Bond Strength to Lithium-Disilicate Ceramic after Different Surface Cleaning Approaches.

PURPOSE: To evaluate the effect of different lithium-disilicate (LiSi) glass-ceramic surface decontamination procedures on the shear bond strength (SBS) to resin cement. MATERIALS AND METHODS: Seventy CAD/CAM LiSi ceramic specimens (IPS e.max CAD, Ivoclar) were cut and sintered. Fifty specimens were treated with 5% hydrofluoric acid (HF) for 20 s, while 20 were left untreated. All 70 specimens were then contaminated with human saliva and try-in silicone paste. The following surface cleaning methods were investigated (n = 10): C: water rinsing (control); PA: 37% H3PO4 etching for 20 s; E: 70% ethanol applied for 20 s; CP: cleaning paste (Ivoclean, Ivoclar) brushed for 20 s; HFSEP: self-etching ceramic primer (Monobond Etch&Prime, Ivoclar) rubbed for 20 s; HF: 5% HF applied for 20 s or no HF etching prior to contamination; SEP: self-etching ceramic primer rubbed for 20 s and no HF etching prior to contamination. Composite cylinders were created and luted with an adhesive resin cement to the decontaminated surfaces. After storage for 24 h at 37°C, the SBS test was conducted. Two fractured specimens per group were observed under SEM to perform fractographic analysis. The data were statistically analyzed with p set at <0.05. RESULTS: The type of surface cleaning approach influenced bond strength (p < 0.001). HFSEP, SEP, and HF attained higher SBS (p < 0.001) compared to other groups. None of the approaches were able to completely remove contaminants from the ceramic surfaces. SEM images showed residual traces of contaminants on CP-treated surfaces. CONCLUSIONS: The self-etching ceramic primer enhanced bond strength to contaminated LiSi ceramic surfaces, irrespective of previous treatment with hydrofluoric acid.

Selective adhesive luting: A novel technique for improving adhesion achieved by universal resin cements.

OBJECTIVE: We aimed to introduce the concept of "Selective adhesive luting-SAL" which is explained through clinical steps and supported by preliminary laboratory evidence. CLINICAL CONSIDERATIONS: Cementation with rubber dam is difficult to perform in case of short abutment teeth and/or subgingival crown margins. By means of universal resin cements/universal adhesive systems, which can be employed in self-adhesive as well as adhesive luting procedures, this paper presents a novel technique allowing clinicians to perform reliable cementation where rubber dam isolation is difficult. The SAL technique entails the application of a universal adhesive system only on easily accessible abutment surfaces, enabling simultaneous adhesive and self-adhesive luting in different portions of the abutment. The SAL clinical workflow is explained through prosthodontic rehabilitation of maxillary right central incisor affected by microdontia and restored with a lithium-disilicate crown. Furthermore, our laboratory microshear bond strength study supports the rationale behind SAL application demonstrating higher bond strength even when the adhesive resin is placed only on one portion of the cementation substrate. CLINICAL SIGNIFICANCE: This article advocates the application of SAL technique in clinical situations where effective adhesive luting is uncertain, since it can improve the adhesion between the tooth and universal resin cements.

Resin composite cements: Current status and a novel classification proposal.

OBJECTIVES: Currently, a classification of resin cements that includes relatively recently formulated ("universal") cements is lacking. Furthermore, the terminology used to define different resin cements in the scientific reports is inconsistent. Accordingly, this work aims to: (i) propose a novel classification of resin composite cements; (ii) disambiguate the term "universal cements" and (iii) present an overview of the properties of these cements. METHODS: An analysis of peer-reviewed literature (PubMed search), as well as market research on definitive resin composite cements were performed. RESULTS: A tendency toward simplified and versatile luting materials was observed both in the scientific literature and on the dental market with the advent of self-adhesive/one-step resin cements. However, additional priming procedures were necessary to improve their bonding performance in certain clinical situations. Hence, several cements that can be applied both in adhesive and self-adhesive mode were introduced. These cements are associated with a universal adhesive resin, that can be used as a tooth and/or restorative material primer, without the need for other priming systems, regardless of the substrate. These systems should be considered truly universal. Therefore, we hereby suggested a new classification of resin-based cements: (1) adhesive/multi-step; (2) self-adhesive/one-step; (3) universal cements (one- or multi-step). Despite promising in vitro results, clinical trials and long-track laboratory studies are necessary to confirm the reliability of the universal cements. CONCLUSIONS: This review presented the current advances in the field of resin-based cements, which are reflected in the proposed classification. The term "universal cement" was disambiguated, which will help standardize the terminology used in published research. CLINICAL SIGNIFICANCE: The classification of resin-based cements and a better understanding of the proper terminology will help standardize the terminology in published research, as well as improve the understanding of the clinical practitioners of the different indications and possible modalities of use of the available cements.

