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Correspondence |

Methylprednisolone Infusion in Early Severe ARDSResponse FREE TO VIEW

Richard H. Savel, MD; Evan B. Goldstein, DO; Herbert Lehman, MD; Yizhak Kupfer, MD
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Affiliations: Maimonides Medical Center, Brooklyn, NY,  Raymond Poincaré Hospital, Garches, France

Correspondence to: Richard H. Savel, MD, Critical Care, Maimonides Medical Center, Brooklyn, NY 11219; e-mail: rhsavel@yahoo.com



Chest. 2007;132(3):1096-1097. doi:10.1378/chest.07-1237
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The current state of the literature surrounding the value of glucocorticoids in ARDS is riddled with complexity and conflict.12 As such, we were surprised by the tone and conclusions of the editorial3accompanying Dr. Meduri’s recently published study4 on the value of methylprednisolone infusion in early severe ARDS. There are significant and fundamental design issues surrounding this study (notably absent from the editorial) that make it difficult to draw definitive conclusions regarding the role of this agent. The patients were randomized in a 2:1 fashion in favor of methylprednisolone. The incidence of catecholamine-dependent shock in the placebo group was nearly twice that of the methylprednisolone group (46.4% vs 23.8%, p = 0.03), yet no clear analysis was presented controlling for this fact. Ten of the 15 control patients (67%) who remained on mechanical ventilation at day 9 received open-label methylprednisolone because their lung injury scores had not improved. The proportion of patients requiring mechanical ventilation at 28 days was not statistically different between the two groups. The likelihood of surviving the hospital admission was also not different between the two groups. Given the aforementioned problems with this study and the limited interpretability of the results (as well as recent recommendations by other important leaders in the field1), we do not feel that the use of glucocorticoids can be promoted as a “standard of care” for patients with ARDS at this time.

The authors have no conflicts of interest to disclose.

The author has no conflict of interest to disclose.

Calfee, CS, Matthay, MA (2007) Nonventilatory treatments for acute lung injury and ARDS.Chest131,913-920. [PubMed] [CrossRef]
 
Steinberg, KP, Hudson, LD, Goodman, RB, et al Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med2006;354,1671-1684. [PubMed]
 
Annane, D Glucocorticoids for ARDS: just do it!Chest2007;131,945-946. [PubMed]
 
Meduri, GU, Golden, E, Freire, AX, et al Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest2007;131,954-963. [PubMed]
 
To the Editor:

Dr. Savel and colleagues correctly argue that recommendations for practice may not rely exclusively on the results of a single trial. For this reason, my recommendation for the routine use of low-dose corticosteroids in combination with secondary prophylaxis in patients with acute lung injury/ARDS was based on strong experimental and translational data and the consistent findings of five randomized controlled trials.1One may argue that these five trials were relatively small in size and that not all of the studies showed a significant survival benefit. However, a metaanalysis integrating the outcome data of these trials shows that prolonged glucocorticoid treatment initiated before day 14 of ARDS is associated with a significant reduction in mortality (84 of 252 patients [33%] vs 108 of 216 patients [50%]; relative risk, 0.71; 95% confidence interval, 0.50 to 0.87; p = 0.001). What should clinicians do when no large randomized controlled trial is available and a metaanalysis of small sized trials shows significant reduction in mortality that can also be supported by biological plausibility? It is this author’s opinion that while waiting for a large-scale trial to investigate mortality as a primary end point, patients with acute lung injury/ARDS should be treated with low-dose corticosteroids because this treatment undoubtedly reduces morbidity and the duration of mechanical ventilation. Additionally, potential glucocorticoid side effects can be prevented by strict surveillance for superinfection and blood glucose control, further increasing the treatment benefit/risk ratio. Regarding the internal validity of the trial of Meduri and colleagues,2 having a treatment allocation based on 2:1 principle is not a problem, assuming that placebo-treated patients will behave roughly similarly. That more patients in the placebo group were in shock was due to chance, and per-protocol analysis failed to reproduce this imbalance in the proportion of vasopressor-dependent patients. In addition, this would suggest that the positive effects of methylprednisolone in this population were unlikely entirely related to shock reversal. As far as mechanical ventilation is concerned, the proportion of patients receiving mechanical ventilation at day 28 was affected by the introduction of open-label methylprednisolone in those failing to improve (8% vs 36%, p = 0.002). Most importantly, the difference in mechanical ventilation-free days at day 28 (16.5 ± 10.1 days vs 8.7 ± 10.2 days, p = 0.001) underscores the significant impact of treatment on disease resolution and supports my argument for the routine use of this protocol in conjunction with measures demonstrated to reduce morbidity associated with glucocorticoids.

References
Annane, D Glucocorticoids for ARDS: just do it!Chest2007;131,945-946. [PubMed] [CrossRef]
 
Meduri, GU, Golden, E, Freire, A, et al Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest2007;131,954-963. [PubMed]
 

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References

Calfee, CS, Matthay, MA (2007) Nonventilatory treatments for acute lung injury and ARDS.Chest131,913-920. [PubMed] [CrossRef]
 
Steinberg, KP, Hudson, LD, Goodman, RB, et al Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.N Engl J Med2006;354,1671-1684. [PubMed]
 
Annane, D Glucocorticoids for ARDS: just do it!Chest2007;131,945-946. [PubMed]
 
Meduri, GU, Golden, E, Freire, AX, et al Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest2007;131,954-963. [PubMed]
 
Annane, D Glucocorticoids for ARDS: just do it!Chest2007;131,945-946. [PubMed] [CrossRef]
 
Meduri, GU, Golden, E, Freire, A, et al Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.Chest2007;131,954-963. [PubMed]
 
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