Survanta Group Research Articles

Excipient Enhanced Growth Aerosol Surfactant Replacement Therapy in an In Vivo Rat Lung Injury Model.

Background: In neonatal respiratory distress syndrome, breathing support and surfactant therapy are commonly used to enable the alveoli to expand. Surfactants are typically delivered through liquid instillation. However, liquid instillation does not specifically target the small airways. We have developed an excipient enhanced growth (EEG) powder aerosol formulation using Survanta®. Methods: EEG Survanta powder aerosol was delivered using a novel dry powder inhaler via tracheal insufflation to surfactant depleted rats at nominal doses of 3, 5, 10, and 20 mg of powder containing 0.61, 0.97, 1.73, and 3.46 mg of phospholipids (PL), whereas liquid Survanta was delivered via syringe instillation at doses of 2 and 4 mL/kg containing 18.6 and 34 mg of PL. Ventilation mechanics were measured before and after depletion, and after treatment. We hypothesized that EEG Survanta powder aerosol would improve lung mechanics compared with instilled liquid Survanta in surfactant depleted rats. Results and Conclusion: EEG Survanta powder aerosol at a dose of 0.61 mg PL significantly improved lung compliance and elastance compared with the liquid Survanta at a dose of 18.6 mg, which represents improved primary efficacy of the aerosol at a 30-fold lower dose of PL. There was no significant difference in white blood cell count of the lavage from the EEG Survanta group compared with liquid Survanta. These results provide an in vivo proof-of-concept for EEG Survanta powder aerosol as a promising method of surfactant replacement therapy.

Comparison of the Efficacy of Three Natural Surfactants (Curosurf, Survanta, and Alveofact) in the Treatment of Respiratory Distress Syndrome Among Neonates: A Randomized Controlled Trial.

BackgroundAlthough several different types of natural surfactants are available, including Alveofact, Curosurf, and Survanta, the preferred type and the magnitude of their effects are unknown.ObjectivesThis study was designed to compare the effects of these three surfactants on the gas exchange and clinical outcomes of neonates with respiratory distress syndrome (RDS).MethodsThis triple-blind randomized clinical trial studied all preterm neonates ≤ 37 weeks with RDS who were admitted to the neonatal intensive care unit (NICU) of Taleghani hospital (Tabriz, Iran) between 2012 and 2013. The patients were divided into three groups, each of which received one of these surfactants. The incidences of ventilator dependency, patent ductus arteriosus (PDA), broncho-pulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), hospital-stay length, and continuous positive airway pressure (CPAP) failure, as well as blood gas levels, were recorded as endpoint measurements and compared.ResultsIn total, 165 neonates of gestational age ≤ 37 weeks with RDS were examined. Neonates were allocated to three different groups randomly, including a Survanta group (n = 49), a Curosurf group (n = 62), and an Alveofact group (n = 54). The mean gestational age of the neonates was 31.6 ± 3.7 weeks, and their mean weight was 1,840 ± 790 grams. The male/female ratio was 2:1 (67% male, 33% female); 104 (63%) neonates were ≤ 32 weeks gestational age, and 61 (37%) were >32 weeks. There were no significant differences for gender or demographic characteristics among the neonates in relation to the type of applied surfactant. According to the clinical parameters (BPD, IVH, ROP, hospital-stay length, and mechanical ventilation requirement), no significant differences were observed between the groups before and after surfactant administration, but the differences between the Survanta and Alveofact groups for the incidence rates of pneumothorax (P = 0.03) and pulmonary hemorrhage (P = 0.03) were statistically significant.ConclusionsNo significant differences were observed in most of the clinical variables between the three types of natural surfactant, but in neonates ≤ 32 weeks, the incidence of pneumothorax was significantly higher in the Alveofact group; in neonates > 32 weeks, the incidences of PDA, mean hospital-stay length, and mean mechanical ventilation time were also significantly higher in the same group. It thus appears that Curosurf and Survanta replacement therapies among premature neonates with RDS perform better than Alveofact replacement therapy.

Comparison of efficacy and safety of two available natural surfactants in Iran, Curosurf and Survanta in treatment of neonatal respiratory distress syndrome: A randomized clinical trial.

