Abstract
Despite great advances in mechanical ventilation and surfactant administration for the newborn infant with life-threatening respiratory failure no specific therapies are currently established to tackle major pro-inflammatory pathways. The susceptibility of the newborn infant with neonatal acute respiratory distress syndrome (NARDS) to exogenous surfactant is linked with a suppression of most of the immunologic responses by the innate immune system, however, additional corticosteroids applied in any severe pediatric lung disease with inflammatory background do not reduce morbidity or mortality and may even cause harm. Thus, the neonatal piglet model of acute lung injury serves as an excellent model to study respiratory failure and is the preferred animal model for reasons of availability, body size, similarities of porcine and human lung, robustness, and costs. In addition, similarities to the human toll-like receptor 4, the existence of intraalveolar macrophages, the sensitivity to lipopolysaccharide, and the production of nitric oxide make the piglet indispensable in anti-inflammatory research. Here we present the physiologic and immunologic data of newborn piglets from three trials involving acute lung injury secondary to repeated airway lavage (and others), mechanical ventilation, and a specific anti-inflammatory intervention via the intratracheal route using surfactant as a carrier substance. The physiologic data from many organ systems of the newborn piglet—but with preference on the lung—are presented here differentiating between baseline data from the uninjured piglet, the impact of acute lung injury on various parameters (24 h), and the follow up data after 72 h of mechanical ventilation. Data from the control group and the intervention groups are listed separately or combined. A systematic review of the newborn piglet meconium aspiration model and the repeated airway lavage model is finally presented. While many studies assessed lung injury scores, leukocyte infiltration, and protein/cytokine concentrations in bronchoalveolar fluid, a systematic approach to tackle major upstream pro-inflammatory pathways of the innate immune system is still in the fledgling stages. For the sake of newborn infants with life-threatening NARDS the newborn piglet model still is an unsettled promise offering many options to conquer neonatal physiology/immunology and to establish potent treatment modalities.
Highlights
Respiratory failure is the leading cause of morbidity and mortality in newborn infants regardless of gestational age
As sufficient analgesia is paramount in any model opioids should be used for instrumentation and for all kinds of painful procedures, for long time sedation and analgesia ketamine seems to be more apt because of its positive inotropic effect even in the presence of muscular blockade
The combined effects of the triple-hit lung injury protocol on cardiovascular parameters are shown in Table 1 covering a time window of 72 h (Spengler et al, 2018)
Summary
Respiratory failure is the leading cause of morbidity and mortality in newborn infants regardless of gestational age. Respiratory failure of the term infant secondary to obvious damage of the lungs in the perinatal period, such as meconium, bile, and blood aspiration, lung hemorrhage, pneumonia, or severe chorioamnionitis and sepsis, leading to secondary impairment of surfactant function and surfactant amount, has not been officially defined before 2017 when the Montreux definition of neonatal ARDS (NARDS) was published (De Luca et al, 2017). The Montreux definition of NARDS requires the following clinical conditions: respiratory failure of acute onset; exclusion of IRDS, transient tachypnea of the newborn (TTN), and congenital malformations of the lung; diffuse, bilateral, and irregular opacities or infiltrates by chest-Xray; lung edema of non-cardiac origin; and an oxygenation deficit expressed by the oxygenation index (OI = MAP ∗ %O2/PaO2, with MAP = mean airway pressure) being mild (OI 4–8), moderate (OI 8–16), or severe (OI > 16)
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