Surfactant Instillation Research Articles

Surfactant instillation in spontaneously breathing preterm infants: a systematic review and meta-analysis.

Respiratory management with LIST decreases the risks of BPD and BPD or death, and the need for invasive ventilation. This strategy appears safe, but long-term follow-up is lacking. What is Known: • Initial management of preterm infants with CPAP decreases the risk of death or BPD, but many still require surfactant or invasive ventilation. • Surfactant can be instilled through a tracheal thin catheter while the infant breathes on CPAP, but improvement in BPD is inconsistent between studies. What is New: • Less invasive surfactant therapy (LIST) strategies decrease the risks of BPD, of death or BPD, and of CPAP failure compared to strategies where surfactant is administered through an endotracheal tube. • LIST strategies decrease the risks of the composite outcome of BPD or death and of early CPAP failure when compared to "intubation-surfactant-extubation" approaches.

OP21.04: Ultrasound guided intra‐amniotic instillation of surfactant before preterm delivery for prevention of neonatal respiratory syndrome: a novel approach

OP21.04: Ultrasound guided intra‐amniotic instillation of surfactant before preterm delivery for prevention of neonatal respiratory syndrome: a novel approach

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: study protocol for a randomized controlled trial.

BackgroundAlthough beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an “optimal” functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria.Methods/designIn this study, 206 spontaneously breathing infants born at 24+0–27+6 weeks’ gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation.DiscussionFrom all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge.Trial registrationClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015.

Intra-amniotic instillation of surfactants for the prevention of neonatal respiratory distress syndrome following preterm delivery

ObjectiveTo assess the efficacy of intra-amniotic administration of surfactants in reducing the incidence and severity of respiratory distress syndrome (RDS), and the need for postnatal endotracheal surfactant during preterm delivery. MethodsA prospective pilot study enrolled pregnant women at 28–34 weeks of pregnancy between July 1, 2013 and December 31, 2014 who were randomly assigned in a 1:1 ratio to a control group or to receive intra-amniotic surfactant (3mL) administered under ultrasonography guidance within 2–8 hours of expected delivery. The primary outcomes, the incidence and severity of RDS, and the need for postnatal surfactants, were analyzed on an intention-to-treat basis. ResultsThe study enrolled 20 patients to each group. The incidence of RDS did not differ between the two groups (P=0.110). Severe RDS was more common in the control group (P=0.018) and postnatal surfactants were required more frequently in the control group (P=0.02). ConclusionIntra-amniotic administration of surfactants reduced RDS severity and the need for postpartum endotracheal surfactants.Clinical Trials Registry India: CTRI/2015/12/006399

Pharmacokinetics of Budesonide Administered with Surfactant in Premature Lambs: Implications for Neonatal Clinical Trials.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature human infants, which may persist through adulthood. Airway inflammation has been firmly established in the pathogenesis of BPD. Previous studies to reduce airway inflammation with high-dose dexamethasone demonstrated adverse neurological outcomes, despite lower incidences of BPD. Instillation of budesonide and surfactant can facilitate early extubation and reduce the incidence of BPD and death among very low birth weight infants. However, the pharmacokinetics of budesonide and its distribution into the lung and brain are unknown. Therefore, 5 premature lambs were administered 0.25 mg/kg budesonide, with surfactant as the vehicle. Plasma and tissue samples were taken from the lambs for measurement of budesonide, 16α- hydroxy prednisolone, and budesonide palmitate using LC/MS/MS. Peak plasma budesonide concentrations were inversely correlated with the oxygenation index (correlation coefficient of -0.75). plasma budesonide concentrations were extremely low (~10% of expected) for two lambs that had high oxygenation indices and were excluded from further analyses. For the remaining 5 premature lambs, a non-compartmental analysis demonstrated an AUCinf of 148.77 ± 28.16 h*μg/L, half-life of 4.76 ± 1.79 h, and Cmax of 46.17 ± 17.71 µg/L. Using population pharmacokinetic methods, a onecompartment model with exponential residual error and first-order absorption adequately described the data. The apparent clearance and apparent volume of distribution of budesonide were estimated at 6.29 L/h (1.99 L/h/kg) and 29.1 L (9.2 L/kg), respectively. Budesonide and budesonide palmitate, but not 16α-hydroxy prednisolone, were detected in lung tissue. In this study, budesonide and its metabolites were not detected in the brain, which suggests that intratracheal instillation suggests that after local pulmonary deposition, there is no evidence of budesonide accumulation in the central nervous system. Overall, these results show that peak plasma budesonide concentrations are inversely correlated with the oxygenation index and that lung-specific delivery of budesonide avoids accumulation of budesonide in the brain.

Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

The effect of exogenous surfactant on alveolar interdependence

To investigate the nature of alveolar mechanical interdependence, we purposefully disturbed the equilibrium condition by administering exogenous surfactant in physiological non-surfactant deprived conditions.Changes in alveolar morphology induced by intra-tracheal delivery of CUROSURF were evaluated after opening a pleural window allowing in-vivo microscopic imaging of sub-pleural alveoli in 6 male anesthetized, tracheotomized and mechanically ventilated rabbits. Surfactant instillation increased the surface area of alveoli smaller than 20,000μm2 up to ∼50% at 15min after instillation, reflecting a lowering of surface tension due to local surfactant enrichment. Conversely, for alveoli greater than 20,000μm2, surface area decreased by ∼5%. Opposite changes in alveolar surface are interpreted as reflecting a new inter-alveolar mechanical equilibrium modified by local surfactant distribution and by a decrease in lung distending pressure. We propose that smaller alveoli, representing the majority of alveolar population, might mostly contribute to improve the oxygenation index following surfactant replacement therapy in case of surfactant deficiency.

The use of artificial pulmonary surfactant in neonatal respiratory distress

Pulmonary surfactant instillation is the treatment of choice in neonatal respiratory distress syndrome. The development of artificial surfactant has three decades of history. Animal-derived artificial surfactant is used in most countries and consists of 80% phospholipids and glycerol. 10% of the formulation is comprised of surfactant proteins, which have the critical role in surfactant function of lowering surface tension in the alveoli. Synthetic surfactants are made using synthetic peptide analogues as the surfactant protein counterparts. These are not the same as the human surfactant protein sequences; however, researchers are attempting to find the ideal synthetic peptide sequence for use in synthetic surfactants. Prophylactic and rescue surfactant therapy are two main therapeutic options. A recent recommendation emphasizes the importance of rescue therapy with continuous positive nasal airway pressure, rather than prophylactic use immediate after birth. This article briefly reviews the history and physiology of surfactant use, as well as clinical practice of surfactant and future studies.

Effect of Surfactant and Budesonide on the Pulmonary Distribution of Fluorescent Dye in Mice

Surfactant is a useful vehicle for the intratracheal delivery of medicine to the distal lung. The aim of this study was to analyze the effect of intratracheal surfactant and budesonide instillation on the pulmonary distribution of fluorescent dye in mice. Male athymic nude mice were assigned randomly as controls, fluorescent dye, fluorescent dye+surfactant (50mg/kg), fluorescent dye+budesonide (0.25mg/kg), and fluorescent dye+surfactant+budesonide groups. A total volume of 60μL fluorescent solutions was intratracheally injected and followed by 60μL of air. We photographed and measured fluorescence in the lungs, from the back, 15 minutes after intratracheal administration using an IVIS Xenogen imaging instrument. The fluorescent dye (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide) was most strongly detected near the trachea and weakly detected in the lungs in mice administered with fluorescent solutions. Almost no fluorescence was seen in the lung region of control mice. Intratracheal administration of surfactant or budesonide increased fluorescent intensity compared with control mice. Combined administration of surfactant and budesonide further increased fluorescent intensity compared with mice given surfactant or budesonide alone. Surfactant and budesonide enhance the pulmonary distribution of fluorescent dye in mice.

The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation.

