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Background Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion.
Methods In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure–free days and measures of lung physiology.
Results The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, –2.6 to 8.4 percent). The mean (±SE) cumulative fluid balance during the first seven days was –136±491 ml in the conservative-strategy group and 6992±502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressurexthe ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100) and the lung injury score and increased the number of ventilator-free days (14.6±0.5 vs. 12.1±0.5, P<0.001) and days not spent in the intensive care unit (13.4±0.4 vs. 11.2±0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06).
Conclusions Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. (ClinicalTrials.gov number, NCT00281268
[ClinicalTrials.gov]
.)
The optimal fluid management of acute lung injury is not settled.4,5,6,7 The usual practice is wide-ranging, and many practitioners weigh the risks and benefits of strategies of conservative as compared with liberal fluid management. In the conservative approach, fluid intake is restricted and urinary output is increased in an attempt to decrease lung edema, shorten the duration of mechanical ventilation, and improve survival. A possible risk of this approach is a decrease in cardiac output and worsening of nonpulmonary-organ function. The liberal fluid approach essentially reverses these potential priorities and risks.
Current evidence is insufficient to support the use of either a liberal or conservative fluid strategy in patients with established acute lung injury.8,9,10,11 We conducted a prospective, randomized clinical trial to investigate the risks and benefits of a fluid-management protocol with a lower (conservative use of fluids) or higher (liberal use of fluids) intravascular pressure (as defined by the pulmonary-artery occlusion pressure or central venous pressure) in patients with acute lung injury. Our primary outcome was death from any cause at 60 days.
Methods
Study Design
The complete protocol for this trial can be found in the Supplementary Appendix (available with the full text of this article at www.nejm.org). Patients were randomly assigned to a strategy involving either conservative or liberal use of fluids with concealed allocation in permuted blocks of eight with the use of an automated system. Participants were simultaneously randomly assigned to receive either a pulmonary-artery catheter or a central venous catheter in a two-by-two factorial design.12
Inclusion Criteria
Eligible patients were intubated and received positive-pressure ventilation, had a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 300 (adjusted if the altitude exceeded 1000 m), and had bilateral infiltrates on chest radiography consistent with the presence of pulmonary edema without evidence of left atrial hypertension.13 If a potential participant did not have a central venous catheter, the primary physician's intent to insert one was required.
Exclusion Criteria
Reasons for exclusion are listed in the Supplementary Appendix. Major reasons for exclusion were the presence of a pulmonary-artery catheter after the onset of acute lung injury; the presence of acute lung injury for more than 48 hours; inability to obtain consent; the presence of chronic conditions that could independently influence survival, impair weaning, or compromise compliance with the protocol (e.g., severe lung or neuromuscular disease or dependence on dialysis); and irreversible conditions for which the estimated six-month mortality rate exceeded 50 percent, such as advanced cancer.
Study Procedures
Ventilation according to the Acute Respiratory Distress Syndrome (ARDS) Network protocol of lower tidal volumes was begun within one hour after randomization and continued until day 28; a protocol was used to wean patients from mechanical ventilation.14 The assigned catheter was inserted within four hours after randomization. Hemodynamic management was started within 2 hours after catheter insertion and continued for seven days or until 12 hours after a patient was able to breathe without assistance.14 After day 3, a pulmonary-artery catheter could be replaced by a central venous catheter if hemodynamic stability (i.e., absence of the need for protocol-directed interventions on the basis of a measurement with a pulmonary-artery catheter for more than 24 hours) was achieved. We monitored compliance with protocol instructions twice each day: once during a morning reference period and again at a randomly selected time. A 100 percent audit of all instructions conducted after the first 82 patients were enrolled showed rates of protocol compliance similar to those obtained during the random checks (data not shown).
