Does Lung-Protective Ventilation Require More Sedation?

Abstract & Commentary

David J. Pierson, MD, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, is Editor for Critical Care Alert.

Synopsis: In this in-depth examination of 111 patients at a center in the original ARDS Net low-tidal-volume study, patients managed with 6 mL/kg or less did not require more sedation during the first 48 hours than those managed with tidal volumes of 12 mL/kg.

Source: Cheng IW, et al. Crit Care Med. 2005;33(1):63-70.

San Francisco General Hospital and Moffitt-Long Hospital of the University of California, San Francisco, were participating sites in the well-known ARDS Net study of low vs traditional tidal volumes in the management of acute lung injury (ALI), and acute respiratory distress syndrome (ARDS).1 Cheng and colleagues at these institutions collected information on hemodynamics, vasopressor use, fluid balance, diuretics, and the use of sedatives and neuromuscular blockade—data in addition to what was required for the larger ARDS Net study—on their 111 patients during the initial 48 hours following entry. Patients were randomized to ventilator tidal volumes of 6 or 12 mL/kg predicted body weight, with reductions if needed to keep end-inspiratory plateau pressures below the designated limits for the 2 groups. Except for ventilator management, which was controlled by protocol, all patients were managed at the discretion of their primary teams.

The groups were not different by any of the demographic or other descriptors recorded at study entry, except that the mean minute ventilation was higher in the patients randomized to receive lower tidal volumes. Hemodynamic variables (systolic, diastolic, and mean blood pressures, plus heart rate) were the same in the 2 groups, both immediately after randomization and during the 48-hour study period. There were no differences in the use of supportive therapies, including vasopressors, intravenous fluids, or diuretics. Similarly, there were no differences in body weight, urine output, or recorded fluid balance.

At the discretion of their physicians, the patients received fentanyl, propofol, midazolam, lorazepam, and/or morphine for sedation, either as intravenous boluses or as continuous infusions. There were no differences, either for the drugs individually or in the aggregate, with respect to the use of these medications in the low- and high-tidal-volume groups. The number of patients who received neuromuscular blocking agents was variable but relatively small, ranging from 16% of patients in the large-tidal-volume group on day 1 to 4% of patients in the low-tidal-volume group on day 2, and there were no statistical differences between the groups in this respect.


In the ARDS Net trial, management of ALI and ARDS with tidal volumes of 6 mL/kg or less as compared to 12 mL/kg of predicted body weight, along with limitation of end-inspiratory static airway pressure to 30 cm H2O or less, reduced overall mortality from 40% to 31%, with a number needed to treat in order to save a life of 11. Very few interventions studied in critically ill patients have effects that come close to this magnitude, and this benefit was achieved not through the use of some expensive new high-tech pharmacologic agent or medical device but simply by setting the ventilator’s tidal volume control in a certain way. That’s the good news. The bad news is that clinicians are not using this information in managing their patients. Several studies have documented that, at least in the first couple of years after the ARDS Net study was published, the large majority of patients with ALI/ARDS, even at participating centers, were still being ventilated with tidal volumes substantially larger than those shown to reduce mortality.2-4

Why should this be? Are there really ICUs and respiratory care departments in the United States where they don’t yet know about lung-protective ventilation? I doubt it. However, there are a number of other possible reasons.5 A major one is failure to make the diagnosis. When accepted, objective diagnostic criteria are deliberately sought, and, as was done for the ARDS Net study, many patients can be identified whose physicians have not diagnosed as having ALI/ARDS. In addition, some clinicians have been unduly influenced by initial criticisms of the ARDS Net study, despite vindication of its methods and results after extensive investigation. Others may succeed in convincing themselves that low-tidal-volume ventilation as used in that study is somehow not applicable to their patients. However, that number needed to treat figure (11 patients managed according to the ARDS Net protocol saves one life) is pretty compelling, and in the absence of good outcome evidence to the contrary (as opposed to extrapolations from short-term surrogate end points) the onus in 2005 would seem to be squarely on those who do not adopt this strategy or something very close to it.

Another potential reason why clinicians may be reluctant to adopt ARDS Net-style lung-protective ventilation is the impression that this strategy is sufficiently distressing to patients to require more sedation or even paralysis in order to be carried out effectively, and that these effects may in turn lead to prolongation of ventilatory support or other adverse effects. I must say that this has been my clinical impression. But is that impression correct? Not according to this study by Cheng et al, at least in the initial 48 hours. Their patients, who were part of the larger ARDS Net cohort, did not require more sedatives or more frequent paralysis when managed with low tidal volumes.

This paper makes the very important point that patients with ALI/ARDS can be ventilated according to best available evidence without increasing the administration of sedatives or muscle relaxants. In the area of sedation and paralysis, however, I believe there is enormous practice variation among different physicians, ICUs, and geographic areas. I have made rounds in ICUs in which patients with ARDS were kept completely motionless, often with neuromuscular blockade added to heavy sedation. I have also rounded in units in more than one country outside the United States in which apparently similar patients were receiving very little sedation and were awake. There is good evidence that, at least in this country, deliberate measures to decrease the amount of sedatives given to ventilated patients gets them off the ventilator and out of the ICU sooner than if these measures are not pursued.6

How the issue of sedation for patients with ALI/ARDS is approached remains largely a matter of local medical culture. However, the study by Cheng et al shows us that, however one chooses to titrate sedation in such patients, the use of lung-protective ventilation may not necessarily require greater quantities or the addition of paralytic agents.


1. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000;342:1301-1308.

2. Rubenfeld GD, et al. Am J Respir Crit Care Med. 2001;163:A295.

3. Weinert CR, et al. Am J Respir Crit Care Med. 2003;167:1304-1309.

4. Young MP, et al. Crit Care Med. 2004;32(6):1260-1265.

5. Rubenfeld GD, et al. Crit Care Med. 2004;32: 1289-1293.

6. Ibrahim EH, Kollef MH. Crit Care Clin. 2001; 17(4):989-1001.