Curosurf vs survanta 2010


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Curosurf vs survanta 2010

  1. 1. Original Article Complications among Premature Neonates Treated with Beractant and Poractant Alfa Manizheh Mostafa Gharehbaghi, Seddigheh Hossein Pour Sakha, Mortaza Ghojazadeh1 and Farahnaz Firoozi Department of Neonatology and Pediatrics, and 1Department of Physiology, Tabriz University, Medical Sciences, Tabriz, Iran ABSTRACT Objective. To compare the complications among preterm infants treated with two different natural surfactants. Methods. In a randomized clinical trial, 150 preterm infants with Respiratory distress syndrome (RDS) treated with exogenous surfactant, were enrolled in the study. Group A consisted of 79 neonates that received poractant (curosurf). Seventy one newborn infants in group B were treated with beractant (Survanta). Results. The mean gestational age for group A and B were 29.40±2.90 wk and 29.50±2.73 wk (P=0.82), respectively. The demographic and clinical variables were similar in both groups. The mean duration of intubation (as a primary outcome) was significantly shorter in infants treated with poractant (3.13±1.80 vs 4.06±2.7 days p=0.05). The mean duration of need for oxygen and hospitalization of patients in group A and B were 17.73±22.25 vs 19.14±17.85days (p=0.67) and 24.89±26.41 vs 29.14±23.54 days (p= 0.32), respectively. There was no significant difference between groups with respect to mortality and morbidity, including pulmonary hemorrhage, intraventricular hemorrhage (IVH), patent ductus arteriosus, sepsis, and bronchopulmonary dysplasia (secondary outcome). Conclusions. In this study, infants who received poractant had shorter duration of intubation than infants treated with beractant, without any difference in the duration of oxygen therapy or hospitalization. There was no significant superiority of poractant over beractant. [Indian J Pediatr 2010; 77 (7) : 751-754] E-mail: Key words: Poractant; Respiratory distress syndrome; Beractant; Morbidity Acute respiratory distress syndrome (RDS) secondary to surfactant deficiency, is a major cause of morbidity in premature infants. Surfactant lines the alveolar surfaces in the lungs, thereby reducing surface tension and preventing atelectasis. Surfactant replacement therapy reduces the severity of RDS and its mortality.1-3 A wide variety of surfactant preparations have been developed. Animal derived surfactants in clinical use are modified or purified from bovine or porcine lungs and contain proteins. 1, 2 Beractant (survanta) are lipid extracts of bovine lung mince, with added dipalmitoyl phosphatidyl choline (DPPC), tripalmitoyl glycerol, and palmitic acid. Poractant (curosurf) is a porcine lung mince that has been subjected to chloroform-methanol extraction and further purified by liquid gel chromatography. It consists of Correspondence and Reprint requests : Dr. Manizheh Mostafa Gharehbaghi, NICU - Al Zahra Hospital, South Arthesh Street 513866449, Tabriz, Iran. [DOI-10.1007/s12098-010-0097-y] [Received May 3, 2009; Accepted March 29, 2010] Indian Journal of Pediatrics, Volume 77—July, 2010 approximately 99% polar lipids (mainly phospholipids ) and 1% hydrophobic low-molecular-weight proteins (SPB,SP-C).4 All commercially available natural surfactants are effective in prevention and treatment of respiratory distress syndrome. There are several studies comparing administration of synthetic surfactants with natural surfactant extracts in the treatment of RDS in preterm infants; that showed greater early improvement in the requirements for ventilator support, fewer air leaks and fewer deaths associated with natural surfactant preparations.1,2,4,5 It must be noted that in these studies synthetic preparations did not contain surfactant protein analogues. Many natural surfactant products are available for clinical use. However, it is unclear whether significant differences exist among the available products. There is no current evidence establishing the superiority of one or more natural surfactant products over others. This study was conducted to compare the effectiveness of two animal derived surfactants with different extraction and formulation in the treatment of RDS in preterm infants. 751
