Use Of Surfactant Therapy Research Articles

Oxidative Stress Levels and Dynamic Thiol-Disulfide Balance in Preterm Newborns with Bronchopulmonary Dysplasia.

The aim of this study was to assess the oxidative stress (OS) levels and dynamic thiol-disulfide balance in preterm newborns with bronchopulmonary dysplasia (BPD). This prospective study included newborns separated into 2 groups, those with BPD (case) or without BPD (control). The 2 groups were compared by clinical and laboratory findings. The OS parameters total oxidant status (TOS), total antioxidant status (TAS), OS index (OSI), native thiol (NT), and total thiol were measured within the first day after birth. Oxygen requirements were measured using the fraction of inspired oxygen (FIO2) recorded in the first hour after birth/admission and the average FIO2 within 28days of the birth. Infants diagnosed with BPD had a significantly lower gestational age and birth weight and a lower 5-min Apgar score (P<.05). Infants with BPD also had a higher rate of respiratory distress syndrome, rate of use of surfactant therapy, duration of ventilation therapy, and duration of hospital stay compared with control (P=.001, P=.001, P=.001, andP=.001, respectively). Plasma TAS and NT levels of newborns with BPD were significantly lower than newborns without BPD (P<.05). In the BPD group, plasma TOS and OSI levels were significantly higher than in the control group. We found that OS was increased in newborns with BPD. The clinical significance of this study will provide the clinician with a different perspective on BPD by determining the dynamic thiol disulfide balance.

Surfactant therapy for pneumonia COVID-19 of obstetric patients

Introduction. Pregnant women may be at increased risk for severe COVID-19 illness. Pregnant women are more likely to be hospitalized at ICU, needed the mechanical ventilation compared to nonpregnant women of childbearing age. Building on the experience of the effective use of the exogenous surfactant for influenza A/H1N1 treatment of pregnant women with COVID-19, the surfactant therapy has also been included in the treatment.The objective. To evaluate the effectiveness of surfactant therapy in the integrated treatment of severe COVID-19 pneumonia of pregnant women and postpartum women.Materials and methods. The study included 135 pregnant and postpartum women with severe COVID-19 pneumonia. All of them received antiviral, anticoagulant, anticytokine and anti-inflammatory therapy. 68 patients (main group) with an initially more severe course of the disease and a greater degree of lung damage (p = 0.026) received inhalations with Surfactant-BL, 67 patients (control group) did not receive the surfactant therapy. Patients received Surfactant-BL through a mesh-nebulizer at a dose of 75 mg 2 times a day for 3–5 days.Result. Patients of the main group showed decreasing risks of requiring the noninvasive ventilation (27.9% vs. 52.2%, р = 0.014) and artificial lung ventilation (2.9% vs. 11.9%, p = 0.047), the length of stay in the intensive care unit (ICU) was reduced (10.6 vs. 13.1 inpatient days, р = 0.045). Сomplications such as pneumomediastinum and pneumothorax occurred less frequently in the surfactant therapy group (24.2% vs. 52.4%, p = 0.037) with a high extent of lung damage (CT-3–4). With early surfactant therapy in the standard oxygen therapy stage or high-flow oxygenation, gas exchange indicators were restored faster, thus avoiding mechanical ventilation and has reduced the duration of intensive care (р = 0.004) and prevented deaths.Conclusion. The use of surfactant therapy for pneumonia associated with COVID-19 in pregnant and postpartum women against the background of ongoing complex therapy helps to prevent further lung damage, reduce the mechanical ventilation risk and improve oxygenation earlier, especially with early start of surfactant therapy.

