Therapy Comparison of Two Fluid-Management Strategies in Acute Lung Injury
This review may be edited
Summary
Posted By:	Robert O'Connor
E-Mail:	robocon@ozemail.com.au
Posted Date:	13 Sept 2006
Title:	Comparison of Two Fluid-Management Strategies in Acute Lung Injury
Authors:	The National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network
Reference:	N Engl J Med 2006; 354:2564-2575, Jun 15, 2006; published at www.nejm.org on May 21, 2006 (10.1056/NEJMoa062200).
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	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 pressure × the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen] × 100) 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 non-pulmonary organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized? ( Was allocation concealment maintained?)
	Patients were randomised with 'concealed allocation' using an ‘automated system’. Fluid management strategy was allocated in permuted blocks of eight. This paper represents one arm of a factorial trial. Patients were simultaneously randomised to central venous or pulmonary arterial monitoring.
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	No. The researchers did not follow all patients until the primary outcome at day 60. Although of the 1001 patients recruited, only one was reported as lost to follow-up in the liberal fluid management group (flow diagram, p.2568, on p.2566 it is noted that “…we assumed patients who went home without the use of assisted ventilation before day 60 were alive at 60 days.” The number of patients who were discharged home prior to day 60 is not recorded.
2b. Were patients analyzed in the groups to which they were randomized?
	Yes. “The primary analysis was conducted according to the intention to treat”. (p.2566).
3. Were patients, health workers, and study personnel blind to treatment?
	Given the nature of the interventions, blinding was impossible. However, some part of the fluid management protocol outlined on p.2567 was applied to all patients.
4. Were the groups similar at the start of the trial?
	Table 1 on p.2569 outlines the baseline characteristics of both groups. Apart from a small difference between groups in the number of patients with concurrent ‘solid tumours’ and ‘leukaemia’, there were no statistically significant differences.
5. Aside from the experimental intervention, were the groups treated equally?
	There is no reported difference in the general care given. The study period was from June 2000 to October 2005.
What are the Results?
1. How large was the treatment effect?
	Death rates at sixty days were 25.5% and 28.4% in the conservative and liberal strategy groups respectively. This did not attain statistical significance (P = 0.30). Ventilator free days (14.6 ± 0.5 vs. 12.1 ± 0.5 days) and ICU free days (13.4 ± 0.4 vs. 11.2 ± 0.4 days) were significantly decreased over the first 28 days of hospital admission (p<0.001). There was no difference between groups in the requirement for dialysis to sixty days. (p.2572)
2. How precise was the estimate of the treatment effect?
	The study was designed to have a 90% power of detecting a 10% difference in mortality to 60 days. Two-sided P values of 0.05 or less were considered to be statistically significant with regard to other outcomes.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	Yes, for a limited subset. There were some major patient co-morbidities which led to exclusion from the trial: pre-existing dialysis dependent renal failure, severe chronic airflow limitation, chronic liver or neuromuscular disease and recent myocardial infarction.
2. Were all clinically important outcomes considered?
	Yes. Also noted in the discussion was a small increase in rates of hypernatraemia and hypokalemia in the conservative fluid group as well as a small increase in decreased level of consciousness (“CNS failure”). This did not appear to change length of stay in ICU or overall survival.
3. Are the likely treatment benefits worth the potential harms and costs?
	The major benefit is an increase in ICU free days and ventilator free days. There appears to be little risk with the conservative fluid strategy, save the adverse effects of frusemide.
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