  2. 2. Manizheh Mostafa Gharehbaghi et al MATERIAL AND METHODS From March 2008 through Mach 2009, a prospective masked randomized control trial was conducted in the neonatal intensive care unit of Al-Zahra Hospital, a university level III neonatal centre in North West of Iran. The study was approved by ethics committee of the university. New born preterm infants diagnosed with RDS, that required exogenous surfactant replacement therapy, were eligible for this study. Infants with major congenital malformations, chromosomal abnormalities, and severe asphyxia (5-min Apgar score less than 3), were excluded. They were randomized into two groups by odd or even number of admission code, after obtaining informed parental consents. The group A was treated with poractant alfa (Curosurf, Chiesi farmaceutici, Italy) 200mg/kg (2.5cc/kg) in two divided doses, administrated by rapid bolus infusion directly in to the distal endotracheal tube after disconnecting the infant from ventilator. The patients in group B was treated with survanta (beractant, Ross, USA) 100 mg/kg (4cc/kg) in four divided doses, intratracheally. Exogenous surfactant replacement therapy was administrated as soon as possible after intubation and stabilization of newborn infant after birth. Primary outcome was that the newborn remained without ventilator support through 7 days of age. Secondary outcomes included death before discharge and complications related to either prematurity or RDS, which included following: (1) Pulmonary hemorrhage, which was diagnosed by a rapid deterioration in clinical condition along with presence of frank blood in the endotracheal tube (2) Bronchopulmonary dyspasia that was defined as oxygen dependency beyond 36 wk post conception age (3) Patent ductus arteriosus (PDA) was defined as confirmation of clinical signs of PDA with echocardiography (4) Air leak syndromes including pneumothorax, and pulmonary interstitial emphysema (5) Retinopathy of prematurity confirmed by ophthalmologic examination performed by same ophthalmologist who was blind to surfactant type received (6) Severe intra ventricular hemorrhage (grade III or IV) that was detected by transfontanel ultrasound evaluation (7) Sepsis documented by positive blood culture The diagnosis of morbidities was recorded by two independent senior attending neonatologists who did not know the group assignment of the neonates. Infants were eligible to receive additional doses of surfactant, if they met following criteria: requirement for assisted ventilation with Fio2 ≥ 0.50 and radiographic evidence of 752 RDS in presence of continued respiratory distress. Statistical analysis was performed using the SPSS package 16. The chi-square (χ2) test was used to analyze the categorical data along with fisher’s exact test when applicable; the student’s t test was used for continuous data. RESULTS There were 309 newborn premature infants admitted to NICU during the one year study period. Of these infants, 120 didn’t develop signs and symptoms of RDS and did not receive surfactant; 27 infants had Apgar score less than 3 at 5 min, 12 neonates had major congenital anomalies. A total of 150 infants had met inclusion criteria in the study: 79 in group A and 71 in group B. The mean gestational age and weight of studied infants were 29.45±2.81 wk and 1444.4±585.58 g, respectively. The mean age of infants at the time of surfactant therapy was 7.78±0.75 h. Demographic characteristics did not differ between two groups (Table 1). FiO2 requirement before and one hour after surfactant replacement therapy was not different between two groups (Table 2). Although the mean duration of intubation and need for assisted ventilation was significantly shorter in infants who received curosurf, but the mean duration of hospitalization and O2 therapy were not significantly different between two groups. There were no significant difference in the morality and morbidity among two groups (Table 3). Seventy four (93.7%) patients in group A were treated with one dose and 5 cases (6.3%) needed two doses of curosurf. Sixty seven (94.4%) patients in group B received one dose and 4 cases (5.6%) two doses of survanta. TABLE 1. Demographic Characteristics of Studied Infants Group A Group B Male, n (%) 45 (57.7) 43 (64.2) Birth weight, gr 1438.7 ± 642.82 1450.7 ± 519.01 Gestational age, wk 29.40 ± 2.90 29.50 ± 2.73 Age of treatment, h 6.89 ± 0.85 8.77 ± 1.28 Cesarean section, n (%) 48 (63.2) 50 (70.4) P.Value 0.49 0.9 0.82 0.21 0.38 * mean ± SD Group A= Poractant Group B= Beractant Maternal treatment with antenatal corticosteroids was completed in 36 (45.5%) cases of curosurf group and 30 (42.3%) cases in survanta group. DISCUSSION All regimens of replacement therapy with surfactant Indian Journal of Pediatrics, Volume 77—July, 2010
