Management Of Respiratory Distress Syndrome Research Articles

Bronchopulmonary dysplasia in preterm infants managed with non-invasive ventilation or surfactant and a brief period of mechanical ventilation: a 6-year cohort study

Objective: Non-invasive ventilation (NIV) is increasingly used as first-line management of respiratory distress syndrome in preterm infants to avoid the lung-damaging effects of mechanical ventilation (MV). We hypothesised that even a short period of MV following surfactant treatment would increase the rate of bronchopulmonary dysplasia (BPD).Methods: Retrospective study including preterm infants <30 weeks gestational age over a six-year period if they required surfactant followed by MV not longer than 24 h (SURF&MV group) or if managed exclusively with NIV (NIV group). Baseline and morbidity variables such as gestation, birth weight, sex, place of birth, antenatal steroids, sepsis, pneumothorax, intraventricular haemorrhage, necrotising enterocolitis, and patent ductus arteriosus were analysed in a multivariate model for potential confounding.Results: 289 infants were included: 150 in the NIV group and 139 in the SURF&MV group. Seventeen infants in the NIV group and 23 in the SURF&MV group developed BPD (odds ratio: 1.55; 95% confidence interval (CI): 0.79–3.05; p = 0.202). After adjusting for potential confounders, the odds ratio was 1.09 for the SURF&MV group to develop BPD (95% CI: 0.52–2.28; p = 0.812).Conclusion: The rate of BPD did not differ between infants managed with NIV or with surfactant administration followed by ≤24 h of MV after adjusting for confounding factors.

An Update of Surfactant

In preterm infants, RDS is primarily caused by deficiency of pulmonary surfactant in an immature lung. For the past 50 years, related research and experiments with regards to surfactant replacement therapy have been encouraging and inspiring.Numerous trials have been conducted to demonstrate that surfactant plays an important role in the management of respiratory distress syndrome in preterm babies, whether it is synthetic, natural or recombinant. The use of surfactant regarding aspects of other disease has been explored as well, including meconium aspiration syndrome, congenital pneumonia and acute respiratory distress syndrome.With the advance of science, the molecular structure and function of most surfactant components has been well understood and well established. Pulmonary surfactant associated proteins (SPs) consist of a heterogeneous composition of lipids and proteins and it has been identified as SP-A, SP-B, SP-C, and SP-D.Recently, US FDA approved the first synthetic peptide-containing surfactant (Lucinactant) to treat RDS in preterm newborns. Surfactant replacement therapy has been one of the greatest achievements in the management of preterm newborns in the past few decades.

Characteristics of Respiratory Distress Syndrome in Infants of Different Gestational Ages

The purpose of this study was to compare the risk factors, clinical characteristics, and complications of respiratory distress syndrome (RDS) in infants delivered very preterm, late preterm, and term in order to help optimize the management of RDS in neonates. A retrospective study was conducted on neonates admitted to the NICU between January 2006 and December 2010. The enrolled infants with RDS were categorized as very preterm (<32(0/7)weeks gestation), moderately preterm (32(0/7)-33(6/7) weeks), late preterm (34(0/7)-36(6/7) weeks), and term (37(0/7)-42(0/7) weeks). The rates, potential risk factors, clinical characteristics, and complications of RDS of these four groups were comparatively analyzed. There was an increasing trend in incidence of RDS among the NICU admissions annually. Caesarean section without labor was significantly associated with RDS in term and late preterm infants (P<0.001). Rates of requirements for ventilator and pulmonary surfactant were similar in very preterm and term infants but significantly lower in late preterm infants (P<0.001). The oxygenation index value was not substantially lower in late preterm and term infants compared to very preterm infants, and the arterial oxygenation efficiency was improved slowly (P<0.001). Incidence of pneumonia and occurrence of pneumothorax were significantly higher in term infants (P<0.001). Term infants with RDS showed an association of RDS with caesarean section without labor and lung infection. These infants also showed slower improvement of oxygenation after surfactant administration and mechanical ventilation, and they experienced a high rate of pneumothorax complication, which was also noticed in late preterm neonates.

