Mechanical ventilation, as the first lifesaving treatment to improve oxygenation in ARDS patients, still presents some challenging aspects for the intensivist. On a theoretical point of view, both the use of cyclic application of high levels of pressure – i.e Lung Recruitment Maneuver (LRM) – to restore aeration in the previously non-aerated lung regions and the maintenance of a Positive End-Expiratory Pressure (PEEP) to keep those regions open should improve gas exchanges in patients with ARDS. Nevertheless, some papers published in the last years have not demonstrated increased benefits of these strategies in terms of relevant clinical outcomes. Moreover, some harmful effects of LMRs have been found in recent trials.
The meta-analysis by Pensier and colleagues is an elegant, rigorous and well conducted study aiming to estimate the impact of systematic LMR on mortality in ARDS. According to the results of fourteen randomized clinical trials, the authors didn’t find any reduction in 28-day mortality rate in the LRM-group (RR 0.92 Confidence Interval 95% (CI) 0.82–1.04, p = 0.21).
However, secondary analyses provide some additional clues:
- Despite no impact on mortality, the expected positive effects of LRMs were confirmed: PaO2/FiO2 ratio at day 1 and at day 7 was significantly higher in the LMR-group (MD 47.6 mmHg 95% CI 33.4-61.8, p < 0.001 and MD 34.2 mmHg 95% CI 8.0-60.4, p = 0.01, respectively), with a significantly lower rate of need of rescue therapies (RR 0.69 95% CI 0.56-0.84, p < 0.001).
- Concerning side effects, no significant difference was observed in the incidence of barotrauma (RR 0.99 95% CI 0.60-1.63, p = 0.96). A higher risk of hemodynamic instability was reported in the LRM-group (RR 1.19 95% CI 1.06-1.33, p = 0.002), thus potentially mitigating a positive effect of the higher oxygenation.
- Interestingly, when considering studies before 2017 and excluding those with no lung protective ventilation, 28-day mortality was significantly lower in LMR-group (RR 0.83 95% CI 0.72-0.95). However, this result was not confirmed when adding RCTs after 2017 (ART, PHARLAP and LIVE Studies) (1-3). Cumulative meta-analysis shows therefore a significative effect of these last studies on the impact of LRMs on mortality rate.
- As described in the Supplementary Appendix of the paper, the driving pressure in LRM-group was significantly lower than in the no-LRM group. This is in contrast with previous works showing how a lower driving pressure has a positive impact on ARDS outcome.
Despite the negative results of the main endpoint of this meta-analysis, it deserves some additional considerations.
First, as reported both by the authors themselves and by previously published papers, there are many techniques to perform LRMs and the maximum pressure applied to respiratory system can vary from 35 cmH2O to 65 cmH2O. This heterogeneity strongly impacts on clinical outcomes and hemodynamic stability and may explain some uncoherent results. Furthermore, two of the analyzed protocols (ART trial and PHARLAT) were prematurely aborted due to safety issues, while the LIVE study presented important misclassification concerns. As a result, these limitations in the studies published after 2017 may explain their impact on 28-day mortality in the cumulative meta-analysis.
Moreover, the correct identification of potentially recruitable lung before performing LRMs and the application of a finely tuned level of PEEP may further personalize the ventilation strategy and play a key role on patients’ outcomes. Bedside tools as EIT, lung ultrasound and esophageal pressure may be useful to guide the ventilation.
In conclusions, in spite of the main results of the work of Pensier et al., several questions about lung recruitment maneuver still remain, and further studies are needed to investigate their role in ARDS management (4).