IntroductionThe benefit of surfactant prescription for respiratory distress syndrome (RDS) has been approved. Curosurf and Survanta are two commonly used natural surfactants in Iran. Previous studies did not report priority for one of these two drugs. The present study aimed to compare the effectiveness and safety of Curosurf and Survanta in treatment of RDS.MethodsIn this randomized clinical trial, neonates were born with RDS diagnosis in two governmental and referral hospitals of Tehran (the capital of Iran) in 2014 were randomly selected. Neonates were randomly assigned into two groups receiving 100 mg/kg Curosurf or Survanta as soon as possible after randomization. Complications, mortality and needing the second dose were compared between the two groups.ResultsA total 112 patients with the mean gestational age of 32.59 ± 3.39 weeks were evaluated (56 patients in each group). There were no significant differences regarding birth weight, gestational age, delivery method, and parity between the two groups (P > 0.05). The complications were occurred in 18 neonates (32.1%) of Curosurf group and 20 neonates (35.7%) of Survanta group (RR = 0.922, 95% CI = 0.617–1.379). There were no significant differences regarding complications, mortality, and needing nasal CPAP and endotracheal tube between the two groups. In the neonates with gestational age of 29–32 weeks the IVH and NEC incidence were significantly more in Curosurf group compared to Survanta group (27.8% vs 0% and 22.3% vs 0%, P < 0.05).ConclusionThere was no significant difference in complications or mortality between those two groups; however Curosurf was associated with less need of ET tube (in >32 birth weeks subgroup) and NCPAP (in 29–32 birth weeks subgroup) (p = 0.008). Further evaluations with longer follow-up duration are needed for comparing these two surfactants.

Comparison of side effect of survanta and curosurf in decreasing mortality due to respiratory distress syndrome (RDS) in premature infants admitted in NICU of Ghaem Hospital On 2006-2008

Background: Using of natural and synthetic surfactant is a rescue treatment for respiratory distress syndrome. In Iran, Survanta and Curosurf are the most frequent used natural surfactant preparations. We compared the clinical response and safety of two surfactants poractant alpha (Curosurf) and beractant (Survanta) for treatment of respiratory distress syndrome (RDS) in preterm infants. Method:This study was a clinical trial study that performed during a 2-year period in Ghaem Center's neonatal care unit.Sample size was calculated with 95% confidence and power 80. 104 premature infants were treated with surfactant, 74 in survanta group and 30 in Curosurf group,. The differences between the two groups were assessed by ANOVA or the calculation of relative risks. Results: There were no statistically significant differences between infants treated with S and C in mean gestational age (30.58 vs. 29.00 weeks) and birth weight (1388 vs.1330 g). Also there was no significant difference between groups, incidence at 28th day of Bronchopulmunary dysplasia (%40.5 vs. %40), Intra ventricular hemorrhage III/IV (%13/5 vs. % 13/3), pneumothorax (%20 vs. % 20), Patent ductus arteriosis (%28/3 vs. % 20), and death (%28 vs. % 26/6). Conclusion:This study concluded that Survanta and Curosurf are similar in treatment of neonatal respiratory distress syndrome.

Randomized clinical trial comparing two natural surfactant preparations to treat respiratory distress syndrome

Objective: Natural surfactant preparations have been shown to reduce the severity and mortality of respiratory distress syndrome (RDS) in preterm infants. The objective of this study was to compare the efficacy of two natural surfactants, namely SF-RI 1 (Alveofact®) and barectant (Survanta®), on the incidence of chronic lung disease (CLD) and other associated complications of RDS in preterm infants.Methods: Preterm infants with RDS requiring artificial ventilation were randomly selected to receive an initial dose of either Alveofact or Survanta. The two treatment groups were tested for variation in gas exchange, ventilatory settings and neonatal complications such as CLD and mortality.Results: After 5 days the Survanta-treated infants had a lower fraction of inspired oxygen (FiO2) compared with the Alveofact-treated infants. There were no differences in the ventilatory settings. More infants in the Survanta group were extubated at 3 days and fewer required the use of postnatal steroids. Less CLD and duration of oxygenation were experienced by the Survanta-treated group.Conclusions: Improved oxygenation and reduced ventilatory requirements were greater with Survanta compared to Alveofact, which in turn was associated with a trend towards a lower incidence of serious pulmonary complications.

