Surfactant Replacement Therapy in ARDS: Response

Abstract

To the Editor: We appreciate the interest of Drs. Wise, Saayman, and Frost in our analysis of patients treated with a recombinant surfactant protein (SP)-C surfactant (Venticute; Nycomed GmbH; Konstanz, Germany).1Taut FJ Rippin G Schenk P et al.A Search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute).Chest. 2008; 134: 724-732Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar They note that the relatively early treatment of ARDS patients with surfactant may be associated with a better outcome and ask whether a lead-time bias might have influenced our observation that the outcome in patients with direct lung injury appeared to be better than that for patients with indirect lung injury. We have compared the time from ARDS diagnosis to randomization (after which treatment was given within 2 h) for patients with direct or indirect lung injury. This mean (± SE) interval was 32.9 ± 1.3 or 26.5 ± 1.1 h (p = 0.0002), respectively. Thus, patients with direct lung injury, who appeared to have a better outcome, actually were randomized and treated 6 to 7 h later than those with indirect injury. Whether this difference is clinically relevant is unknown, but it appears that lead-time bias does not explain our observations. While we would also like to compare the time intervals from intubation to randomization (or treatment), this information is not available. We caution against using published information, including that cited by the correspondents, to compare the time course of surfactant abnormalities in patients with direct lung injury vs those with indirect lung injury. Studies to date have included patients treated with tidal volumes > 12 mL/kg body weight (volumes now known to be inherently injurious2Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10146) Google Scholar) and have not directly compared patients with direct or indirect lung injury. Future comparisons should require that patients be treated with a lung-protective ventilation strategy and that patients with direct or indirect lung injury be prospectively enrolled into a common study. It is very likely that surfactant abnormalities persist for several days after the onset of either direct or indirect lung injury. Although our pooled analysis focused on only the first 24 h of treatment, study of the loss of exogenous surfactant from the lungs of treated patients has previously led us to suggest,3Spragg RG Lewis JF Wurst W et al.Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant.Am J Respir Crit Care Med. 2003; : 167Google Scholar as do the correspondents, that treatment extend beyond that period. Composition of the ideal surfactant for treating patients with lung injury is unknown, and, in addition to either SP-C or SP-B (or relevant analogs), the list of suggested components includes the hydrophilic surfactant proteins SP-A and SP-D, antioxidants, protease inhibitors, phospholipase inhibitors, phospholipase-resistant phosphonolipids, and anticoagulants. Designing the optimal surfactant is clearly a challenging task!