Differential Performance and Lung Deposition of Levofloxacin with Different Nebulisers Used in Cystic Fibrosis.

We compared the performance and levofloxacin (Quinsair) lung deposition of three nebulisers commonly used in CF (I-Neb Advance, eFlow rapid, and LC Plus) with the approved nebuliser Zirela. The delivered dose, delivery rate, and aerosol particle size distribution (APSD) for each device were determined using the methods described in the Pharmacopeia. High-resolution computed tomography scans obtained from seven adult patients with mild CF were used to generate computer-aided, three-dimensional models of their airway tree to assess lung deposition using functional respiratory imaging (FRI). The eFlow rapid and the LC Plus showed poor delivery efficiencies due to their high residual volumes. The I-Neb, which only delivers aerosols during the inspiratory phase, achieved the highest aerosol delivery efficiency. However, the I-Neb showed the largest particle size and lowest delivery rate (2.9 mg/min), which were respectively associated with a high extrathoracic deposition and extremely long nebulisation times (>20 min). Zirela showed the best performance considering delivery efficiency (159.6 mg out of a nominal dose of 240 mg), delivery rate (43.5 mg/min), and lung deposition (20% of the nominal dose), requiring less than 5 min to deliver a full dose of levofloxacin. The present study supports the use of drug-specific nebulisers and discourages the off-label use of general-purpose devices with the present levofloxacin formulation since subtherapeutic lung doses and long nebulisation times may compromise treatment efficacy and adherence.

Preclinical Assessment of Nebulized Surfactant Delivered through Neonatal High Flow Nasal Cannula Respiratory Support.

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

Nebulization of High-Dose Poractant Alfa in Newborn Piglets on Nasal Continuous Positive Airway Pressure Yields Therapeutic Lung Doses of Phospholipids.

OBJECTIVE: It is not known how much surfactant must be nebulized to reach a lung dose of phospholipids equivalent to that obtained by the instillation of 200 mg/kg of surfactant. We aimed to assess the feasibility of nebulizing a high-dose of poractant alfa with the eFlow-Neos investigational vibrating-membrane nebulizer in newborn piglets on nasal continuous positive airway pressure (nCPAP) and to determine whether this intervention would yield therapeutic lung doses of phospholipids. STUDY DESIGN: Twelve 1-day-old piglets on nCPAP received 600 mg/kg of poractant alfa admixed with technetium-99m via nebulization. Six piglets receiving 200 mg/kg of instilled synthetic surfactant served as controls. Lung deposition (percentage of the nominal dose) was determined by gamma scintigraphy, and the phospholipids' lung dose was calculated. RESULTS: The lung dose of phospholipids (mean ± standard deviation [SD]) was 138 ± 96 mg/kg with nebulization, and 172 ± 24 mg/kg with instillation (p = 0.42). Nebulization took 58 ± 12 minutes. The arterial partial pressure of carbon dioxide increased from 6.7 ± 1.1 to 7.2 ± 1.1 kPa during nebulization (p = 0.04). Cerebral oximetry remained stable, and there was no hemodynamic instability. CONCLUSION: Nebulization was well tolerated, and the mean lung dose of phospholipids was above 100 mg/kg, that is, not different from the instillation group. These experimental findings suggest that it may be feasible to reach therapeutic lung doses of phospholipids by surfactant nebulization during nCPAP. KEY POINTS: · It is not known if effective lung doses of surfactant can be delivered by nebulization.. · Nebulization of high-dose surfactant in newborn piglets on nCPAP was well tolerated.. · A high-dose of nebulized poractant alfa yielded therapeutic lung doses of phospholipids..

