First Dose Of Surfactant Research Articles

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Extreme prematurity-associated alterations of pulmonary inflammatory mediators before and after surfactant administration.

The role of prematurity and pulmonary inflammation in the pathogenesis of bronchopulmonary dysplasia (BPD) is very well-defined. However, there is limited knowledge about whether the level of prematurity and surfactant therapy alter the pulmonary cytokines and endothelial growth factor (VEGF). This study analyzed the VEGF and cytokines, including interleukin (IL)-1β, IL-6, IL-8, and IL-10, and tumor necrosis factor α (TNF-α) in the tracheal aspirate (TA) of preterm infants obtained before (within 2h after birth) and 10-12h after the administration of the first dose of surfactant. TA was collected from 40 infants of 35 or fewer weeks of gestation, including extremely (Group 1, n=19), very (Group 2, n=13), and moderate/late (Group 2, n=8) preterm neonates. In addition to univariate analysis, controlled regression models estimated the association of perinatal factors with the tested parameters and their role in the development of BPD. We recorded significantly lower post-partum levels of VEGF and higher IL-8, IL-1β, and TNF-α in the TA of Group 1 infants than in Group 2 and 3. Compared to the infants in Group 2 and 3, the post-surfactant increases of pulmonary VEGF, IL-8, IL-10, and TNF-α were more significant in Group 1. All tested parameters in Group 1 and 2 infants, before and after surfactant administration, were comparable. BPD was recorded in nearly 60% of the extremely preterm survivors and was significantly predicted by increased IL-8 before, and elevated TNF-α level after surfactant administration. This study indicates the association of birth at extremely preterm gestation with reduction in pulmonary VEGF and exacerbation of pro-inflammatory cytokines followed by greater elevation post-surfactant administration levels of VEGF, IL-8, TNF-α, and IL-10 than in neonates born with gestational age of 28-35 weeks.

Effect of surfactant dose on outcomes in preterm infants with respiratory distress syndrome: the OPTI-SURF study protocol

IntroductionRespiratory distress syndrome is a condition seen in preterm infants primarily due to surfactant insufficiency. European guidelines recommend the dose and method of surfactant administration. However, in routine practice, clinicians...

Effect of T-Piece Resuscitator versus Self Inflating Bag on Arterial CO2 Levels in Preterm Neonates.

ObjectiveTo compare the effect of self-inflating bag (SIB) vs. T-piece resuscitator (TPR) on PaCO2 levels, when used for brief manual ventilation during administration of first dose of surfactant.MethodsPreterm neonates were randomized to receive positive pressure ventilation with either self-inflating bag or T-piece resuscitator during administration of first dose of surfactant. Arterial blood gases were obtained at baseline and 1 h after the intervention. Primary outcome was the mean change in PaCO2 levels 1 h after the intervention.ResultsEighty neonates were enrolled (40 in each group). The drop in PaCO2 at 1 h was significantly greater in the self inflating bag group as compared to the T-piece resuscitator group [8.96 ± 9.06 mmHg vs. 1.37 ± 9.06 mmHg, Mean difference = 7.58 mmHg, (95% CI: 3.78 to 11.4); P < 0.01]. The PaCO2 change was also statistically significant in the subgroup of infants that required only non-invasive ventilation. The need for second dose of surfactant was higher in the self-inflating bag group [77% vs. 55%, RR - 1.41 (95% CI: 1.02 to 1.94); P = 0.03].ConclusionsT-piece resuscitator results in smaller reduction in PaCO2 levels compared to the self inflating bag, when used for brief manual ventilation during surfactant administration.

Does lung ultrasound score predict the need for surfactant in extremely preterm neonates?

