Fluid-Management Strategies in Acute Lung Injury To the Editor: The results of the Fluid and more ventilator-free days and 2.7 more ICU-free Catheter Treatment Trial (FACTT) conducted by days at day 28.1 The investigators’ conclusions the National Heart, Lung, and Blood Institute regarding the management of ARDS with restric- Acute Respiratory Distress Syndrome (ARDS) Clin- tive fluids and methylprednisolone seem contra- ical Trials Network (June 15 issue)1 support a dictory. If less time on ventilators and shorter ICU conservative strategy of fluid management in pa- stays are important end points, then methylpred- tients with acute lung injury. This strategy should nisolone seems a more potent means to achieve be recognized as only a step in the right direc- those goals than fluid-restrictive therapy. How- tion. The furosemide dosing algorithm in the ever, if we are to focus only on survival, then nei- conservative-strategy group (range, 128 to 167 mg ther therapy should be advocated. per 24 hours) simply resulted in an even — not Alex Morizio, M.D.
negative — net fluid balance, which may have Yizhak Kupfer, M.D.
mitigated the potential magnitude of the benefit. Sidney Tessler, M.D.
Protocol-guided diuretic management, with indi- Maimonides Medical Center
vidualized titration of the dose to achieve a net Brooklyn, NY 11219 diuresis, can be readily and safely implemented stessler@maimonidesmed.org in the intensive care unit (ICU) and is typically 1. The National Heart, Lung, and Blood Institute Acute Respi- associated with higher doses of furosemide (range, ratory Distress Syndrome (ARDS) Clinical Trials Network. Effi- 400 to 440 mg per 24 hours) than those used in cacy and safety of corticosteroids for persistent acute respiratory
distress syndrome. N Engl J Med 2006;354:1671-84.
FACTT, with the potential for even faster resolu- tion of pulmonary edema.2 The FACTT algorithm should not yet be viewed as “optimal” therapy, but To the Editor: Investigators in the ARDS Clini- only as an improvement on what heretofore has cal Trials Network report the results of a random- been considered “conventional” therapy.
ized study of two strategies for volume resuscita-
tion. They conclude that “the conservative strategy of fluid management improved lung function and
shortened the duration of mechanical ventilation
and intensive care” without affecting mortality ad-
versely. Unfortunately, the number of days without
mechanical ventilation is presented in Figure 3 of
the report but is not analyzed. The “free-day” analy-sis presented in the article is a combined end point
1. The National Heart, Lung, and Blood Institute Acute Respi- ratory Distress Syndrome (ARDS) Clinical Trials Network. Com-
including mortality; therefore, it is inappropriate
parison of two fluid-management strategies in acute lung injury.
to draw conclusions about the duration of me-
chanical ventilation as compared with free days. 2. Schuller D, Lynch JP, Fine D. Protocol-guided diuretic man- agement: comparison of furosemide by continuous infusion and
The authors should provide the duration of
intermittent bolus. Crit Care Med 1997;25:1969-75.
mechanical ventilation and ICU stay (mean, medi-an, and a measure of dispersion) in the two groups
To the Editor: The investigators from the ARDS for all patients, and these data should be separated Clinical Trials Network recommend a conserva- according to survivors and nonsurvivors.1 tive strategy of fluid management because it Andre C.K.B. Amaral, M.D.
“shortened the duration of mechanical ventila- Hospital São Lucas
tion and intensive care.” As compared with the 70390 155 Brasilia, Brazilliberal-strategy group, from day 1 to day 28 there decopastorius@yahoo.com.brwere 2.5 more ventilator-free days and 2.2 more Veronica M. Amado, M.D., Ph.D. ICU-free days in the conservative-strategy group. University of BrasiliaYet, the investigators do not recommend the use 70840 901 Brasilia, Brazilof methylprednisolone for ARDS despite report-
Dr. Amaral reports having received funding from Eli Lilly.
ing previously that patients who received methyl- 1. McMahon RP, Harrell FE Jr. Joint testing of mortality and a prednisolone, as compared with placebo, had 4.2 non-fatal outcome in clinical trials. Stat Med 2001;20:1165-72.
n engl j med 355;11 www.nejm.org september
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Copyright 2006 Massachusetts Medical Society. All rights reserved.