Randomized trial comparing two natural surfactants (Survanta vs. bLES) for treatment of neonatal respiratory distress syndrome

Exogenous surfactants have been used as an effective treatment of neonatal respiratory distress syndrome (RDS). Different preparations of surfactant carry different biophysical and clinical properties. To study the response pattern and treatment outcome of two natural surfactants (bLES and Survanta) for the treatment of RDS, we conducted a randomized clinical trial at the neonatal unit of a university teaching hospital. Premature babies with birth weight between 500-1,800 g who developed RDS requiring mechanical ventilation with an oxygen requirement of more than 30% within 6 hr of life were randomized into two treatment groups. Oxygenation indices (OIs) within 12 hr of treatment were compared as primary outcomes, while neonatal complications were analyzed as secondary outcomes of the study. Sixty babies were recruited, with 29 in the bLES and 31 in the Survanta treatment group. Both groups had significant and sustained improvements in OI after surfactant replacement therapy (SRT), while the bLES group was associated with a significantly lower OI throughout the initial 12 hr after treatment compared with the Survanta group. There was no difference in secondary outcomes including mortality, ventilator days, and occurrence of chronic lung disease. We conclude that infants with RDS respond favorably to both types of surfactant replacement, and that bLES achieved a faster clinical response in terms of improvement in OI than Survanta.

Serial phospholipid analysis in preterm infants: Comparison of Exosurf and Survanta

The initial clinical response to synthetic or natural surfactant is different and long-term complications from meta-analysis suggest that bronchopulmonary dysplasia and retinopathy of prematurity may be increased in infants given synthetic surfactant. It is possible that this is due to differences in the phospholipid composition of lung fluid following administration of these surfactants. Infants less than 32 weeks gestation with respiratory distress syndrome (RDS) were randomly assigned to receive either Exosurf, an artificial surfactant, or Survanta, a natural surfactant. Endotracheal or hypopharyngeal aspirates were obtained from these infants and from control infants who had normal lungs. The aspirates were taken prior to and up to 28 days following surfactant administration. The different phospholipids were separated by thin layer chromatography and expressed as a percent of total phospholipid measured. Infants with normal lungs had a higher proportion of phosphatidylcholine than those with RDS prior to treatment. The infants with normal lungs had a greater proportion of phosphatidylinositol in their lung aspirates than both treatment groups at 24 h. Infants in the Survanta group had a higher proportion of phosphatidylglycerol at 48 h than the group with normal lungs. No other differences were found in phospholipid composition up to 28 days. There were no major differences in the phospholipid profile in infants with RDS treated with either Exosurf or Survanta. In conclusion, neither the clinical differences initially seen between infants treated with either Exosurf or Survanta, nor the long-term outcome could be explained by the phospholipid composition of serial samples of lung aspirates.

Acute effects on systemic circulation after intratracheal instillation of Curosurf or Survanta in surfactant‐depleted newborn piglets

Systemic vasodilatation in surfactant‐depleted newborn piglets is induced by 200 mg/kg of modified porcine lung surfactant (Curosurf™). The aim of this investigation was to study whether this effect is dependent on dose and could further be induced by instillation of a bovine surfactant preparation (Survanta™). Twenty‐two 3–5‐d old piglets were subjected to repeated saline lung lavage and then randomized to one of three groups. Instillation of either Curosurf 100 mg/kg (n= 8), Survanta 100 mg/kg (n= 7) or Curosurf 200 mg/kg (n= 7) was performed through the endotracheal tube. Systemic vascular resistance decreased 7 (± 4)%, 15 (± 12)% and 18 (± 6)% in the three groups, respectively (p &lt; 0:05 in all three groups). A significant difference between the high and low dose Curosurf groups was found (p &lt; 0:05), whereas no significant difference was seen between the Curosurf 100 mg group and the Survanta group. The decrease in vascular resistance was compensated by an increase in cardiac output, resulting in a stable mean arterial blood pressure. In conclusion, both Curosurf and Survanta induce a significant decrease in systemic vascular resistance in surfactant‐depleted newborn piglets. A more pronounced effect was observed after 200 mg/kg than after 100 mg/kg of Curosurf.

