New Surfactant with SP-B and C Analogs Gives Survival Benefit after Inactivation in Preterm Lambs

Schumacher, Matthias; Collins, Jennifer J. P.; Kuypers, Elke; Jellema, Reint K.; Ophelders, Daan; Ospina, Olga L.; Pérez‐Gil, Jesús; Bianco, Federico; Garzia, Raffaella; Razzetti, Roberta; Kramer, Boris W.

doi:10.1371/journal.pone.0047631

Cited by 80 publications

(69 citation statements)

References 36 publications

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“…Lambs were operatively delivered prematurely at a gestational age of 128-132 d (term ~150 d) via a modified EXIT procedure, equipped with umbilical artery and vein catheters and intubated orally with a cuffed tube (41). The arterial catheter was used to monitor heart rate and blood pressure, and to frequently obtain blood for blood gas analysis.…”

Section: Resuscitationmentioning

confidence: 99%

Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs

et al. 2015

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Articles Translational Investigation nature publishing groupBackground: Hyperoxia and hypoxia influence morbidity and mortality of preterm infants. Automated closed-loop control of the fraction of inspired oxygen (FiO 2 ) has been shown to facilitate oxygen supplementation in the neonatal intensive care unit (NICU), but has not yet been tested during preterm resuscitation. We hypothesized that fully automated FiO 2 control based on predefined oxygen saturation (SpO 2 ) targets was applicable in both preterm resuscitation and ventilation. Methods: Twenty-two preterm lambs were operatively delivered and intubated in a modified EXIT procedure. They were randomized to receive standardized resuscitation with either automated or manual FiO 2 control, targeting SpO 2 according to the Dawson curve in the first 10 min and SpO 2 90-95% hereafter. Automated FiO 2 control also was applied during surfactant replacement therapy and subsequent ventilation. results: Time within target range did not differ significantly between manual and automated FiO 2 control during resuscitation, however automated FiO 2 control significantly avoided hyperoxia. Automated FiO 2 control was feasible during surfactant replacement and kept SpO 2 within target range significantly better than manual control during subsequent ventilation. conclusion: In our model, fully automated FiO 2 control was feasible in rapidly changing physiologic conditions during postnatal resuscitation and prevented hyperoxia. We conclude that closed loop FiO 2 control is a promising tool for the delivery room.o xygen supplementation is one of the most common therapeutic interventions in resuscitation and neonatal intensive care of term and preterm infants (1). However, both hypoxia and hyperoxia must be avoided because of their detrimental effects on morbidity and mortality in these children. While hypoxia may lead to direct and indirect cellular damage, hyperoxia has been associated with oxygen toxicity, oxidative stress (2), and chronic diseases of preterm infants such as bronchopulmonary dysplasia (3) and retinopathy of prematurity (4).Increase in oxygenation after birth is a gradual process (5). Measurement of oxygen saturation (SpO 2 ) by pulse oximetry in the delivery room is feasible in newborn resuscitation (6) and in preterm infants within the first minutes of life (7). SpO 2 reference values of preterm infants increase within the first 10 min of life (5). This has led to SpO 2 target values incorporated in the current European Resuscitation Council guidelines on resuscitation of newborns (8). In order to avoid hyperoxia, current recommendations advise resuscitation of preterm infants with a mixture of air and oxygen, and to use fraction of inspired oxygen (FiO 2 ) between 0.21 and 0.30 (9). FiO 2 should subsequently be titrated according to SpO 2 (10,11). General use of pulse oximetry has been shown to extensively reduce O 2 -derived toxicity in preterm infants (12). However, keeping SpO 2 manually within changing saturation limits during a hectic period of resu...

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Section: Resuscitationmentioning

confidence: 99%

Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs

et al. 2015

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“…From the lambs that received surfactant, the thorax was opened by a midline incision as previously described (24). An endotracheal tube was inserted when necessary and connected to a manometer.…”

Section: Postmortem Analysismentioning

confidence: 99%

Effects of less-invasive surfactant administration on oxygenation, pulmonary surfactant distribution, and lung compliance in spontaneously breathing preterm lambs