Commentary on: De Martino L, Yousef N, Ben-Ammar R, et al. Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates. Pediatrics. 2018;142(3):e20180463. PMID 30108142. Respiratory distress syndrome (RDS) is almost universal in the extremely preterm neonate, and select patients benefit from timely administration of surfactant therapy 1. Use of lung ultrasonography to assign a semi-quantitative lung ultrasound score (LUS) may predict which neonates will require surfactant therapy 2. This was a prospective cohort diagnostic accuracy study to assess the ability of the LUS to predict the need for surfactant treatment and re-treatment in neonates ≤30 weeks’ gestational age with RDS on continuous positive airway pressure (CPAP). Patients had a lung ultrasound performed to assign a LUS, and then need for treatment and re-treatment with surfactant relied solely on the inspired fraction of oxygen (FiO2) requirement 3. We evaluated the study using the QUADAS-2 tool–see attached supplement 4. Patients were enrolled consecutively with appropriate inclusion/exclusion criteria. The study was well-powered. The index test was the LUS with no pre-specified thresholds. Of note, lung ultrasonography is the first-line imaging to evaluate RDS at this institution. The ultrasound operator was not blinded to the patient's FiO2 requirement, which increases the risk of bias, although previous studies demonstrated good inter-rater reliability under similar conditions 2. The physician was blinded to the LUS results, however, when determining the need for surfactant therapy based on the FiO2 reference standard. The authors report that a lung ultrasound was performed on average at 30 minutes of life, and that the first dose of surfactant was administered at a mean of four hours of life, but it is unclear how long the patient had to exceed the FiO2 requirement before a decision was made to treat. Receiver operating characteristic analysis demonstrated good predictive value with an area under the curve ≥0.9 across all gestational ages. It was closer to 0.8, however, when predicting the need for re-treatment. LUS cut-offs also predicted the need for treatment and re-treatment with surfactant. The authors did not provide clinical characteristics for patients requiring treatment or re-treatment versus no treatment, so it is unclear whether there were confounding factors. For example, only 60% of study patients received a full antenatal steroid course, but the authors did not report whether this varied between the treatment versus no treatment groups. The secondary outcome correlating LUS with oxygenation index demonstrated good agreement. Overall, the results support the reliability of the LUS to predict the need for surfactant treatment in this population. This study's primary limitation is applicability. While the authors used low FiO2 cut-offs (30% for ≤ 28 weeks and 40% for > 28 weeks) to administer surfactant, the FiO2 requirement constituting CPAP failure varies in the literature from 30-75% 1, 5, 6–restricting the applicability of these results to institutions which utilise similar thresholds. Additionally, although other studies report good reliability of the LUS 3, 7, 8, a recent systemic review by Hiles, et al., found only moderate quality evidence to support its use 9. Thus, more research is needed prior to universal implementation, so for now this study's results are limited to NICUs with similar expertise. https://ebneo.org/2019/01/lung-ultrasound-score/ None. None.

Does inhaled salbutamol before surfactant therapy have any beneficial effect?

Çelik HT, Yurdakök M, Korkmaz A, Yiğit Ş. Does inhaled salbutamol before surfactant therapy have any beneficial effect? Turk J Pediatr 2018; 60: 669-674. Beta (β)2 adrenergic receptors are present in alveolar type II cells. Previously, the beneficial effects of inhaled salbutamol treatment on respiratory outcomes were shown in premature infants with transient tachypnea of the newborn. We hypothesized that inhaled salbutamol would increase the effects of surfactant on oxygenation in premature infants with respiratory distress syndrome (RDS). Inhaled salbutamol (0.15 mg/kg) or normal saline solution (0.30 ml/ kg) was administered as a single dose by micropump nebulizer 10 minutes before the first dose of surfactant (Poractant alfa) treatment in 40 infants with gestational ages ranging from 26 to 36 weeks. The effects of salbutamol therapy were evaluated by determining the duration of respiratory support, number of doses of surfactant, respiratory rate, heart rate, fraction of inspired oxygen, and partial pressure of arterial oxygen before and after salbutamol nebulization. No statistically significant difference was detected between the two groups in duration of respiratory support, number of doses of surfactant, respiratory rate, fraction of inspired oxygen, or partial pressure of arterial oxygen. In this study, no significant effect of inhaled salbutamol treatment on the surfactant therapy in premature infants with RDS was detected.