Respiratory Support of Infants With Congenital Diaphragmatic Hernia

Optimisation of respiratory support of infants with congenital diaphragmatic hernia (CDH) is critical. Infants with CDH often have severe lung hypoplasia and abnormal development of their pulmonary vasculature, leading to ventilation perfusion mismatch. It is vital that lung protective ventilation strategies are employed during both initial stabilisation and post-surgical repair to avoid ventilator induced lung damage and oxygen toxicity to prevent further impairment to an already diminished gas-exchanging environment. There is a lack of robust evidence for the routine use of surfactant therapy during initial resuscitation of infants with CDH and thus administration cannot be recommended outside clinical trials. Additionally, inhaled nitric oxide has been shown to have no benefit in reducing the mortality rates of infants with CDH. Other therapeutic agents which beneficially act on pulmonary hypertension are currently being assessed in infants with CDH in randomised multicentre trials. The role of novel ventilatory modalities such as closed loop automated oxygen control, liquid ventilation and heliox therapy may offer promise for infants with CDH, but the benefits need to be determined in appropriately designed clinical trials.

Neonatal Morbidity and Mortality in Advanced Aged Mothers—Maternal Age Is Not an Independent Risk Factor for Infants Born Very Preterm

Background: As childbearing is postponed in developed countries, maternal age (MA) has increased over decades with an increasing number of pregnancies between age 35–39 and beyond. The aim of the study was to determine the influence of advanced (AMA) and very advanced maternal age (vAMA) on morbidity and mortality of very preterm (VPT) infants.Methods: This was a population-based cohort study including infants from the “Effective Perinatal Intensive Care in Europe” (EPICE) cohort. The EPICE database contains data of 10329 VPT infants of 8,928 mothers, including stillbirths and terminations of pregnancy. Births occurred in 19 regions in 11 European countries. The study included 7,607 live born infants without severe congenital anomalies. The principal exposure variable was MA at delivery. Infants were divided into three groups [reference 18–34 years, AMA 35–39 years and very(v) AMA ≥40 years]. Infant mortality was defined as in-hospital death before discharge home or into long-term pediatric care. The secondary outcome included a composite of mortality and/or any one of the following major neonatal morbidities: (1) moderate-to-severe bronchopulmonary dysplasia; (2) severe brain injury defined as intraventricular hemorrhage and/or cystic periventricular leukomalacia; (3) severe retinopathy of prematurity; and (4) severe necrotizing enterocolitis.Results: There was no significant difference between MA groups regarding the use of surfactant therapy, postnatal corticosteroids, rate of neonatal sepsis or PDA that needed pharmacological or surgical intervention. Infants of AMA/vAMA mothers required significantly less mechanical ventilation during NICU stay than infants born to non-AMA mothers, but there was no significant difference in length of mechanical ventilation and after stratification by gestational age group. Adverse neonatal outcomes in VPT infants born to AMA/vAMA mothers did not differ from infants born to mothers below the age of 35. Maternal age showed no influence on mortality in live-born VPT infants.Conclusion: Although AMA/vAMA mothers encountered greater pregnancy risk, the mortality and morbidity of VPT infants was independent of maternal age.

Ten-year trend of care practices, morbidities and survival of very preterm neonates in the Malaysian National Neonatal Registry: a retrospective cohort study

ObjectivesTo determine a 10-year trend of survival, morbidities and care practices, and predictors of in-hospital mortality in very preterm neonates (VPTN, gestation 22 to <32 weeks) in the Malaysian National...

Использование сурфактант-терапии в комплексном лечении острого респираторного дистресс-синдрома при COVID-19