Deposition of Inhaled Levofloxacin in Cystic Fibrosis Lungs Assessed by Functional Respiratory Imaging.

Pulmonary infections caused by Pseudomonas aeruginosa (PA) represent the leading cause of pulmonary morbidity in adults with cystic fibrosis (CF). In addition to tobramycin, colistin, and aztreonam, levofloxacin has been approved in Europe to treat PA infections. Nevertheless, no lung deposition data on inhaled levofloxacin are yet available. We conducted a Functional Respiratory Imaging (FRI) study to predict the lung deposition of levofloxacin in the lungs of patients with CF. Three-dimensional airway models were digitally reconstructed from twenty high-resolution computed tomography scans obtained from historical patients' records. Levofloxacin aerosols generated with the corresponding approved nebuliser were characterised according to pharmacopeia. The obtained data were used to inform a computational fluid dynamics simulation of levofloxacin lung deposition using breathing patterns averaged from actual CF patients' spirometry data. Levofloxacin deposition in the lung periphery was significantly reduced by breathing patterns with low inspiratory times and high inspiratory flow rates. The intrathoracic levofloxacin deposition percentages for moderate and mild CF lungs were, respectively, 37.0% ± 13.6 and 39.5% ± 12.9 of the nominal dose. A significant albeit modest correlation was found between the central-to-peripheral deposition (C/P) ratio of levofloxacin and FEV1. FRI analysis also detected structural differences between mild and moderate CF airways. FRI revealed a significant intrathoracic deposition of levofloxacin aerosols, which distributed preferentially to the lower lung lobes, with an influence of the deterioration of FEV1 on the C/P ratio. The three-dimensional rendering of CF airways also detected structural differences between the airways of patients with mild and moderate CF.

Lung Deposition of Surfactant Delivered via a Dedicated Laryngeal Mask Airway in Piglets.

It is unknown if the lung deposition of surfactant administered via a catheter placed through a laryngeal mask airway (LMA) is equivalent to that obtained by bolus instillation through an endotracheal tube. We compare the lung deposition of surfactant delivered via two types of LMA with the standard technique of endotracheal instillation. 25 newborn piglets on continuous positive airway pressure support (CPAP) were randomized into three groups: 1-LMA-camera (integrated camera and catheter channel; catheter tip below vocal cords), 2-LMA-standard (no camera, no channel; catheter tip above the glottis), 3-InSurE (Intubation, Surfactant administration, Extubation; catheter tip below end of endotracheal tube). All animals received 100 mg·kg-1 of poractant alfa mixed with 99mTechnetium-nanocolloid. Surfactant deposition was measured by gamma scintigraphy as a percentage of the administered dose. The median (range) total lung surfactant deposition was 68% (10-85), 41% (5-88), and 88% (67-92) in LMA-camera, LMA-standard, and InSurE, respectively, which was higher (p < 0.05) in the latter. The deposition in the stomach and nasopharynx was higher with the LMA-standard. The surfactant deposition via an LMA was lower than that obtained with InSurE. Although not statistically significant, introducing the catheter below the vocal cords under visual control with an integrated camera improved surfactant LMA delivery by 65%.

Is clinical behavior of composite restorations placed in non-carious cervical lesions influenced by the application mode of universal adhesives? A systematic review and meta-analysis.

