Therapy For Respiratory Distress Syndrome Research Articles

Extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) has become a more or less accepted standard in the algorithm of advanced acute respiratory distress syndrome therapy in adult patients when all other treatment options have failed. This article reviews the current status of ECMO therapy with particular focus on new technical developments and their potential implications for performance and indications for ECMO therapy. A recently published review on a single-center experience in 255 adult ECMO patients identified using multivariate logistic regression analysis age, sex, initial pH 7.10 or lower and PaO2/FiO2 ratio, and days of mechanical ventilation before ECMO as a significant predictors of survival. Additionally, a careful cost-effectiveness study for neonatal ECMO relating a 4-year base to the UK neonatal ECMO trial has clearly demonstrated cost-effectiveness. Over the years, the technique for ECMO therapy underwent substantial changes in indications and the materials used. Impressive technical progress has been made in pumps, oxygenators, and coating of artificial surfaces, leading to a higher biocompatibility and to a lower rate of procedure-related complications. The potential of new inline pumps in combination with a decreasing rate of procedure-related complications might lead to a re-evaluation of the role of extracorporeal lung support in acute respiratory distress syndrome therapy. A very recent development is the use of spontaneous arteriovenous devices for carbon dioxide removal, allowing significant reduction of ventilator settings at decreased carbon dioxide partial pressures and at increased pH values. Ongoing studies are looking at the potential of this approach to reduce side effects of mechanical ventilation further.

117 Early and Late Adverse Effects Following Surfactant Therapy

Background: Exogenous surfactant (S) therapy improved mortality and morbidity of premature babies with respiratory distress syndrome. The commercial S preparation used in our NICU is natural “bovine” type. The adverse effects of this therapy have not been clarified yet. Objective: To estimate the early and later risks of S therapy for respiratory distress syndrome (RDS). Methods: Data from all premature newborns with or without RDS treated or not with S in our NICU the last 10 years were analyzed. The incidence and the relative risk(RR) of the lung and intracerebral hemorrhage as well as of the infection were calculated. Three hundred ninenty three of them accepted to participate in a retrospective study and were examined for allergic disorders, such as allergic rhinitis, asthma and adverse food reactions. Results: Three thousands forty premature newborns graduated our NICU from 1994 to 2004.Pulmonary hemorrhage was observed in the 57 of the 330 newborns with RDS who received S and the 6 over 198 of those newborns untreated with S,chi squared= 19.489, p= 0.00001,RR= 5.756. Intraventricular hemorrhage was diagnosed in 106 of the 281 and 20 over 184, respectively, chi square = 24.629, p= 0.00001,RR= 3.490.Infection in 115 of 272 and 87 in 117,respectively, chi squared = 9.291,p= 0.00167,RR= 1.768. Positive history of allergy was estimated in the 44% of the children treated with S for RDS and in the 25% of those with RDS not treated with S, chi squared= 11.363, p= 0.000749.From the premature babies without RDS allergy was noted in 28%,x= 0.8061,p= 0.3692. Conclusion: Despite the undoubtfull benefits of the S therapy for RDS attention should be paid to its possible early and late adverse effects. The S therapy increases the risk for severe even lethal complications such as pulmonary or intraventricular hemorrhage and infection. It is impressive the almost two-fold increase in the incidence of allergy during childhood in babies treated with S compared to non-treated ones. Prospective clinical trials and basic research would help to minimize the early risks and optimize late prognosis in newborns treated with S.

Surfactant for RDS: When and how?