Study personnel underwent training in the conduct of the protocol (Figure 1) and the measurement of vascular pressure. Vascular pressures were measured in supine patients at end expiration (identified with an airway pressure signal) but were not adjusted for airway pressure.15
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A National Heart, Lung, and Blood Institute protocol-review committee, a data and safety monitoring board, and the institutional review board of each participating hospital approved the study. Written informed consent was obtained from participants or legally authorized surrogates. The data and safety monitoring board conducted interim analyses after the enrollment of 82 patients and then after the enrollment of approximately every 200 patients. Sequential stopping rules for safety and efficacy used the method of O'Brien and Fleming.16
Organ Failure
For 28 days, we monitored patients daily for cardiovascular, renal, and hepatic failure; coagulation abnormalities; and the need for assisted ventilation.14 The severity of lung injury was scored according to the method of Murray et al.17; the scores can range from 0 to 4, with a lower score indicating better lung function.
Statistical Analysis
The study had a statistical power of 90 percent to detect a reduction by 10 percentage points (from 31 percent to 21 percent) in the primary end point, death before discharge home during the first 60 days after randomization, with the planned enrollment of 1000 patients. We assumed patients who went home without the use of assisted ventilation before day 60 were alive at 60 days. Data on patients who were receiving mechanical ventilation or in a hospital were censored on the last day of follow-up. The Kaplan–Meier method was used to estimate the mean (±SE) 60-day mortality rate at the time of the last death that occurred before 60 days. Differences in mortality between the groups were assessed by a z test. The primary analysis was conducted according to the intention to treat. We assessed differences in continuous variables with analysis of variance, differences in categorical variables with a Mantel–Haenszel test, and differences between continuous variables over time with repeated-measures analysis of variance. For continuous variables, means ±SE are reported. Two-sided P values of 0.05 or less were considered to indicate statistical significance. We used SAS software (version 8.2, SAS Institute) for the analysis.
Results
Enrollment and Exclusions
We screened patients at 20 North American centers between June 8, 2000, and October 3, 2005. The trial was halted on July 25, 2002, for a review by the Office of Human Research Protection and resumed unchanged on July 23, 2003, except for the introduction of a modified consent form.18,19,20 Figure 2 shows the most common reasons for exclusion for the 10,511 patients who were screened but not enrolled and the follow-up for the 503 patients who were randomly assigned to conservative fluid management and the 498 who were assigned to liberal fluid management (all reasons for exclusion are listed in Table 1 of the Supplementary Appendix).
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The two groups were similar with respect to demographic characteristics, type of intensive care unit (ICU), cause of lung injury, coexisting illnesses, severity of illness, organ function, fluid balance before the study began, vasopressor use, and presence of shock (Table 1).
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The mean time from admission to the ICU to the first protocol instruction was 41.3±1.6 hours in the liberal-strategy group and 43.8±2.5 hours in the conservative-strategy group (P=0.42). The rate of compliance with instructions was similar in the two groups (91 percent in the liberal-strategy group and 88 percent in the conservative-strategy group, P=0.06), even though patients in the former group received more protocol instructions per day (5.1 vs. 4.1, P<0.001). Patients in the conservative-strategy group received furosemide more frequently than did patients in the liberal-strategy group (41 percent vs. 10 percent of instructions, P<0.001), whereas patients in the latter group more often received a fluid bolus (15 percent vs. 6 percent of instructions, P<0.001). More furosemide was given to the conservative-strategy group (Table 2). Dobutamine use was similar and uncommon in both groups (4 percent in the liberal-strategy group and 6 percent in the conservative-strategy group). At least one blood transfusion was given to 29 percent of patients in the conservative-strategy group and to 39 percent of patients in the liberal-strategy group (P<0.001). During the study, there was no significant difference in the use of drotrecogin alfa (19 percent in the conservative-strategy group vs. 21 percent in the liberal-strategy group, P=0.70) or systemic corticosteroids (32 percent vs. 37 percent, P=0.09).
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Each study day the liberal-strategy group received more fluid than the conservative-strategy group and on days 1 through 4 had a lower urinary output, resulting in a higher cumulative fluid balance (Table 2). During the study, the seven-day cumulative fluid balance was –136±491 ml in the conservative-strategy group, as compared with 6992±502 ml in the liberal-strategy group (P<0.001) (Figure 1 of the Supplementary Appendix). For patients who were in shock at baseline, the cumulative seven-day fluid balance was 2904±1008 ml in the conservative-strategy group and 10,138±922 ml in the liberal-strategy group (P<0.001). For patients who were not in shock at baseline, the cumulative fluid balance was –1576±519 ml in the conservative-strategy group and 5287±576 ml in the liberal-strategy group (P<0.001).