BackgroundIt is now recognized that preterm infants ≤28 weeks gestation can be effectively supported from the outset with nasal continuous positive airway pressure. However, this form of respiratory therapy may fail to adequately support those infants with significant surfactant deficiency, with the result that intubation and delayed surfactant therapy are then required. Infants following this path are known to have a higher risk of adverse outcomes, including death, bronchopulmonary dysplasia and other morbidities. In an effort to circumvent this problem, techniques of minimally-invasive surfactant therapy have been developed, in which exogenous surfactant is administered to a spontaneously breathing infant who can then remain on continuous positive airway pressure. A method of surfactant delivery using a semi-rigid surfactant instillation catheter briefly passed into the trachea (the “Hobart method”) has been shown to be feasible and potentially effective, and now requires evaluation in a randomised controlled trial.Methods/designThis is a multicentre, randomised, masked, controlled trial in preterm infants 25–28 weeks gestation. Infants are eligible if managed on continuous positive airway pressure without prior intubation, and requiring FiO2 ≥ 0.30 at an age ≤6 hours. Randomisation will be to receive exogenous surfactant (200 mg/kg poractant alfa) via the Hobart method, or sham treatment. Infants in both groups will thereafter remain on continuous positive airway pressure unless intubation criteria are reached (FiO2 ≥ 0.45, unremitting apnoea or persistent acidosis). Primary outcome is the composite of death or physiological bronchopulmonary dysplasia, with secondary outcomes including incidence of death; major neonatal morbidities; durations of all modes of respiratory support and hospitalisation; safety of the Hobart method; and outcome at 2 years. A total of 606 infants will be enrolled. The trial will be conducted in >30 centres worldwide, and is expected to be completed by end-2017.DiscussionMinimally-invasive surfactant therapy has the potential to ease the burden of respiratory morbidity in preterm infants. The trial will provide definitive evidence on the effectiveness of this approach in the care of preterm infants born at 25–28 weeks gestation.Trial registrationAustralia and New Zealand Clinical Trial Registry: ACTRN12611000916943; ClinicalTrials.gov: NCT02140580.

Minimally invasive surfactant therapy with a gastric tube is as effective as the intubation, surfactant, and extubation technique in preterm babies

Preterm infants requiring surfactant replacement have been treated using the INSURE technique, which requires sedation and comprises tracheal intubation, surfactant instillation and extubation. However, minimally invasive surfactant therapy (MIST) does not require sedation, minimises airway injury and avoids placing positive pressure ventilation on an immature lung. This study compared the feasibility of the two techniques and the outcomes in preterm babies with respiratory distress syndrome (RDS). Preterm infants with RDS prospectively received surfactant via a gastric tube placed in the trachea by direct laryngoscopy with no sedation. Technique-related complications and respiratory outcomes were analysed. We compared 44 patients who received MIST with a historic cohort of 31 patients who received INSURE. This showed no differences in the rate of intubation and mechanical ventilation in the first 72h, or secondary respiratory outcomes and relevant morbidities, between the babies who received INSURE and those who received MIST. More babies in the MIST group (35%) needed a second dose of surfactant than the INSURE group (6.5%) (p<0.0001). Surfactant administration using MIST, with no sedation, is feasible in preterm infants with RDS. No significant differences in secondary respiratory outcomes were found between the MIST and INSURE techniques.

Capnodynamic Estimation of Lung Volumes: Teething Issues of a Potential Early Warning System

I would like to commend Albu et al.1 for their well-designed study evaluating the correlation between effective lung volume (ELV) and end-expiratory lung volume (EELV) in healthy and surfactant-depleted rabbit lungs with various levels of positive end-expiratory pressure.The results have indicated that the correlation between ELV and EELV improves with higher positive end-expiratory pressure, and is best in surfactant-depleted lungs, with the ELV being an overestimate of ELV in healthy lungs by as much as 150 ± 13% at 0 cm H2O. The authors have hypothesized that this is due to carbon dioxide being an intrinsic gas and the ELV/EELV difference is affected by changes in pulmonary capillary volume and ventilation–perfusion mismatch. There are other methodological factors that may affect this correlation, but no method is able to satisfactorily correct for those, and any attempt may potentially require a more complicated set-up than the elegant one Albu et al. propose.2However, for neonatal patients (whom a rabbit model is supposed to simulate), lung injury is on a continuum from healthy to surfactant-depleted. Generally a surfactant-depleted state is avoided by the following two interventions—antenatal glucocorticoid therapy and the instillation of exogenous surfactant into the neonatal lung. Therefore, most neonates requiring ventilator support for perioperative or critical care will be somewhere in the middle—having neither healthy nor surfactant-depleted lungs. The lack of demonstrable reliability of ELV in this gray zone undermines the utility of its absolute value as an estimation of the EELV in this setting.The authors imply that trending the change in ELV would be more useful than the absolute value. I would be concerned however that the percentage change in ELV and EELV postlavage differs significantly between different positive end-expiratory pressure values. The difference is greatest at 0 and 9 cm H2O, but this mitigates the issue somewhat because an optimal and protective lung ventilation strategy in neonates is unlikely to be at these extremes. Nevertheless, it may be difficult to estimate the degree of change in actual lung volumes after a decrease in ELV, and may lead a provider to utilize an overly aggressive recruitment strategy that could potentially result in barotrauma.It should be noted that the sensitivity of ELV to changes to effectiveness in ventilation and as a rough measure of physiological dead space could be useful when paired with other indices that together may indicate lung dysfunction.3 For example, a decreasing ELV with increasing airway resistance and pressures can serve as a preliminary warning before an appreciable increase in ETco2 or a suboptimal arterial blood gas result. At present, such dysfunction is only detected after an arterial blood gas result, and there is no simple, continuous and noninvasive method to detect lung atelectasis and institute recruitment measures early.I believe the greatest value of this study is that the method they describe can be easily implemented as part of an early warning protocol for recruitment manoeuvres, and then a gauge of the effectiveness of the intervention.3 Further studies and modification of the algorithm should be done to improve the accuracy of ELV as an estimate of EELV in various lung states and ventilator settings. This may then allow its potential to be realized as a simple yet powerful tool currently absent from the arsenal available to modern anesthesiologists and intensivists.The author declares no competing interests.

