Auteur: Caroline Brown
Date: 02.03.2022
Approaches include use of lower tidal volumes and limited driving pressure (
The use of esophageal pressure (Pes) – an estimate of pleural pressure – as a guide may help more precise, individual PEEP titration to reduce atelectrauma while still limiting overdistension. It enables us to separate lung from chest wall mechanics, identify the lung’s propensity to recruit/derecruit, and estimate global lung stress (
The EPVent-2 trial addressed the question of whether PEEP titration using an esophageal balloon was superior to an empirical high PEEP–FiO2 strategy in terms of outcomes in patients with moderate to severe ARDS. The investigators found no significant difference in terms of either death or ventilator-free days between the Pes-guided PEEP group and the empirical high PEEP–FiO2 group (
In a recent secondary analysis (
The analysis included all 200 patients enrolled in the EPVent-2 trial. The risk of death at baseline due to multiorgan dysfunction and chronic morbidities was quantified using the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. The median value was 27.5; values below the median were classified as low APACHE-II scores and those above as high APACHE-II scores. APACHE-II scores were distributed evenly between the two groups ((Pes-guided vs. empirical high PEEP: 27.0 ± 7.7 vs. 27.7 ± 7.4; P = 0.35). The median baseline risk of death by day 60 was 36.6% (interquartile range, 29.0–43.0%) in the Pes-guided PEEP group and 37.6% (31.9–44.3%) for the empirical high PEEP group (P = 0.34).
Results of the primary analysis for 60-day mortality showed a significant association between the effect of Pes-guided PEEP and the severity of illness at baseline. Among patients with a low APACHE-II score, 60-day mortality was 20% in the Pes-guided PEEP group and 39.6% in the empirical high PEEP group. In patients with high APACHE-II scores however, the effect seemed to be reversed. Mortality at 60 days in those patients with more severe multiorgan dysfunction at baseline was higher with Pes-guided PEEP than with empirical high PEEP. This association for mortality remained consistent across all analyses performed, regardless of which modeling technique was used and even when the APACHE-II score was replaced by the Sequential Organ Failure Assessment (SOFA) score.
The authors offer two potential explanations for these findings. Firstly, that individual PEEP titration is more likely to benefit severe ARDS patients who are primarily at risk of dying due to lung injury as opposed to multiorgan failure. In patients with severe multiorgan failure, the greater risk of hemodynamic instability due to tidal overdistension may outweigh the lung-protective benefit. Secondly, end-inspiratory PL was significantly higher for two of the first three days in the subgroup of patients with high APACHE-II scores assigned to Pes-guided PEEP. As higher end-inspiratory PL indicates tidal hyperinflation, this may explain the poorer outcomes in those patients.
In terms of secondary outcomes, namely ventilator-free and shock-free days, data showed a similar association. The treatment effect of Pes-guided PEEP was dependent on overall illness severity at baseline and in patients with low APACHE-II scores, Pes-guided PEEP was associated with more ventilator- and shock-free days than empirical high PEEP. In contrast to the primary outcome, however, this association did not withstand post hoc sensitivity analyses.
The second important finding of this study was the association between survival and the proximity of end-expiratory transpulmonary pressure to 0 cmH2O. In all patients, regardless of the treatment group or the APACHE-II score, mortality was lowest when PEEP was titrated to end-expiratory PL near 0 cmH2O. Instead of a linear association between end-expiratory PL and mortality, the authors found that values between +2 and -2 cmH2O were associated with greater survival, while values outside this range in either direction were shown separately to be associated with lower survival. This association remained statistically significant even when end-inspiratory PL was taken into account. Values within this protective range were also associated with more ventilator- and shock-free days.
Also of interest was the narrower range of values for end-expiratory PL in the Pes-guided PEEP group for each of the first 4 days, which may indicate more precise PEEP titration to PL. In addition, end-expiratory PL was closer to 0 cmH2O in the Pes-guided PEEP group, despite this not being a specific target of that strategy.
These findings – although stemming from a re-analysis not specified in the original trial protocol – demonstrate that further investigation is needed in prospective trials to evaluate PEEP titration to an end-expiratory PL near 0 cmH2O, while taking into account heterogeneity of multiorgan dysfunction at baseline.
They also remind us of the importance of considering the hemodynamic condition when selecting PEEP, and suggest that PEEP should be set to target an end-expiratory PL near 0 cmH2O. Therefore, we should be careful about using high PEEP in patients with severe shock, especially where the chosen PEEP results in end-expiratory PL much greater than 0 cmH2O.
The HAMILTON-G5/S1 (
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