Hemodynamics
Intravascular pressures declined in the conservative-strategy group but remained essentially unchanged in the liberal-strategy group (Figure 2 in the Supplementary Appendix). The conservative-strategy group had a slightly lower mean arterial pressure, stroke volume, and cardiac index, but the heart rate, mixed venous oxygen saturation, and percentage of patients receiving vasopressors did not differ significantly between the two groups (Table 2A in the Supplementary Appendix). For patients in shock at randomization, approximately 40 percent of subsequent measurements met the criteria for shock in both treatment groups. For patients who were not in shock at baseline, there were no significant differences between groups in the incidence of shock during study (32 percent in the liberal-strategy group and 28 percent in the conservative-strategy group, P=0.29) or in the proportions of protocol reassessments classified as shock (6 percent and 7 percent, respectively; P=0.78).
Lung Function
Ventilator settings and lung-function data are shown in Table 2B of the Supplementary Appendix. The conservative-strategy group had better lung injury scores and oxygenation indexes, as well as lower plateau pressures and positive end-expiratory pressures. The partial pressure of arterial carbon dioxide, arterial pH, and the PaO2:FIO2 were slightly higher in the conservative-strategy group on all study days, but this difference did not reach significance for the PaO2:FIO2 (P=0.07).
Metabolic and Renal Function
The conservative-strategy group had slightly higher creatinine values than the liberal-strategy group during the study, but this difference did not reach significance (P=0.06) (Table 2C of the Supplementary Appendix). The conservative-strategy group had higher levels of blood urea nitrogen, bicarbonate, hemoglobin, albumin, and calculated colloid osmotic pressure during the study.21 There were no significant differences in mean serum sodium levels during the study.
Safety
Metabolic alkalosis and electrolyte imbalances were reported as an adverse event (none with associated arrhythmias) more frequently with the conservative strategy (42 events, 3 serious) than with the liberal strategy (19 events, 1 serious) (P=0.001). More patients in the conservative-strategy group than in the liberal-strategy group had at least one potassium value of 3.0 mmol per liter or less (26 percent vs. 22 percent, P<0.001), one sodium value of at least 150 mmol per liter (25 percent vs. 18 percent, P=0.009), or one bicarbonate value of more than 40 mmol per liter (6 percent vs. 2 percent, P<0.001). There was no significant difference in the percentage of patients with at least one potassium value of 2.5 mmol per liter or less (4 percent vs. 3 percent, P=0.23).
Major Outcomes
Major outcomes are shown in Table 3 and Figure 3. There was no interaction between the interventions of the factorial design (type of fluid management and type of catheter, P=0.26). Therefore, results are reported according to the fluid-management strategy, irrespective of catheter assignment. The in-hospital death rate during the first 60 days after randomization was 25.5±1.9 percent in the conservative-strategy group and 28.4±2.0 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, –2.6 to 8.4 percent). The conservative-strategy group had more ventilator-free days, days free of central nervous system failure, and ICU-free days during the first 28 days. There were no significant differences in the number of failure-free days for other organs during the first 28 days, although there was a small (0.3 day) increase in the number of cardiovascular-failure–free days during the first 7 days with the liberal strategy. Within the first 60 days, there were no significant differences in either the percentage of patients receiving renal-replacement therapy (10 percent in the conservative-strategy group vs. 14 percent in the liberal-strategy group, P=0.06) or the average number of days of renal support (11.0±1.7 vs. 10.9±1.4, P=0.96). There were no significant interactions between baseline shock status and treatment with respect to the mortality rate or the number of ventilator-free days or ICU-free days (Table 3 of the Supplementary Appendix).