OBJECTIVE: To answer the following PICOS question: "Is the risk of retention loss, marginal discoloration, marginal adaptation and postoperative sensitivity (POS) equal for etch-and-rinse (EAR) compared to self-etch (SE) or selective-enamel etch (SEE) mode when restoring non carious cervical lesions (NCCLs) with universal adhesives?". METHODS: PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Scientific Electronic Library Online, LILACS, OpenGrey and Google Scholar™ were searched. Randomized controlled clinical trials in which resin composites and universal adhesives were used for restoration of NCCLs were considered. Cochrane Risk of Bias Tool was used to assess the risk of bias. Meta-analyses were performed using Revman; random-effects models were applied, and heterogeneity was tested using the I2 index. The significance level was set at p < 0.05. Certainty of evidence was assessed by GRADE tool. RESULTS: After screening, 20 articles were included in qualitative, while 14 articles were used for quantitative synthesis. Twelve studies ranked as "low", while 8 studies scored as "unclear" for risk of bias. At 12- and 18/24-months the risk for retention loss was higher for SE than for EAR groups (p = 0.005; RR = 0.22, 95% CI [0.08, 0.63],[moderate certainty of evidence and p = 0.0002; RR = 0.32, 95% CI [0.17, 0.58], moderate certainty of evidence, respectively). No significant differences were observed for marginal discoloration and adaptation (p > 0.05). The probability of POS occurrence was less in SE than in EAR groups (RR = 2.12, 95% CI [1.23, 3.64], moderate certainty of evidence). The certainty of evidence for other outcomes was scored as "low" or "moderate", depending on the follow-up period. SIGNIFICANCE: Using universal adhesives in EAR or SEE mode provides more predictable retention, while SE strategy reduces the risk of POS occurrence.

Surfactant nebulization therapy during NIPPV ventilation in surfactant-deficient newborn piglets.

BACKGROUND: In recent years, nasal intermittent positive pressure ventilation (NIPPV) has been growing in popularity as a form of noninvasive ventilation for respiratory support in the initial treatment of neonates with surfactant (SF) deficiency. The combination of this type of ventilation with noninvasive SF administration (by nebulization) is an attractive treatment option for respiratory distress syndrome (RDS)-associated pathophysiology of the neonatal lungs. In this study, we aimed to test the tolerability and efficacy of SF nebulization during NIPPV for the treatment of neonatal RDS. METHODS: Spontaneously-breathing newborn piglets (n = 6/group) with bronchoalveolar lavage (BAL)-induced RDS were assigned to receive during NIPPV (180 min): poractant alfa (400 mg/kg) via an investigational customized vibrating-membrane nebulizer (eFlow-Neos) or poractant alfa (200 mg/kg) as a bolus using the Insure method or no surfactant (controls). MEASUREMENT AND RESULTS: We assessed pulmonary, hemodynamic and cerebral effects and performed histological analysis of lung and brain tissue. After repeated BAL, newborn piglets developed severe RDS (FiO2 : 1, pH < 7.2, PaCO2 > 70 mmHg, PaO2 < 70 mmHg, Cdyn < 0.5 ml/cmH2 O/kg). In both SF-treated groups, we observed rapid improvement in pulmonary status and also similar hemodynamic, cerebral behavior, and lung and brain injury scores. CONCLUSION: Our results in newborn piglets with severe BAL-induced RDS show the administration of nebulized poractant alfa using the eFlow-Neos nebulizer during NIPPV to be well tolerated and efficacious, suggesting that this noninvasive SF administration option should be explored further.

Bonding to dentin using an experimental zirconium oxynitrate etchant.

OBJECTIVE: To investigate, by means of microtensile bond strength test (µTBS), nanoleakage expression analysis (NL), gelatin zymography and in situ zymography, the effects of an experimental metal salt-based zirconium oxynitrate etchant [ZrO(NO3)2,] - ZON with two simplified adhesives on long-term bond strength and endogenous enzymatic activities. METHODS: Middle/deep coronal dentin surfaces (N = 32) were conditioned either with a traditional 37 % H3PO4 etchant (TE) or with ZON. Further, a single-component etch-and-rinse adhesive (EF) or a universal adhesive (AU) were applied and µTBS and NL tests were performed. Additional freshly extracted teeth were processed for gelatin zymography and in situ zymography evaluation. The tests were performed at baseline and (T0) and after 1-year-aging (T12). Bond strength and in situ zymography results were analyzed using analysis of variance (ANOVA) (three-way and one-way, respectively), while Chi-squared test was used for the NL results. Statistical significance was preset at α = 0.05. RESULTS: All the investigated factors (adhesive system, dentin conditioner and aging) significantly influenced µTBS, with the AU and ZON performing better compared to EF and TE, respectively, and with lower bond strength values after aging (p < 0.05). Incremented silver nitrate deposits were observed at the adhesive interfaces after aging, especially for the TE groups (p < 0.05). Further, the experimental groups treated with ZON had significantly lower levels of enzymatic activity compared to TE, as shown by gelatin and in situ zymography (p < 0.05). CONCLUSIONS: The experimental etchant demonstrated promising results in hybrid-layer preservation over time when used with simplified bonding systems, and could therefore be recommended in the clinical practice.

