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Fluid restriction is superior in acute lung injury and ARDS

A perspective on the Fluids and Catheters Treatment Trial (FACTT)
Cleveland Clinic Journal of Medicine. 2008 January;75(1):42-48
January 1, 2008|Cleveland Clinic Journal of Medicine
Herbert P. Wiedemann, MD
Author and Disclosure Information

Herbert P. Wiedemann, MD
Chairman, Department of Pulmonary, Allergy, and Critical Care Medicine, Cleveland Clinic; Co-chair, Fluid and Catheters Treatment Trial, National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network

Address: Herbert P. Wiedemann, MD, Department of Pulmonary, Allergy, and Critical Care Medicine A90, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195;e-mail wiedemh@ccf.org

Medical Grand Rounds articles are based on edited transcripts from presentations at Cleveland Clinic. They are approved by the author but are not peer-reviewed.

ABSTRACTRestricting fluid intake and promoting fluid excretion (a "dry" or conservative strategy) is more effective than a "we or liberal strategy in patients with acute lung injury and acute respiratory distress syndrome. In a multicenter, randomized, prospective clinical comparison of the two strategies in 1000 patients, those in the conservative-strategy group experienced faster improvement in lung function and spent significantly fewer days on ventilation and in the intensive care unit (N Engl J Med 2006; 354:2564-2574). No significant differences were observed in the incidence of death by 60 days or of nonpulmonary organ failure at 28 days except for days of central nervous system failure, which were fewer in the conservative-strategy group.

KEY POINTS

  • In the conservative-strategy group, the target filling pressures were a pulmonary artery occlusion pressure less than 8 mm Hg for those with a pulmonary artery catheter and a central venous pressure less than 4 mm Hg for those with only a central venous catheter. Pressures were brought into these ranges by diuresis.
  • The conservative-strategy group did not experience more frequent need for dialysis or more shock.
  • Although the number of adverse events—particularly ,metabolic alkalosis and electrolyte imbalance—was significantly higher in the conservative-strategy group, the overall incidence was low.

RESULTS

Protocol compliance

Clinicians adhered to the protocol instructions during approximately 90% of the time.

Diuretic administration. In response to high filling pressures, patients in the conservative-strategy and liberal-strategy groups received furosemide during 41% and 10% of assessment periods, respectively (P < .0001). By day 7, the average patient in the conservative-strategy group had received a cumulative dose of approximately 1,000 mg of furosemide, while the average patient in the liberal-strategy group had received 500 mg.

Fluid administration. Low filling pressure prompted the administration of a fluid bolus to the liberal-strategy group during 15% of the assessment periods, compared with 6% in the conservative-strategy group (P < .0001).

Figure 1. Cumulative fluid balance in the two study groups and in two earlier studies in which fluid management was not specified by protocol.
Fluid balance. By day 7, patients in the liberal-strategy group had received an average of about 1 L/day of fluid, for an overall net gain of 7 L. The conservative-strategy group had a net gain of 0 L by day 7 (Figure 1).8

The conservative-strategy patients who were in shock at study entry had a net gain of approximately 3 L of fluid by day 7, while the liberal-strategy group had a gain of approximately 10 L. Among the patients who were shock-free at baseline, the conservative-strategy group had a net loss of almost 2 L at day 7 while the liberal-strategy group had a net gain of about 5 L.

Figure 2. Central venous pressure (top) and pulmonary artery occlusion pressure (bottom) in the study groups.
Central venous pressure. At day 7, the filling pressure in the conservative-strategy group had fallen from 11.9 to slightly less than 9 mm Hg, meaning that not all patients met their targets. The filling pressure in the liberal-strategy group was essentially unchanged from the baseline level of 12.2 mm Hg (Figure 2).

The pulmonary artery occlusion pressure fell from 15.6 mm Hg to just below 13 mm Hg in the conservative-strategy group by day 7, although there was a wide variation among individual patients. The pressure in the liberal-strategy group (15.7 mm Hg at baseline) was unchanged at day 7 (Figure 2).