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Discussion
Although we did not detect a significant difference between the conservative strategy and the liberal strategy of fluid management in the primary outcome of 60-day mortality, the conservative strategy improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. The overall difference in mortality according to race or ethnic group has previously been described in patients with acute lung injury22 and could be due to several factors, including socioeconomic disparities or genetic determinants.23
The two strategies were designed to be prudent but distinctly different approaches to fluid therapy. To place the results of our study in context, it is useful to consider how these fluid strategies compare with usual practice. In this regard, it is of interest that the cumulative seven-day fluid balance in the liberal-strategy group (6992±502 ml) was similar to that among patients in ARDS Network studies in which the approach to fluid management was not specified14,24 (Figure 1 of the Supplementary Appendix). These findings are similar to those reported by Simmons et al.8 in 1987, suggesting that the liberal approach to fluid management reflects long-standing practices. The usual practice resembles the liberal approach in another aspect: the prestudy baseline measurements for central venous pressure (12.2 mm Hg) and pulmonary-artery–occlusion pressure (15.7 mm Hg) were both within the target ranges for the liberal fluid strategy (10 to 14 mm Hg and 14 to 18 mm Hg, respectively).
Comparisons of our study to other studies of goal-directed management in critically ill patients are problematic because of differences in protocols, patient populations, and timing of the interventions. Whereas we targeted central venous pressure or pulmonary-artery occlusion pressure in patients with recent onset of acute lung injury, previous studies targeted the cardiac index, oxygen delivery, or mixed venous oxygen saturation in heterogeneous populations of critically ill patients.25,26,27,28,29,30,31 Rivers et al.32 demonstrated in patients with severe sepsis or septic shock the efficacy of six hours of early, goal-directed resuscitation in the emergency department before admission to the ICU. In contrast, our patients received their first protocol intervention an average of 43 hours after admission to the ICU and 24 hours after meeting the criteria for acute lung injury.
The conservative-strategy group had higher serum oncotic pressures and lower intravascular pressures — characteristics that would be expected to limit the development of pulmonary edema. With lung injury, small increases in the pulmonary-artery occlusion pressure are associated with large increases in extravascular lung water.2 The higher albumin and hemoglobin levels in the conservative-strategy group appear to be primarily related to hemoconcentration (or less hemodilution), since the rate of albumin use was low and not significantly different between groups and red-cell transfusions were more frequent in the liberal-strategy group.
Our results are consistent with those obtained in studies in animals suggesting improved lung function with diuretics and fluid restriction33,34,35,36,37 and with the results of observational studies in humans indicating increased survival with a lower fluid balance and a reduction in the pulmonary-artery occlusion pressure.6,8,9 Mitchell and colleagues10 randomly assigned 89 patients with pulmonary edema to receive diuretics and fluid restriction based on extravascular lung water or routine fluid management; the group with fluid restriction had a lower fluid balance, fewer days of ventilator use, and fewer days in the ICU. Martin and coworkers11 randomly assigned 37 patients with hypoproteinemia and acute lung injury to receive either a five-day specified regimen of furosemide and colloid replacement or placebo infusions. The treated group had an increase in the PaO2:FIO2 within 24 hours. We do not know whether using lung-water measurements to drive protocol instructions or increasing the use of colloid would have increased the benefits of the conservative strategy in our study.
The hemodynamic consequences of the conservative strategy were small and apparently of minimal clinical significance. Although the mean arterial pressure, stroke volume, and cardiac index were slightly lower in the conservative-strategy group than in the liberal-strategy group, there were no significant differences in mixed venous oxygenation or in the incidence or duration of shock. Although the conservative strategy was associated with a slightly higher blood urea nitrogen level, the creatinine level, the number of days without renal failure, and the need for dialysis were similar in the two groups. Possible reasons for the greater number of days without central nervous system failure in the conservative-strategy group include a reduced incidence of cerebral edema, differences in acid–base status, or a lower rate of use of sedation as improved lung function permitted earlier removal from the ventilator. The available data are not sufficient to distinguish among these or other potential explanations.
The protocols were designed to minimize risks. During shock, physicians treated patients according to their usual practice. Because of concern that a conservative approach might worsen cardiovascular or renal function, diuretic administration was suspended until 12 hours after a fluid bolus or the reversal of shock, and prompt fluid administration was provided in the event of oliguria or ineffective circulation. Diuretic therapy was titrated on the basis of the patient's response, avoided in patients with worsening renal function, and limited to a daily maximum. To minimize the risk of excessive fluid therapy, protocol-mandated fluid administration in patients without shock was limited to three boluses per day and was withheld in patients without shock who had severe hypoxemia (FIO2
0.7) or a cardiac index of at least 4.5 liters per minute per square meter of body-surface area.