English

Respiratory distress syndrome (RDS) is a common cause of mortality and complications in the preterm neonates. Specific treatment of this disease is endotracheal surfactant administration. Some neonates need more than one dose of drug (re-dosing) so that in addition to the cost, avoidace of treatment complications and, if necessary, timely prescribtion are of high importance. In this study, the effects of the contributing factors, including prescription or non-prescription of corticosteroid to the mother, the gestational age, fetal gender, birth weight, the first and fifth minute APGAR score, respiratory distress score, time of first dose of surfactant administration, type of delivery, type of surfactant, in the case of re-dosing of surfactant in neonates with RDS, and in NICU of Motahari Maternity-Children Hospital, Urmia, Iran were compared and the positive and negative effects of each of the above-mentioned factors were examined. Few studies have been conducted on the effect of the administration of the second dose of surfactant and its subsequent doses compared with the used doses. All hospitalized neonates, who were diagnosed with RDS after birth during 2011 to 2013, were included in the study. Data was collected from a designed form and analyzed by SPSS version 22. They included 213 (60.9%) male and 137 (39.1%) females with a mean weight of 1782.03 &plusmn; 387.04 g. 66 males (31%) and 32 females (23.4%) received more than one dose of surfactant. 227 neonates (64.9%) were discharged with a recovery and 123 neonates (35.1%) died. Findings of our study showed that neonates with the low birth weight have received more than one dose of surfactant. Moreover, neonates born between 32 to 36 weeks of gestation needed re-dosing of more surfactant. Neonates with first dose of surfactant for 6 to 24 h after birth need significantly more re-dosing of surfactant. There was a significant difference between the re-dosing of surfactant and type of delivery. In addition, re-dosing of more surfactant was needed with the increasing numbers of neonate per delivery. In contrast; the need to re-dosing of surfactant in the neoantes whose mothers had received one dose of prenatal corticosteroid was greater than the neoantes whose mothers had received two doses of prenatal corticosteroid. Moreover, the type of the surfactant products (curosurf and Survanta) had no effect on the re-dosing of doses of surfactant in the studied infants. The percentage of the use of more than one dose of surfactant was higher in male neonates than the female ones. Inaddition, the first and fifth minute APGAR scores were significantly lower in re-dosing group. In this study, the need for re-dosing of surfactant was significantly greater in the neonates with the higher respiratory distress score (&gt;8) than the neonates with the mild to moderate respiratory distress scores (&le;8). &nbsp; Key words: Respiratory distress syndrome, surfactant, re-dosing.

Effects of beractant and poractant administration on cerebral hemodynamics

Objective: To determine whether type and timing of surfactant preparation affect cerebral blood flow (CBF) hemody- namics differently. Study design: Two sites monitoring cerebral hemodynamics during surfactant administration. Beractant (4.0 ml/kg) and poractant (2.5 ml/kg first dose, 1.25 ml/kg subsequent doses) were administered according to the manufacturer. CBF velocity (CBFv) was assessed before and after the first (Site A) and second (Site B) doses of beractant and poractant. Results: At Site A, 10 infants (birth weight 690 ± 133 g) were studied. CBFv decreased 28.9 ± 5.1% following the first dose of surfactant; there were no differences between beractant and poractant. At Site B, 16 infants (birth weight 896 ± 311 g) were studied. CBFv increased 47.4 ± 35.7% after the second dose of beractant and did not change after the second dose of poractant. Conclusion: This is a preliminary report of two related trials examining CBFv responses to beractant and poractant. CBFv decreased similarly after the first dose of beractant and poractant. CBFv increased after the second dose of beractant, but not after poractant. Cerebral hemodynamic responses between the first and second doses may be due to differences in quantities of airway fluid, while second dose differences between beractant and poractant may be due to differences in dose-volume.

