According to multivariate regression analysis, MP on Day 1 and ARDS were independent factors associated with 28-day mortality. Patients with lower MP on Day 1 had better chances to survive compared to those with higher MP on Day 1. In initial univariate regression analysis, driving pressure on Day 1 was a factor associated with 28-day mortality. However, the significant association was not observed in multivariate regression analysis. In ROC curves of the ARDS group, driving pressure did not discriminate survivors from non-survivors, but driving pressure could discriminate between survivors and non-survivors in all patients and the non-ARDS group. It suggests that ARDS confounds the association between driving pressure and 28-day mortality.
Our study first found that ventilated patients with pneumonia with or without ARDS demonstrated higher serial MP in non-survivors than in survivors from Day 1 to Day 11 of ICU admission. The MP between survivors and non-survivors was similar only on Day 18 of ICU admission in all patients statistically. Our study not only confirmed that baseline MP was associated with mortality [11-14], but also found that the association persisted for 11 days. In the Kaplan-Meier curves of the ARDS group, the two curves were similar within the first 10 days and separated later evidently. This implied that the benefit of lower MP required a period of time to develop in patients with more severe pneumonia. Furthermore, deep sedation significantly reduced MP in patients with moderate to severe ARDS, thereby reducing the occurrence of VILI . All the above suggested that MP might be the cause of VILI, resulting in increased mortality rate. Certainly, it is reasonable since all mechanical factors in ventilation-tidal volume, driving pressure, flow, resistances, RR, and PEEP-are different components of a unique physical variable, which is the energy delivered into the lung. Up to now, there is no study reporting the results of mortality using MP as a guide of ventilator settings to manage critically ill patients. Further studies are required to elucidate whether MP is a predictor or cause.
In our study, driving pressure was not an independent factor associated with 28-day mortality in ventilated patients with severe pneumonia, but MP was an independent factor. In experimental mild ARDS of rats, even at low VT, high MP promoted VILI . In a computational study, MP showed a strong correlation with the relative risk of death across all ranges of driving pressures and PEEP . Moreover, the areas under the ROC of MP were higher than those of driving pressure among the ARDS group, the non-ARDS group, and all patients in our study. This implied that MP might be a better predictor of 28-day mortality than VT or driving pressure in patients with severe pneumonia with or without ARDS. The positive and negative predictive values of MP using the cutoff value ≥ 27 J/min for 28-day mortality were 50.1% and 75.4%, respectively. This suggests that approximately 75% of ventilated patients with severe pneumonia and low MP would survive for 28 days. Discrimination ability of MP and MP normalized to PBW in predicting 28-day mortality was nearly similar in this study. This result was similar to that of Zhang’s study, which found 0.747 and 0.751 of areas under ROC curve for MP and MP normalized to PBW, respectively . For easy use in routine clinical practice, calculation of MP instead of MP normalized to PBW might be sufficient.
The MP was first determined with the simplified formula suggested by Gattinoni et al. for VCV: . As the equation for calculation of MP is based on the assumption of VCV with a linear increase of airway pressure during inspiration, it is not suitable for calculating MP during PCV . For PCV, two accurate equations have been proposed, but both require using some parameters (resistances, respiratory system compliance) that are not usually continuously quantified and displayed in the ventilator [26,30]. Finally, we used the simplified formula for PCV proposed by Becher et al.  since this equation had acceptable accuracy and routine record by our respiratory therapeutist. Our study demonstrated that this simplified formula was easy to use, and the MP calculated had acceptable discrimination for 28-day mortality in ventilated patients with severe pneumonia.
The most important current recommendation to provide lung protective ventilation in ventilated patients with pneumonia is low tidal volumes . However, despite the use of lung protective ventilation proposed by ARDSnet protocol, overall ICU and hospital mortality of ARDS patients is still higher than 40% . Low tidal volume ventilation did not show estimated benefit in patients with ARDS. It seems that only low tidal volume ventilation is insufficient to protect the lung. Since 2015, Amato et al. reported the results of a retrospective analysis and concluded that driving pressure was better associated with 60-day mortality in patients with ARDS than tidal volume . Following this, Guerin et al. demonstrated this viewpoint , and a meta-analysis from Neto et al. showed that an increase of driving pressure was associated with more postoperative pulmonary complications . Our previous study further found that higher driving pressure was associated with 28-day mortality in patients with severe pneumonia without ARDS . In this study, results showed that MP on Day 1 was independently positively associated with 28-day mortality and had better predicted value than driving pressure either in patients with ARDS or without ARDS. Our results support the hypothesis that a marker with several important indices is better than that with one index. The predicted value of MP, which included tidal volume, inspiratory pressure, RR, and PEEP, was better than driving pressure alone.
This study has an important strength. We presented serial data over the course of 21 days with consistent results during the first 11 days in patients with or without ARDS. This study also has three limitations. First, this study was a single-center trial without thousands of case number. More studies are required to confirm our results. Second, there were significantly few patients who developed ARDS after a period of 1 week. Third, chest radiograph findings might have been misinterpreted considering the presence of unilateral infiltrates or opacities due to the limitations of traditional chest radiography. Computed tomography may be a preferred technique to detect lung injury. Considering the similar results between the ARDS and non-ARDS groups, it did not significantly influence the final conclusion.