Electrolyte levels were managed by the clinician. The conservative-strategy group had a higher partial pressure of arterial carbon dioxide, arterial pH, and bicarbonate level than did the liberal-strategy group. Although mean differences between the groups in the serum sodium, potassium, and bicarbonate levels were small, a higher percentage of patients in the conservative-strategy group had at least one potassium value between 2.5 and 3.0 mmol per liter, at least one sodium value of 150 mmol per liter or more, and at least one bicarbonate value of 40 mmol per liter or more. Hence, close monitoring of electrolyte levels is warranted during diuretic therapy.
Since we tested specific management strategies that used several variables and safeguards, we do not know whether the safety and benefit of the conservative protocol could be realized by using the simplified target of a zero fluid balance. Departures from the specific hemodynamic and ventilator protocols used in this trial may lead to clinical outcomes that differ from those observed in this study.
In conclusion, we found that use of a conservative fluid-management protocol with a lower central venous pressure or pulmonary-artery occlusion pressure target resulted in a major reduction in net fluid balance without an increase in adverse events, as compared with a liberal fluid-management protocol targeting higher intravascular filling pressures. Although we did not detect a difference in the mortality rate between the two approaches, the conservative strategy improved lung function and shortened the duration of mechanical ventilation and intensive care, without increasing nonpulmonary organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury.
Supported by contracts (NO1-HR-46046-64 and NO1-HR-16146-54) with the National Heart, Lung, and Blood Institute, National Institutes of Health.
No potential conflict of interest relevant to this article was reported.
Source Information
The members of the Writing Committee (Herbert P. Wiedemann, M.D., Cleveland Clinic, Cleveland; Arthur P. Wheeler, M.D., and Gordon R. Bernard, M.D., Vanderbilt University, Nashville; B. Taylor Thompson, M.D., and Douglas Hayden, M.A., Massachusetts General Hospital, Boston; Ben deBoisblanc, M.D., Louisiana State University Health Sciences Center, New Orleans; Alfred F. Connors, Jr., M.D., Case Western Reserve University at MetroHealth Medical Center, Cleveland; R. Duncan Hite, M.D., Wake Forest University Health Sciences Center, Winston-Salem, N.C.; and Andrea L. Harabin, Ph.D., National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, Md.) assume responsibility for the integrity of the article.
This article was published at www.nejm.org on May 21, 2006.
Address reprint requests to Dr. Wiedemann at the Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic, 9500 Euclid Ave., Desk A-90, Cleveland, OH 44195, or at wiedemh{at}ccf.org.
References
The following persons and institutions participated in the trial: Writing Committee — H.P. Wiedemann, A.P. Wheeler, G.R. Bernard, B.T. Thompson, B. deBoisblanc, A.F. Connors, R.D. Hite, D. Hayden, A.L. Harabin; Steering Committee Chair — G.R. Bernard; Clinical Coordinating Center — D.A. Schoenfeld, B.T. Thompson, N. Ringwood, C. Oldmixon, F. Molay, A. Korpak, R. Morse, D. Hayden, M. Ancukiewicz, A. Minihan; Protocol-Review Committee — J.G.N. Garcia, R. Balk, S. Emerson, M. Shasby, W. Sibbald; Data Safety and Monitoring Board — R. Spragg, G. Corbie-Smith, J. Kelley, K. Leeper, A.S. Slutsky, B. Turnbull, C. Vreim; National Heart, Lung, and Blood Institute — A.L. Harabin, D. Gail, P. Lew, M. Waclawiw; ARDS