ntroduction. The COVID-19 pandemic caused an outbreak of viral lung infections with severe acute respiratory syndrome complicated with acute respiratory failure. Despite the fact that the pandemic has a lengthened run, none of the therapeutic approaches have proved to be sufficiently effective according to the evidence-based criteria. We consider the use of surfactant therapy in patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS) as one of the possible methods for treating COVID-19 related pneumonia. Objective. To prove the clinical efficacy and safety of orally inhaled Surfactant-BL, an authorized drug, in the combination therapy of COVID-19 related ARDS. Materials and methods. A total of 38 patients with COVID-19 related severe pneumonia and ARDS were enrolled in the study. Of these, 20 patients received the standard therapy in accordance with the temporary guidelines for the prevention, diagnosis and treatment of the novel coronavirus infection (COVID-19) of the Ministry of Health of the Russian Federation, version 9. And 18 patients received the surfactant therapy in addition to the standard therapy. Surfactant-BL was used in accordance with the instructions on how to administer the drug for the indication – prevention of the development of acute respiratory distress syndrome. A step-by-step approach to the build-up of the respiratory therapy aggressiveness was used to manage hypoxia. We used oxygen inhalation via a face mask with an oxygen inflow of 5–15 l/min, highflow oxygen therapy via nasal cannulas using Airvo 2 devices, non-invasive lung ventilation, invasive lung ventilation in accordance with the principles of protective mechanical ventilation. Results and discussion. Significant differences in the frequency of transfers to mechanical ventilation, mortality, Intensive Care Unit (ICU) and hospitalization length of stay (p &lt;0.05) were found between the groups. Patients receiving surfactant therapy who required a transfer to mechanical ventilation accounted for 22% of cases, and the mortality rate was 16%. In the group of patients receiving standard therapy without surfactant inhalation 45% were transferred to mechanical ventilation, and 35% died. For patients receiving surfactant therapy, the hospital stay was reduced by 20% on average, and ICU stay by 30%. Conclusion. The inclusion of surfactant therapy in the treatment of COVID-19 related severe pneumonia and ARDS can reduce the progression of respiratory failure, avoid the use of mechanical ventilation, shorten the ICU and hospitalization length of stay, and improve the survival rate of this patient cohort.

EXOGENOUS SURFACTANTS OF NATURAL ORIGIN IN THE TREATMENT OF RESPIRATORY DISTRESS SYNDROME - COMPARATIVE COMPOSITION, BIOPHYSICAL PROPERTIES AND CLINICAL EFFECTIVENESS

Respiratory distress syndrome (RDS) remains an important cause of morbidity and mortality in premature infants in Ukraine and around the world. Since the determination of surfactant deficiency as the main cause of this disease, significant progress has been made in studying the structure and function of the pulmonary surfactant system, as well as the possibilities of creating and effective use of exogenous surfactant preparations. Unprecedented long-term fundamental, experimental and clinical studies have ensured the clinical availability of numerous exogenous surfactant preparations, the use of which is currently considered one of the standards of neonatal care, regardless of the level of development of the country. However, all these surfactants are not alike. Although all surfactants licensed for clinical practice significantly reduce mortality in preterm infants from RDS, they differ in phospholipid and protein composition, phospholipid concentration, biophysical properties, dosage, possibilities of less invasive administration, applicability, and clinical efficacy. Comparative clinical studies have shown the benefits of poractant-α, which can be administered at a dose that provides more phospholipids in a smaller volume, contains more surfactant-specific proteins (primarily SPB), and is licensed for administration by the less invasive method. The developers of third-generation synthetic surfactants, which have already demonstrated their clinical effectiveness, place their main hopes on the imitation of these properties. This review presents current data on the structure, composition, and biophysical properties of pulmonary surfactant, provides a comparative description of the most commonly used preparations of exogenous surfactant of animal origin, and characterizes additional prerequisites for the effective use of surfactant therapy.

Intratracheal Instillation of Stem Cells in Term Neonatal Rats.

Prolonged exposure to high concentrations of oxygen leads to inflammation and acute lung injury, which is similar to human bronchopulmonary dysplasia (BPD). In premature infants, BPD is a major complication despite early use of surfactant therapy, optimal ventilation strategies, and noninvasive positive pressure ventilation. Because pulmonary inflammation plays a crucial role in the pathogenesis of BPD, corticosteroid use is one potential treatment to prevent it. Nevertheless, systemic corticosteroid treatment is not usually recommended for preterm infants due to long-term adverse effects. Preclinical studies and human phase I clinical trials demonstrated that use of mesenchymal stromal cells (MSCs) in hyperoxia-induced lung injuries and in preterm infants is safe and feasible. Intratracheal and intravenous MSC transplantation has been shown to protect against neonatal hyperoxic lung injury. Therefore, intratracheal administration of stem cells and combined surfactant and glucocorticoid treatment has emerged as a new strategy to treat newborns with respiratory disorders. The developmental stage of rat lungs at birth is equivalent to that in human lungs at 26-28 week of gestation. Hence, newborn rats are appropriate for studying intratracheal administration to preterm infants with respiratory distress to evaluate its efficacy. This intratracheal instillation technique is a clinically viable option for delivery of stem cells and drugs into the lungs.