Changes of the electroencephalographic background in preterm infants before and after instillation of pulmonary surfactant in different ways

Objective To monitor the electroencephalographic background activities of preterm infants before and after using pulmonary surfactant(PS), so as to investigate an appropriate way to endotracheally instill PS through the changes of electroencephalographic background activities. Methods Thirty-five preterm infants who were hospita-lized in Neonatal Intensive Care Unit of Guangzhou Women and Children's Medical Center from Jun.2011 to Apr.2013 and treated with PS were involved.They were divided into the normal pressure group and the high pressure group, based on the peak inspiratory pressure when PS instilled.The electroencephalographic background activities of the preterm infants before using PS and 15 min, 30 min, 60 min and 120 min after using PS were monitored continuously by using cerebral function monitor.The changes of 2 groups were compared.Oxygen saturation and heart rate were recorded at the same time. Results 1.In normal pressure group, lower amplitude decreased and the duration of interburst interval(IBI) increased 15 min after instillation of PS compared with before using PS(t=-6.012, 5.202, all P 0.05). There were significant differences between the 2 groups(t=-4.832, 4.029, all P 0.05). Between the 2 groups, there were significant differences in lower amplitude(t=-2.828, P 0.05). Lower amplitude and IBI of the normal pressure group returned to the level before using PS at 60 min and 120 min after using PS(lower amplitude: t=0.557, 1.849, all P 0.05). Moreover, in the high pressure group, lower amplitude even increased at 60 min and 120 min after using PS(t=2.153, 3.112, all P<0.05).2.After using PS, desaturation happened in 8 preterm infants of the normal pressure group and 2 preterm infants of the high pressure group.There was significant difference between the 2 groups(P=0.025).3.Bradycardia accompanied with desaturation happened in 2 preterm infants of the normal pressure group, but none in the high pressure group. Conclusions Instillation of PS may cause embolism and obstruct the airway, which may induce hypoxia, and then lead to the depression of the elec-troencephalographic background.Therefore, when instilling PS, giving high pressure can shorten or avoid the hypoxia episode, and make PS reach alveoli as soon as possible to play a role in lung compliance. Key words: Pulmonary surfactant; Amplitude-integrated electroencephalogram; Background activity; Preterm infant

Comparison of Effectiveness of Nasal Continuous Positive Airway Pressure and Nasal Intermittent Positive Pressure Ventilation for the Initial Treatment of Preterm Respiratory Distress Syndrome: A Prospective Pilot Study