Clinical Trials Network Consultant — P. Parsons; Clinical Centers — University of Washington, Harborview — L. Hudson, K. Steinberg, M. Neff, R. Maier, K. Sims, C. Cooper, T. Berry-Bell, G. Carter, L. Andersson; University of Michigan — G.B. Toews, R.H. Bartlett, C. Watts, R. Hyzy, D. Arnoldi, R. Dechert, M. Purple; University of Maryland — H. Silverman, C. Shanholtz, A. Moore, L. Heinrich, W. Corral; Johns Hopkins University — R. Brower, D. Thompson, H. Fessler, S. Murray, A. Sculley; Cleveland Clinic Foundation — H.P. Wiedemann, A.C. Arroliga, J. Komara, T. Isabella, M. Ferrari; University Hospitals of Cleveland — J. Kern, R. Hejal, D. Haney; MetroHealth Medical Center — A.F. Connors; University of Colorado Health Sciences Center — E. Abraham, R. McIntyre, F. Piedalue; Denver Veterans Affairs Medical Center — C. Welsh; Denver Health Medical Center — I. Douglas, R. Wolkin; St. Anthony Hospital — T. Bost, B. Sagel, A. Hawkes; Duke University — N. MacIntyre, J. Govert, W. Fulkerson, L. Mallatrat, L. Brown, S. Everett, E. VanDyne, N. Knudsen, M. Gentile; University of North Carolina — P. Rock, S. Carson, C. Schuler, L. Baker, V. Salo; Vanderbilt University — A.P. Wheeler, G. Bernard, T. Rice, B. Christman, S. Bozeman, T. Welch; University of Pennsylvania — P. Lanken, J. Christie, B. Fuchs, B Finkel, S. Kaplan, V. Gracias, C.W. Hanson, P. Reilly, M.B. Shapiro, R. Burke, E. O'Connor, D. Wolfe; Jefferson Medical College — J. Gottlieb, P. Park, D.M. Dillon, A. Girod, J. Furlong; LDS Hospital — A. Morris, C. Grissom, L. Weaver, J. Orme, T. Clemmer, R. Davis, J. Gleed, S. Pies, T. Graydon, S. Anderson, K. Bennion, P. Skinner; McKay-Dee Hospital — C. Lawton, J. d'Hulst, D. Hanselman; Utah Valley Regional Medical Center — K. Sundar, T. Hill, K. Ludwig, D. Nielson; University of California, San Francisco — M.A. Matthay, M. Eisner, B. Daniel, O. Garcia; San Francisco General — J. Luce, R. Kallet; University of California, San Francisco, Fresno — M. Peterson, J. Lanford; Baylor College of Medicine — K. Guntupalli, V. Bandi, C. Pope; Baystate Medical Center — J. Steingrub, M. Tidswell, L. Kozikowski; Louisiana State University Health Sciences Center — B. deBoisblanc, J. Hunt, C. Glynn, P. Lauto, G. Meyaski, C. Romaine; Louisiana State University Earl K. Long Center — S. Brierre, C. LeBlanc, K. Reed; Alton-Ochsner Clinic Foundation — D. Taylor, C. Thompson; Tulane University Medical Center — F. Simeone, M. Johnston, M. Wright; University of Chicago — G. Schmidt, J. Hall, S. Hemmann, B. Gehlbach, A. Vinayak, W. Schweickert; Northwestern University — J. Dematte D'Amico, H. Donnelly; University of Texas Health Sciences Center — A. Anzueto, J. McCarthy, S. Kucera, J. Peters, T. Houlihan, R. Steward, D. Vines; University of Virginia — J. Truwit, A.F. Connors, M. Marshall, W. Matsumura, R. Brett; University of Pittsburgh — M. Donahoe, P. Linden, J. Puyana, L. Lucht, A. Verno; Wake Forest University — R.D. Hite, P. Morris, A. Howard, A. Nesser, S. Perez; Moses Cone Memorial Hospital — P. Wright, C. Carter-Cole, J. McLean; St. Paul's Hospital, Vancouver — J. Russell, L. Lazowski, K. Foley; Vancouver General Hospital — D. Chittock, L. Grandolfo; Mayo Foundation — M. Murray.
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Related Letters:
Fluid-Management Strategies in Acute Lung Injury
Schuller D., Schuster D. P., Morizio A., Kupfer Y., Tessler S., Amaral A. C.K.B., Amado V. M., Wiedemann H. P., Wheeler A. P., Hayden D.
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N Engl J Med 2006;
355:1175-1176, Sep 14, 2006.
Correspondence
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