Noninvasive Strategies for Management of Respiratory Problems in Neonates

Multiple techniques have been developed to provide noninvasive strategies for respiratory support of the newborn that provide positive airway pressure continuously, with or without ventilation cycles, in nonintubated infants. The core physiologic variable is positive airway pressure used clinically as nasal continuous positive airway pressure (CPAP). CPAP can be augmented with intermittent positive pressure breaths that are, or are not, synchronized to the breathing of the infant. Pressures delivered by high-flow nasal cannula are less predictable than those delivered by a CPAP device. A renewed interest in testing and innovating to improve noninvasive respiratory support techniques has resulted from efforts to avoid intubation, mechanical ventilation, and ultimately bronchopulmonary dysplasia. These noninvasive techniques now are used to stabilize respiratory status after birth, to manage respiratory distress syndrome, and to facilitate extubation of infants. Large trials, in aggregate, demonstrate a modest benefit from the use of CPAP soon after birth, relative to intubation, surfactant treatment, and ventilation. Small trials yield conflicting results for the relative benefits of different noninvasive techniques for the clinical management of respiratory distress syndrome and for attempts at extubation. Success with noninvasive ventilation for the management of preterm infants depends greatly on the skills and commitment of the personnel caring for the infant.

Controversies in the Management of Respiratory Distress Syndrome in Premature Neonates

Controversies in the Management of Respiratory Distress Syndrome in Premature Neonates

Controversies in the Management of Respiratory Distress Syndrome in Premature Neonates

Controversies in the Management of Respiratory Distress Syndrome in Premature Neonates

Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life

To evaluate the outcome of a cohort of extremely low gestational age newborn infants (ELGAN) below 26-week gestation who were treated following a revised, gentle delivery room protocol to assist them in the transition and adaptation to extrauterine life. A cohort of infants with a gestational age (GA) below 26 weeks (study group; n = 164) was treated according to a revised delivery room protocol. The protocol included an optimized prenatal management, strict use of continuous positive airway pressure (CPAP), avoiding mechanical ventilation and early administration of surfactant without intubation. The parameters management of respiratory distress syndrome, survival, neonatal morbidity and neurodevelopmental outcome were compared with a historical control group (n = 44). Seventy-four per cent of the study group infants were initially treated with CPAP and surfactant administration without intubation. In comparison with the control group, significantly less children were intubated in the delivery room (24% vs. 41%) and needed mechanical ventilation (51% vs. 72%; both p < 0.05). Furthermore, compared with the historical control overall mortality (20% vs. 39%), rate of bronchopulmonary dysplasia (18% vs. 37%) and IVH > II° (10% vs. 33%) in survivors were significantly lower during the observational period (all p < 0.05). Neurodevelopmental outcome was normal in 70% of examined study group infants. A revised delivery room management protocol was applied safely to infants with a GA below 26 completed weeks with improved rates of survival and morbidity.

393 High-Flow Nasal Cannula Versus Nasal Continuous Positive Airway Pressure in the Management of Respiratory Distress Syndrome

Background and AimsAlthough nasal continuous positive airway pressure (NCPAP) in the treatment of respiratory distress syndrome (RDS) is an effective and a non-invasive method, some complications such as septal trauma...

Italian survey of neonatal respiratory support strategies

Although the management of respiratory distress syndrome (RDS) in preterm infants has been characterized by significant progress in recent years, it is difficult to translate the research results into clinical practice. Previous surveys have demonstrated that in some areas, the current management of RDS does not reflect evidence from randomized trials. Therefore, the Pulmonology Study Group of the Italian Society of Neonatology decided to perform a similar survey in Italy with the aim of identifying possible aspects of respiratory management of preterm infants with RDS that merit improvement, and of suggesting focused interventions for their resolution.