Purpose: To compare respiratory and clinical outcomes between the currently used strategy of Intubation, Surfactant, Extubation (InSurE) and nasal continuous positive airway pressure (NCPAP) and the alternative strategy of InSurE and nasal intermittent positive pressure ventilation (NIPPV) for the initial treatment of respiratory distress syndrome (RDS) in preterm newborns ≤32 weeks. Methods: Twenty-six comparable preterm infants with RDS were included in the study; 13 were randomized to NCPAP and 13 to NIPPV. In both groups, the InSurE procedure consisted of intubation, surfactant instillation and 2 h positive pressure ventilation followed by extubation, after which spontaneously breathing newborns were placed on NCPAP or NIPPV. Results: There were no differences in demographic characteristics or cardiorespiratory status among preterm infants enrolled in the study. The reinutation rate was lower among the infants treated with NIPPV than among those on NCPAP (8% vs. 46%, P<0.05) and the rate of aminophylline use between 4 and 7 days of age of was lower in the NIPPV group compared to the NCPAP group (8% vs. 30%, P <0.05). In addition, “InSurE with NIPPV” significantly reduced the overall duration of endotracheal ventilation and shortened the time to first feed compared to “InSurE with NCPAP” . Conclusion: “InSurE with NIPPV” displayed therapeutic benefits as the initial treatment of preterm RDS when compared with the currently used ventilator strategy, “InSurE with NCPAP” by preventing re-intubation and shortening the duration of endotracheal ventilation.

Intubation in the delivery room: Experience with nasal midazolam

BackgroundNeonates are often intubated in the delivery room (DR) without anesthesia because vascular access is impossible. AimsTo assess neonatal comfort and adverse events after use of nasal midazolam (nMDZ) for intubation in the DR. Study designProspective data collection over 6months on the intubation of neonates with respiratory distress requiring tracheal instillation of surfactant. SubjectsTwenty-seven neonates with median (Q25–75) gestational age and birthweight of, respectively, 29 (27–33)weeks and 1270 (817–1942)g received a 0.1mg/kg dose of nMDZ, and intubation was performed at the onset of tonus resolution or apnea. Outcome measuresComfort was assessed with a scale of hetero-pain assessment and electrical skin conductance monitoring. Continuous pulse oximetry was recorded in the first postnatal hour, with oscillometric blood pressure measurement every 10min. ResultsSeventy percent of the patients required a single dose, with intubation performed 4.8 (3–9)min after administration. Combined electro-clinical assessment found adequate comfort during the procedure in 68% of neonates. Mean blood pressure decreased from 39 (34–44)mmHg before to 31 (25–33)mmHg 1h following nMDZ (p=0.011). ConclusionnMDZ provided rapid and effective sedation to intubate neonates in the DR but potentially exposed them to hypotension, thus requiring close hemodynamic monitoring.

The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury

BackgroundMechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.MethodsMice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).ResultsFor both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.ConclusionsThe data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.

Surfactant Administration via Thin Catheter during Spontaneous Breathing: Randomized Controlled Trial in Alzahra hospital

Introduction Respiratory distress syndrome (RDS) is a current cause of morbidity in premature infants resulted from surfactant deficiency. The primary aim of this randomized study was to describe the feasibility of early administration of surfactant via a thin catheter during spontaneous breathing (TEC) and compare its outcomes with the InSurE (Intubate, Surfactant, Extubate) procedure Materials and Methods Premature infants with RDS, who were ≤ 32 weeks old and stabilized with nasal continuous positive airway pressure (nCPAP), were randomized to receive surfactant either by the TEC or InSurE technique. Tracheal instillation of 200 mg/kg Curosorf via 5-F catheter during spontaneous breathing under nCPAP was performed in the intervention group (n=38). In the InSurE group (n=40), infants were intubated, received positive pressure ventilation for 30 seconds after surfactant instillation, and placed on nCPAP immediately Results Necrotizing enterocolitis rate was significantly lower in TEC group, than InSurE group, [p<0.02, RR=0.49, CI=%95(0.39_0.62)]. But rate of other morbidities did not significant difference between two groups. Although Mechanical ventilation duration did not significant different between two groups (p=0.2), but Total CPAP duration was shorter in TEC group, significantly [P<0.01, RR=8.2, CI=%95 (-37.9_-4.8)]. Need for O2 supplement and mean of total hospital duration was also lower in TEC group, but was not significant, statistically Conclusion The TEC technique is feasible for the treatment of respiratory distress syndrome in infants with very low birth weight and decreases total nCPAP duration, significantly. But Judgment of substitution TEC instead of InSurE as a routine technique need to more studies.