Aerosol drug delivery to spontaneously-breathing preterm neonates: lessons learned.

Delivery of medications to preterm neonates receiving non-invasive ventilation (NIV) represents one of the most challenging scenarios for aerosol medicine. This challenge is highlighted by the undersized anatomy and the complex (patho)physiological characteristics of the lungs in such infants. Key physiological restraints include low lung volumes, low compliance, and irregular respiratory rates, which significantly reduce lung deposition. Such factors are inherent to premature birth and thus can be regarded to as the intrinsic factors that affect lung deposition. However, there are a number of extrinsic factors that also impact lung deposition: such factors include the choice of aerosol generator and its configuration within the ventilation circuit, the drug formulation, the aerosol particle size distribution, the choice of NIV type, and the patient interface between the delivery system and the patient. Together, these extrinsic factors provide an opportunity to optimize the lung deposition of therapeutic aerosols and, ultimately, the efficacy of the therapy.In this review, we first provide a comprehensive characterization of both the intrinsic and extrinsic factors affecting lung deposition in premature infants, followed by a revision of the clinical attempts to deliver therapeutic aerosols to premature neonates during NIV, which are almost exclusively related to the non-invasive delivery of surfactant aerosols. In this review, we provide clues to the interpretation of existing experimental and clinical data on neonatal aerosol delivery and we also describe a frame of measurable variables and available tools, including in vitro and in vivo models, that should be considered when developing a drug for inhalation in this important but under-served patient population.

The effect of chlorhexidine primer application on the clinical performance of composite restorations: a literature review.

To discuss the effectiveness of chlorhexidine (CHX) used as therapeutic dentin primer in adhesively bonded composite restorations. OVERVIEW: An electronic search in MEDLINE database, accessed through PubMed was conducted. No restrictions of languages and date of publication were made. The following key words were used: "chlorhexidine", "composite" and "composite resins." Clinical studies in which CHX was used during bonding procedures were included in this review. Six studies met the inclusion criteria. Of these, five studies were carried out on noncarious cervical lesions (NCCL). Only one study was carried out on class II preparation of permanent molars. In all studies, either etch-and-rinse and self-etch adhesive systems were used during bonding procedures. On the basis of the reviewed clinical trials, it can be concluded that CHX primer application does not seem to influence clinical outcome of composite restorations. CLINICAL SIGNIFICANCE: Current scientific evidence cannot neither strongly recommend nor discourage the application of CHX as therapeutic primer in composite restorations. Studies with longer follow-up periods with adhesive restorations placed on dentin after caries removal, rather than only on NCCL, are desirable to further investigate the therapeutic effect of CHX during bonding procedures.

A Compartment-Based Mathematical Model for Studying Convective Aerosol Transport in Newborns Receiving Nebulized Drugs during Noninvasive Respiratory Support.

Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (DDL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying DDL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient-ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on DDL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the DDL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures.

Impact of Body Position on Lung Deposition of Nebulized Surfactant in Newborn Piglets on Nasal Continuous Positive Airway Pressure.

INTRODUCTION: The ideal body position during surfactant nebulization is not known. OBJECTIVE: The aim of this study was to determine whether body positioning during surfactant nebulization influences surfactant distribution and deposition in the lungs. METHODS: Twenty-four 12- to 36-h-old full-termpiglets (1.3-2.2 kg) on nasal continuous positive airway pressure (nCPAP) were randomized into four groups: lateral decubitus with right or left side up, prone or supine positions (n = 6 each). All animals received 200 mg kg-1 of poractant alfa mixed with 200 MBq of 99mtechnetium-nanocolloid via a customized eFlow-Neos investigational vibrating-membrane nebulizer. Surfactant deposition (percentage of the administered dose) was measured by gamma scintigraphy. RESULTS: Comparing all groups, the mean total lung surfactant deposition was significantly higher in the prone position (32.4 ± 7.7%, p = 0.03). The deposition in this group was higher in the right lung (21.0 ± 8.6 vs. 11.3 ± 5.7%, p = 0.04). When nebulization was performed in the lateral decubitus, most of the surfactant was found in the dependent lung, regardless of which side the piglet lay on (right side up 15.3 ± 1.0 vs. 3.4 ± 1.0%, p = 0.06, and left side up 11.2 ± 9.8 vs. 1.8 ± 0.7%, p = 0.04). CONCLUSIONS: In spontaneously breathing animals on nCPAP, the prone position yielded the highest lung dose. Higher deposition rates in the dependent lung while on lateral decubitus indicates that deposition was also influenced by gravity.