Lucinactant attenuates pulmonary inflammatory response, preserves lung structure, and improves physiologic outcomes in a preterm lamb model of RDS

Acute inflammatory responses to supplemental oxygen and mechanical ventilation have been implicated in the pathophysiological sequelae of respiratory distress syndrome (RDS). Although surfactant replacement therapy (SRT) has contributed to lung stability, the effect on lung inflammation is inconclusive. Lucinactant contains sinapultide (KL4), a novel synthetic peptide that functionally mimics surfactant protein B, a protein with anti-inflammatory properties. We tested the hypothesis that lucinactant may modulate lung inflammatory response to mechanical ventilation in the management of RDS and may confer greater protection than animal-derived surfactants. Preterm lambs (126.8 ± 0.2 SD d gestation) were randomized to receive lucinactant, poractant alfa, beractant, or no surfactant and studied for 4 h. Gas exchange and pulmonary function were assessed serially. Lung inflammation biomarkers and lung histology were assessed at termination. SRT improved lung compliance relative to no SRT without significant difference between SRT groups. Lucinactant attenuated lung and systemic inflammatory response, supported oxygenation at lower ventilatory requirements, and preserved lung structural integrity to a greater degree than either no SRT or SRT with poractant alfa or beractant. These data suggest that early intervention with lucinactant may more effectively mitigate pulmonary pathophysiological sequelae of RDS than the animal-derived surfactants poractant alfa or beractant.

The role of surfactant in respiratory distress syndrome.

The key feature of respiratory distress syndrome (RDS) is the insufficient production of surfactant in the lungs of preterm infants. As a result, researchers have looked into the possibility of surfactant replacement therapy as a means of preventing and treating RDS. We sought to identify the role of surfactant in the prevention and management of RDS, comparing the various types, doses, and modes of administration, and the recent development. A PubMed search was carried out up to March 2012 using phrases: surfactant, respiratory distress syndrome, protein-containing surfactant, protein-free surfactant, natural surfactant, animal-derived surfactant, synthetic surfactant, lucinactant, surfaxin, surfactant protein-B, surfactant protein-C.Natural, or animal-derived, surfactant is currently the surfactant of choice in comparison to protein-free synthetic surfactant. However, it is hoped that the development of protein-containing synthetic surfactant, such as lucinactant, will rival the efficacy of natural surfactants, but without the risks of their possible side effects. Administration techniques have also been developed with nasal continuous positive airway pressure (nCPAP) and selective surfactant administration now recommended; multiple surfactant doses have also reported better outcomes. An aerosolised form of surfactant is being trialled in the hope that surfactant can be administered in a non-invasive way. Overall, the advancement, concerning the structure of surfactant and its mode of administration, offers an encouraging future in the management of RDS.

Respiratory distress syndrome (RDS) in premature infants is underscored by the magnitude of Th1 cytokine polarization

Respiratory distress syndrome (RDS) is a common problem and the leading cause of death in premature infants (PI). The introduction of surfactant treatment for RDS management has lowered mortality and morbidity; nevertheless, some neonates do not improve and are at increased risk of pulmonary hemorrhage. Inflammation, not only local but also systemic, seems to play an important role in the pathogenesis of RDS. To determine whether cytokine patterns characterize RDS and its outcome, we measured type-1 (IL-2, TNF-α, IFN-γ, IL-6) and type-2 (IL-4, IL-5, IL-10, TGF-β1) serum cytokines of 47 PI with established RDS and a control group of 30 healthy, appropriate for gestational age, full-term neonates. Cord blood samples were obtained at the time of delivery from PI and controls. Venous blood samples were collected from PI who received surfactant treatment and/or developed pulmonary hemorrhage. Significantly elevated cord blood cytokine levels were observed in PI at time of delivery, compared to controls, except for IL-5 and TNF-α levels that were within control range. The type-1/type-2 cytokine ratio was significantly increased in PI vs controls. Neonates who developed pulmonary hemorrhage between 2 and 3days of life and/or died, presented the strongest Th1 and type-1 cytokine polarization that was mainly due to increased IFN-γ and TNF-α, and decreased TGF-β1. The majority of these PI were female with very low gestational age. Overall, PI with RDS present a Th1/type-1 cytokine polarization, which persists irrespective of the treatment provided, and is amplified when complications appear. Th1 polarization is associated with poor prognosis.