A randomized controlled trial of synchronized nasal intermittent positive pressure ventilation in RDS

Comparison of outcomes of infants with respiratory distress syndrome (RDS), post-surfactant, extubated to synchronized nasal intermittent positive pressure ventilation (SNIPPV) or continued on conventional ventilation (CV). Prospective post-surfactant randomized controlled trial of primary mode SNIPPV compared with CV in infants (born from July 2000 to March 2005) with birth weights (BW) of 600 to 1250 g. Primary mode SNIPPV was defined as its use in the acute phase of RDS, following the administration of the first dose of surfactant. There were no significant differences in the maternal demographics, antenatal steroid use, mode of delivery, BW, gestational age, gender or Apgar at 5 min between infants continued on CV (n=21) and those extubated to primary mode SNIPPV (n=20). Significantly, more babies in the CV group had the primary outcome of bronchopulmonary dysplasia (BPD)/death, compared to the SNIPPV group (52 versus 20%, P=0.03). There was no difference in the incidence of other common neonatal morbidities. There were no differences in the Mental or Psychomotor Developmental Index scores on follow-up between the two groups. Infants of BW 600 to 1250 g with RDS receiving surfactant with early extubation to SNIPPV had a significantly lower incidence of BPD/death. Primary mode SNIPPV is a feasible method of ventilation in small premature infants.

Factores en la morbilidad respiratoria de los recién nacidos de muy bajo peso con membrana hialina

Very low birth weight (VLBW) infants, with a birth weight below 1500 g and a structurally immature lung, are at high risk for developing bronchopulmonary dysplasia. This risk is even higher if respiratory distress syndrome is present. Other acute lung diseases, such as air leak and pulmonary hemorrhage, can also be present. The aim of this study was to analyze the statistical relevance of several neonatal factors in the development of pulmonary complications in a sample of VLBW infants with respiratory distress syndrome. A total of 209 VLBW infants with respiratory distress syndrome were studied. The variables analyzed were delivery date, respiratory distress syndrome grade, sex, birth weight, gestational age, referral (from within the hospital or elsewhere), prenatal corticosteroid administration, type of gestation, type of delivery, amniorrhexis time, Apgar test at 1 and 5 minutes, surfactant administration, hours of life at which the first dose of surfactant was administered, and early sepsis. A multiple logistic regression analysis was developed using Hosmer-Lemeshow methodology. In the multivariate analysis, air leak was related to respiratory distress syndrome grade and surfactant administration. Pulmonary hemorrhage was related to lower birth weight and absence of prenatal corticosteroid administration. Bronchopulmonary dysplasia was related to single pregnancies, absence of prenatal corticosteroid administration, lower birth weight, lower Apgar score at 1 minute, and higher respiratory distress syndrome grade. Respiratory morbidity in VLBW infants with respiratory distress syndrome could be influenced by several interrelated intrinsic and extrinsic variables.

Reduction of Bronchopulmonary Dysplasia After Participation in the Breathsavers Group of the Vermont Oxford Network Neonatal Intensive Care Quality Improvement Collaborative

The objective of this study was to compare the primary and secondary outcomes of very low birth weight infants before and after participation in the Breathsavers Group of the Vermont Oxford Network-sponsored Neonatal Intensive Care Quality Collaborative. Hospitals that participated in the Breathsavers Group contributed clinical data on the outcomes of their very low birth weight infants to the Vermont Oxford Network using standardized clinical definitions, data forms, and inclusion criteria. Outcomes from the last year of the collaborative, 2003, were compared with those from the baseline year, 2001. Models for treatment practices and outcomes measures were adjusted for within-hospital correlation (clustering) and standard risk factors that were present at birth. Bronchopulmonary dysplasia dropped significantly in 2003 compared with the baseline year. Survival improved but not significantly. In addition, severe retinopathy of prematurity, severe intraventricular hemorrhage, and supplemental oxygen at discharge dropped significantly. The use of conventional ventilation at any time during the initial hospitalization, postnatal steroids, and time to first dose of surfactant all decreased significantly. The use of nasal continuous positive airway pressure at any time during hospitalization increased. The use of high-frequency ventilation, delivery room intubation, and surfactant at any time during hospitalization did not change. The Breathsavers Group improved both clinical care processes and clinical outcomes during the Neonatal Intensive Care Quality Collaborative.