This issue of The Journal contains two articles about surfactant therapy for respiratory distress syndrome (RDS). The big picture is that surfactant treatments for RDS are safe and very effective and are the standard of care. However, considerable controversy remains about when to treat infants at risk for or with RDS, how to give those treatments, and what sort of ventilatory support is best and for how long. Variables generating uncertainty are timing of treatment (at delivery/after initial stabilization), ventilatory support before and after treatment (continuous positive airway pressure [CPAP]/mechanical ventilation and type of mechanical ventilation), techniques for treatment (pharyngeal at delivery, number and volumes of boluses for each treatment, management after treatment). Each variable is further complicated by the gestational age/birth weight of each infant and the clinical status of the infant at birth. The Texas Neonatal Research Group performed a multicenter randomized trial to ask if larger infants (≥1250 g) with RDS and an oxygen requirement of ≥40% would benefit from immediate intubation and surfactant treatment compared with expectant management with surfactant treatment if the respiratory disease progressed. For this group of infants, an early intervention with surfactant treatment was of no benefit. This result supports the current clinical trend to use CPAP therapy for larger infants with RDS. Kaiser, Gauss, and Williams evaluated the effect of surfactant treatment on cerebral blood flow in very-low-birth-weight (VLBW) infants using continuous monitoring. They demonstrate that routine surfactant treatments result in a peak increase in Pco2 of about 20 mm Hg 15 minutes after the surfactant treatment. The increase in Pco2 is associated with an increase in cerebral blood flow velocity, demonstrating intact autoregulation of cerebral blood flow in these VLBW infants. The peak increase in Pco2 at 15 minutes probably results from airway occlusion with the surfactant suspension. The importance of the study is that it points out that surfactant therapy does cause transient physiologic changes that need to be balanced against benefit. For example, the decision to treat an infant on CPAP with surfactant requires intubation followed by surfactant instillation. Both procedures cause physiologic abnormalities that need to be recognized. Strategies for when to treat which patient and how remain hot topics in neonatology.

Surfactant for RDS: When and how?

This issue of The Journal contains two articles about surfactant therapy for respiratory distress syndrome (RDS). The big picture is that surfactant treatments for RDS are safe and very effective and are the standard of care. However, considerable controversy remains about when to treat infants at risk for or with RDS, how to give those treatments, and what sort of ventilatory support is best and for how long. Variables generating uncertainty are timing of treatment (at delivery/after initial stabilization), ventilatory support before and after treatment (continuous positive airway pressure [CPAP]/mechanical ventilation and type of mechanical ventilation), techniques for treatment (pharyngeal at delivery, number and volumes of boluses for each treatment, management after treatment). Each variable is further complicated by the gestational age/birth weight of each infant and the clinical status of the infant at birth. The Texas Neonatal Research Group performed a multicenter randomized trial to ask if larger infants (≥1250 g) with RDS and an oxygen requirement of ≥40% would benefit from immediate intubation and surfactant treatment compared with expectant management with surfactant treatment if the respiratory disease progressed. For this group of infants, an early intervention with surfactant treatment was of no benefit. This result supports the current clinical trend to use CPAP therapy for larger infants with RDS. Kaiser, Gauss, and Williams evaluated the effect of surfactant treatment on cerebral blood flow in very-low-birth-weight (VLBW) infants using continuous monitoring. They demonstrate that routine surfactant treatments result in a peak increase in Pco2 of about 20 mm Hg 15 minutes after the surfactant treatment. The increase in Pco2 is associated with an increase in cerebral blood flow velocity, demonstrating intact autoregulation of cerebral blood flow in these VLBW infants. The peak increase in Pco2 at 15 minutes probably results from airway occlusion with the surfactant suspension. The importance of the study is that it points out that surfactant therapy does cause transient physiologic changes that need to be balanced against benefit. For example, the decision to treat an infant on CPAP with surfactant requires intubation followed by surfactant instillation. Both procedures cause physiologic abnormalities that need to be recognized. Strategies for when to treat which patient and how remain hot topics in neonatology.

The Role of the Hospital of Birth on Survival of Extremely Low-birthweight, Extremely Preterm Infants