Опыт применения сурфактант-терапии при пневмонии, ассоциированной с COVID-19, у пациенток акушерского профиля

Introduction. Pregnant women may be at increased risk for severe COVID-19 illness. Pregnant women are more likely to be hospitalized at ICU, needed the mechanical ventilation compared to nonpregnant women. The pregnant women are currently excluded from the most of the clinical trials of COVID-19 drug therapy. This limits the formulation of appropriate recommendations for the treatment of pregnant women with SARS-CoV-2 infection. Building on the experience of the effective use of surfactant therapy for influenza A/H1N1 treatment of pregnant women with COVID-19, the domestic/local drug Surfactant BL was included in the complex therapy. The objective. To evaluate the effectiveness of surfactant therapy in the integrated treatment of severe COVID-19 pneumonia of pregnant women and postpartum women. Materials and methods. The study included 69 pregnant and postpartum women with severe COVID-19 pneumonia. All ofthem received antiviral, anticoagulant and anti-inflammatory therapy. 47 patients (group 1) with an initially more severe course of the disease received inhalations with Surfactant BL in 1–2 days after admission to the intensive care unit, 22 patients (group 2) were prescribed surfactant therapy for 4–5 days, due to the progression of respiratory failure. Surfactant BL was administered at a dose of 75 mg 2 times a day through a nebulizer for 2–5 days. Result. In group 1 patients, SpO2 recovered faster and dyspnea decreased. All patients of group 1 did not require mechanical ventilation; in group 2, 3 patients (14.3%) required mechanical ventilation. In the group of early use of surfactant therapy with CT control, in most cases, there was a positive trend (67.6%), in contrast to group 2 (37.5%). Stay in ICU conditions in group 1 was 8.6 days, in group 2 – 13.2 days. No lethal outcomes were observed with surfactant therapy in both groups. Conclusion. Early surfactant therapy against the background of complex therapy allows to avoid mechanical ventilation, reducing the length of stay of patients in the intensive care unit and preventing mortality from COVID-19 pneumonia.

Surfactant Replacement Therapy for Respiratory Distress Syndrome in the Newborn: A Review

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in low birth weight premature infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Exogenous surfactant therapy has become well established in newborn infants with respiratory distress. Many aspects of its use have been well evaluated in high-quality trials and systematic reviews. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/ sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This article summarizes the evidence and gives recommendations for the use of surfactant therapy for respiratory distress syndrome (RDS) in newborn.Bangladesh J Child Health 2016; VOL 40 (1) :26-30

The Role of Surfactant Therapy in Nonrespiratory Distress Syndrome Conditions in Neonates.

While treatment of respiratory distress syndrome (RDS) with surfactant in premature neonates is well established, evidence for its use in non-RDS conditions, especially in the term neonate, has been less abundant. The last published review on a PubMed search was in 2001. In this review, we comprehensively and critically evaluated the evidence from the literature regarding the use of surfactant in specific non-RDS disorders in neonates. Surfactant administered as a bolus should be considered in the treatment of meconium aspiration syndrome with progressive respiratory failure. While controversial in congenital diaphragmatic hernia, it should be considered in Group B streptococcal pneumonia. As evidence evolves, we anticipate the broader application and more routine use of surfactant therapy for respiratory failure because of causes other than RDS.

Oxygen requirement and surfactant therapy in preterm infants after delivery.

Several reports have shown the beneficial effects of early or prophylactic surfactant therapy for preterm infants, who often develop respiratory distress syndrome. No report, however, has addressed which infants should receive surfactant therapy in the delivery room. Therefore, the aim of this study was to assess the validity of identifying infants who need surfactant therapy based on fraction of inspiratory oxygen (FiO2 ) requirement in the delivery room. In this observational, retrospective study, FiO2 given in the delivery room, use of surfactant therapy, stable microbubble test (SMT) results, and changes in FiO2 both before and after surfactant therapy were reviewed in infants born at <33 weeks' gestation. Overall, 170 infants were included. Forty infants were given oxygen with FiO2 ≥0.6, and all received surfactant therapy. Of these 40 infants, FiO2 could be reduced in 36 (90%) by an average of 0.46 after surfactant therapy. SMT was done in 22 of 40 infants, and surfactant insufficiency was suspected in 20 (91%). In contrast, 81 of 102 infants (79%) with FiO2 <0.4 did not need surfactant therapy within 48 h after birth. Preterm infants who need FiO2 ≥0.6 in the delivery room appear to be at high risk of surfactant insufficiency and would benefit from surfactant. Surfactant therapy would provide a more effective resuscitation method for preterm infants, and thus a larger prospective study is needed to confirm these results.

