Respiratory system compliance at the same PEEP level is similar in COVID and non-COVID ARDS

Background The comparison of respiratory system compliance (Crs) between COVID and non-COVID ARDS patients has been the object of debate, but few studies have evaluated it when considering applied positive end expiratory pressure (PEEP), which is one of the known determinants of Crs itself. The aim of this study was to compare Crs taking into account the applied PEEP. Methods Two cohorts of patients were created: those with COVID-ARDS and those with non-COVID ARDS. In the whole sample the association between Crs and type of ARDS at different PEEP levels was adjusted for anthropometric and clinical variables. As secondary analyses, patients were matched for predicted functional residual capacity and the same association was assessed. Moreover, the association between Crs and type of ARDS was reassessed at predefined PEEP level of 0, 5, 10, and 15 cmH2O with a propensity score-weighted linear model. Results 367 patients were included in the study, 276 patients with COVID-ARDS and 91 with non-COVID ARDS. The association between Crs and type of ARDS was not significant in both the complete cohorts (p = 0.17) and in the matched cohorts (p = 0.92). This was true also for the propensity score weighted association at PEEP 5, 10 and 15 cmH2O, while it was statistically significant at PEEP 0 (with a median difference of 3 ml/cmH2O, which in our opinion is not clinically significant). Conclusions The compliance of the respiratory system is similar between COVID ARDS and non-COVID ARDS when calculated at the same PEEP level and while taking into account patients’ anthropometric characteristics.

Respiratory effects of lung recruitment maneuvers depend on the recruitment-to-inflation ratio in patients with COVID-19-related acute respiratory distress syndrome

Background In the context of acute respiratory distress syndrome (ARDS), the response to lung recruitment maneuvers (LRMs) varies considerably from one patient to another and so is difficult to predict. The aim of the study was to determine whether or not the recruitment-to-inflation (R/I) ratio could differentiate between patients according to the change in lung mechanics during the LRM. Methods We evaluated the changes in gas exchange and respiratory mechanics induced by a stepwise LRM at a constant driving pressure of 15 cmH2O during pressure-controlled ventilation. We assessed lung recruitability by measuring the R/I ratio. Patients were dichotomized with regard to the median R/I ratio. Results We included 30 patients with moderate-to-severe ARDS and a median [interquartile range] R/I ratio of 0.62 [0.42–0.83]. After the LRM, patients with high recruitability (R/I ratio ≥ 0.62) presented an improvement in the PaO2/FiO2 ratio, due to significant increase in respiratory system compliance (33 [27–42] vs. 42 [35–60] mL/cmH2O; p < 0.001). In low recruitability patients (R/I < 0.62), the increase in PaO2/FiO2 ratio was associated with a significant decrease in pulse pressure as a surrogate of cardiac output (70 [55–85] vs. 50 [51–67] mmHg; p = 0.01) but not with a significant change in respiratory system compliance (33 [24–47] vs. 35 [25–47] mL/cmH2O; p = 0.74). Conclusion After the LRM, patients with high recruitability presented a significant increase in respiratory system compliance (indicating a gain in ventilated area), while those with low recruitability presented a decrease in pulse pressure suggesting a drop in cardiac output and therefore in intrapulmonary shunt.

Effect of Trendelenburg position during prone ventilation in fifteen COVID-19 patients. Observational study

Background Prone position ventilation has shown to improve oxygenation and mortality in severe ARDS. The data of prone position ventilation during severe ARDS secondary to COVID-19 have shown similar benefit in oxygenation and mortality. Usually, patient placed in prone position are placed flat or in reverse Trendelenburg positioning to decrease risk of aspiration and abdominal girth compressing the chest. To date, no studies are available to compare the effects of positioning the bed in different angles during the prone position ventilation. Methods An observational study in fifteen patients with severe ARDS secondary to COVID-19 who were placed in the prone position for the first time. All the patients were sedated and chemically paralyzed with no spontaneous effort. All patients were ventilated with the pressure-controlled mode with set PEEP according to the pressure-volume curves. Five patients had esophageal balloon manometry to estimate pleural pressures and trans-pulmonary pressures. Patients were initially placed in reverse Trendelenburg position and later in Trendelenburg position. Tidal volume and respiratory compliance were observed for 30 minutes after bed positioning has been achieved. Tidal volume and total respiratory compliance in both Trendelenburg and reverse Trendelenburg position were compared. Ventilator settings were not changed during the observation. No patients were suspected of increased intra-cranial or intra-ocular pressures. T-test was done to compare the values. Results Tidal volume significantly increased by 80.26 ± 23.4 ml/breath (95% CI 37.7 - 122.9) from 391.3 ± 52.7 to 471.6 ± 60.9 (20.5%) P 0.001. The respiratory system compliance significantly increased by 4.9 ml/cmH2O (95% CI 1.4 - 8.4) from 34.6 ± 4.7 to 39.5 ± 4.6 (14%) P 0.001. Of the five patients with esophageal balloon, the lung compliance significantly increased by 16.7 ml/cmH2O (95% CI 12.8 – 20.6) from 66.6 ± 1.7 to 83.3 ± 3.3 (25%) P 0.001. The chest wall compliance had small but non-significant increase by 1.5 ml/cmH2O (95% CI -1.3 – 4.3) from 65 ± 1.4 to 66.5 ± 2.3 (2%) P 0.085. Conclusion In this study, statistically significant increase in tidal volume, lung and respiratory system compliance were observed in patients placed in the Trendelenburg position during prone position ventilation. The results reflect the effect of body positioning during prone position ventilation. These effects may be the reflection of altered ventilation distribution throughout the lungs and change in pleural pressure as well as trans-pulmonary pressure during body positioning. More studies need to be done to confirm and examine this phenomenon. Precautions should be taken as this maneuver can increase the intra-cranial and intra-ocular pressures. Keywords: COVID-19, Trendelenburg, Reverse Trendelenburg, ARDS

Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects

Background We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5–15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. Methods Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54–67] years, PaO2/FiO2 113 [79–158] mmHg and PEEP 10 [10–10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. Results At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial–venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. Conclusions In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Electrical Impedance Tomography Analysis Between Two Similar Respiratory System Compliance During Decremetal PEEP Titration in ARDS Patients

Purpose The positive end-expiratory pressure (PEEP) level with best respiratory system compliance (Crs) is frequently used for PEEP selection in acute respiratory distress syndrome (ARDS) patients. On occasion, two similar best Crs (where the difference between the Crs of two PEEP levels is < 1 ml/cm H2O) may be identified during decremental PEEP titration. Selecting PEEP under such conditions is challenging. The aim of this study was to provide supplementary rationale for PEEP selection by assessing the global and regional ventilation distributions between two PEEP levels in this situation. Methods Eight ARDS cases with similar best Crs at two different PEEP levels were analyzed using examination-specific electrical impedance tomography (EIT) measures and airway stress index (SIaw). Five Crs were measured at PEEP values of 25 cm H2O (PEEP25), 20 cm H2O (PEEP20), 15 cm H2O (PEEPH), 11 cm H2O (PEEPI), and 7 cm H2O (PEEPL). The higher PEEP value of the two PEEPs with similar best Crs was designated as PEEPupper, while the lower designated as PEEPlower. Results PEEPH and PEEPI shared the best Crs in two cases, while similar Crs was found at PEEPI and PEEPL in the remaining six cases. SIaw was higher with PEEPupper as compared to PEEPlower (1.06 ± 0.10 versus 0.99 ± 0.09, p = 0.05). Proportion of lung hyperdistension was significantly higher with PEEPupper than PEEPlower (7.0 ± 5.1% versus 0.3 ± 0.5%, p = 0.0002). In contrast, proportion of recruitable lung collapse was higher with PEEPlower than PEEPupper (18.6 ± 4.4% versus 5.9 ± 3.7%, p < 0.0001). Cyclic alveolar collapse and reopening during tidal breathing was higher at PEEPlower than PEEPupper (34.4 ± 19.3% versus 16.0 ± 9.1%, p = 0.046). The intratidal gas distribution (ITV) index was also significantly higher at PEEPlower than PEEPupper (2.6 ± 1.3 versus 1.8 ± 0.7, p = 0.042). Conclusions PEEPupper is a rational selection in ARDS cases with two similar best Crs. EIT provides additional information for the selection of PEEP in such circumstances.

Prone Positioning May Increase Lung Overdistension in COVID-19-Induced ARDS

Background: Real-time effects of changing body position and positive end-expiratory pressure (PEEP) on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension in mechanically ventilated patients with coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse.Methods: In this prospective observational study, patients with COVID-19-induced ARDS under mechanical ventilation were included. We used electrical impedance tomography (EIT) with decremental PEEP titration algorithm (PEEPEIT-titration), which provides information on regional lung overdistension and collapse, along with global respiratory system compliance, to individualize PEEP and body position. PEEPEIT-titration in supine position straightaway followed by PEEPEIT-titration in prone position were performed. Immediately before each PEEPEIT-titration, the same lung recruitment maneuver was performed: 2 min of PEEP 24 cmH2O and driving pressure of 15 cmH2O.Results: Forty-two PEEPEIT-titration were performed in ten patients (21 pairs supine and prone positions). We have found larger % of overdistension along the PEEP titration in prone than supine position (P = 0.042). A larger % of collapse along the PEEP titration was found in supine than prone position (P = 0.037). A smaller respiratory system compliance was found in prone than supine position (P < 0.0005).Conclusions: In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H2O.Trial registration number: NCT04460859

The Correlation of Respiratory System Compliance and Mortality in COVID-19 Acute Respiratory Distress Syndrome: Do Phenotypes Really Exist?

