Fluid restriction is superior in acute lung injury and ARDS
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.
Management
Ventilation according to a low tidal volume strategy (6 mg/kg) was initiated within 1 hour after randomization. The pulmonary artery catheter or central venous catheter was inserted within 4 hours of randomization, and fluid management was started within 2 hours after catheter insertion. Fluid management was continued for 7 days or until 12 hours after extubation in patients who became able to breathe without assistance, whichever occurred first.
Target filling pressures. In the conservative-strategy group, the target filling pressures were low—a pulmonary artery occlusion pressure less than 8 mm Hg for those randomized to receive a pulmonary artery catheter, and a central venous pressure less than 4 mm Hg for those randomized to receive a central venous catheter. Barring adverse effects, patients were to undergo diuresis with furosemide (Lasix) until their goal was achieved, and then they would be maintained on that dosage through day 7. If we experienced difficulty in safely reaching these goals—say, if a patient developed hypoxemia, oliguria, or hypotension—we backed off the diuresis until the patient stabilized, and then we tried again. An inability to reach these filling pressure targets was not considered to be a treatment failure; our actual aim was to get as close to the target as possible as long as the patient tolerated the treatment.
In the liberal-strategy group, the target pressures were in the high-to-normal range—14 to 18 mm Hg for those with a pulmonary artery catheter and 10 to 14 mm Hg for those with a central venous catheter.
Patients with a pulmonary artery catheter who were hemodynamically stable after 3 days could be switched to a central venous catheter at the discretion of the clinician.
Monitoring. Patients were monitored once every 4 hours—more often if the clinician felt it necessary—for four variables:
- Pulmonary artery occlusion pressure or central venous pressure, depending on the type of catheter
- Shock, indicated by a mean arterial pressure of less than 60 mm Hg or the need for a vasopressor
- Oliguria, indicated by a urine output of less than 0.5 mL/kg/hour
- Ineffective circulation, represented by a cardiac index of less than 2.5 L/minute/cm2 in the pulmonary artery catheter group and by the presence of cold, mottled skin and a capillary-refilling time of more than 2 seconds in the central venous catheter group.
Depending on what the clinician found during monitoring, patients could receive a fluid bolus (if the filling pressure was too low), furosemide (if the filling pressure was too high), dobutamine (in certain rare circumstances), or nothing.
We monitored compliance with the protocol instructions twice each day—at a set time each morning and later in the day at a randomly selected time. An important aspect of this study is that we had no protocol instructions for managing shock. Individual clinicians were free to treat shock however they deemed best. In essence, then, our study was a comparison of liberal and conservative strategies during the nonshock phase of ALI/ARDS.
End points
The primary end point was the mortality rate at 60 days. Patients who were discharged earlier were assumed to be alive at 60 days.
The secondary end points were the number of ICU-free and ventilator-free days and the number of organ-failure-free days at day 28. Other end points included various indicators of lung physiology.
Statistical analysis
This intention-to-treat analysis was powered so that we had a 90% chance of detecting a 10% difference in mortality rate at day 60 (statistical significance: P < .05).
Protocol safeguards
Prior to treatment, we knew that some patients in the liberal-strategy group would not reach their filling-pressure targets despite the infusion of large amounts of fluid. To avoid “overdosing” these patients, we limited all patients to a maximum of three fluid boluses per 24 hours. Also, we withheld fluid boluses if a patient’s FIO2 level reached or exceeded 0.7 or if the cardiac index rose to 4.5 L/minute/cm2 or higher.
Diuretics were withheld when a patient had received a vasopressor or had emerged from shock within the preceding 12 hours. Also, diuretics were not given to any patient who had received a fluid bolus within the preceding 12 hours or when renal failure was present (these patients were given renal support therapy).
Finally, physicians and coordinators were instructed to assess each protocol instruction for safety and clinical validity before implementing the particular instruction. If, in their medical judgment, a particular protocol instruction should not be implemented, they were authorized to override the instruction and record the reason for doing so in the case report form.