Surfactant era and obstetric decision making

Introduction: The management of women with pregnancy complications at the peri-viability period involves a complex set of medical, ethical, emotional, and social challenges for the obstetrician. The survival rate of preterm babies has been improving along with advancement in neonatal intensive care unit (NICU) technology. Our recent experience has shown survival of even very preterm infants with the use of surfactant therapy. Objective: This observational study was conducted in order to evaluate the survival benefit of surfactant therapy on preterm neonates, to enable straight forward decisions to be taken by the obstetricians regarding antenatal steroid prophylaxis, in-utero transfer and mode of delivery in case of inevitable preterm births. Material and Methods: This study was conducted in the NICU of a tertiary hospital over a period of 3 years (2009-2011). We recruited only those preterm neonates who received surfactant therapy and the records were obtained and analyzed. Survival benefits of surfactant therapy, role of antenatal steroids, in utero transfer and mode of delivery were studied. Results: Almost all (98.6%) neonates who did not receive antenatal steroids at all, landed up in respiratory distress syndrome (RDS) requiring surfactant therapy. Among the outborns 59.2% had an extended NICU stay as compared to 49.4% in the inborn group. The overall incidence of RDS was found to be more in caesarean delivery group (96.3%). However if the period of gestation at the time of delivery was less than 28 weeks, caesarean delivery had lesser incidence (12.5%) of RDS compared to vaginal delivery (27.1%). Similar finding was noted when comparing mortality. In less than 28 weeks gestation, when caesarean was done 2.5% newborn babies died, whereas in the vaginal delivery group 12.5% babies succumbed to death. Conclusion: 1) Even in centers with facilities of surfactant therapy, steroids prophylaxis should be considered before delivery 2) Obstetricians should practice in utero transfer, to centers with NICU, having availability and technical expertise of surfactant prophylaxis 3) With the availability and wide spread usage of surfactant for premature neonates caesarean delivery should not be deferred for fetal benefit. DOI: http://dx.doi.org/10.4038/sljog.v34i3.4882 Sri Lanka Journal of Obstetrics and Gynaecology 2012; 34 : 99-105

Prevention of bronchopulmonary dysplasia by infants that have an increased risk for the development of the disease

Methods: Investigating the combined effect of administering surfactant at delivery, antenatal steroid prophylaxis, reduced oxygen concentration and lowered pressure of mechanical ventilation, early weaning and extubation, as well as supplementation of vitamins A and C on the development of bronchopulmonary dysplasia of very low birth weight infants. Experimental subjects were 13 very low birth weight preterm infants, born between September 2007 and February 2008, selected as being at high risk of developing bronchopulmonary dysplasia on the basis of their IL-6 levels (obtained from tracheal aspirate and whole blood) taking CRP into consideration as well. These subjects were given the aforementioned treatment alternative to the one generally used and professionally recommended. Newborns with normal IL-6 levels in tracheal aspirate were considered the “normal” group and received the treatment traditionally recommended for premature babies. Results: 50% of the infants needed HFO ventilation (for 4 to 11 days). All infants needed synchronized intermittent mandatory ventilation (for 2 to 17 days). 17% of them also received continuous positive airway pressure treatment (for 2 to 7 days). The incidence of bronchopulmonary dysplasia was 16.66%. Conclusions: For very low birth weigh infants with risk for developing bronchopulmonary dysplasia the combined use of surfactant therapy, antenatal steroid prophylaxis, lowered oxygen saturation goals, early weaning and extubation, and A and C vitamin supplementation has resulted in decreased incidence of bronchopulmonary dysplasia.

