increasing gestational age in both ethnic groups.Regardless of the reason for meconium passage, its presence may be associated with adverse fetal and neonatal outcomes, including death, acute respiratory complications, and long-term pulmonary and neurologic abnormalities. Depending on various factors, including the population studied and the criteria used for making a diagnosis, meconium aspiration syndrome (MAS) will develop in 2% to 33% of infants born through MSAF. 3,4,10,11 As many as 30% or more of infants with MAS require mechanical ventilation. 3,12 Accompanying persistent pulmonary hypertension of the newborn (PPHN) is present in approximately one-third of these infants. 13 The mortality associated with MAS is disturbingly high, ranging from 4% to 19% 3,12,14 ; a large proportion of this mortality is attributable to PPHN.Early-onset neonatal seizures, secondary to hypoxic events, have been reported in infants born through thick MSAF. 15 Berkus et al. 16 observed a sevenfold increased risk of neonatal seizures and a fivefold increased likelihood of hypotonia in infants born through moderate to thick compared with thin meconium-stained or clear amniotic fluid. Some investigators have noted an increased likelihood of cerebral palsy in surviving infants with a low Apgar score who were born through MSAF. 17 In addition, there may be long-term pulmonary sequelae associated with MAS. Yuksel et al. 18 have shown increased functional residual capacity and airway reactivity at 6 months of age in infants with MAS; infants who required more respiratory support in the neonatal period had significantly more symptoms and required bronchodilator therapy more often. MAS has also been implicated in increased airway reactivity and abnormal pulmonary function tests in later childhood. 19,20 PATHOPHYSIOLOGY OF MECONIUM PASSAGEMeconium is a viscous green substance composed primarily of water (72% to 80%). Other components of meconium include gastrointestinal secretions, bile, bile acids, mucus, pancreatic juice, cellular debris, and swallowed amniotic fluid, lanugo, vernix caseosa, and blood. 1,21 The substance may first be noted in the fetal gastrointestinal tract as early as 10 to 16 weeks' gestation. At birt...

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Surfactant displacement by meconium free fatty acids: An alternative explanation for atelectasis in meconium aspiration syndrome

Cited by 139 publications

References 16 publications

The Future of Exogenous Surfactant Therapy

The Future of Exogenous Surfactant Therapy

Surfactant for Pediatric Acute Lung Injury

Resuscitation of the Meconium-Stained Infant and Prevention of Meconium Aspiration Syndrome

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