Factores de riesgo en la mortalidad de los recién nacidos de muy bajo peso con membrana hialina

In the last few years the life expectancy of very low birth weight (VLBW) infants has improved. When these patients have respiratory distress syndrome, it is difficult to know with any certainty which factors have the greatest influence on mortality. The aim of this study was to determine which variables, among a series, have the greatest influence on mortality from a multivariate perspective. A sample of 209 VLBW infants born over a long period (15 years and 7 months) was studied. The following variables were analyzed: date of birth, degree of respiratory distress syndrome, sex, birth weight, weeks of gestation, born within or elsewhere, prenatal corticoid administration, type of gestation, type of delivery, amniorrhexis time, Apgar test at 1 and 5 minutes, surfactant administration, hours of life at which the first dose of surfactant was administered, and early sepsis. A multiple logistic regression analysis was developed using Hosmer-Lemeshow methodology. The following variables were identified as significant: birth weight, Apgar test at 5 minutes, prenatal corticoids, degree of respiratory distress syndrome, and surfactant administration. The remaining variables were less important in the multivariate analysis. Higher birth weight and Apgar score at 5 minutes, prenatal corticoid and surfactant administration, and a lower degree of respiratory distress syndrome reduce mortality. The logistic regression model used quantifies how these factors behave and allows the probability of mortality in VLBW infants with respiratory distress syndrome to be estimated.

Collaborative quality improvement to promote evidence based surfactant for preterm infants: a cluster randomised trial

Objective To test a multifaceted collaborative quality improvement intervention designed to promote evidence based surfactant treatment for preterm infants of 23-29 weeks' gestation.Design Cluster randomised controlled trialSetting and participants 114...

Efficacy of a Single Dose of Antenatal Steroid in Surfactant-treated Babies Under 31 Weeks’ Gestation

Antenatal steroid therapy can lessen morbidity from respiratory distress syndrome in preterm infants. Two doses 24 hours apart generally are recommended, starting 1-7 days before delivery. Experience with women who present in preterm labor and can receive only 1 dose shows that their infants do as well as those given what is thought to be optimal 2-dose treatment. This retrospective study evaluated single-dose treatment in 226 infants less than 31 weeks' gestation whose mothers received surfactant (Survanta®, Exosuif®, or Curosurf®) prophylactically. Eighty-nine of them (group 1) received no steroid antenatally; 68 (group 2) received a single dose 4-24 hours before delivery; and 69 (group 3) were given 2 or more doses 1-7 days before delivery. Each dose consisted of 12 mg betamethasone, injected intramuscularly. The groups were well matched for birth weight, gestational age, gender, and multiple births. Timing of the first dose of surfactant also was similar in all groups. Group 2 and group 3 infants had significantly higher 1-minute Apgar scores than those not given steroid. CRIB scores, a clinical risk index, were 47% lower in group 2 than in group 1 infants, and 38% lower in group 3. Scores did not differ significantly between groups 2 and 3. There were no significant group differences in the duration of ventilation or oxygen dependence. Compared to untreated infants, severe intraventricular hemorrhage was reduced 23% in group 2 and 22% in group 3, again with no significant difference between these groups. Mortality was 31.5% in the untreated group, 8.6% in the single-dose group, and 7.4% when 2 or more steroid doses were given. A single antenatal dose of steroid, given 4-24 hours before delivery of a surfactant-treated preterm infant, is as effective as 2 or more doses.