Extended Pharmacopeial Characterization of Surfactant Aerosols Generated by a Customized eFlow Neos Nebulizer Delivered through Neonatal Nasal Prongs.

The delivery of nebulized medications to preterm infants during Non-Invasive Ventilation (NIV) remains an unmet clinical need. In this regard, the effective delivery of nebulized surfactant has been particularly investigated in preclinical and clinical studies. In this work, we investigated the feasibility of delivering nebulized surfactant through various commercially available nasal prong types. We first performed a compendial characterization of surfactant aerosols generated by the eFlow Neos nebulizer, customized to be used in neonates, determining the amount of surfactant delivered by the device as well as the aerodynamic characteristics of surfactant aerosols. Additionally, we extended the compendial characterization by testing the effect of different nasal prong types on the estimated lung dose using a realistic Continuous Positive Airway Pressure (CPAP) circuit that included a cast of the upper airways of a preterm neonate. The compendial characterization of surfactant aerosols delivered through different nasal prongs achieved relatively high delivered surfactant doses (in the range 63-74% of the nominal dose), with aerodynamic characteristics displaying mass median aerodynamic diameters ranging between 2.52 and 2.81 µm. Nevertheless, when using a representative in vitro setup mimicking NIV in a clinical setting, significant differences were observed in terms of the estimated lung dose accounting for up to two-fold differences (from 10% to 20% estimated lung deposition of the nominal dose) depending on the chosen nasal prong type. Considering that surfactant lung deposition rates are correlated with therapeutic efficacy, this study points out the relevance of choosing the appropriate NIV interface to maximize the lung dose of nebulized medications.

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

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.

In Vitro Performance of an Investigational Vibrating-Membrane Nebulizer with Surfactant under Simulated, Non-Invasive Neonatal Ventilation Conditions: Influence of Continuous Positive Airway Pressure Interface and Nebulizer Positioning on the Lung Dose.

Non-invasive delivery of nebulized surfactant has been a long-pursued goal in neonatology. Our aim was to evaluate the performance of an investigational vibrating-membrane nebulizer in a realistic non-invasive neonatal ventilation circuit with different configurations. Surfactant (aerosols were generated with a nebulizer in a set-up composed of a continuous positive airway pressure (CPAP) generator with a humidifier, a cast of the upper airway of a preterm infant (PrINT), and a breath simulator with a neonatal breathing pattern. The lung dose (LD), defined as the amount of surfactant collected in a filter placed at the distal end of the PrINT cast, was determined after placing the nebulizer at different locations of the circuit and using either infant nasal mask or nasal prongs as CPAP interfaces. The LD after delivering a range of nominal surfactant doses (100-600 mg/kg) was also investigated. Surfactant aerosol particle size distribution was determined by laser diffraction. Irrespective of the CPAP interface used, about 14% of the nominal dose (200 mg/kg) reached the LD filter. However, placing the nebulizer between the Y-piece and the CPAP interface significantly increased the LD compared with placing it 7 cm before the Y-piece, in the inspiratory limb. (14% ± 2.8 vs. 2.3% ± 0.8, nominal dose of 200 mg/kg). The customized eFlow Neos showed a constant aerosol generation rate and a mass median diameter of 2.7 µm after delivering high surfactant doses (600 mg/kg). The customized eFlow Neos nebulizer showed a constant performance even after nebulizing high doses of undiluted surfactant. Placing the nebulizer between the Y-piece and the CPAP interface achieves the highest LD under non-invasive ventilation conditions.