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Reference: ART trial (JAMA 2017 Sep 27 early online) (level 2 [mid-level] evidence)
- It is unclear whether the expected advantages of positive end-expiratory pressure (PEEP) ventilation are associated with improved clinical outcomes in patients with acute respiratory distress syndrome (ARDS).
- In the ART trial, 1,010 adults with ARDS (ratio of partial pressure of oxygen to fraction of inspired oxygen [PaO2:FIO2] ≤ 200) were randomized to ventilation with lung recruitment maneuver and PEEP titration based on maximum respiratory-system compliance vs. a low-PEEP strategy.
- The lung recruitment strategy with PEEP titration based on respiratory-system compliance increased both 28-day (55.3% vs. 49.3% with low-PEEP, p = 0.041, NNH 16) and 6-month mortality (65.3% vs. 59.9% with low-PEEP, p = 0.04, NNH 18). These findings do not support the use of this ventilation strategy in patients with moderate-to-severe ARDS.
The benefits attributed to higher positive end-expiratory pressure (PEEP) ventilation include the opening up of collapsed or fluid-filled alveoli and reduction in lung injury by preventing repeated opening and closing of small airspaces. It is unclear, however, whether these potential advantages translate into improved clinical outcomes in patients with acute respiratory distress syndrome (ARDS). Three randomized trials comparing high- vs. low-PEEP mechanical ventilation strategies with target tidal volumes of < 8 mL/kg in patients with acute lung injury or ARDS found no significant differences in mortality up to 60 days (N Engl J Med 2004, JAMA 2008, JAMA 2008). However, an analysis of these three trials using pooled individual data from 1,892 patients with ARDS suggested a possible benefit for in-hospital mortality associated with a high-PEEP ventilation strategy (adjusted relative risk 0.9, 95% CI 0.81-1) (JAMA 2010).
The recent ART trial investigated whether mechanical ventilation with lung recruitment maneuvers and PEEP based on the highest lung compliance improves mortality compared to a low-PEEP (N Engl J Med 2000) strategy. In this trial, 1,010 adults (mean age 51 years) with ARDS for < 72 hours were randomized to 1 of 2 PEEP strategies. All patients received low-PEEP ventilation at baseline consisting of PEEP and FIO2 adjustments to optimize PaO2 while maintaining plateau pressure ≤ 30 cm H2O and tidal volume 4-6 mL/kg, and this strategy was continued in the low-PEEP group. The lung recruitment and PEEP titration strategy consisted of three steps: an initial recruitment maneuver, determination of maximum compliance, and a second recruitment maneuver. First, a lung recruitment maneuver was performed with stepwise increasing pressures of PEEP up to a maximum of 45 cm H2O. PEEP was then decreased in a stepwise fashion to determine the pressure at which maximum respiratory-system compliance was achieved. After a one-step increase in PEEP to 45 cm H2O as a second recruitment maneuver, ventilation was performed in volume-assist control mode using the PEEP that resulted in the maximum respiratory-system compliance plus 2 cm H2O. If PaO2:FIO2 was stable or increasing for ≥ 24 hours, PEEP was decreased by 2 cm H2O every 8 hours. The maximum alveolar recruitment maneuver could be repeated every 24 hours if certain parameters were met. Due to resuscitated cardiac arrest in 3 patients in the recruitment group after enrollment of 555 patients, the recruitment maneuvers were modified to consist of PEEP levels up to a maximum of 35 cm H2O.
Compared to the low-PEEP strategy, lung recruitment and PEEP titration increased both 28-day mortality (55.3% vs. 49.3% with low-PEEP, p = 0.041, NNH 16) and 6-month mortality (65.3% vs. 59.9% with low-PEEP, p = 0.04, NNH 18). Other adverse effects were also more common in the lung recruitment and PEEP titration group: the need to start or increase vasopressors or a drop in mean arterial pressure to < 65 mm Hg within 1 hour occurred in 34.8% vs. 28.3% with low-PEEP (p = 0.03, NNH 15); barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema, or pneumatocele > 2 cm) within 7 days occurred in 5.6% vs. 1.6% with low-PEEP (p = 0.001, NNH 25); pneumothorax requiring drainage occurred in 3.2% vs. 1.2% with low-PEEP (p = 0.03, NNH 50). The maximum difference in PEEP between the two groups over the first 7 days was 4.2 cm H2O on day 1 (mean PEEP 16.2 cm H2O with lung recruitment vs. 12 cm H2O with low-PEEP, p< 0.001).
The ART trial demonstrated that a strategy of lung recruitment and PEEP titration based on respiratory system compliance is associated with increased 28-day and 6-month mortality compared to the low-PEEP ventilation strategy in patients with moderate-to-severe ARDS. In addition, hypotension and barotrauma were more common in the patients having the recruitment ventilation strategy and may provide a possible explanation for the increased mortality in this group. The authors note that responsiveness to PEEP was not evaluated at baseline. The question of whether clinical benefit from the recruitment and PEEP titration based on compliance strategy could be gained in patients who respond to PEEP by recruiting more lung remains unanswered. Finally, a potential source of bias in this trial is the lack of blinding, as knowledge of group assignment may have influenced the use of cointerventions by the attending physicians. In summary, the findings from the ART trial do not support the use of mechanical ventilation with lung recruitment maneuver and PEEP titration based on respiratory-system compliance in patients with moderate-to-severe ARDS.
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