Exogenous Surfactant Therapy in Newborn Infants

Exogenous surfactant therapy has an established role in the management of neonatal respiratory distress syndrome (RDS). This article summarises the current evidence on surfactant therapy. The use of surfactant for the treatment or prophylaxis of neonatal RDS results in a 30% to 65% relative reduction in the risk of pneumothorax and up to a 40% relative reduction in the risk of mortality. Adverse effects, of which pulmonary haemorrhage is of most concern, are infrequent and long-term follow-up studies of treated patients are reassuring. Natural surfactants have advantages over synthetic surfactants, including a lower frequency of pneumothorax and a lower mortality. Prophylactic administration of surfactant is preferred over ‘rescue’ administration, especially in infants of &lt;30 weeks’ gestation, as it decreases the risk of pneumothorax, pulmonary interstitial emphysema and neonatal mortality. Prophylaxis can be administered after initial resuscitation and stabilisation. In preterm infants who do not receive prophylactic surfactant, the first dose of surfactant should be administered as early as possible – early selective treatment decreases the risk of pneumothorax, pulmonary interstitial emphysema, chronic lung disease and neonatal mortality. A regimen of using multiple doses of surfactant if required has advantages over a single dose regimen. Exogenous surfactant therapy has also been used in neonatal respiratory disorders other than RDS. In trials in severe meconium aspiration syndrome, surfactant therapy reduced the need for extracorporeal membrane oxygenation. Its role in other disorders requires testing. The development and testing of newer surfactants is in progress.

CENTER DIFFERENCES IN SURVIVAL WITHOUT CHRONIC LUNG DISEASE (CLD) IN VERY-LOW-BIRTH-WEIGHT (VLBW) INFANTS ARE NOT EXPLAINED BY POPULATION DIFFERENCES, OR THE PRESENCE AND EARLY MANAGEMENT OF RESPIRATORY DISTRESS SYNDROME (RDS) • 1524

Important differences among centers in survival without CLD at 28 days in VLBW infants have been reported (Avery et al, Pediatrics 79:26-30, 1987). That study was conducted before the use of surfactant, did not include infants<700g, and adjusted only for birth weight (BW), gender, and race. We analyzed prospectively collected data from 12 large, demographically diverse NICU's in the NICHD Neonatal Research Network to explore these differences. A total of 6104 inborn infants with BW 501-1500g born 3/93-12/96 were included. The unadjusted percent survival without CLD (defined as supplemental oxygen at 36 wks) ranged from 32% to 80%. Using a logistic regression model to adjust for BW, gender, race, and antenatal steroids, the center differences persisted(p<0.0001). The center differences persisted when either SGA or gestational age was included in the analysis. Potential explanations for this finding are center differences in acute lung disease (shortly after birth) that are not explained by the above demographic and obstetrical factors or differences in neonatal management. An additional analysis was performed to include the presence of clinical features of RDS in the first 24 hours of life and the use of supplemental oxygen between 6 and 24 hours of age. In this model, the center differences were still highly significant (P<0.0001). Available information about neonatal management includes the use of surfactant, the age at administration of surfactant, and ventilator support parameters prior to the first dose of surfactant. Even after including these predictors in the model, the center differences persisted (p<0.0001). We conclude that significant differences among NICU's in percent survival without CLD are not explained by center differences in BW, gender, race, gestational age, antenatal steroids, RDS, surfactant use, or ventilator settings prior to surfactant therapy. Further research will be needed to explore other factors in the management of these neonates to determine which management strategies provide the best outcomes.