An Audit of Management of Respiratory Distress Syndrome in the Context of the 2007 European Consensus Guidelines

Background and aims: To audit compliance and variation in management of neonatal respiratory distress syndrome (RDS) in an era post publication of the 2007 European Consensus Guidelines. Methodology: Retrospective review of inborn preterms less than (< )37 weeks with RDS for the period from January 1st 2008 to December 31st 2008. Results: Of 197 infants, 29(14.72%) infants were < 27 weeks, 31(15.74%) between 27 to < 30 weeks, 91(46.19%) between 30 to < 34 weeks, and 46(23.35%) between 34 to < 37 weeks. All infants< 27weeks received surfactant, administered before 15mins in 28 of 29 infants. 80.65% infants in the 27 to < 30 weeks age group received surfactant, in comparison to 37.36%of infants between 30 to < 34 weeks, and 15.22% infants between 34 to < 37 weeks. Prophylactic surfactant was administered in 58% of infants between 27 to < 30 weeks age group. This did not correlate with the use or non-use of prenatal steroids. Only 1 of 29 infants < 27 weeks was immediately extubated post-surfactant. Timing of surfactant re-dosing was variable and initiated at a higher mean FiO266% and alveolar-arterial ratio 0.14 in prohylaxed infants < 27 weeks compared to rescue/re-dosing surfactant at mean FiO2 48% in infants between 27 to < 30 weeks. Conclusions: Overall compliance was achieved in prophylactic surfactant administration in infants < 27 weeks. For babies more than 27 weeks, significant variation was demonstrated in management strategies. This practice variation prompts generation of a unit policy of when to intervene with progression of RDS.

European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants-2010 update

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the updated recommendations of a European panel of expert neonatologists who had developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. These updated guidelines are based upon published evidence up to the end of 2009. Strong evidence exists for the role of a single course of antenatal steroids in RDS prevention, but the potential benefit and long-term safety of repeated courses are unclear. Many practices involved in preterm neonatal stabilisation at birth are not evidence-based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS, but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be lifesaving, but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure or nasal ventilation. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.

Ventilatory strategy based on biphasic positive airway pressure (BIPAP/APRV), preventive ventilation, and high PEEP for patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) associated to H1N1 virus infection

pressure release ventilation as a rescue therapy was used in 49%, high-frequency ventilation in 26%, prone position in 14%, nitric oxide in 7%, and muscle relaxant in 43% of patients. Mortality increased steadily with increasing severity of illness, with an overall mortality rate of 35% for a mean APACHE IV score of 105.6. Mortality was 19% for the APACHE IV group of 40 to 90, 33% for the group of 91 to 140, and 73% for the group of 141 to 190. Mortality in pregnant women was 33%. Patients who received steroid therapy as part of adult respiratory distress syndrome management had a mortality rate of 47% compared with 23% for those who did not receive steroid therapy, with P value b .01 and odd ratio of 2.87 (95% confidence interval, 1.14-7.25). Late administration of oseltamivir (N48 hours of initial presentation) was associated with an overall mortality of 82% compared with 28% in those who received early oseltamivir, with a P value b .005 and odd ratio of 11.6 (95% CI, 2.3-58). Conclusions: Patients who were admitted to intensive care unit with severe 2009 H1N1 infection were young and had a relatively high severity of illness score. Most common risk factors were bronchial asthma, obesity, and pregnancy. Overall hospital mortality was 35%. Late administration of oseltamivir was associated with at least 12-fold increase in mortality. Steroid use was associated with about 3-fold increase in mortality.

