The main findings of this study were that (1) the PEEP level, titrated by both EIT method and ARDSnet protocol was lower in ARDS patients with COPD as compared to patients without COPD and (2) the PEEP level selected by EIT method was lower in patients with ARDS patient with COPD as compared that by the ARDSnet protocol. Combined with the PaO2/FiO2 and GI index, the possible benefits of PEEP titrated by EIT in such patients include improvement in PaO2/FiO2, opening of partially collapsed alveoli, and maintenance of the alveoli in an open state without a significant increase in the proportion of lung tissue that is excessively expanded. This is the first study to optimize titration of PEEP by EIT and the ARDSnet protocol in patients with ARDS and COPD. These patients have obvious PEEPi and greater lung compliance and EELV than their counterparts without COPD. A questionnaire-based study by Rose et al [16] showed that the PEEP level required in mechanically ventilated patients with acute exacerbation of COPD was lower than that needed in patients with ARDS but higher than that in patients requiring mechanical ventilation after surgery. A lung-protective smart ventilation study showed that patients with COPD requiring mechanical ventilation had a higher PEEP level than those without underlying pulmonary disease but a lower PEEP level than patients with ARDS and no comorbidities [17]. The pathophysiological characteristics in the lungs of patients with ARDS and COPD may be different from those typically seen in patients with ARDS alone. The potential negative effects of application of PEEP include increased risks of PEEPi and dynamic pulmonary hyperinflation, which may be more severe in patients with acute exacerbation of COPD requiring mechanical ventilation. Therefore, EIT, which helps to avoid excessive inflation, worsening dyspnea, and hemodynamic disturbances, may be more suitable for titration of PEEP in patients with ARDS and COPD [18].
We found no statistically significant difference in improvement of oxygenation according to whether PEEP was titrated by EIT or the ARDSnet protocol in patients with ARDS and COPD. The peak airway pressure, plateau airway pressure, VR, mechanical power, Vd/Vt, and EELV were lower and lung compliance was better when EIT was used, which indicates that the respiratory mechanics indices used by EIT are better than those used in the ARDSnet protocol. Guérin et al [19] investigated the relationship between mechanical energy during the second 24 hours of mechanical ventilation and the prognosis in 8207 patients with ARDS and found that higher mechanical energy was independently associated with an increased in-hospital mortality risk that was particularly high when mechanical energy exceeded 17 J/ min. In another study that included 1294 patients with ARDS, Tonna et al [20] similarly found that mechanical energy was independently associated with an increased risk of in-hospital mortality. Furthermore, Sinha et al [21] retrospectively investigated 1307 patients with ARDS using the VR, which can be used as one of the indicators of ventilation efficiency at the bedside. They found that patients with a high VR had an increased risk of death, indicating that the VR could be used as an indicator of the mortality risk. In another study by Sinha et al [22], VR was significantly associated with dead space ventilation and was an independent predictor of mortality. Improvements in respiratory mechanics may help to improve patient outcomes. The findings of our present study show that the respiratory mechanics index is better when the PEEP level is titrated by EIT than by the ARDSnet protocol and may be beneficial in terms of the prognosis in patients with ARDS and COPD.
Another aspect of the application of PEEP in patients with ARDS is its impact on cardiac function. Our study found that the cardiac index was higher and the dose of vasoactive therapy required was lower when EIT was used instead of the ARDSnet protocol. High PEEP levels may reduce the cardiac index by increasing intrathoracic pressure, impeding venous return, and possibly increasing pulmonary vascular resistance by compressing alveolar vessels. In an early clinical study of PEEP, Suter et al [23] assessed the effect of different PEEP levels on the cardiac index. However, no lung-protective ventilation strategy was used in that study. Dantzker et al [24] investigated the relationship between cardiac output and mechanical ventilation-related intrapulmonary shunt in 20 patients with ARDS and found that a high PEEP or tidal volume ventilation resulted in increased shunting and decreased cardiac output. These authors pointed out that hemodynamic changes need to be taken into account when considering improvements in gas exchange in patients with ARDS. A study by Barthélémy et al in patients with COVID-19-related ARDS found a gradual decrease in cardiac output with increasing PEEP level [6]. In another report, Mercado et al suggested that lung recruitment and high PEEP ventilation caused a decline in cardiac function, especially in right ventricular function [25]. Other researchers have found that about 25% of patients with ARDS who are mechanically ventilated develop pulmonary hypertension or right ventricular insufficiency even if a lung-protective mechanical ventilation strategy is used [26], and right ventricular insufficiency is a risk factor for death in these patients [27, 28]. Elevated PEEP levels cause a more marked decrease in cardiac output in patients with cardiac disease [29] and COPD is a risk factor for right ventricular dysfunction [30]. In our study, two-thirds of patients with ARDS and COPD had right ventricular insufficiency. PEEP titration by EIT reduced the risk of decreased cardiac function. This personalized ventilation strategy may be one of the reasons for the lower 90-day mortality rate in our study.