Exogenous Surfactant Therapy for Pediatric Patients with Acute Respiratory Distress Syndrome

Exogenous surfactant administration is currently being tested in patients with the acute respiratory distress syndrome (ARDS). The results of the studies have varied because several factors may influence the host’s response to this therapy. This clinical pilot study was designed to evaluate the safety and efficacy of exogenous surfactant administration in pediatric patients with ARDS. Surfactant was administered to 13 patients with severe lung dysfunction, and eight of these patients experienced a significant improvement in oxygenation after the first dose of surfactant. In these patients the exogenous surfactant was administered within 48 h of the diagnosis of ARDS, whereas in the five patients who did not respond, surfactant was administered several days after the onset of ARDS. Responders also spent fewer days on a mechanical ventilator and less time in intensive care compared with nonresponders. Based on the results of this pilot study, a more appropriate multicentre clinical trial should be designed to evaluate this treatment strategy.

Surfactant Replacement Therapy for Meconium Aspiration Syndrome

The pathophysiology of meconium aspiration syndrome (MAS) is related not only to mechanical obstruction of the airways and chemical injury to the respiratory epithelium but also to surfactant inactivation by meconium. A randomized, controlled study was performed to determine whether high-dose surfactant therapy improves the pulmonary morbidity of term infants ventilated for MAS. Forty term infants receiving mechanical ventilation for MAS were enrolled in this trial, in which the infants in the study group (n = 20) received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air placebo. Mean arterial-to-alveolar PO2 ratio values increased from 0.09 to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of surfactant. Oxygenation improved cumulatively after the second and third dose of surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of 0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at 6 hours after the third dose of surfactant, eliminating the need for a fourth dose in any infant in the study group. After three doses of surfactant, persistent pulmonary hypertension had resolved in all but one of the infants in the study group versus none of the infants in the control group. No air leaks developed in any of the 20 infants in the study group after surfactant therapy, and only 1 infant required extracorporeal membrane oxygenation. Air leaks developed in 5 of the 20 infants in the control group, and 6 underwent extracorporeal membrane oxygenation. The duration of mechanical ventilation, oxygen therapy, and admission was significantly shorter in the surfactant group than in the control group. Surfactant replacement therapy, if started within 6 hours after birth, improves oxygenation and reduces the incidence of air leaks, severity of pulmonary morbidity, and hospitalization time of term infants with MAS.

Static respiratory compliance in the newborn. III: Early changes after exogenous surfactant treatment.

Static respiratory system compliance (Crs) was measured by a single breath passive expiratory flow technique in 73 newborn infants treated with exogenous surfactant. The first 39 received Curosurf, a natural porcine surfactant. The other 34 received Exosurf Neonatal, a synthetic surfactant. All had a diagnosis of respiratory distress syndrome with an arterial/alveolar oxygen ratio < 0.22. Static Crs and arterial blood gases were measured shortly before, and at three and 12 hours after the first dose of surfactant. In 32 infants treated with Curosurf with initial static Crs < 1.8 ml/cm H2O/m body length, which is consistent with surfactant deficiency, static Crs improved by 18% at three hours and by 39% at 12 hours along with a median reduction in fractional inspired oxygen (FIO2) at three hours by 0.32. In 26 infants treated with Exosurf with initial Crs < 1.8 ml/cm H2O/m, Crs did not improve three and 12 hours after treatment and oxygenation improved less than after Curosurf, with a median reduction in FIO2 at three hours of 0.11. Fifteen of the 73 (21%) infants had initial static Crs of > or = 1.8 ml/cm H2O/m, not consistent with surfactant deficiency. Thirteen of these 15 infants showed a fall in static Crs after surfactant treatment, raising the question whether exogenous surfactant did them more harm than good. Initial static Crs and surfactant type both appear to determine the early response to the first dose of surfactant. Only a considerably larger, randomised study can show which surfactant is more effective in reducing adverse clinical outcome.

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 μg/kg per h for 2 h followed by 25 μg/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0·4 [95% C·I -1·1 to -0·3] nmol/L, p<0·001), which was not seen in the placebo group (median change 0·2 [-0·6 to 0·6] nmol/L, p=0·79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.