This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Guérin, C. Articles by Richard, J.-C. Search for Related Content PubMed PubMed Citation Articles by Guérin, C. Articles by Richard, J.-C.

On the Randomized Trial of Activated Protein C in Acute Lung Injury

With regard to the report by Dr. Liu and colleagues on their randomized trial (1), we suggest that the following points need further elucidation.

The authors should include the time spent between the administration of activated protein C (APC) (2) and the onset of acute lung injury. In animal models of acute lung injury, the timing of intravenous administration of APC has been found to be important. Pretreatment with APC worsened oxygenation in Pseudomonas-induced lung injury in rats (3) and in a porcine model of oleic acid–induced lung injury (4). This finding was related to further alveolar flooding resulting from a reduction of the lung liquid clearance with APC in the former (3) and to pulmonary blood continuing to flow toward the dorsal edematous lung regions whose ventilation did not change in the latter (4). By contrast, the administration of APC after the induction of lung injury was found to be beneficial in terms of oxygenation (5). It was then suggested that a greater efficacy of the compound should be expected if its administration matches full alteration in the lung coagulation pathway during acute lung injury (6).

At baseline, the lungs in the APC group were more severely injured from the underlying disease and/or mechanical ventilation, even though the differences were not significant, presumably by lack of power. In addition to the greater value of dead space fraction, plateau pressure was on average 1 cm H₂O greater than in the placebo group; but in some patients, it was greater than 30 cm H₂O and the Pa_O2/FI_O2 ratio tended to be lower.

The authors did not provide information about the set respiratory rate and the values of Pa_CO2 at inclusion and over time.

Claude Guérin and Jean-Christophe Richard

Hôpital de la Croix Rousse
Lyon, France

FOOTNOTES

Conflict of Interest Statement: Neither author has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

REFERENCES

1. Liu KD, Levitt J, Zhuo H, Kallet RH, Brady S, Steingrub J, Tidswell M, Siegel MD, Soto G, Peterson MW, et al. Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med 2008;178:618–623.[Abstract/Free Full Text]
2. El Solh A, Bhora M, Pineda L, Aquilina A, Abbetessa L, Berbary E. Alveolar plasminogen activator inhibitor-1 predicts ARDS in aspiration pneumonitis. Intensive Care Med 2006;32:110–115.[Medline]
3. Robriquet L, Collet F, Tournoys A, Prangere T, Neviere R, Fourrier F, Guery BP. Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response. Respir Res 2006;7:41–50.[CrossRef][Medline]
4. Richard J, Bregeon F, Leray V, Le Bars D, Costes N, Tourvielle C, Lavenne F, Devousassoux-Shiseboran M, Gimenez G, Guerin C. Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury. Intensive Care Med 2007;33:2199–2206.[Medline]
5. Maybauer MO, Maybauer DM, Fraser JF, Traber LD, Westphal M, Enkhbaatar P, Cox RA, Huda R, Hawkins HK, Morita N, et al. Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis. Crit Care Med 2006;34:2432–2438.[CrossRef][Medline]
6. Velik-Salchner C, Wenzel V, Maybauer DM, Maybauer MO. Recombinant human activated protein C in experimental models of acute lung injury: the timing is critical! Intensive Care Med 2007;33:2048–2050.[Medline]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Guérin, C. Articles by Richard, J.-C. Search for Related Content PubMed PubMed Citation Articles by Guérin, C. Articles by Richard, J.-C.