Reconditioning of an injured lung graft with intrabronchial surfactant instillation in an ex vivo lung perfusion system followed by transplantation

BackgroundWe tested whether an injured lung graft from category-3 donation after cardiac death donor could be reconditioned with an ex vivo lung perfusion (EVLP) system by intrabronchial diluted surfactant lavage before transplantation. MethodsIn a pig model, cardiac arrest was induced by deconnecting from the ventilator. Left lung injury was done by intrabronchial instillation of 1 mL/kg pepsin + HCl. After retrieval, the heart–lung block was stored at 4°C for 2 h. In the treated group, transplantation was performed after reconditioning with intrabronchial diluted surfactant lavage in EVLP system. ResultsDuring EVLP, surfactant group showed better oxygenation and lower pulmonary vascular resistance. After transplantation, better oxygenation, lower mean pulmonary artery pressure, and lower lung edema were observed in surfactant group. Lower blood IL-1 beta and IL-6 cytokine levels were measured in the surfactant group. In bronchoalveolar lavage, the percentage of neutrophils, IL-1 beta and IL-6 cytokine levels, amount of protein, and neutrophil infiltration in the lung tissue at the end of the experiment were significantly lower in the surfactant group. ConclusionsOur data demonstrate the feasibility of reconditioning and transplantation of an acutely damaged lung graft due to aspiration from a category-3 DCD donor. Implementation of an EVLP system is an efficacious tool to recondition and assess a questionable graft before transplantation.

Acute and sustained effects of aerosolized vs. bolus surfactant therapy in premature lambs with respiratory distress syndrome

Surfactant (SF) instillation may produce acute deleterious effects on gas exchange and both systemic and cerebral hemodynamics. Our aim was to compare the effects of aerosolized SF (SF-aero) with those of bolus SF (SF-bolus) administration on gas exchange, lung mechanics, and cardiovascular function in premature lambs with respiratory distress syndrome (RDS). Fourteen preterm lambs (85% gestation) were randomly assigned to receive SF-aero or SF-bolus. Oxygenation index (OI), PaCO2, cardiovascular parameters, carotid blood flow (CBF), lung compliance (mean dynamic compliance), and tidal volume (VT) were measured every 30 min for 6 h. Biochemical and histological analyses were performed. After delivery, lambs developed severe RDS (inspiratory fraction of oxygen: 1; pH < 7.15; PaCO2 > 80 mm Hg; PaO2 < 30 mm Hg, mean dynamic compliance < 0.08 ml/cm H2O/kg). By 60 min after treatment, both groups showed an improvement in OI, PaCO2, mean dynamic compliance, and VT that was maintained until the end of the experiment. PaCO2 and CBF increased significantly in the SF-bolus group during the first 15-30 min, without concomitant changes in cardiovascular parameters, whereas in the SF-aero group, PaCO2 and CBF decreased gradually. SF-aero induced less alveolar hemorrhage and inflammation. SF-aero produced improvements in gas exchange and lung mechanics similar to those produced by bolus administration but with less lung injury and fewer cerebral hemodynamic changes.

Surfactant Administration via Thin Catheter During Spontaneous Breathing: Randomized Controlled Trial

The primary aim of this randomized study was to describe the feasibility of early administration of surfactant via a thin catheter during spontaneous breathing (Take Care) and compare early mechanical ventilation (MV) requirement with the InSurE (Intubate, Surfactant, Extubate) procedure. Preterm infants, who were <32 weeks and stabilized with nasal continuous positive airway pressure (nCPAP) in the delivery room, were randomized to receive early surfactant treatment either by the Take Care or InSurE technique. Tracheal instillation of 100 mg/kg poractant α via 5-F catheter during spontaneous breathing under nCPAP was performed in the intervention group. In the InSurE procedure, infants were intubated, received positive pressure ventilation for 30 seconds after surfactant instillation, and placed on nCPAP immediately. One hundred infants in each group were analyzed. The MV requirement in the first 72 hours of life was significantly lower in the Take Care group when compared with the InSurE group (30% vs 45%, P = .02, odds ratio -0.52, 95% confidence interval -0.94 to -0.29). Mean duration of both nCPAP and MV were significantly shorter in the Take Care group (P values .006 and .002, respectively). Bronchopulmonary dysplasia rate was significantly lower among the infants treated with the Take Care technique (relative risk -0.27, 95% confidence interval -0.1 to -0.72) The Take Care technique is feasible for the treatment of respiratory distress syndrome in infants with very low birth weight. It significantly reduces both the need and duration of MV, and thus the bronchopulmonary dysplasia rate in preterm infants.