957 Use of Therapeutic Surfactant Lavage in a Preterm Infant with Massive Pulmonary Hemorrhage

Introduction: Pulmonary hemorrhage (PH) is a potentially life-threatening complication occurring in 10-16% of extremely low birth infants (ELBW), leading to chronic lung disease in 60% of cases. Surfactant is mainly used for early management of respiratory distress syndrome in preterm infants. Recently, therapeutic surfactant lavage with diluted surfactant has been proposed for the management of infants suffering from severe meconium aspiration syndrome (MAS). Case presentation: We report a case of a preterm infant (26 weeks GA) presenting with recurrent pulmonary hemorrhage in whom we performed a therapeutic lavage with diluted surfactant after an acute episode of massive bleeding with severe intractable hypoxemia. Repeated small aliquots of diluted surfactant (10 x 2 ml) allowed for marked improvement in oxygenation allowing to reduce mean airway pressures during high frequency oscillatory ventilation rapidly. The infant showed further progressive improvement allowing switching from HFOV back to conventional ventilation and finally extubation within 25 days. Conclusion: Bronchoalveolar lavage with diluted surfactant might be beneficial in massive pulmonary hemorrhage in infants. Further investigations are needed to clarify the potential benefit of such a therapeutic intervention on outcome of infants suffering from life-threatening PH.

Nasal respiratory support through the nares: its time has come

Respiratory distress syndrome (RDS) is the most common respiratory morbidity in preterm infants. Surfactant therapy and invasive mechanical ventilation through the endotracheal tube (ETT) have been the cornerstones in RDS management. Despite improvements in the provision of mechanical ventilation, bronchopulmonary dysplasia (BPD), a multifactorial disease in which invasive mechanical ventilation is a known contributory factor, remains an important cause of morbidity among preterm infants. Barotrauma, volutrauma or oxygen-induced lung inflammation (oxy-trauma) contributes significantly to the development of BPD in neonates ventilated through an ETT. Recently, nasal respiratory support has been increasingly used in preterm infants in an attempt to decrease post-extubation failure and, perhaps, BPD, and for the treatment of apnea of prematurity in nonventilated neonates. Observational studies using noninvasive respiratory support, such as nasal continuous positive airway pressure (NCPAP), have shown a decrease in the incidence of BPD when used to avoid intubation or minimize the duration of invasive mechanical ventilation through the ETT. Moreover, synchronized as well as nonsynchronized nasal intermittent positive-pressure ventilation (NIPPV) have been shown to significantly decrease post-extubation failure compared with NCPAP and their use has been associated with a reduced risk of BPD in small randomized controlled clinical trials. More recently, early surfactant administration followed by extubation to NIPPV has been suggested to be synergistic in decreasing BPD. Although these findings are promising, additional studies evaluating different nasal interfaces, flow synchronization, synchronization using neurally adjusted ventilatory assist mode, and closed loop control of oxygen during nasal ventilation to minimize lung injury are needed in an attempt to further decrease the incidence of lung injury in preterm neonates requiring respiratory support.

Early nasal continuous positive airway pressure versus INSURE in VLBW neonates

BackgroundEvidence suggests the INSURE strategy (INtubate-SURfactant administration and Extubate to nasal continuous positive airway pressure [nCPAP]) is superior to mechanical ventilation (MV) with rescue surfactant for the management of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates. There is limited data, however, to assess whether INSURE is superior to nCPAP alone. We aimed to compare these two strategies regarding early and late outcomes. MethodsRetrospective cohort study from Jan/2002 to Aug/2008. We included VLBW neonateswith gestational age (GA) ≤ 30 weeks registered in the Vermont Oxford Network that used either nCPAP alone (nCPAP group, N=40), or with INSURE (INSURE group, N=56). We assessed early (RDS, need for rescue surfactant, and CPAP failure with MV) and late outcomes (chronic lung disease of prematurity (CLD), mortality, and composite outcome of mortality and/or CLD). ResultsNeonates in the INSURE group had lower mean GA, while other baseline variables were comparable. The proportion of RDS was significantly superior in the nCPAP group (53% vs. 30%; adjusted OR [95% CI] – 0.2 [0.1-0.6]). Therapeutic surfactant was administered to all cases with RDS in the nCPAP group, but to none from the INSURE group. MV was more frequently required in the nCPAP group (11/ 40, 28% vs. 9/ 56, 12%; p=0.04). No statistically significant differences were found in either of the late outcomes. ConclusionThe use of nCPAP alone in VLBW neonates with GA ≤ 30 weeks may be associated with slightly poorer early outcomes than the INSURE strategy, but there were no significant differences in CLD or mortality.