After completing this article, readers should be able to: 1. Explain the differences between population-based and institutional-based outcome studies of extremely low-birthweight (ELBW)/extremely preterm (EPT) infants. 2. Define three commonly used mortality/survival outcome measures for neonatal intensive care unit admissions. 3. Explain the role of population-specific factors in the survival potential of ELBW/EPT infants. 4. Explain the role of selection bias for maternal and neonatal transport in site-of-care mortality/survival statistics for ELBW/EPT infants. 5. Explain the role of the hospital of birth in current survival statistics for United States ELBW/EPT infants. Advances in perinatal health care in the past 15 years have resulted in a marked decrease in neonatal mortality throughout the industrialized world. Prior to the late 1980s, the greater portion of improved survival among preterm infants occurred primarily in infants older than 28 weeks’ gestation at birth. Refinements in the design and operation of mechanical ventilators and intravenous nutrition support, the implementation of continuous pulse oximetry monitoring, and the introduction of medical closure of the patent ductus arteriosus with indomethacin and of surfactant replacement therapy for respiratory distress syndrome have been major contributors to the improved survival in recent years among more immature infants (<28 weeks’ gestation). In addition, use of antenatal steroid therapy for induction of lung maturity and tocolytics to delay delivery as well as aggressive management of maternal medical and obstetric complications of pregnancy have been associated with decreased severity of illness in extremely preterm infants. The organization of perinatal health services into regional networks improved the outcome of high-risk pregnancies in the 1970s. However, in the United States, during the recent time of advances in perinatal health care capabilities, regional organization was dismantled in many states due, in large part, to the economics of health care funding. There followed a proliferation of community hospital-based neonatal intensive care units (NICUs) …

Surfactant therapy for respiratory distress syndrome in premature neonates: a comparative review.

Exogenous surfactant therapy has been part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since the beginning of the 1990s. Discoveries that led to its development as a therapeutic agent span the whole of the 20th century but it was not until 1980 that the first successful use of exogenous surfactant therapy in a human population was reported. Since then, randomized controlled studies demonstrated that surfactant therapy was not only well tolerated but that it significantly reduced both neonatal mortality and pulmonary air leaks; importantly, those surviving neonates were not at greater risk of subsequent neurological impairment. Surfactants may be of animal or synthetic origin. Both types of surfactants have been extensively studied in animal models and in clinical trials to determine the optimum timing, dose size and frequency, route and method of administration. The advantages of one type of surfactant over another are discussed in relation to biophysical properties, animal studies and results of randomized trials in neonatal populations. Animal-derived exogenous surfactants are the treatment of choice at the present time with relatively few adverse effects related largely to changes in oxygenation and heart rate during surfactant administration. The optimum dose of surfactant is usually 100 mg/kg. The use of surfactant with high frequency oscillation and continuous positive pressure modes of respiratory support presents different problems compared with its use with conventional ventilation. The different components of surfactant have important functions that influence its effectiveness both in the primary function of the reduction of surface tension and also in secondary, but nonetheless just as important, role of lung defense. With greater understanding of the individual surfactant components, particularly the surfactant-associated proteins, development of newer synthetic surfactants has been made possible. Despite being an effective therapy for RDS, surfactant has failed to have a significant impact on the incidence of chronic lung disease in survivors. Paradoxically the cost of care has increased as surviving neonates are more immature and consume a greater proportion of neonatal intensive care resources. Despite this, surfactant is considered a cost-effective therapy for RDS compared with other therapeutic interventions in premature infants.

In vitro evaluation of surfactants with eucalyptus oil for respiratory distress syndrome

The effects of low doses of eucalyptus oil (EO) were studied on the surface properties of phospholipid suspensions as exogenous surfactants, by in vitro analysis using a pulsating bubble surfactometer and a Wilhelmy balance. Survanta, ALEC and Exosurf, commonly used surfactants in therapy of respiratory distress syndrome were used as controls for comparison. The test surfactants, in Ringer's lactate at 1%, were pulsated at 40cpm in the surfactometer. EO caused a significant improvement of adsorption of the surfactants. In the case of the binary mixture of dipalmitoylphosphatidylcholine and phosphatidylethanolamine (2:3), EO significantly improved the adsorption, stability and minimum surface tension obtained. This combination performed better than ALEC and Exosurf and was comparable to Survanta with respect to minimum surface tension attained. The re-spreading of a surface excess film of this mixture in a Wilhelmy balance was higher than that of ALEC and Exosurf. The ultrastructure of the EO enriched surfactants using cryogenic scanning electron microscopy showed easy facturability and formation of open membranous structures, which could have been associated with the improved surface activity.