et al. 2014

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Background: A new technique was proposed to administer surfactant to spontaneous breathing preterm infants by placing a thin catheter through the vocal cords. This technique was not studied with respect to oxygenation, gas exchange, surfactant distribution, and lung mechanics. We tested the technique of less-invasive surfactant administration (LISA) in a spontaneous breathing preterm lamb model. Methods: Preterm lambs (n = 12) of 133-134 d gestational age were randomized to the following three groups: (i) continuous positive airway pressure (CPAP) only, (ii) CPAP + LISA, and (iii) intubation and mechanical ventilation with surfactant administration. Surfactant was labeled with samarium oxide. During the next 180 min, blood gas analyses were performed. Postmortem, lungs were removed and surfactant distribution was assessed, and pressure-volume curves were performed. results: Pao 2 in the LISA-treated lambs was significantly higher than in the lambs that exclusively received CPAP. Moreover, Pao 2 values were similar between the LISA-treated and the intubated lambs. Overall, surfactant deposition was less in the LISA lambs, with significantly less surfactant distributed to the right upper lobe. Lung compliance was better in the intubated lambs compared with the LISA-treated lambs, although this did not reach significance. conclusion: LISA improved oxygenation, similar to conventional surfactant application techniques, despite lower surfactant deposition and lung compliance.i n the past decades, preterm infants have been treated with surfactant bolus replacement therapy for respiratory distress syndrome, which usually requires intubation and mechanical ventilation. Surfactant treatment in ventilated infants leads to a relative reduction in bronchopulmonary dysplasia, pneumothorax, and mortality (1,2). Randomized trials indicated that early surfactant therapy compared to delayed rescue surfactant treatment resulted in better respiratory and neurologic outcomes in preterm infants (3).Early surfactant treatment has therefore been combined with intubation and mechanical ventilation. Intubation of the trachea may lead to laryngeal or tracheal injury and requires premedication, which can delay the time to extubation. In addition, mechanical ventilation can damage the vulnerable preterm lungs. It has been hypothesized that avoidance of mechanical ventilation might lead to less bronchopulmonary dysplasia (4,5), as infants that failed initial continuous positive airway pressure (CPAP) therapy and needed subsequent mechanical ventilation showed higher bronchopulmonary dysplasia rates (6).In order to avoid the negative effects of mechanical ventilation, a new technique was recently introduced to administer surfactant endotracheally to spontaneously breathing preterm infants by placing a small feeding or arterial catheter through the vocal cords (7,8). This technique proved to be feasible in clinical practice with first attempt success rate above 80% (8-10). This technique was referred to as minimally invasive surfactant therap...

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“…Individual lung lobes were prepared and weighed. Selective bronchoalveolar lavages (BAL) of each lung lobe were performed with NaCl 0.9% as described (23).…”

Section: Methodsmentioning

confidence: 99%

Amplification of steroid-mediated SP-B expression by physiological levels of caffeine

Fehrholz¹,

Hütten

Kramer

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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Factors positively influencing surfactant homeostasis in general and surfactant protein B (SP-B) expression in particular are considered of clinical importance regarding an improvement of lung function in preterm infants. The objective of this study was to identify effects of physiological levels of caffeine on glucocorticoid-mediated SP-B expression in vitro and in vivo. Levels of SP-B and pepsinogen C were quantified by quantitative real-time RT-PCR or immunoblotting in NCI-H441 cells daily exposed to caffeine and/or dexamethasone (DEX). In vivo, SP-B expression was analyzed in bronchoalveolar lavage (BAL) of preterm sheep exposed to antenatal DEX and/or postnatal caffeine. If DEX and caffeine were continuously present, SP-B mRNA and protein levels were increased for up to 6 days after induction (P Ͻ 0.05). Additionally, caffeine enhanced SP-B mRNA expression in DEX-pretreated cells (P Ͻ 0.05). Moreover, caffeine amplified DEXinduced pepsinogen C mRNA expression (P Ͻ 0.05). After short-term treatment with caffeine in vivo, only slightly higher SP-B levels could be detected in BAL of preterm sheep following antenatal DEX, combined with an increase of arterial oxygen partial pressure (P Ͻ 0.01). Our data demonstrated that the continuous presence of caffeine in vitro is able to amplify DEX-mediated SP-B expression. In contrast, short-term improvement of lung function in vivo is likely to be independent of altered SP-B transcription and translation. An impact of caffeine on release of surfactant reservoirs from lamellar bodies could, however, quickly affect SP-B content in BAL, which has to be further investigated. Our findings indicate that caffeine is able to amplify main effects of glucocorticoids that result from changes in surfactant production, maturation, and release.

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New Surfactant with SP-B and C Analogs Gives Survival Benefit after Inactivation in Preterm Lambs

Cited by 80 publications

References 36 publications

Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs

Fully automated predictive intelligent control of oxygenation (PRICO) in resuscitation and ventilation of preterm lambs

Effects of less-invasive surfactant administration on oxygenation, pulmonary surfactant distribution, and lung compliance in spontaneously breathing preterm lambs

Amplification of steroid-mediated SP-B expression by physiological levels of caffeine

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