Primary end point

Figure 3. Probability of survival to hospital discharge and of breathing without assistance during the first 60 days after randomization.
At 60 days, the mortality rate was 25.5% in the conservative-strategy treatment group and 28.4% in the liberal-strategy group; the difference was not statistically significant (P = .30) (Figure 3).

Secondary end points

Through day 7, the average patient in the conservative-strategy group experienced significantly more ICU-free days (0.9 vs 0.6; P <.001) and more days free of central nervous system (CNS) failure (3.4 vs 2.9; P = .02). No significant differences were observed in the number of days free from coagulation abnormalities and renal or hepatic failure at day 28.

Through day 28, the average patient in the conservative-strategy group experienced significantly more ventilator-free days (14.6 vs 12.1; P < .001). The other 7-day results held up after 28 days, as the average conservative-strategy patient continued to experience more ICU-free days (13.4 vs 11.2; P < .001) and more days free of CNS failure (18.8 vs 17.2; P = .03). Again, no significant differences were observed in the number of days free of coagulation abnormalities and cardiovascular, renal, or hepatic failure.

It is not clear if the conservative strategy’s advantage in terms of more CNS-failure-free days was actually the result of the strategy itself or due to the fact that these patients were weaned off ventilation earlier and therefore received less sedation.

Other outcomes

Shock. One concern we had with the conservative strategy was that it might induce shock more frequently, but this did not occur. The percentage of patients who developed shock at least once during the 7-day treatment protocol was quite similar in the two groups. Also, it is interesting that patients who presented with no baseline shock had only about a 30% chance of developing shock during therapy. There was no significant difference in vasopressor use between the two groups.

Lung function. The conservative-strategy group had a significantly better Murray lung injury score at day 7: 2.03 vs 2.27 (P < .001).

Tidal-volume scores (7.4 mL/kg in both groups at baseline) dropped at an equal rate and were virtually identical at day 7 (6.36 mL/kg in the conservative-strategy group and 6.34 in the liberal-strategy group), as expected.The plateau pressure, positive end-expiraory pressure, PaO2–FIO2 ratio, and oxygenation index were slightly but not significantly better in the conservative-strategy group at day 7.

Overall, lung function was considerably better in the conservative-strategy group.

Cardiovascular function. The mean arterial pressure was significantly lower in the conservative-strategy group at day 7 (81.00 vs 84.36 mm Hg; P = .03). It is interesting that both levels were higher than the baseline levels (77.1 and 77.2, respectively; not significant).

The stroke volume index and the cardiac index were slightly lower in the conservative-strategy group at day 7, but not significantly so. No differences were seen in heart rate and venous oxygen saturation levels.

Renal and metabolic function. At day 7, the conservative-strategy group had a significantly higher blood urea nitrogen level (33.62 vs 28.44 mg/dL; P = .009). No significant differences were seen between the groups in creatinine levels at day 7 and day 28.

At day 60, dialysis was needed by 10% of the conservative-strategy group and 14% of the liberal-strategy group (P = .06). The important finding here is that there was no trend toward a more frequent need for dialysis in the conservative-strategy group. Also, the average number of days on dialysis in the two groups was essentially the same (11.0 and 10.9, respectively).

Again, there was no difference in the number of renal-failure-free days at either day 7 or day 28.

Hematologic factors. At day 7, the conservative-strategy group had significantly higher hemoglobin (10.22 vs 9.65 g/dL) and albumin (2.30 vs 2.11 g/dL) levels and capillary osmotic pressure (19.18 vs 17.39 mm Hg), even though significantly more patients in the liberal-strategy group received transfusions through day 7 (39% vs 29%; P = .0007).

Safety. Although the number of adverse events—particularly, metabolic alkalosis and electrolyte imbalance—was significantly higher in the conservative-strategy group (42 vs 19; P = .001), the overall incidence was low. No adverse event was associated with arrhythmia.

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