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Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets.

ABSTRACT: OBJECTIVES:We have setup for the first time a long-term (72?hr) respiratory distress syndrome model in spontaneously breathing surfactant-deficient newborn piglets to investigate the continuous positive airway pressure failure rate with nebulized poractant alfa compared with that with the intubation surfactant extubation technique or continuous positive airway pressure only. DESIGN:Prospective randomized animal study. SETTING:Biocruces-Bizkaia Health Research Institute Animal Facility. SUBJECTS-INTERVENTIONS:Eighteen newborn piglets (n = 6/group) with surfactant-deficient respiratory distress syndrome were randomized to three continuous positive airway pressure-ventilated groups: 1) nebulized surfactant (poractant alfa 400 mg/kg) via a customized investigational eFlow-Neos vibrating membrane nebulizer system, 2) bolus administration using the Intubation Surfactant Extubation method (200 mg/kg), or 3) continuous positive airway pressure alone. MEASUREMENTS AND MAIN RESULTS:Pulmonary and hemodynamic variables were assessed at 6-hour intervals for 72 hours. Lung and brain histological analyses were performed. After bronchoalveolar lavages, piglets developed respiratory distress syndrome. Over the follow-up, both surfactant-treated groups had significantly better pulmonary outcomes than the continuous positive airway pressure alone group. Furthermore, unlike in the continuous positive airway pressure group, there were no cases of respiratory failure in either of the surfactant-treated groups. CONCLUSIONS:In newborn piglets with respiratory distress syndrome, the nebulization of 400?mg/kg of poractant alfa using a customized investigational eFlow-Neos nebulizer was found to be safe and effective in reducing the risk of respiratory failure in the 72 hours after treatment.

SUBMITTER: Rey-Santano C

PROVIDER: S-EPMC7237025 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets.

Rey-Santano Carmen C Mielgo Victoria E VE Gomez-Solaetxe Miguel Angel MA Bianco Federico F Salomone Fabrizio F Loureiro Begoña B

Critical care medicine 20200601 6

<h4>Objectives</h4>We have setup for the first time a long-term (72 hr) respiratory distress syndrome model in spontaneously breathing surfactant-deficient newborn piglets to investigate the continuous positive airway pressure failure rate with nebulized poractant alfa compared with that with the intubation surfactant extubation technique or continuous positive airway pressure only.<h4>Design</h4>Prospective randomized animal study.<h4>Setting</h4>Biocruces-Bizkaia Health Research Institute Anim ...[more]

PMID: 32301841

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Project description:BackgroundThe reductions in mortality levels among children under five years are observed in most populations, including populations that were lagging the progress in the past. However, the reduction is not uniform across ages during childhood. The mortality declines within the first month have shown relatively slow progress. Early initiation of breastfeeding and discarding pre-lacteal feed protects the newborn from acquiring infection and, thereby, reduces mortality. This paper assesses the change in the prevalence of early initiation of breastfeeding and pre-lacteal feed along with their associated factors, and their association with neonatal mortality in India.MethodsWe used data from the three rounds of National Family Health Surveys conducted during 2005-06, 2015-16 and 2019-21 in India. We used bivariate and multivariate analyses to examine prevalence rates, risk factors, and relationships between breastfeeding practices, including early initiation of breastfeeding and pre-lacteal feed, and neonatal mortality.ResultsEarly initiation of breastfeeding within one hour after birth increased rapidly from 25% in 2005-06 to 42% in 2019-21, and the pre-lacteal feeding practice declined from 57% in 2005-06 to 15% in 2019-21. Pre-lacteal feed is lower in states/districts where early breastfeeding initiation is predominant and vice versa. The role of health professionals during pregnancy and the first two days after delivery significantly improved breastfeeding practice. Further, the findings suggest that an early breastfeeding initiation is associated with lower neonatal mortality, whereas pre-lacteal feed is not harmful compared to late breastfeeding initiation.ConclusionPrevalence of pre-lacteal feed reduced, and initiation of early breastfeeding increased considerably after the launch of the National Rural Health Mission in India. However, after 2015-16, early breastfeeding initiation has stagnated, and the decline in pre-lacteal feed has slowed down. The future program needs special attention to emphasize the availability and accessibility of breastfeeding advisers and observers in health facilities to help mitigate adverse neonatal outcomes.

