Letters to the Editor

Calfactant: Is There a Potential Role in Acute Lung Injury? To the Editor:


e read with great interest the article by Willson et al (1) published in Pediatric Critical Medicine in September 2013. The lack of improvement in oxygenation and long-term outcomes seen in this study could be explained by the potential causes listed by the authors. In comparison with the previous trials, the authors did not perform recruitment maneuvers after instillation of calfactant, used only two positions to facilitate equal distribution of calfactant, and used a more concentrated phospholipid, in an effort to minimize the liquid load. Based on the previous findings by Willson et al (2), we conducted a prospective trial in 20 piglets using calfactant administered to the collapsed lung during one lung ventilation (OLV) (3). OLV is a technique commonly used to facilitate thoracoscopic surgery, thus simulating a model of direct lung injury secondary to atelectasis (4). The calfactant group showed overall greater values for Pao2 compared with the control group at all time points. This difference achieved statistical significance at measurements taken after 3 hours of OLV and again at the end of the experiment. An improvement in the proinflammatory cytokines was observed from the serum and bronchioalveolar lavage specimens obtained from the subjects. We administered 1 mg/kg of calfactant to the collapsed lung in four different positions, followed by instillation of air to ensure adequate distribution and delivery. Acute lung injury has multifactorial etiologies. Atelectasis and ­re-expansion lead to systemic inflammation and lung injury (5). Calfactant administered prior to the actual insult, as seen in OLV, may have a role in attenuating this injury by improving the biophysical profile and decreasing inflammation. This work was performed at AI DuPont Hospital for Children, Thomas Jefferson University, Wilmington, DE. The authors have disclosed that they do not have any potential conflicts of interest. Rahul Bhatia, MD, Division of Pediatric Critical Care, Department of Pediatrics, Loyola University Medical Center, Stritch School of Medicine, Maywood, IL; Scott Penfil, MD, Anesthesiology and Critical Care, AI dupont Hospital for Children, Thomas Jefferson University, Wilmington, DE


1. Willson DF, Thomas NJ, Tamburro R, et al; Pediatric Acute Lung and Sepsis Investigators Network: Pediatric Calfactant in Acute Respiratory Distress Syndrome Trial. Pediatr Crit Care Med 2013; 14:657–665

Copyright © 2014 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Pediatric Critical Care Medicine

2. Willson DF, Thomas NJ, Markovitz BP, et al: Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: A randomized controlled trial. JAMA 2005; 293:470–476; Erratum in JAMA 2005; 294:900 3. Bhatia R, Shaffer TH, Hossain J, et al: Surfactant administration prior to one lung ventilation: Physiological and inflammatory correlates in a piglet model. Pediatr Pulmonol 2011; 46:1069–1078 4. Yin K, Gribbin E, Emanuel S, et al: Histochemical alterations in one lung ventilation. J Surg Res 2007; 137:16–20 5. Williams EA, Evans TW, Goldstraw P: Acute lung injury following lung resection: Is one-lung anaesthesia to blame? Thorax 1996; 51:114–116 DOI: 10.1097/PCC.0000000000000079

The authors reply:


e greatly appreciate the letter by Bhatia and Penfil (1) in response to our study (2). We are particularly heartened by the fact that these investigators have returned to the animal laboratory in an attempt to better understand the physiological effects of exogenous surfactant administration. In our discussion of the disappointing results of the calfactant in acute respiratory distress syndrome trial, we conjectured that the lack of improvement in oxygenation with calfactant relative to our previous studies might relate to a failure to achieve adequate distribution of the surfactant. In their piglet model, Bhatia and Penfil (1) demonstrated that calfactant instillation directly into the atelectatic lung resulted in improved oxygenation and diminished systemic inflammatory cytokines. The oxygenation effects are certainly consistent with our earlier studies (3–5). As the authors point out, the hypothesized role of exogenous surfactant is to prevent or attenuate the lung injury consequent to positive pressure ventilation. In theory, outcomes might be improved by aborting the cycle of collapse and re-expansion (atelectrauma) and by preventing overdistension (volutrauma or barotrauma) and promoting more homogeneous distribution of ventilation. Attenuating ventilator-induced lung injury might also mitigate the inflammatory response and the systemic consequences thereof. If this is true, exogenous surfactant is likely to be ineffective if given late or unevenly distributed. It is also likely that attention to lung protective strategies of mechanical ventilation may render this therapy less necessary. We continue to believe that exogenous surfactant may have a place in our therapeutic armamentarium for acute respiratory distress syndrome. Controlled animal studies such as that of Bhatia and Penfil (1) will hopefully elucidate where this therapy might be helpful. Dr. Thomas consulted for Discovery Labs (advisory board). His institution received grant support from the Food and Drug Administration (FDA) (RO1 grant). Dr. Tamburro received royalties from Springer Publishers (textbook co-editor). His institution received grant support from Pneuma Partners, www.pccmjournal.org


Calfactant: is there a potential role in acute lung injury?

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