Surfactant Replacement
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The phase 3 studies on the effect of recombinant surfactant protein C in the acute respiratory distress syndrome, reported by Spragg et al. (Aug. 26 issue),1 address an important question. I would be interested in an explanation (biologic or otherwise) for the observed improvement in oxygenation in the first 24 hours in the group receiving active treatment, as compared with the control group, but an observed (albeit nonstatistical) trend toward a reduction in ventilator-free days (3.5 vs. 6 days) and a lower survival rate at 28 days (68 vs. 75 percent) in the North American Study. Could improved oxygenation early on facilitate greater free-radical formation (in the context of high concentrations of inspired oxygen) and promote further injury?
Andrew R.L. Medford, M.B., Ch.B.
Southmead Hospital
Bristol BS10 5NB, United Kingdom
andrew.medford@bris.ac.uk
References
Spragg RG, Lewis JF, Walmrath H-D, et al. Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med 2004;351:884-892.
Dr. Spragg replies: Dr. Medford questions whether the improvement in blood oxygenation after the administration of recombinant surfactant C–based surfactant might be causally related to a worsening of lung function, as reflected in a decrease in ventilator-free days and survival. My colleagues and I believe that a causal relationship is highly unlikely for three reasons. First, the magnitude of the difference observed in blood oxygenation is, as far as we are aware, not associated with any mechanism of injury, including increased oxygen-radical production. Second, the improvement in oxygenation, as measured by an increase in the area under the curve for the ratio of the partial pressure of arterial oxygen to the fraction of oxygen in inspired gas over time (from 0 to 24 hours), is positively correlated with survival (P=0.001 when the area under the curve is added to the multivariate logistic model, and P=0.01 for a univariate approach [Wilcoxon test]). Finally, the differences between the treated and untreated groups in ventilator-free days and survival were not statistically significant.
Roger G. Spragg, M.D.
San Diego Veterans Affairs Healthcare System
San Diego, CA 92161
rspragg@ucsd.edu
Andrew R.L. Medford, M.B., Ch.B.
Southmead Hospital
Bristol BS10 5NB, United Kingdom
andrew.medford@bris.ac.uk
References
Spragg RG, Lewis JF, Walmrath H-D, et al. Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome. N Engl J Med 2004;351:884-892.
Dr. Spragg replies: Dr. Medford questions whether the improvement in blood oxygenation after the administration of recombinant surfactant C–based surfactant might be causally related to a worsening of lung function, as reflected in a decrease in ventilator-free days and survival. My colleagues and I believe that a causal relationship is highly unlikely for three reasons. First, the magnitude of the difference observed in blood oxygenation is, as far as we are aware, not associated with any mechanism of injury, including increased oxygen-radical production. Second, the improvement in oxygenation, as measured by an increase in the area under the curve for the ratio of the partial pressure of arterial oxygen to the fraction of oxygen in inspired gas over time (from 0 to 24 hours), is positively correlated with survival (P=0.001 when the area under the curve is added to the multivariate logistic model, and P=0.01 for a univariate approach [Wilcoxon test]). Finally, the differences between the treated and untreated groups in ventilator-free days and survival were not statistically significant.
Roger G. Spragg, M.D.
San Diego Veterans Affairs Healthcare System
San Diego, CA 92161
rspragg@ucsd.edu