In vitro evaluation of surfactants with eucalyptus oil for respiratory distress syndrome

The effects of low doses of eucalyptus oil (EO) were studied on the surface properties of phospholipid suspensions as exogenous surfactants, by in vitro analysis using a pulsating bubble surfactometer and a Wilhelmy balance. Survanta, ALEC and Exosurf, commonly used surfactants in therapy of respiratory distress syndrome were used as controls for comparison. The test surfactants, in Ringer's lactate at 1%, were pulsated at 40 cpm in the surfactometer. EO caused a significant improvement of adsorption of the surfactants. In the case of the binary mixture of dipalmitoylphosphatidylcholine and phosphatidylethanolamine (2:3), EO significantly improved the adsorption, stability and minimum surface tension obtained. This combination performed better than ALEC and Exosurf and was comparable to Survanta with respect to minimum surface tension attained. The re-spreading of a surface excess film of this mixture in a Wilhelmy balance was higher than that of ALEC and Exosurf. The ultrastructure of the EO enriched surfactants using cryogenic scanning electron microscopy showed easy facturability and formation of open membranous structures, which could have been associated with the improved surface activity.

The significance of recurrent lung opacities in neonates on surfactant treatment for respiratory distress syndrome.

To determine the significance of recurrent opacities in chest radiographs of neonates on surfactant therapy for respiratory distress syndrome (RDS) after an initial period of improvement. Serial pre-and post-surfactant chest radiographs on 94 preterm infants with RDS were analyzed and the pattern of chest radiographic response was classified as (a) clear, (b) recurrent opacities, and (c) no response. Their clinical characteristics were also recorded. In 34 infants the RDS changes cleared within 3 days. 31 infants developed lung opacities within 10 days after an initial period of improvement. Twenty-nine infants failed to respond to the surfactant. The corresponding mean birth weights for the three groups were 1.74, 1.19, and 0.76 kg and the mean gestation ages 32.6, 27.7, and 25.4 weeks. The incidence of bronchopulmonary dysplasia (BPD) was highest among the slumping infants (72% vs. 50% in no responders, P<0.001) The pattern of chest radiographic response is primarily affected by gestation age and birth weight. Recurrent lung opacity after an initial positive response to surfactant therapy may be caused by such factors as edema from barotrauma and patent ductus arteriosus. Infants with intraventricular hemorrhage may demonstrate neurogenic edema. Other contributory factors include pneumonia and abnormal consumption of surfactant. Recurrent lung opacities after surfactant may be a predictor of chronic lung disease in the preterm infant.

Changes in dead space/tidal volume ratio and pulmonary mechanics after surfactant replacement therapy in respiratory distress syndrome of the newborn infants.

This study was performed to elucidate the mechanism of improved oxygenation after surfactant replacement therapy in respiratory distress syndrome (RDS) of the newborn infants. In 26 newborns with RDS, end tidal-CO2 tension (PetCO2), arterial blood gas analysis and pulmonary function tests were measured at baseline, 30 min, 2 hr and 6 hr after surfactant administration. The changes in dead space/tidal volume ratio (VD/VT ratio=(PaCO2-PetCO2)/PaCO2), oxygenation index and arterial-alveolar partial pressure difference for oxygen ((A-a)DO2) were elucidated and correlated with pulmonary mechanics. Oxygenation index and (A-a)DO2 improved, and VD/VT ratio decreased progressively after surfactant administration, becoming significantly different from the baseline at 30 min and thereafter with administration of surfactant. Pulmonary mechanics did not change significantly during the observation period. VD/VT ratio showed close correlation with OI and (A-a)DO2, but not with pulmonary mechanics. These results suggest that decreased physiologic dead space resulting from the recruitment of atelectatic alveoli rather than improvement in pulmonary mechanics is primarily responsible for the improved oxygenation after surfactant therapy in the RDS of newborn.

Analysis of dynamic surface properties of therapeutic surfactants and lung phospholipids.