  3. 3. Complications among Premature Neonates Treated with Beractant and Poractant Alfa TABLE 2. Primary Outcome and Treatment Requirements of Infants in the Two Groups Group A P.Value 72.78±20.15 40.81±15.36 89.40±17.70 94.64±2.00 9/79 3.13±1.80 2.52±1.29 24.89±26.41 17.73±22.25 FiO2 before surfactant FiO2 after surfactant O2 saturation before surfactant O2 saturation after surfactant Need for reintubation, n Intubation duration, d CPAP duration, d Duration of hospitalization, d Duration of oxygen administration, d Group B 70.96±19.00 42.66±15.42 92.08±8.39 94.53±2.16 12/71 4.06±2.72 2.49±1.38 29.14±23.54 19.14±17.85 0.59 0.48 0.25 0.74 0.40 0.05 0.89 0.32 0.67 *mean ± SD; Group A= Poractant treated group; Group B= Beractant treated group TABLE 3. Secondary Outcome in the Two Groups Group A Group B Pulmonary hemorrhage Bronchopulmonary dysplasia Patent ductus arteriosus Sepsis Air leak syndromes Severe intra ventricular hemorrhage Retinopathy of prematurity Death before discharge(n) 8/79 20/79 8/79 3/79 2/79 7/79 5/79 21/79 9/71 20/71 14/71 7/71 5/71 12/71 4/71 15/71 P.value 0.79 0.71 0.11 0.19 0.25 0.14 0.57 0.45 *mean ± SD; Group A= Poractant treated group; Group B= Beractant treated group appear to decrease the incidence of air leaks and improve oxygenation of ventilated preterm infants. Mortality from RDS and even the overall mortality of ventilated preterm infants, is significantly reduced especially when early surfactant therapy used for these infants.1-3, 6-11 Despite differences in chemical composition and manufacturing methods for various natural surfactants, currently FDAapproved formulations demonstrate comparable clinical efficacy. Comparison of different natural surfactants has shown modest differences in oxygenation during the first few hrs after treatment, without significant effect on mortality or morbidity.8-19 In the comparison of infasurf and beactant, Clark et al did not find significant influence on the outcome.13 Speer and co workers compared Beractant and Poractant and concluded that treatment with beractant associated with reduced incidence of severe pulmonary and non pulmonary complications. 14 In the comparison of beractant, alveofact and poractant, Baroutis reported fewer days of mechanical ventilation and oxygen administration with alveofact and poractant. They had administered beractant by pump via a side port in the endotracheal tube adaptator.15 Malloy reported lower FiO2 requirement during first 48 hrs in patients treated by poractant, without difference in time to extubation, reintubation rate, intubation time or incidence of BPD in a small number of patients.8 The present study shows that poractant reduces the duration of intubation and need for ventilator support in premature infants but the mean length of admission was not shorter in these infants. The Indian Journal of Pediatrics, Volume 77—July, 2010 apparent superiority of poractant over beractant with respect to reduced days of intubation could be the result from higher doses of SP-B and phospholipids used with poractant alfa (double dose of beractant). Poractant contains 1mg/dl of proteins including, 0.3 mg of SP-B, whereas, beractant contains less than 1mg/dl of proteins but exact amount of its SP-B is not quantified. The effect of quantitative difference in SP-B on clinical outcome has not been shown. 1, 2, 4 There are reports showing that new synthetic peptide-containing surfactants are effective and safe for prevention or treatment of RDS among preterm infants and reduce the incidence of common complications of prematurity.1 The ability to enhance the efficacy of new synthetic surfactants is related to addition of peptide that mimic the action of SP-B.19 BPD continues to be an important problem despite widespread use of exogenous surfactant and strategies to minimize the lung injury from mechanical ventilation. This may reflect the changing pathogenesis of BPD and the multiplicity of factors involved, among which surfactant deficiency is only one.20,21 This is the first report of surfactant replacement therapy in a large number of preterm infants from authors country. The authors have relatively little experience with natural surfactants for treatment of RDS in premature newborn infants, but the results are encouraging and compatible with studies published from developed countries. One limitation of the present study was a possibility odd enrolment bias. CONCLUSIONS These results show that treatment with poractant is associated with reduced duration of intubation and ventilatory support, but short term outcome of these infants is not different from preterm infants treated with beractant. Thus, there was no significant superiority of poractant over beractant. Acknowledgements We are grateful for financial support of vice chancellor of Tabriz University of Medical Sciences and assistance of Heidarzadeh M, MD, Bargh nema R, MD, and Abedini K. Tabriz, Iran. 753