T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e
The Authors Reply: In response to Schuller and However, the difference in the proportion of pa- Schuster, we emphasize that patients in the con- tients who were breathing without assistance servative-strategy group in FACTT received indi- narrowed substantially after day 28.2 Twenty pa- vidualized protocol-guided diuretic management tients in the methylprednisolone group required in which the use of furosemide was titrated to an resumption of ventilatory assistance after attain- end point (e.g., central venous pressure <4 mm Hg) ment of unassisted breathing as compared with or to a physiological event usually considered to only six patients in the placebo group. Further- be limiting (e.g., hypotension). We believe that more, serious adverse events of neuromyopathy diuretic therapy was essentially maximized in were reported in nine patients, all of whom were these patients. Although the mean fluid balance in the methylprednisolone group. In view of these over a period of 7 days in this group was 0 ml, considerations, the ARDS Clinical Trials Network some subgroups had a negative fluid balance. For investigators do not think that the routine use of example, in the conservative-strategy group, for methylprednisolone for ARDS can be supported, patients who were not in shock at baseline, the unless the risk–benefit profile can be modified. mean fluid balance was −1576 ml. Comparisons In contrast, the conservative fluid-management between our study and that of Schuller and col- strategy in FACTT was safe, and the benefit in the leagues1 are confounded by major differences in proportion of patients breathing without assis- patient characteristics. Whereas the 1000 patients tance was sustained beyond day 28. enrolled in FACTT all had a clinical diagnosis of
Amaral and Amado are correct in pointing out
acute lung injury and ARDS, all 33 patients in the that ventilator-free days and the duration of me-study by Schuller and colleagues had a condition chanical ventilation are not equivalent. In stating for which “aggressive intravenous diuresis was that the conservative fluid-management strategy intended.” Twenty-six (79%) of these patients had shortened the duration of mechanical ventilation, congestive heart failure, and some others had re- we were referring only to survivors. The data to nal failure with fluid overload. It is not surpris- support this statement (Table 1) were not included ing that these patients received a higher average in our report for the sake of brevity. daily dose of furosemide and had a more nega- Herbert P. Wiedemann, M.D.
tive fluid balance than patients in FACTT.
Morizio and colleagues correctly point out that Cleveland, OH 44195
the use of corticosteroids increased ventilator-free wiedemh@ccf.orgdays at day 28 in patients with persistent ARDS.2 Arthur P. Wheeler, M.D. Table 1. Duration of Mechanical Ventilation.* Fluid Strategy No. of Patients No. of Days of Mechanical Ventilation 1. Schuller D, Lynch JP, Fine D. Protocol-guided diuretic man-
agement: comparison of furosemide by continuous infusion and intermittent bolus. Crit Care Med 1997;25:1969-75. 2. The National Heart, Lung, and Blood Institute Acute Respi- ratory Distress Syndrome (ARDS) Clinical Trials Network. Effi-
cacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006;354:1671-84.
n engl j med 355;11 www.nejm.org september
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Copyright 2006 Massachusetts Medical Society. All rights reserved.
FINAL VERSION “Oiling the Hinges” Notes for a presentation at the School of the Arts, Singapore Professor Tony Jones CBE Chancellor, The School of the Art Institute of Chicago, USA Firstly, my thanks to Rebecca NG for her invitation to join the Arts Forum - and for the opportunity to talk with you this morning. Rebecca is leading an extraordinary project, with an excellent team, and I know
http://elsegundousd.com/eshs/bayeagle/news/november/anthrax.htmAnthrax and biochemical warfare is now a concern of theAmerican people. As the anthrax contamination spreads,health officials have changed the way they are handling theinvestigation and treatment of the bacteria threat. Thirteen people have been infected with the anthraxbacteria across the United States, and thirty tw