Exogenous surfactant is a specialized biomaterial used for substitution of the lipoprotein mixture normally present in lungs--pulmonary surfactant. Respiratory Distress Syndrome is a disease of preterm infants mainly caused by a deficiency of mature lung surfactant. Pulmonary surfactant is known to stabilize small alveoli and prevent them from collapsing during expiration due to its unique surface properties. A pulsating bubble surfactometer was used for in vitro analysis of surface parameters of therapeutic surfactants and of test formulations to be used for exogenous therapy in Respiratory Distress Syndrome. Surface parameters that were considered for comparison were minimum surface tension (gamma(min)) at three different frequencies (20, 40 and 60 cpm), adsorption at two extreme bubble radii (Rmin and Rmax), stability index at the three frequencies, recruitment index and the surface viscoelastic parameters. Survanta, ALEC and Exosurf were compared with formulations consisting of the main phospholipids of pulmonary surfactant, namely dipalmitoyl phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) as well as binary mixtures of these phospholipids in the ratio 2:3. Survanta performed much better than the non-protein therapeutic surfactants in all parameters and at all three frequencies. Exosurf had a very low stability index and a very low modulus of surface dilatational elasticity at all three frequencies. The test compounds showed a frequency dependence in their performance. At 20 cpm, PC:PG (2:3) was the best test combination. It achieved a gamma(min) and stability index equivalent to Survanta at this frequency. None of the test compounds were comparable to Survanta at 40 and 60 cpm. These findings may have important therapeutic implications for exogenous surfactants.

Changes of neonatal mortality rate between 'pre' and 'post' surfactant period.

The objective of this study was to determine how the neonatal mortality rate has changed since surfactant (S) therapy was introduced in our Neonatal Intensive Care Unit (NICU), and to evaluate the efficacy of surfactant therapy in respiratory distress syndrome (RDS) patients. Incidences of risk babies such as outborns, prematurity, low birth weight infants and RDS, and neonatal mortality rates were compared between 'pre' (control, 1988 to 1991, n=4,861) and 'post' S period (study, 1993 to 1996, n=5,430). In RDS patients of 'post' S period, neonatal mortality rate was compared between S-treated and non-treated patients, and chest X-ray and ventilatory parameters were compared between pre- and post-72 hr of surfactant treatment. Surfactant therapy showed short term effects, judging by the decrease of early neonatal deaths and improvement of chest X-ray and ventilatory parameters in RDS patients. The overall neonatal mortality rate had a tendency to decrease in spite of increased incidences of risk babies in 'post' S period but it was less than expected. The reasons were thought to be that we had a high proportion of risk babies, and there was some bias in patient selection for surfactant therapy and its use. In conclusion, with the active prevention of risk baby delivery and appropriate use of surfactant, better results could be expected.

Current perspectives on the drug treatment of neonatal respiratory distress syndrome.

Respiratory distress syndrome (RDS) in preterm neonates is caused by a lack of alveolar surfactant, which leads to decreased pulmonary compliance and increased work of breathing. Effective therapy for RDS has reduced mortality at the expense of increasing the number of preterm survivors with chronic lung disease. Drugs such as corticosteroids, proterelin (thyrotropin-releasing hormone) and ambroxol have all been administered to mothers to promote fetal lung maturation, but of these only corticosteroids have been proven to be of benefit. The management of RDS includes assisted ventilation and surfactant replacement therapy. There are several surfactant preparations, some synthetic and others derived from animal lungs, and recent research has been directed at finding which, if any, is superior. The timing of the first dose has also been studied. Prophylactic surfactant administration within the first 15 minutes of life appears to be more efficacious than later treatment for very preterm babies, but could lead to some neonates being treated unnecessarily and perhaps being exposed to adverse effects. Newer treatments for neonates with RDS are aimed at reducing the pulmonary inflammation that occurs as a result of ventilatory barotrauma and oxygen toxicity. Superoxide dismutase, along with other antioxidants, may be beneficial as a free radical scavenger to reduce oxygen toxicity. Inhaled nitric oxide may reduce oxygen requirements by reducing ventilation-perfusion mismatching, and early treatment with corticosteroids may reduce pulmonary inflammation. All of these treatments are currently undergoing clinical trials.