Comparison of the changes in the a/A oxygen ratio after administration of two surfactants for the treatment of neonatal respiratory distress syndrome

The aim of this study was to compare the acute changes in a/A O2 ratio after administration of two surfactants, Survanta (Ross Laboratories), and Exosurf Neonatal (Glaxo Wellcome Co.) in prematures with respiratory distress syndrome. Twenty-seven premature infants weighing 1030 + 1680 g with respiratory distress syndrome were ventilated and randomly assigned to receive two doses of either Survanta (n = 15) or Exosurf (n = 12) when a/A O2 ratio was < 0.22. The assigned surfactant was prepared and administered in accordance with the manufacturer's instructions. a/A O2 ratio was measured before each dose and 2 and 6 h later. The percentage change of the ratio from the first measurement has been calculated. There was no significant difference between the two groups as regard to birth weight, gestational age, Apgar Score, and a/A O2 ratio before administration of the drug. However, the age at commencement of treatment was significantly lower in Survanta group. The mean of changes in a/A O2 ratio was significantly higher in Survanta than in Exosurf on all occasions (P < 0.05). There was no correlation between the initial improvement in the ratio and the age of administration of the first dose of the drugs. The initial improvement in a/A O2 ratio after Survanta may be explained by either smaller volume of the drug (4 ml/kg) compared to Exosurf (5 ml/kg) or better spreading properties of the drug. Earlier administration of the second dose of Exosurf may accelerate the response to the drug.

Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.

Randomised clinical trial of two treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome.

To compare treatment regimens of two widely used natural surfactant preparations Curosurf and Survanta in respiratory distress syndrome (RDS). The effects of the two treatment regimens on gas exchange, ventilatory requirements, and 28 day outcome in infants with RDS were compared. Seventy five preterm infants (birth weight 700-1500 g) with RDS requiring artificial ventilation with an FIO2 of > or = 0.4, were randomly selected at 1-24 hours of age. One group received an initial dose of Curosurf (200 mg/kg); the other group Survanta (100 mg/kg). Patients who remained dependent on artificial ventilation with an FIO2 of > or = 0.3 received up to two additional doses of Curosurf (each of 100 mg/kg) after 12 and 24 hours or up to three additional doses of Survanta (each of 100 mg/kg) between six and 48 hours after the initial dose. There was a rapid improvement in oxygenation and ventilatory requirements were reduced in both groups. However, infants treated with Curosurf had a higher arterial:alveolar oxygen tension ratio and required a lower peak inspiratory pressure and mean airway pressure at several time points within 24 hours of randomisation (p < 0.05-0.001). The incidences of pneumothorax in the Curosurf and Survanta groups were 6% and 12.5%, respectively; the corresponding figures for grades 3-4 intracerebral haemorrhage were 3% and 12.5%, respectively. Mortality was 3% in the Curosurf group and 12.5% in the Survanta group. However, these differences did not reach significance. The Curosurf treatment regimen resulted in a more rapid improvement in oxygenation than Survanta and reduced ventilatory requirements up to 24 hours after start of treatment. This was associated with a trend towards reduced incidence of serious pulmonary and non-pulmonary complications.

A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome

To compare the efficacy of two surfactants, Exosurf Neonatal (Burroughs Wellcome Co.) and Survanta (Ross Laboratories), for the treatment of neonatal respiratory distress syndrome. Multicenter randomized trial. Eleven tertiary care university neonatal intensive care units participating in the National Institute of Child Health and Human Development Neonatal Research Network. Newborn infants (n = 617) weighing 501 to 1500 gm with respiratory distress syndrome who were receiving assisted ventilation with 30% oxygen or more within 6 hours of birth were enrolled between January 1991 and January 1992. Infants were randomly assigned to receive up to four intratracheal doses of either Exosurf Neonatal (n = 309) or Survanta (n = 308). The occurrence of death or bronchopulmonary dysplasia 28 days after birth and the average fraction of inspired oxygen (FIO2) and mean airway pressure (MAP) during the first 72 hours after treatment. Death or bronchopulmonary dysplasia occurred in 67% of the infants in the Exosurf group and 62% of those in the Survanta group (adjusted relative risk, 1.07; 95% confidence interval, 0.96 to 1.20). During the 72 hours after the first surfactant dose, the average FIO2 (+/- SEM) was 0.50 +/- 0.01 for Exosurf and 0.42 +/- 0.01 for Survanta (difference, 0.08; 95% confidence interval, 0.05 to 0.11); the average MAP (+/- SEM) was 7.64 +/- 0.21 cm H2O for Exosurf and 6.93 +/- 0.21 cm H2O for Survanta (difference, 0.71 cm H2O; 95% confidence interval, 0.13 to 1.29 cm H2O). There was no difference between the groups in the incidence of other neonatal morbidities or in the duration of hospitalization, assisted ventilation, or supplemental oxygen administration. We found no difference between treatment groups in the incidence of death or bronchopulmonary dysplasia, although we did observe a difference in the initial response to treatment as measured by FIO2 and MAP.