Project description:ObjectivesTo compare the efficacy and safety of poractant alfa and bovine lipid extract surfactant in preterm infants.Study designRandomized, partially-blinded, multicenter trial. Infants <32 weeks needing surfactant before 48 hours were randomly assigned to receive poractant alfa or bovine lipid extract surfactant. The primary outcome was being alive and extubated at 48 hours post-randomization. Secondary outcomes included need for re-dosing, duration of respiratory support and oxygen, bronchopulmonary dysplasia, mortality and complications during administration.ResultsThree centers recruited 87 infants (mean 26.7 weeks and 906 grams) at a mean age of 5.9 hours, between March 2013 and December 2015. 21/42 (50%) were alive and extubated at 48 hours in the poractant alfa group vs 26/45 (57.8%) in the bovine lipid extract surfactant group; adjusted OR 0.76 (95% CI 0.30-1.93) (p = 0.56). No differences were observed in the need to re-dose. Duration of oxygen support (41.5 vs 62 days; adjusted OR 1.69 95% CI 1.02-2.80; p = 0.04) was reduced in infants who received poractant alfa. We observed a trend in bronchopulmonary dysplasia among survivors (51.5% vs 72.1%; adjusted OR 0.35 95%CI 0.12-1.04; p = 0.06) favoring poractant alfa. Twelve infants died before discharge, 9 in the poractant alfa group and 3 in the bovine lung extract group. Severe airway obstruction following administration was observed in 0 (poractant alfa) and 5 (bovine lipid extract surfactant) infants (adjusted OR 0.09 95%CI <0.01-1.27; p = 0.07).ConclusionNo statistically significant difference was observed in the proportion of infants alive and extubated within 48h between the two study groups. Poractant alfa may be more beneficial and associated with fewer complications than bovine lipid extract surfactant. However, we observed a trend towards higher mortality in the poractant alfa group. Larger studies are needed to determine whether observed possible benefits translate in shorter hospital admissions, or other long term benefits and determine whether there is a difference in mortality.

Project description:Poractant alfa and Calsurf are two natural surfactants widely used in China for the treatment of neonatal respiratory distress syndrome, which are extracted from porcine and calf lungs, respectively. The purpose of this experimental study was to compare their in vitro characteristics and in vivo effects in the improvement of pulmonary function and protection of lung injury. The biophysical properties, ultrastructure, and lipid composition of both surfactant preparations were respectively analysed in vitro by means of Langmuir-Blodgett trough (LBT), atomic force microscopy (AFM), and liquid-chromatography mass-spectrometry (LC-MS). Then, as core pharmacological activity, both head-to-head (100 and 200 mg/kg for both surfactants) and licensed dose comparisons (70 mg/kg Calsurf vs. 200 mg/kg Poractant alfa) between the two surfactants were conducted as prophylaxis in preterm rabbits with primary surfactant deficiency, assessing survival time and rate and dynamic compliance of the respiratory system (Cdyn). Intrapulmonary surfactant pools, morphometric volume density as alveolar expansion (Vv), and lung injury scores were determined post mortem. AFM and LC-MS analysis revealed qualitative differences in the ultrastructure as well as in the lipid composition of both preparations. Calsurf showed a longer plateau region of the LBT isotherm and lower film compressibility. In vivo, both surfactant preparations improved Cdyn at any dose, although maximum benefits in terms of Vv and intrapulmonary surfactant pools were seen with the 200 mg/kg dose in both surfactants. The group of animals treated with 200 mg/kg of Poractant alfa showed a prolonged survival time and rate compared to untreated but ventilated controls, and significantly ameliorated lung injury compared to Calsurf at any dose, including 200 mg/kg. The overall outcomes suggest the pulmonary effects to be dose dependent for both preparations. The group of animals treated with 200 mg/kg of Poractant alfa showed a significant reduction of mortality. Compared to Calsurf, Poractant alfa exerted better effects if licensed doses were compared, which requires further investigation.

Project description:ObjectivesEffective treatment options for surfactant therapy in acute respiratory distress syndrome and coronavirus disease 2019 have not been established. To conduct preclinical studies in vitro and in vivo to evaluate efficiency, particle size, dosing, safety, and efficacy of inhaled surfactant using a breath-synchronized, nebulized delivery system in an established acute respiratory distress syndrome model.DesignPreclinical study.SettingResearch laboratory.SubjectsAnesthetized pigs.InterventionIn vitro analysis included particle size distribution and inhaled dose during simulated ventilation using a novel breath-synchronized nebulizer. Physiologic effects of inhaled aerosolized surfactant (treatment) were compared with aerosolized normal saline (control) in an adult porcine model (weight of 34.3 ± 0.6 kg) of severe acute respiratory distress syndrome (Pao2/Fio2 <100) with lung lavages and ventilator-induced lung injury during invasive ventilation.Measurements and main resultsMass median aerosol diameter was 2.8 µm. In vitro dose delivered distal to the endotracheal tube during mechanical ventilation was 85% ± 5%. Nebulizers were functional up to 20 doses of 108 mg of surfactant. Surfactant-treated animals (n = 4) exhibited rapid improvement in oxygenation with nearly full recovery of Pao2/Fio2 (~300) and end-expiratory lung volumes with nominal dose less than 30 mg/kg of surfactant, whereas control subjects (n = 3) maintained Pao2/Fio2 less than 100 over 4.5 hours with reduced end-expiratory lung volume. There was notably greater surfactant phospholipid content and lower indicators of lung inflammation and pathologic lung injury in surfactant-treated pigs than controls. There were no peridosing complications associated with nebulized surfactant, but surfactant-treated animals had progressively higher airway resistance post treatment than controls with no differences in ventilation effects between the two groups.ConclusionsBreath-synchronized, nebulized bovine surfactant appears to be a safe and feasible treatment option for use in coronavirus disease 2019 and other severe forms of acute respiratory distress syndrome.

Dataset Information

Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets.

Publications

Nebulized Poractant Alfa Reduces the Risk of Respiratory Failure at 72 Hours in Spontaneously Breathing Surfactant-Deficient Newborn Piglets.

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