  4. 4. Manizheh Mostafa Gharehbaghi et al Contributions: MMG; act as a guarantor. SHPS and FF; did data collection. MG; did statistical analysis. Conflict of Interest: None. 11. Role of Funding Source: None. REFERENCES 1. Engle WA and committee on fetus and newborns. American academy of pediatrics. Surfactant replacement therapy for respiratory distress syndrome. Pediatrics 2008; 121: 419-432. 2. Rodiguez RJ, Martin RJ, Fanaroff AA. Respiratory distress and its management. In Fanaroff AA, Martin RJ, eds. Neonatalperinatal medicine. Disease of the fetus and infant, 8 th ed, Philadelphia; Mosby, 2006; 2: 1097-1107. 3. Rodiguez RJ, Martin RJ. Exogenous surfactant therapy in newborns. Respir Care Clin N Am 1999; 5: 595-616. 4. Suresh GK, Soll RF. Pharmacologic adjuncts II: exogenous surfactant. In Goldsmith JP, Karotkin EH, ed. Assisted ventilation of the neonate, 4th ed. Philadelphia; Saunders, 2003; 329-344. 5. Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2001; 2: CD000144. 6. Stevens TP, Blennow M, Myers E, Soll R. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for RDS. Cochrane Database Syst Rev 2002; 2: CD003063. 7. Ainsworth SB, Beresford MW, Milligan DWA. Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at25-29 weeks’ gestation: a randomized trial. Lancet 2000; 355: 1387-1392. 8. Moya FR, Gadzinowski J, Bancalari E et al. A multicenter randomized masked comparison trial of lucinactant, colfoceril palmitate and beractant for the prevention of respiratory distress syndrome in very preterm infants. Pediatrics 2005; 115: 1018-1029. 9. Hammound M, Al Kazmi N, Alshemmiri M et al. randomized clinical trial comparing two natural surfactant preparations to treat respiratory distress syndrome. J Matern Fetal Neonatal Med 2004; 15: 167-175. 10. Horbar JD, Carpenter JH, Buzas J et al. Collaborative quality improvement to promote evidence based surfactant for 754 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. preterm infants: a cluster randomized trial. BMJ 2004; 329: 1004. Walti H, Paris-Liado J, Egberts J et al. Prophylactic administration of porcine-derived lung surfactant is a significant factor in reducing the odds for peri-intraventricular hemorrhage in premature infants. Biol Neonat 2002; 81: 182187. Bloom BT, Katwinkel J, Hall RT et al. Comparison of infasurf (calf lung extract)to survanta (beractant)in the treatment and prevention of respiratory distress syndrome. Pediatrics 1997; 100: 31-38. Clark RH, Auten RL, Peabody J. A comparison of the outcomes of neonates treated with two different natural surfactants. J Pediatr 2001; 139: 828-831. Speer CP, Gefeller O, Groneck P et al. Randomized clinical trial of two different treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome. Arch Dis Child 1995; 72: P8-P13. Baroutis G, Kaleyias J, Liarout et al. Comparison of three treatment regimens of natural surfactant preparations in neonatal respiratory distress syndrome. Eu J Pediatr 2003; 162: 476-480. Ramanthan R, Ramussen MR, Gerstmann D et al. For the North American study group. A randomized, multicenter masked comparison trial of proctant alfa (curosurf) versus beractant (survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol 2004; 21: 109-119. Lam BC, Ng YK, Wong KY. Randomized trial comparing two natural surfactants (survanta vs bLES ) for treatment of neonatal respiratory distress syndrome. Pediatr Pulmonol 2005; 39: 64-69. Yalaz M, Arslanolu S, Akisu M, Atik T, Ergun O, Kultursay N. A comparison of efficacy between two natural exogenous surfactant preparations in premature infants with respiratory distress syndrome. Klin Padiatr 2004; 216: 230-235. Sinha S, Lacaze-Masmonteil T,Valis i Soler A et al. A multicenter, randomized, controlled trial of Lucinactant versus Poractant alfa among very premature infants at high risk for respiratory distress syndrome. Pediatrics 2005; 115: 1030-1038. Chotigeat U, Promwong N, Kanjanapattanakul W, Khorana M, Sangtawesin V, Horpaopan S. Comparison outcomes of surfactant therapy in respiratory distress syndrome in two periods. J Med Assoc Thai 2008; 91: S109-S114. Bncalari E, Del Moral T. Bronchopulmonary dysplasia and surfactant. Biol Neonate 2001; 80: 7-13. Indian Journal of Pediatrics, Volume 77—July, 2010