Ventilation with Lower Tidal Volume Reduces ARDS Mortality
Abstracts & Commentary
Synopsis: In patients with acute lung injury and acute respiratory distress syndrome (ARDS), mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use.
Sources: The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:1301-1308; Tobin MJ. N Engl J Med 2000;342:1360-1361.
The acute respiratory syndrome network carried out a multicenter, randomized study to assess whether mechanical ventilation with a lower tidal volume (Vt) than is traditionally used results in decreased mortality. Patients who were intubated and receiving mechanical ventilation were eligible for the study if they had an acute decrease in the ratio of partial pressure of arterial oxygen (PaO2) to fraction of inspired oxygen (FiO2) to 300 mm Hg or less, bilateral pulmonary infiltrates, and no clinical evidence of left atrial hypertension. The volume-assist-control mode was used during the study. Patients were randomized to be ventilated with usual (traditional) Vt or a reduced Vt. In the patient group treated with traditional Vt, the initial Vt was 12 mL/kg of predicted (ideal) body weight. This was subsequently adjusted if necessary to maintain the end-inspiratory plateau pressure 50 cm H2O or less (minimal Vt used in the study was 4 mL/kg). In the group treated with lower Vt, the Vt was reduced to 6 mL/kg within four hours after randomization and was subsequently adjusted if necessary to maintain a plateau pressure of 30 cm H2O or less (minimal Vt in this group was also 4 mL/kg). Plateau pressures more than 50 cm H2O in the patients in the group treated with traditional Vt, and more than 30 cm H2O in patients in the group treated with lower Vt were allowed if the Vt was 4 mL/kg or if arterial pH was less than 7.15.
The trial was stopped after the enrollment of 861 patients because mortality was lower in the group treated with lower Vt than in the group treated with traditional Vt (31.0% vs 39.8%, respectively; P = 0.007; 95% confidence interval for the difference between groups, 2.4-15.3%). In addition, the number of ventilator-free days (i.e., the number of days without ventilator use from day 1 to day 28), a second primary outcome of the study, was significantly higher in the group treated with lower Vt than in the group treated with traditional Vt (12 ± 11 vs 10 ± 11, respectively; P = 0.007).
The Vt and plateau pressures were significantly lower in the group treated with lower Vt than in the group treated with traditional Vt. The mean (± SD) Vt on days 1 to 3 were 6.2 ± 0.8 and 11.8 ± 0.8 mL/kg, respectively (P < 0.001), and the mean plateau pressures were 25 ± 6 and 33 ± 8 cm H2O (P < 0.001), respectively. The PaO2 was similar in the two groups, but levels of positive end-expiratory pressure (PEEP) and FiO2 were significantly higher in the group treated with lower Vt on days 1 and 3.
The incidence of barotrauma after randomization also was similar in the two groups. Moreover, there were no significant differences between groups in the percentages of days on which neuromuscular-blocking drugs were used (or in the percentages of days in which sedatives were used) among patients who were discharged home or among those who died.
| Table | ||||||
Randomized, Controlled Trials Using Lower Tidal Volumes in Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome |
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| Author (Reference) | Patients | No. of patients | Interventions | Mortality (%) | ||
| Low Vt | Controls | |||||
| Amato MB, et al. N Engl J Medc 1998; 338:347-354. |
LIS ³ 2.5 | 53 | PEEP above the lower inflection point of the static P-V curve + Vt < 6 mL/kg + Pplat-PEEP < 20 cm H2O + permissive hypercapnia vs. normal PaCO2 levels + Vt 12 mL/kg | 38* | 71 | |
| Stewart TE, et al. N Engl J Med 1998; 338:355-361. |
PaO2/FiO2 < 250 within 24 hours of intubation | 120 | PIP £ 30 cm H2O + Vt £ 8 mL/kg vs. PIP £ 50 cm H2O + Vt 10-15 mL | 50 | 47 | |
| Brochard L, et al. Am J Respir Crit Care Med 1998; 158:1831-1838. |
LIS > 2.5 for < 72 hours and no severe organ failure other than the lung | 116 | Pplat £ 25 cm H2O + Vt < 10 mL/kg vs. Vt ³ 10 mL/kg + close to normal PaCO2 levels | 46.6 | 37.9 | |
| Brower RG, et al. Crit Care Med 1999; 27:1492-1498. |
PaO2/FiO2 £ 200 | 52 | Vt 5-8 mL/kg + Pplat < 30 cm H2O vs.Vt 10-12 mL/kg + Pplat £ 55 cm H2O | 50 | 46 | |
| The ARDS Network. N Engl J Med 2000; 342:1301-1308. |
PaO2/FiO2 £ 300 | 861 | Vt £ 6 mL/kg + Pplat £ 30 cm H2O vs. Vt £ 12 mL/kg + Pplat £ 50 cm H2O | 31.0* | 39.8 | |
| lung injury score (LIS); peak inspiratory pressure (PIP); plateau pressure (Pplat) *significantly lower compared with controls |
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COMMENT BY FRANCISCO BAIGORRI, MD, PhD
In the past few years, an increasing amount of attention has been paid to the modalities of mechanical ventilation, particularly the delivery of Vt, as a factor able to modify the mortality rate from acute lung injury (ALI) and ARDS. However, most of the randomized, controlled trials of ventilation using lower Vt in patients with ALI and ARDS had found that mortality was not reduced by this strategy. Only the recent work by Amato and associates (N Engl J Med 1998;338:347-354) indicated that a protective ventilation approach improved survival. Notwithstanding, the study of Amato et al merits closer examination. The study included only a small number of patients. Also, the mortality of the control group was much higher than is generally seen today in patients with ARDS (see Table), raising questions about the relevance of these results to other patients with ARDS.
The study of the Acute Respiratory Distress Syndrome Network convincingly proves the beneficial effect of small Vt. Several factors could explain the difference in results between this trial and the previous studies that had found that lowering Vt had no benefit (see Table). The main one may be that this trial had a greater difference in Vt between groups. In the previous negative studies, the mean Vt of the patients in the control group was only slightly higher than 10 mL/kg. Consequently, differences in plateau pressures were also smaller (see Figure). All in all, the most sensible conclusion that emerges from these studies is that the standard Vt should be not more than 10 mL/kg, and that plateau pressures of more than 32 cm H2O should be avoided.
It will be objected that as the chest wall may play an important role in the pressure read on the ventilator, the plateau pressure would be misinterpreted and could lead to excessive hypoventilation of patients in case of major impairment of chest wall properties (Brochard L, Lemaire F. Crit Care Med 1999;27:1661-1662). Nevertheless, plateau pressures of more than 32 cm H2O appear to be predictive of a higher risk of death among groups of patients with ARDS.
Another aspect of this study that deserves consideration is the treatment of acidosis. Increases in ventilator rate and infusions of bicarbonate were allowed in order to correct acidosis in the study of the Acute Respiratory Distress Syndrome Network, which resulted in smaller differences in PaCO2 and pH between the study groups than in the previous trials. The ARDS Network investigators suggested that the deleterious effects of acidosis in the previous studies may have counteracted a protective effect of the lower Vt.
As stated in the related editorial of this study, these results tell us that the treatment of patients with ARDS requires a gentler form of mechanical ventilation.
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