Surfactant Maturation Is Not Delayed in Human Fetuses with Diaphragmatic Hernia

BackgroundPulmonary hypoplasia and persistent pulmonary hypertension account for significant mortality and morbidity in neonates with congenital diaphragmatic hernia (CDH). Global lung immaturity and studies in animal models suggest the presence of surfactant deficiency that may further complicate the pathophysiology of CDH. However, data about surfactant status in human fetuses with CDH at birth are contradictory. The lack of a chronological study of surfactant content in late pregnancy has been a significant limitation. The appropriateness of administering surfactant supplements to neonates with CDH is therefore a debated question.Methods and FindingsWe investigated surfactant content in human fetuses with CDH compared to age-matched fetuses with nonpulmonary diseases used as controls. Concentrations of disaturated phosphatidylcholine and surfactant proteins were found to be similar at a given stage of pregnancy, with both components showing a similar pattern of increase with progressing pregnancy in fetuses with CDH and in control fetuses. Thyroid transcription factor 1, a critical regulator of surfactant protein transcription, similarly displayed no difference in abundance. Finally, we examined the expression of three glucocorticoid-regulated diffusible mediators involved in lung epithelial maturation, namely: keratinocyte growth factor (KGF), leptin, and neuregulin 1 beta 1 (NRG1-β1). KGF expression decreased slightly with time in control fetuses, but remained unchanged in fetuses with CDH. Leptin and NRG1-β1 similarly increased in late pregnancy in control and CDH lungs. These maturation factors were also determined in the sheep fetus with surgical diaphragmatic hernia, in which surfactant deficiency has been reported previously. In contrast to the findings in humans, surgical diaphragmatic hernia in the sheep fetus was associated with decreased KGF and neuregulin expression. Fetoscopic endoluminal tracheal occlusion performed in the sheep model to correct lung hypoplasia increased leptin expression, partially restored KGF expression, and fully restored neuregulin expression.ConclusionsOur results indicate that CDH does not impair surfactant storage in human fetuses. CDH lungs exhibited no trend toward a decrease in contents, or a delay in developmental changes for any of the studied surfactant components and surfactant maturation factors. Surfactant amounts are likely to be appropriate to lung size. These findings therefore do not support the use of surfactant therapy for infants with CDH. Moreover, they raise the question of the relevance of CDH animal models to explore lung biochemical maturity.

A collaborative quality improvement intervention was effective for promoting use of surfactant therapy in preterm infants

Horbar JD, Carpenter JH, Buzas J, et al . Collaborative quality improvement to promote evidence based surfactant for preterm infants: a cluster randomised trial. BMJ 2004;329:1004. Q Is a multifaceted...

Cerebral hemodynamic change and intraventricular hemorrhage in very low birth weight infants with patent ductus arteriosus

The aims of this study were to assess the hemodynamics of the cerebral arteries and intraventricular hemorrhage in very-low-birthweight (VLBW) infants with and without patent ductus arteriosus (PDA) by cranial Doppler sonography. VLBW infants with significant PDA were recruited into the study (sPDA) group. Arterial blood gas analysis and complete blood counts were done near the time of the cranial sonography examination. Mechanical ventilator settings and daily fluid intake were recorded. The cranial Doppler sonographic examinations were repeated after PDA closure by indomethacin therapy and/or surgical ligation. A total of 40 preterm infants fulfilled the criteria of the study group. Another 37 preterm infants were recruited into a control group. Mean birth weight and gestational age did not differ significantly between the two groups. Differences in heart rate, blood pH, pCO 2, pO 2, use of surfactant therapy, mean airway pressure, ventilation index and FiO 2 were statistically significant. In the sPDA group before closure of the PDA, the left atrial diameter/aorta diameter ratio demonstrated a positive relationship with resistance index (RI) and an inverse relationship with end diastolic velocities ( Vd). After closure of the PDA, these changes neared those of the control group. The overall incidence of intraventricular hemorrhage (IVH) was higher in the sPDA than in the control group. There was no statistical difference in the grading and severity of IVH between the two groups. However, all preterm infants with severe IVH were found in the sPDA group, and their RIs were all higher than 0.80. Cranial Doppler sonography can be a useful tool to evaluate cerebral hemodynamic changes in VLBW infants with sPDA. Increased RI and decreased Vd of the cerebral artery may indicate a probable sPDA, and normalization of the RI and Vd may suggest closure of the sPDA. (E-mail: waitim@ms1.mmh.org.tw)