Corrigendum

Corrigendum

Advances in conventional and innovative therapies for respiratory distress syndrome in children.

Adult respiratory distress syndrome is a phenomenon encountered by many pediatric critical care nurses. Care of these complex patients is multifaceted and requires an in-depth understanding of pathophysiology and therapeutic intervention. Several innovative treatments are now available as biomedical and technical advances have evolved. Outcomes will improve as clinicians improve patient selection, identify therapeutic endpoints, and risk/benefits. This article addresses the current understanding of pathophysiology, innovative treatments, and nursing care issues.

Controversies: synthetic or natural surfactant. The case for natural surfactant.

Surfactant replacement therapy for respiratory distress syndrome (RDS) is not new, the first trials having been performed over 30 years ago. These early trials used synthetic protein-free surfactants administered as aerosols and were unsuccessful. Since 1980 a variety of natural and synthetic surfactant preparations have been used to treat or prevent RDS, and both demonstrate clinical effects. I have used evidence derived from 3 areas to demonstrate the superiority of natural surfactants: in vitro physical properties, in vivo physiological effects and the results of comparative clinical trials. using the pulsating bubble surfactometer, the surface tension at maximum and minimum bubble size are significantly lower for natural compared to synthetic surfactants (31 and 0 mN/m versus 53 and 29 mN/m respectively). Physiological effects of surfactants have been compared in immature rabbits and lambs and both models demonstrate the superiority of natural surfactants. For example in immature rabbits lung compliance values after 60 minutes of ventilation are 0.60 ml/cmH2O in natural surfactant treated animals, 0.44 ml/cmH2O in synthetic surfactant treated animals and 0.34 ml/cmH2O in controls (p < 0.01). The technique of meta-analysis was used to analyse the outcome of 6 comparative clinical trials of natural and synthetic surfactants. These 6 studies included 3536 babies and 5 of them compared Survanta (a bovine natural surfactant) and Exosurf (a synthetic protein-free surfactant). One study compared Infasurf (another bovine natural surfactant with Exosurf). Meta-analysis shows a 19% reduction in the odds of neonatal death for natural compared to synthetic surfactant treated babies (OR, 0.81; 95% CI 0.66-0.98). For bronchopulmonary dysplasia there was a non-significant reduction in risk for Survanta-treated babies (OR, 0.93; 95% CO 0.78-1.10). In summary, there is now clear evidence of physiological and clinical superiority of natural compared to synthetic surfactants. Surfactant proteins B and C are needed to facilitate rapid adsorption and spreading of phospholipids. They also account for the more rapid clinical action allowing oxygen and ventilator pressures to be lowered soon after administration. The odds of neonatal mortality are reduced by about 20% if natural surfactants are preferred to their synthetic protein-free counterparts. Long-term follow-up studies of babies treated with both types of surfactant should be a top priority.

Surface tension measurements on pharyngeal and tracheal aspirate samples from newborns without and with respiratory distress syndrome.

A rapid test determining surfactant deficiency or dysfunction might help in controlling therapy of respiratory distress syndrome (RDS). Forty tracheal aspirate samples (TA) from 40 newborns with RDS (group 1) and 46 pharyngeal from 46 newborns without RDS (reference group) were analyzed by surface tension measurement with the pulsating bubble surfactometer. Five surface tension parameters were compared. Marked differences between both groups could be noted for the parameters: minimum surface tension (gamma min) and stability index (S), while maximum surface tension (gamma max), surface tension after a 10-second adsorption period and hysteresis area did not have striking differences. The parameters gamma min and S have the highest diagnostic value for determining surfactant deficiency or dysfunction. For a rapid test it is sufficient to compare gamma min with reference values, because S is calculated from gamma min and gamma max.

Hypocarbia before surfactant therapy appears to increase bronchopulmonary dysplasia risk in infants with respiratory distress syndrome.

