Krishnamurthy Sekar

Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks' gestation: a randomized, controlled trial

Objective:To compare the effect of early extubation to nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) on the need for mechanical ventilation via endotracheal tube (MVET) at 7 days of age in preterm infants <30 weeks’ gestation requiring intubation and surfactant for respiratory distress syndrome (RDS) within 60 min of delivery.Study Design:Multicenter, randomized, controlled trial. A total of 57 infants were randomized within 120 min of birth to NCPAP (BW 1099 g and GA 27.8 weeks) and 53 infants to NIPPV (BW 1052 g, and GA 27.8 weeks). Infants were stabilized on NCPAP at birth and were given poractant alfa combined with MVET within 60 min of age. When stabilized on MVET, they were extubated within the next hours or days to NCPAP or NIPPV.Result:A total of 40% of infants needed MVET at 7 days of age in the NCPAP group compared with 17% in the NIPPV group (OR: 3.6; 95% CI: 1.5, 8.7). Days on MVET were 12±11 days in NCPAP group compared with 7.5±12 days in the NIPPV group (median 1 vs 7 days; P=0.006). Clinical bronchopulmonary dysplasia (BPD) was 39% in the NCPAP group compared to 21% in the NIPPV group (OR: 2.4; 95% CI: 1.02, 5.6). Physiological BPD was 46% in the NCPAP group compared with 11% in the NIPPV group (OR: 6.6, 95% CI: 2.4, 17.8; P=0.001). There were no differences in any other outcomes between the two groups.Conclusion:NIPPV compared with NCPAP reduced the need for MVET in the first week, duration of MVET, and clinical as well as physiological BPD in preterm infants receiving early surfactant for RDS.

Mortality in preterm infants with respiratory distress syndrome treated with poractant alfa, calfactant or beractant: a retrospective study

Objective:The objective of this study is to compare all-cause in-hospital mortality in preterm infants with respiratory distress syndrome (RDS) treated with poractant alfa, calfactant or beractant.Study Design:A retrospective cohort study of 14 173 preterm infants with RDS, treated with one of three surfactants between 2005 and 2009, using the Premier Database was done. Multilevel, multivariable logistic regression modeling, adjusting for patient- and hospital-level factors was performed.Result:Calfactant treatment was associated with a 49.6% greater likelihood of death than poractant alfa (odds ratio (OR): 1.496, 95% confidence interval (CI): 1.014–2.209, P=0.043). Beractant treatment was associated with a non-significant 37% increase in mortality, compared with poractant alfa (OR: 1.370, 95% CI: 0.996–1.885, P=0.053). No differences in mortality were observed between calfactant and beractant treatment (OR: 1.092, 95% CI: 0.765–1.559, P=0.626).Conclusion:Poractant alfa treatment for RDS was associated with a significantly reduced likelihood of death when compared with calfactant and a trend toward reduced mortality when compared with beractant.

Catecholamine-resistant hypotension and myocardial performance following patent ductus arteriosus ligation

Objective:We performed a multicenter study of preterm infants, who were about to undergo patent ductus arteriosus ligation, to determine whether echocardiographic indices of impaired myocardial performance were associated with subsequent development of catecholamine-resistant hypotension following ligation.Study Design:A standardized treatment approach for hypotension was followed at each center. Infants were considered to have catecholamine-resistant hypotension if their dopamine infusion was >15 μg kg–1min–1. Echocardiograms and cortisol measurements were obtained between 6 and 14 h after the ligation (prior to the presence of catecholamine-resistant hypotension).Result:Forty-five infants were enrolled, 10 received catecholamines (6 were catecholamine-responsive and 4 developed catecholamine-resistant hypotension). Catecholamine-resistant hypotension was not associated with decreased preload, shortening fraction or ventricular output. Infants with catecholamine-resistant hypotension had significantly lower levels of systemic vascular resistance and postoperative cortisol concentration.Conclusion:We speculate that low cortisol levels and impaired vascular tone may have a more important role than impaired cardiac performance in post-ligation catecholamine-resistant hypotension.

A Cost Minimization Comparison of Two Surfactants—Beractant and Poractant alfa—Based Upon Prospectively Designed, Comparative Clinical Trial Data

OBJECTIVES To compare the pharmacoeconomic profiles of beractant (Survanta(®), Ross Laboratories, Columbus, Ohio) and poractant alfa (Curosurf(®), DEY LP, Napa, CA) via a cost-minimization analysis. METHODS This analysis was based upon clinical data from two previously published studies (Speer C, et al. Arch Dis Child 1995;72: F8-13; and Ramanathan R, et al. Am J Perinatol 2004; 21:109-19) where investigators found significant differences in the number of doses required to achieve a similar clinical response. Our analyses employed several models based upon single-use or multiple-use of single-use vial scenarios, average wholesale pricing, and costs computed on a per-patient basis. Model 1 involved single-dose vials and mean weight of the infants (both trials). Models 2 and 3, based on individual patient weights, assessed single-dose and multiple-use of single-dose vials cost scenarios, respectively. Individual patient weights allowed for statistical evaluation in Models 2 and 3. RESULTS Model 1 savings with poractant alfa treatment was

Response to Cummings.

949.67 (53%) based upon Speer and

Response to Dr Egan’s letter

617.90 (46%) based upon Ramanathan. Models 2 and 3 reported savings for poractant alfa of

A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome.