Uso do método INSURE versus CPAP nasal isolado em recém-nascidos de muito baixo peso com 30 ou menos semanas de gestação

Background: Evidence suggests the INSURE strategy (INtubate-SURfactant administration and Extubate to nasal continuous positive airway pressure [nCPAP]) is superior to mechanical ventilation (MV) with rescue surfactant for the management of respiratory distress syndrome (RDS) in very low birth weight (VLBW) neonates. There is limited data, however, to assess whether INSURE is superior to nCPAP alone. We aimed to compare these two strategies regarding early and late outcomes. Methods: Retrospective cohort study from Jan/2002 to Aug/2008. We included VLBW neonateswith gestational age (GA)≤30 weeks registered in the Vermont Oxford Network that used either nCPAP alone (nCPAP group, N=40), or with INSURE (INSURE group, N=56).We assessed early (RDS, need for rescue surfactant, and CPAP failure with MV) and late outcomes (chronic lung disease of prematurity (CLD), mortality, and composite outcome of mortality and/or CLD). Results: Neonates in the INSURE group had lower mean GA, while other baseline variables were comparable. The proportion of RDS was significantly superior in the nCPAP group (53% vs. 30%; adjusted OR [95% CI] – 0.2 [0.1-0.6]). Therapeutic surfactant was administered to all cases with RDS in the nCPAP group, but to none from the INSURE group. MV was more frequently required in the nCPAP group (11/ 40, 28% vs. 9/ 56, 12%; p=0.04). No statistically significant differences were found in either of the late outcomes. Conclusion: The use of nCPAP alone in VLBW neonates with GA≤30 weeks may be associated with slightly poorer early outcomes than the INSURE strategy, but there were no significant differences in CLD or mortality.Rev Port Pneumol 2010; XVI (5): 779-795

Bubble CPAP: Can we predict success or failure?

urrent modalities of ventilatory assistancein the management of respiratory distresssyndrome (RDS) in preterm infants rangefrom continuous positive airway pressure(CPAP) to various modes of mechanical ventilation.The use of CPAP has been associated with a lowerincidence of chronic lung disease when used as theinitial respiratory support. In contrast, mechanicalventilation has the potential to injure the airways andlung parenchyma.Recently, there has been a renewed interest ingentle ventilation strategies, such as CPAP as a wayto improve outcomes for very preterm infants. Awide variety of devices are used to deliver CPAP,including variable flow driver devices, single or bi-nasal prongs where pressure is generated by acolumn of water (bubble CPAP) or a ventilator.Bubble CPAP (BCPAP) is appealing because of itssimplicity and low cost. With this technique gasflows past the nasal device and the pressure isgenerated in the circuit by placing the distal limb ofthe CPAP circuit under a known depth of water thatcreates bubbles and pressure oscillations in thecircuit. Gas flow is increased until continuousbubbling is achieved. It has been suggested that useof BCPAP in the poorly compliant lung may promotelung volume recruitment and augment the efficiencyof gas mixing. The usefulness of BCPAP in the initialmanagement of infants with RDS remains controver-sial as little data are available. Additionally, not allextremely premature infants with RDS arecandidates for initial treatment with CPAP, and notall those who are given CPAP can be successfullymanaged with this modality.The prospective observational study of Murki,