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  • Letter to the Editor
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Response to Dr Egan’s letter

Journal of Perinatology volume 33, pages 166–167 (2013)Cite this article

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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

In light of the evidence cited above, it is incorrect to assume that decreased mortality will automatically lead to longer LOS, especially, when comparing treatment with different surfactants, different timing of administration such as early vs delayed treatment, and different doses such as high vs low dose. It is very likely that higher doses of PA contributed to the positive results seen with PA in all the randomized, controlled trials as well as from meta-analysis published to date. Reasons for shorter LOS accompanying decreased mortality are likely multifactorial. For example, in six of the randomized trials published to date comparing PA with BE, PA treatment was associated with faster weaning of oxygen and pressures, less need for redosing, earlier extubations, less PDA and air-leaks, and improved survival free of bronchopulmonary dysplasia. All of these secondary outcomes might have contributed to the shorter LOS observed in PA treated-infants.

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References

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Authors and Affiliations

  1. Premier Research Services, Premier Healthcare Alliance, Charlotte, NC, US

    R Ramanathan, J J Bhatia, K Sekar & F R Ernst

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  1. R Ramanathan
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  2. J J Bhatia
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  3. K Sekar
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  4. F R Ernst
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Correspondence to F R Ernst.

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Ramanathan, R., Bhatia, J., Sekar, K. et al. Response to Dr Egan’s letter. J Perinatol 33, 166–167 (2013). https://doi.org/10.1038/jp.2012.171

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