EXPANDED USES OF SURFACTANT THERAPY

There are few therapies for which the cumulative evidence of benefit is as much as that for surfactant therapy for RDS in premature infants. Exogenous surfactant therapy does seem to be beneficial for a number of non-RDS disorders. Although there are some trials supporting its use in MAS and ALI-ARDS, there are only a few small prospective, randomized, controlled trials supporting surfactant use in non-RDS disorders. Use of surfactant therapy for any disorder other than RDS must be considered "off the shelf" and experimental. Much work remains to be done to address the role of surfactant therapy in the myriad disorders discussed. Of import for each of the disorders is addressing the optimum type of surfactant to use, and the appropriate dose, method of delivery, and duration of treatment regimens.

Trend in mortality from respiratory distress syndrome in the United States, 1970-1995

Objective: We examined the trend in mortality caused by respiratory distress syndrome (RDS) and its impact on changes in infant and neonatal mortality rates (IMR, NMR) in the United States. Study design: Data on infant deaths in the United States for the period 1970 through 1995 were used to compare RDS-specific IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through 1991 were used to examine birth weight- and RDS-specific NMRs. Results: IMR from RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More than three quarters of this decline occurred between 1970 and 1985. RDS-specific NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that is, 28%, between 1988 and 1991. There was also a significant reduction in postneonatal mortality from chronic lung diseases between 1988 and 1991. Conclusions: Most of the reduction in mortality from RDS occurred before the introduction of surfactant therapy. The recent accelerated reduction in mortality from RDS between 1988 and 1991 was temporally associated with widespread use of surfactant therapy and was the single most important factor for reduction in overall NMR in the United States.(J Pediatr 1999;134:434-40)

Pulmonary surfactant composition early in development of acute lung injury after cardiopulmonary bypass: prophylactic use of surfactant therapy.

Cardiopulmonary bypass surgery (CPB) causes lung injury and at least 2% of adult patients and more children develop the most severe from acute respiratory distress syndrome (ARDS). Pulmonary surfactant deficiency contributes to the pathogenesis of ARDS. It has been proposed that surfactant therapy immediately after CPB might arrest progression to ARDS. However, many patients develop only mild lung injury after CPB. Thus early markers are needed to identify those patients at highest risk to guide selection for treatment. The aim of this study was to determine whether changes in surfactant phospholipids occur, and reflect severity of lung injury within the first few hours after bypass. Because of the relatively low incidence of ARDS in adult patients, this study was conducted using young pigs highly susceptible to bypass-induced lung injury. Eight pigs were given 2 hours bypass. Six controls underwent 'sham' bypass. At 3 h after bypass pulmonary vascular endothelial permeability was assessed by transcapillary leakage of radiolabelled transferrin. A 4 hour broncho-alveolar lavage (BAL) was used to assess intra-alveolar levels of surfactant, inflammatory cells and oedema protein. Bypass caused falls in arterial oxygenation and lung compliance (P < 0.01), but at this early stage in progression of lung injury BAL surfactant phospholipid and albumin levels were within the control range indicating that the alveolar epithelium had not yet suffered major damage. The main abnormalities were increases in vascular endothelial permeability (P < 0.01), BAL neutrophils (P < 0.01), total protein and sphingomyelin (SM) (P < 0.05). Lung histology showed that the main damage was interstitial oedema located around the bronchioles and their associated vessels. A single instilled dose of surfactant phospholipids in 5 animals caused excess in vivo supplementation and did not reduce the early pathophysiologic changes. Our findings suggest that surfactant phospholipid deficiency does not make a major contribution in the initial stages of lung injury after CPB, and that excessive phospholipid supplementation at this stage can be deleterious.