In this study, oxygen delivery in patients with ARDS and COPD was greater when PEEP was titrated by EIT than by the ARDSnet table. Suter et al [23] identified oxygen delivery as the variable that provides the best compromise for reconciling oxygenation requirements and hemodynamics. In the critical state of acute hypoxemia that occurs in ARDS, oxygen consumption increases, oxygen delivery decreases, and tissue hypoxia leads to a series of vicious circles. One of the main treatment goals in patients with ARDS is to increase oxygen delivery and improve tissue hypoxia. Use of oxygen-related indicators, including oxygen delivery and consumption, are now used widely as clinical indicators of hypoxia in critically ill patients. Many patients with ARDS have pathological oxygen dependence [31, 32], alteration of which is also a key goal of mechanical ventilation in ARDS. Studies have shown a relationship between maintenance of adequate oxygen delivery and a good prognosis. Maintenance of oxygen delivery at approximately 600 mL/min/m2 can reduce complications and shorten the hospital stay after surgery in patients with ARDS [33]. In our present study, oxygen delivery was not improved by increasing FiO2 or transfusion of red blood cells, but only by use of EIT as the PEEP titration method. This may be attributed to the improvement of respiratory mechanics and circulatory function by EIT.
Before 1998, there were few studies on comorbidities in patients with ARDS. Zilberberg et al [34, 35] prospectively observed the comorbidities of ARDS (including COPD) and identified patient age and the etiology of ARDS to be independent predictors of in-hospital mortality. Azoulay et al [35] have reported a multicenter prospective observational study that spanned 17 years and included 4953 patients with ARDS, of whom 51.4% had severe comorbidities, including COPD, chronic cardiac insufficiency, and tumors. In that study, the most common comorbidity was COPD (n = 948), and ARDS had a mortality rate of 27.2% in patients without comorbidities and 31.1–56% in those with comorbidities. These findings require more attention and inclusion in randomized controlled studies of patients with ARDS and severe comorbidities. In the future, with improved life expectancy, patients with ARDS and chronic complications will become increasingly common in clinical practice. However, reviewing the large-scale clinical trials of mechanical ventilation in ARDS published after 2000, when lung-protective ventilation strategies such as small tidal volume ventilation were first promoted, it is not difficult to find that the inclusion criteria for most clinical trials did not include patients with ARDS and COPD [36], which may greatly reduce the ability to generalize the results of clinical research. In recent years, the deepening understanding of the pathophysiology of ARDS has led to further development and refinements of mechanical ventilation in patients with ARDS. Currently, it is believed that the application and management of ventilation in patients with ARDS should be based on individual pulmonary pathophysiological changes to improve the prognosis [1, 37]. The PEEP setting should be individualized based on indicators such as gas exchange, hemodynamics, recruitment potential, end-expiratory transpulmonary pressure, and driving pressure [38]. Individualized lung-protective ventilation based on pathophysiological changes may be an important factor in improving patient outcomes.
This study has some limitations. First, it was performed at a single center and the study population was small. Therefore, our findings must be considered preliminary. Second, we did not compare the effects of the two PEEP titration methods according to duration of mechanical ventilation. Multicenter prospective randomized trials that include larger sample sizes are needed in the future to explore regional gas distribution and regional blood perfusion under different PEEP levels.