220.50 (20%) (P = 0.11) and

A RANDOMIZED, MULTICENTER MASKED COMPARISON TRIAL OF PORACTANT ALFA (CUROSURF) VERSUS BERACTANT (SURVANTA) IN THE TREATMENT OF RESPIRATORY DISTRESS SYNDROME IN PRETERM INFANTS

180 (20%) (P = 0.018), respectively over beractant. CONCLUSIONS These analyses would suggest poractant alfa may offer a less costly, clinically-equivalent option. Savings may vary with vial usage and mix, patient weight distribution, and how surfactants are used in practice. Institutions utilizing surfactants may wish to examine usage patterns, dosing protocols, and patient mix to determine what potential savings may exist.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

We would like to thank Dr Cummings for giving us the opportunity to explain our study results. Results from nine randomized, controlled, trials (RCTs),1, 2, 3, 4, 5, 6, 7, 8, 9 including the one that has been just published (e-pub ahead of print) by Dizdar et al.9 and meta-analyses10, 11, 12 comparing animal-derived surfactants, namely, poractant alfa (PA), beractant (BE), bovactant (BO) and/or calfactant (CA), have consistently shown faster weaning of oxygen and mean airway pressure, less need for redosing, fewer days on oxygen and mechanical ventilation, shorter length of stay (LOS) as well as survival advantage in babies treated with PA. These advantages with PA over BE, CA or BO are likely related to major biological and/or biochemical differences between these animal-derived surfactant preparations. PA contains the highest amount of phospholipids when compared with BE or CA. Higher amount of phospholipids has been shown to downregulate oxidative functions in monocytes and confer better anti-inflammatory properties.13 In addition, bacterial growth in different surfactant preparations is influenced by microbial species and the composition and dose of the surfactant. PA was bactericidal in a dose-dependent fashion and differed from BE and BO, a surfactant preparation similar to CA.14 PA contains the highest amount of plasmalogens (PL) when compared with BE.15 BO contains the lowest amount of PL.15 PL are anti-oxidant phospholipids and presence of higher amounts of PL in the tracheal aspirates from pre-term infants has been shown to be associated with a lower risk for bronchopulmonary dysplasia (BPD).16 Also, the amount of surfactant-associated protein B (SP-B) is highest in PA when compared with BE or CA. SP-B is the most important SP in helping the phospholipids to rapidly adsorb at the air–liquid interphase and in decreasing surface tension. Furthermore, the phospholipid molecular species of PA is much closer to that of human surfactant.17, 18

Neonatal radiologic casebook. Group B streptococcal infection/cerebral necrosis.

Thank you for the opportunity to respond to the letter from Dr Edmund A Egan, Chief Medical Officer of ONY, Inc., manufacturer of Infasurf (Calfactant, (CA)). In the letter by Dr Egan, he refers to the studies presented as abstracts in 2007 (ref. 1,2 in his letter) and our study published electronically as a peer reviewed manuscript in 2011 and included in this print issue. These are different studies, in which different protocols, different timeframes (abstract 2007: Jan 2003 to June 2006; full publication 2011:Jan 2005 to Dec 2009) different infants, different number of patients and different statistical models were used. Dr Egan discusses the increased length of stay (LOS) resulting from improvement in mortality due to surfactant therapy in studies comparing surfactant vs placebo. Based on evidence, the introduction of surfactant therapy has led to significantly decreased mortality and morbidity without increasing resource utilization. The statements of Dr Egan regarding inverse correlation between mortality and LOS are based on a very old study (ref. 3 in his letter) comparing surfactant with placebo in a different ‘era’ of neonatology, where respiratory distress syndrome (RDS) was the major cause of death and had a major influence on LOS. Most important is the fact that surfactant therapy compared with placebo has shown decrease in cost both in infants who survived as well as in infants who died. Subsequent studies on resource utilization are clearly different and these have reported LOS in patients who received one of the three animal-derived surfactants.1, 2 Baroutis et al.3 reported decreased mortality and significantly shorter LOS with poractant alfa (PA), when compared to alveofact or beractant (BE) in a randomized, controlled trial. Fujii et al.4 reported a nonsignificant decrease in mortality (8 vs 19%) and shorter LOS in a PA-treated group compared with that in the BE-treated group (87 vs 97 days, P=0.179). In two randomized, controlled trials comparing PA and BE, incidence of patent ductus arteriosus (PDA), as well as the need for medical or surgical ligation of PDA, were significantly less in patients treated with PA,4, 5 which might therefore contribute to shorter LOS. In a study comparing high vs low dose surfactant therapy, LOS was shorter in the high dose group when compared with low dose group (82 vs 99 days).6 A recently published systematic review and meta-analysis,7 demonstrated a good correlation between higher surfactant efficacy (mortality reduction) and reduced LOS with poractant alfa (PA). Indeed, in the meta-analysis, PA was associated with both a significant reduced risk of death vs BE (P=0.02) and a significantly shorter LOS (weighted mean difference: −26.3 [95% CI: −36.5 to −16.07]; P<0.00001). In the most recent randomized trial comparing PA with BE, LOS was not increased in PA group despite a 50% reduction in mortality rate in the PA-treated group (9.8 vs 20%).8