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Purpose: This study aimed to investigate the effects of inspired oxygen fraction (FiO2) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with COVID-19. Methods: Two FiO2 (100%, 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH2O). At each FiO2 and PEEP, gas exchange, respiratory mechanics, hemodynamics, and the distribution of ventilation and perfusion were assessed with electrical impedance tomography. The impact of FiO2 on the intrapulmonary shunt (delta shunt) was analyzed as the difference between the calculated shunt at FiO2 100% (shunt) and venous admixture at FiO2 40% (venous admixture). Results: Fourteen patients were studied. Decreasing PEEP from 15 to 10 cmH2O did not change shunt (24 [21-28] vs 27 [24-29]%) or venous admixture (18 [15-26] vs 23 [18-34]%) while partial pressure of arterial oxygen (FiO2 100%) was higher at PEEP 15 (262 [198-338] vs 256 [147-315] mmHg; P <.05). Instead when PEEP was decreased from 10 to 5 cmH2O, shunt increased to 36 [30-39]% (P <.05) and venous admixture increased to 33 [30-43]% (P <.05) and partial pressure of arterial oxygen (100%) decreased to 109 [76-177] mmHg (P <.05). At PEEP 15, administration of 100% FiO2 resulted in a shunt greater than venous admixture at 40% FiO2, ((24 [21-28] vs 18 [15-26]%, P =.005), delta shunt 5.5% (2.3-8.8)). Compared to PEEP 10, PEEP of 5 and 15 cmH2O resulted in decreased global and pixel-level compliance. Cardiac output at FiO2 100% resulted higher at PEEP 5 (5.4 [4.4-6.5]) compared to PEEP 10 (4.8 [4.1-5.5], P <.05) and PEEP 15 cmH2O (4.7 [4.5-5.4], P <.05). Conclusion: In this study, PEEP of 15 cmH2O, despite resulting in the highest oxygenation, was associated with overdistension. PEEP of 5 cmH2O was associated with increased shunt and alveolar collapse. Administration of 100% FiO2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. Trial registration: NCT05132933. [ABSTRACT FROM AUTHOR]

Purpose To describe the variability and determinants of the effect of extracorporeal CO.sub.2 removal (ECCO.sub.2R) on tidal volume (V.sub.t), driving pressure ([DELTA]P), and mechanical power (Power.sub.RS) and to determine whether highly responsive patients can be identified for the purpose of predictive enrichment in ECCO.sub.2R trial design. Methods Using data from the SUPERNOVA trial (95 patients with early moderate acute respiratory distress syndrome), the independent effects of alveolar dead space fraction (ADF), respiratory system compliance (Crs), hypoxemia (PaO.sub.2/FiO.sub.2), and device performance (higher vs lower CO.sub.2 extraction) on the magnitude of reduction in V.sub.t, [DELTA]P, and Power.sub.RS permitted by ECCO.sub.2R were assessed by linear regression. Predicted and observed changes in [DELTA]P were compared by Bland-Altman analysis. Hypothetical trials of ECCO.sub.2R, incorporating predictive enrichment and different target CO.sub.2 removal rates, were simulated in the SUPERNOVA study population. Results Changes in V.sub.t permitted by ECCO.sub.2R were independently associated with ADF and device performance but not PaO.sub.2/FiO.sub.2. Changes in [DELTA]P and Power.sub.RS were independently associated with ADF, Crs, and device performance but not PaO.sub.2/FiO.sub.2. The change in [DELTA]P predicted from ADF and Crs was moderately correlated with observed change in [DELTA]P (R.sup.2 0.32, p < 0.001); limits of agreement between observed and predicted changes in [DELTA]P were ± 3.9 cmH.sub.2O. In simulated trials, restricting enrollment to patients with a larger predicted decrease in [DELTA]P enhanced the average reduction in [DELTA]P, increased predicted mortality benefit, and reduced sample size and screening size requirements. The increase in statistical power obtained by restricting enrollment based on predicted [DELTA]P response varied according to device performance as specified by the target CO.sub.2 removal rate. Conclusions The lung-protective benefits of ECCO.sub.2R increase with higher alveolar dead space fraction, lower respiratory system compliance, and higher device performance. ADF and Crs, rather than severity of hypoxemia, should be the primary factors determining whether to enroll patients in clinical trials of ECCO.sub.2R., Author(s): Ewan C. Goligher [sup.1] [sup.2] [sup.3], Alain Combes [sup.4], Daniel Brodie [sup.5] [sup.6], Niall D. Ferguson [sup.1] [sup.2] [sup.3] [sup.7] [sup.8], Antonio M. Pesenti [sup.9] [sup.10], V. Marco Ranieri [...]

Purpose: This study aimed to investigate the effects of inspired oxygen fraction (FiO 2 ) and positive end-expiratory pressure (PEEP) on gas exchange in mechanically ventilated patients with COVID-19. Methods: Two FiO 2 (100%, 40%) were tested at 3 decreasing levels of PEEP (15, 10, and 5 cmH 2 O). At each FiO 2 and PEEP, gas exchange, respiratory mechanics, hemodynamics, and the distribution of ventilation and perfusion were assessed with electrical impedance tomography. The impact of FiO 2 on the intrapulmonary shunt (delta shunt) was analyzed as the difference between the calculated shunt at FiO 2 100% (shunt) and venous admixture at FiO 2 40% (venous admixture). Results: Fourteen patients were studied. Decreasing PEEP from 15 to 10 cmH 2 O did not change shunt (24 [21-28] vs 27 [24-29]%) or venous admixture (18 [15-26] vs 23 [18-34]%) while partial pressure of arterial oxygen (FiO 2 100%) was higher at PEEP 15 (262 [198-338] vs 256 [147-315] mmHg; P  < .05). Instead when PEEP was decreased from 10 to 5 cmH 2 O, shunt increased to 36 [30-39]% ( P  < .05) and venous admixture increased to 33 [30-43]% ( P  < .05) and partial pressure of arterial oxygen (100%) decreased to 109 [76-177] mmHg ( P  < .05). At PEEP 15, administration of 100% FiO 2 resulted in a shunt greater than venous admixture at 40% FiO 2, ((24 [21-28] vs 18 [15-26]%, P  = .005), delta shunt 5.5% (2.3-8.8)). Compared to PEEP 10, PEEP of 5 and 15 cmH 2 O resulted in decreased global and pixel-level compliance. Cardiac output at FiO 2 100% resulted higher at PEEP 5 (5.4 [4.4-6.5]) compared to PEEP 10 (4.8 [4.1-5.5], P  < .05) and PEEP 15 cmH 2 O (4.7 [4.5-5.4], P  < .05). Conclusion: In this study, PEEP of 15 cmH 2 O, despite resulting in the highest oxygenation, was associated with overdistension. PEEP of 5 cmH 2 O was associated with increased shunt and alveolar collapse. Administration of 100% FiO 2 was associated with an increase in intrapulmonary shunt in the setting of high PEEP. Trial registration: NCT05132933., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AMP reports personal fees from Baxter, Maquet, Boehringer Ingelheim, and Xenios outside the submitted work. GG reports consultation fees from Getinge, Draeger, Pfizer, Thermo Fisher, MSD, and Gilead. The remaining authors declare that they have no conflicts of interest.