To determine to what extent the risk of bronchopulmonary dysplasia is affected by ventilatory management before the first dose of rescue artificial surfactant. Retrospective cohort study. One hundred eighty-eight low-birth-weight infants (< or = 1700 g) who received artificial surfactant therapy for respiratory distress syndrome and who were alive at 36 weeks of gestational age. Bronchopulmonary dysplasia was defined by a need for supplemental oxygen to maintain an arterial saturation of 92% or more at 36 weeks of gestational age. Thirty-seven percent (70/188) of the cohort met study criteria for bronchopulmonary dysplasia. Early determinants significantly associated with bronchopulmonary dysplasia (given as odds ratio, 95% confidence interval) in the most parsimonious backward stepwise logistic regression model included the following: birth weight of 1000 g or less (5.1, 2.4 to 10.7), cesarean birth because of fetal distress (4.4, 1.7 to 11.4), ventilatory efficiency index of 0.15 or less before surfactant therapy (3.1, 1.4 to 6.8), arterial-alveolar oxygen ratio of 0.15 or less before surfactant therapy (2.2, 1.01 to 4.6), and a low arterial PCO2 (< or = 29 vs > or = 40 mm Hg, 5.6, 2.0 to 15.6; 30 to 39 vs > or = 40 mm Hg, 3.3, 1.3 to 8.3). The inverse relationship between hypocarbia and bronchopulmonary dysplasia persisted even in stratified analyses limited to infants with measures of cardiovascular or respiratory illness that suggested less severe manifestations of disease. Ventilatory management before rescue treatment with artificial surfactant therapy that result in hypocarbia may increase the risk of bronchopulmonary dysplasia. These findings suggest that early ventilatory management should not only provide adequate oxygenation but also limit hyperventilation.

Pulmonary Hemorrhage Risk in Infants With a Clinically Diagnosed Patent Ductus Arteriosus: A Retrospective Cohort Study

To determine if an early, clinically detectable patent ductus arteriosus (PDA) was associated with pulmonary hemorrhage (PH) in infants who received rescue artificial surfactant therapy. This retrospective cohort study of 233 low birth weight infants (< or = 1700 g) who received artificial surfactant therapy for respiratory distress syndrome compared antenatal and postnatal characteristics of infants with PH and without PH. Pulmonary hemorrhage was defined by an onset of bright red blood from the endotracheal tube in quantities that resulted in increased ventilatory support and a new infiltrate on a chest radiograph. Pulmonary hemorrhage occurred in 6% (15/233) of the infants. Thirty-three percent (5/15) of the infants with PH died within 14 days of the hemorrhage. Of the 15 PH, 73% occurred within 48 hours of the first surfactant dose. Pulmonary hemorrhage was more common in male infants and infants of mothers who received antibiotic therapy during labor (P < or = .04). Infants with PH received surfactant earlier than those without PH (P = .04). Nursery events or therapies occurring following surfactant therapy that were associated with PH included: little improvement in ventilatory efficiency index (P = .01), dopamine infusion (P = .04), and the presence of a clinically detectable PDA before, or at the time of, the PH [60% (9/15) vs 33% (71/217), P = .03]. After adjusting for severity of illness before surfactant therapy, risk of PH remained greater in infants who developed symptoms of a PDA. Dopamine support appeared to modify the association between PDA and PH. In this retrospective cohort study, pulmonary hemorrhage, was associated with the presence of a clinically detectable patent ductus arteriosus before, or at the time of, pulmonary hemorrhage.

Surfactant therapy in respiratory distress syndrome: The effect of a learning curve in improving outcome

A retrospective study of all premature neonates who received artificial surfactant (Curosurf) at the Rotunda Hospital was performed. The period from October 1990 to June 1992 (n = 48) was compared with the initial experience from June 1987 to January 1988 (n = 15). In the initial period mortality rate was 67% in surfactant treated infants, and use of surfactant was not associated with an improvement in outcome compared with the previous six years. In the more recent period overall mortality was 21%. Overall survival in normally formed very low birthweight infants improved from 59% in 1986 to 86% in 1991-1992. Improvement in survival rates was most noticeable in infants with birthweight 750-999 grams, with survival increasing from 44% (before introduction of surfactant treatment) to 91% (in 1991-1992). It is probable that a certain level of experience with use of surfactant is required before optimal effects can be obtained.