Background: Recent literature suggests respiratory system compliance (Crs) based phenotypes exist among COVID-19 ARDS patients. We sought to determine whether these phenotypes exist and whether Crs predicts mortality. Methods: A retrospective observational cohort study of 111 COVID-19 ARDS patients admitted March 11-July 8, 2020. Crs was averaged for the first 72-hours of mechanical ventilation. Crs < 30ml/cmH2O was defined as poor Crs(phenotype-H) whereas Crs ≥ 30ml/cmH2O as preserved Crs(phenotype-L). Results: 111 COVID-19 ARDS patients were included, 40 phenotype-H and 71 phenotype-L. Both the mean PaO2/FiO2 ratio for the first 72-hours of mechanical ventilation and the PaO2/FiO2 ratio hospital nadir were lower in phenotype-H than L(115[IQR87] vs 165[87], p = 0.016), (63[32] vs 75[59], p = 0.026). There were no difference in characteristics, diagnostic studies, or complications between groups. Twenty-seven (67.5%) phenotype-H patients died vs 37(52.1%) phenotype-L(p = 0.115). Multivariable regression did not reveal a mortality difference between phenotypes; however, a 2-fold mortality increase was noted in Crs < 20 vs > 50ml/cmH2O when analyzing ordinal Crs groups. Moving up one group level (ex. Crs30-39.9ml/cmH2O to 40-49.9ml/cmH2O), was marginally associated with 14% lower risk of death(RR = 0.86, 95%CI 0.72, 1.01, p = 0.065). This attenuated(RR = 0.94, 95%CI 0.80, 1.11) when adjusting for pH nadir and PaO2/FiO2 ratio nadir. Conclusion: We identified a spectrum of Crs in COVID-19 ARDS similar to Crs distribution in non-COVID-19 ARDS. While we identified increasing mortality as Crs decreased, there was no specific threshold marking significantly different mortality based on phenotype. We therefore would not define COVID-19 ARDS patients by phenotypes-H or L and would not stray from traditional ARDS ventilator management strategies.

Effect of prone positioning on oxygenation and static respiratory system compliance in COVID-19 ARDS vs. non-COVID ARDS

Background Prone positioning is recommended for patients with moderate-to-severe acute respiratory distress syndrome (ARDS) receiving mechanical ventilation. While the debate continues as to whether COVID-19 ARDS is clinically different from non-COVID ARDS, there is little data on whether the physiological effects of prone positioning differ between the two conditions. We aimed to compare the physiological effect of prone positioning between patients with COVID-19 ARDS and those with non-COVID ARDS. Methods We retrospectively compared 23 patients with COVID-19 ARDS and 145 patients with non-COVID ARDS treated using prone positioning while on mechanical ventilation. Changes in PaO2/FiO2 ratio and static respiratory system compliance (Crs) after the first session of prone positioning were compared between the two groups: first, using all patients with non-COVID ARDS, and second, using subgroups of patients with non-COVID ARDS matched 1:1 with patients with COVID-19 ARDS for baseline PaO2/FiO2 ratio and static Crs. We also evaluated whether the response to the first prone positioning session was associated with the clinical outcome. Results When compared with the entire group of patients with non-COVID ARDS, patients with COVID-19 ARDS showed more pronounced improvement in PaO2/FiO2 ratio [adjusted difference 39.3 (95% CI 5.2–73.5) mmHg] and static Crs [adjusted difference 3.4 (95% CI 1.1–5.6) mL/cmH2O]. However, these between-group differences were not significant when the matched samples (either PaO2/FiO2-matched or compliance-matched) were analyzed. Patients who successfully discontinued mechanical ventilation showed more remarkable improvement in PaO2/FiO2 ratio [median 112 (IQR 85–144) vs. 35 (IQR 6–52) mmHg, P = 0.003] and static compliance [median 5.7 (IQR 3.3–7.7) vs. − 1.0 (IQR − 3.7–3.0) mL/cmH2O, P = 0.006] after prone positioning compared with patients who did not. The association between oxygenation and Crs responses to prone positioning and clinical outcome was also evident in the adjusted competing risk regression. Conclusions In patients with COVID-19 ARDS, prone positioning was as effective in improving respiratory physiology as in patients with non-COVID ARDS. Thus, it should be actively considered as a therapeutic option. The physiological response to the first session of prone positioning was predictive of the clinical outcome of patients with COVID-19 ARDS.