Surfactant Replacement Improves Lung Recoil in Rabbit Lungs after Acid Aspiration

SUMMARY We tested the hypothesis that surfactant replacement would be beneficial In the acld­ aspiration model of acute lung Injury. HCI (0.1 N, 2 mllkg) was Injected Into the trachea of excised rabbit lungs (n = 8). Control lungs (n = 4) had no Intervention. All were perfused with lYrode's solution mixed 1:1 with autologous whole blood at 40 mllmin/kg for 30 min, and then degassed. A modified natural surfactant (Survanta@, Ross Laboratories) was then Injected Into the trachea of four lungs Injured with HCI (100 mg/kg at 25 mg/ml). lWo quasi-static pressure-volume curves were determined. The mean alveolar pressures at 50,60,70,80, and 90% of TLC were greater In the HCI group than In the control group (p < 0.05). However, no difference was observed between the control lungs and thosethat received HCI + Survanta. In 13 anesthetized, paralyzed, and venti­ lated rabbits, deflation pressure-volume curvas were determined from TLC to FRC (measured by helium dilution). Then, 0.1 N HCI (3 ml/kg) was Injected into the trachea and, in seven, Survanta was Instilled 5 min later. The mean alveolar pressures at 60, 70, 80, and 90% TLC were higher at 15 and 60 min In the HCI group compared with their pre-HCI time point (p < 0.05). In the HCI + Survanta group, no differences were seen at 15 min, and only slight Increased were seen at 60 min. No effect of surfactant replacement on arterial blood gases was observed. HCI aspiration Increased recoil In both excised and in "i"o lungs, and surfactant replacement with Survanta returned recoil to normal. AM REV RESPIR DIS 1990; 142:1279-1283

Surfactant Replacement Improves Lung Recoil in Rabbit Lungs after Acid Aspiration

We tested the hypothesis that surfactant replacement would be beneficial in the acid-aspiration model of acute lung injury. HCl (0.1 N, 2 ml/kg) was injected into the trachea of excised rabbit lungs (n = 8). Control lungs (n = 4) had no intervention. All were perfused with Tyrode's solution mixed 1:1 with autologous whole blood at 40 ml/min/kg for 30 min, and then degassed. A modified natural surfactant (Survanta, Ross Laboratories) was then injected into the trachea of four lungs injured with HCl (100 mg/kg at 25 mg/ml). Two quasi-static pressure-volume curves were determined. The mean alveolar pressures at 50, 60, 70, 80, and 90% of TLC were greater in the HCl group than in the control group (p less than 0.05). However, no difference was observed between the control lungs and those that received HCl + Survanta. In 13 anesthetized, paralyzed, and ventilated rabbits, deflation pressure-volume curves were determined from TLC to FRC (measured by helium dilution). Then, 0.1 N HCl (3 ml/kg) was injected into the trachea and, in seven, Survanta was instilled 5 min later. The mean alveolar pressures at 60, 70, 80, and 90% TLC were higher at 15 and 60 min in the HCl group compared with their pre-HCl time point (p less than 0.05). In the HCl + Survanta group, no differences were seen at 15 min, and only slight increased were seen at 60 min. No effect of surfactant replacement on arterial blood gases was observed. HCl aspiration increased recoil in both excised and in vivo lungs, and surfactant replacement with Survanta returned recoil to normal.