Effect of nocturnal EPAP titration to abolish tidal expiratory flow limitation in COPD patients with chronic hypercapnia: a randomized, cross-over pilot study

Background Tidal expiratory flow limitation (EFLT) promotes intrinsic PEEP (PEEPi) in patients with chronic obstructive pulmonary disease (COPD). Applying non-invasive ventilation (NIV) with an expiratory positive airway pressure (EPAP) matching PEEPi improves gas exchange, reduces work of breathing and ineffective efforts. We aimed to evaluate the effects of a novel NIV mode that continuously adjusts EPAP to the minimum level that abolishes EFLT. Methods This prospective, cross-over, open-label study randomized patients to one night of fixed-EPAP and one night of EFLT-abolishing-EPAP. The primary outcome was transcutaneous carbon dioxide pressure (PtcCO2). Secondary outcomes were: peripheral oxygen saturation (SpO2), frequency of ineffective efforts, breathing patterns and oscillatory mechanics. Results We screened 36 patients and included 12 in the analysis (age 72 ± 8 years, FEV1 38 ± 14%Pred). The median EPAP did not differ between the EFLT-abolishing-EPAP and the fixed-EPAP night (median (IQR) = 7.0 (6.0, 8.8) cmH2O during night vs 7.5 (6.5, 10.5) cmH2O, p = 0.365). We found no differences in mean PtcCO2 (44.9 (41.6, 57.2) mmHg vs 54.5 (51.1, 59.0), p = 0.365), the percentage of night time with PtcCO2 > 45 mm Hg was lower (62(8,100)% vs 98(94,100)%, p = 0.031) and ineffective efforts were fewer (126(93,205) vs 261(205,351) events/hour, p = 0.003) during the EFLT-abolishing-EPAP than during the fixed-EPAP night. We found no differences in oxygen saturation and lung mechanics between nights. Conclusion An adaptive ventilation mode targeted to abolish EFLT has the potential to reduce hypercapnia and ineffective efforts in stable COPD patients receiving nocturnal NIV. Trial registration: ClicalTrials.gov, NCT04497090. Registered 29 July 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04497090.

Physiological effects of adding ECCO2R to invasive mechanical ventilation for COPD exacerbations

Background Extracorporeal CO2 removal (ECCO2R) could be a valuable additional modality for invasive mechanical ventilation (IMV) in COPD patients suffering from severe acute exacerbation (AE). We aimed to evaluate in such patients the effects of a low-to-middle extracorporeal blood flow device on both gas exchanges and dynamic hyperinflation, as well as on work of breathing (WOB) during the IMV weaning process. Study design and methods Open prospective interventional study in 12 deeply sedated IMV AE-COPD patients studied before and after ECCO2R initiation. Gas exchange and dynamic hyperinflation were compared after stabilization without and with ECCO2R (Hemolung, Alung, Pittsburgh, USA) combined with a specific adjustment algorithm of the respiratory rate (RR) designed to improve arterial pH. When possible, WOB with and without ECCO2R was measured at the end of the weaning process. Due to study size, results are expressed as median (IQR) and a non-parametric approach was adopted. Results An improvement in PaCO2, from 68 (63; 76) to 49 (46; 55) mmHg, p = 0.0005, and in pH, from 7.25 (7.23; 7.29) to 7.35 (7.32; 7.40), p = 0.0005, was observed after ECCO2R initiation and adjustment of respiratory rate, while intrinsic PEEP and Functional Residual Capacity remained unchanged, from 9.0 (7.0; 10.0) to 8.0 (5.0; 9.0) cmH2O and from 3604 (2631; 4850) to 3338 (2633; 4848) mL, p = 0.1191 and p = 0.3013, respectively. WOB measurements were possible in 5 patients, indicating near-significant higher values after stopping ECCO2R: 11.7 (7.5; 15.0) versus 22.6 (13.9; 34.7) Joules/min., p = 0.0625 and 1.1 (0.8; 1.4) versus 1.5 (0.9; 2.8) Joules/L, p = 0.0625. Three patients died in-ICU. Other patients were successfully hospital-discharged. Conclusions Using a formalized protocol of RR adjustment, ECCO2R permitted to effectively improve pH and diminish PaCO2 at the early phase of IMV in 12 AE-COPD patients, but not to diminish dynamic hyperinflation in the whole group. A trend toward a decrease in WOB was also observed during the weaning process. Trial registration ClinicalTrials.gov: Identifier: NCT02586948.

Individualized mechanical ventilation in a shared ventilator setting: limits, safety and technical details.

Background- The COVID-19 pandemic has resulted in an increased need for ventilators. The potential to ventilate more than one patient with a single ventilator, a so-called split ventilator setup, provides an emergency solution. Our hypothesis is that ventilation can be individualized by adding a flow restrictor to limit tidal volumes, add PEEP, titrate FiO 2 and monitor ventilation. This way we could ensure optimization of patient safety and clinical applicability. We performed bench testing to test our hypothesis and identify limitations. Methods- We performed a bench testing in two lungs: 1) determine lung compliance 2) determine volume, plateau pressure and PEEP, 3) illustrate individualization of airway pressures and tidal volume with a flow restrictor, 4a) illustrate that PEEP can be applied and individualized 4b) create and measure intrinsic PEEP 4c-d) determine PEEP as a function of flow restriction, 5) individualization of FiO 2 . Results- The lung compliance varied between 13 and 27 mL/cmH 2 O. Set ventilator settings could be applied and measured. Extrinsic PEEP can be applied except for settings with a large expiratory time. Volume and pressure regulation is possible between 70-39% flow restrictor valve closure. Flow restriction in the tested circuit had no effect on the other circuit or on intrinsic PEEP. FiO 2 could be modulated individually between 0.21 and 0.8 by gradually adjusting the additional flow, and minimal affecting FiO 2 in the other circuit. Conclusions- Tidal volumes, PEEP and FiO2 can be individualized and monitored in a bench testing of a split ventilator. In vivo research is needed to further explore the clinical limitations and outcomes, making implementation possible as a last resort ventilation strategy.

Dynamic hyperinflation and intrinsic positive end-expiratory pressure in ARDS patients

Background In ARDS patients, changes in respiratory mechanical properties and ventilatory settings can cause incomplete lung deflation at end-expiration. Both can promote dynamic hyperinflation and intrinsic positive end-expiratory pressure (PEEP). The aim of this study was to investigate, in a large population of ARDS patients, the presence of intrinsic PEEP, possible associated factors (patients’ characteristics and ventilator settings), and the effects of two different external PEEP levels on the intrinsic PEEP. Methods We made a secondary analysis of published data. Patients were ventilated with a tidal volume of 6–8 mL/kg of predicted body weight, sedated, and paralyzed. After a recruitment maneuver, a PEEP trial was run at 5 and 15 cmH2O, and partitioned mechanics measurements were collected after 20 min of stabilization. Lung computed tomography scans were taken at 5 and 45 cmH2O. Patients were classified into two groups according to whether or not they had intrinsic PEEP at the end of an expiratory pause. Results We enrolled 217 sedated, paralyzed patients: 87 (40%) had intrinsic PEEP with a median of 1.1 [1.0–2.3] cmH2O at 5 cmH2O of PEEP. The intrinsic PEEP significantly decreased with higher PEEP (1.1 [1.0–2.3] vs 0.6 [0.0–1.0] cmH2O; p < 0.001). The applied tidal volume was significantly lower (480 [430–540] vs 520 [445–600] mL at 5 cmH2O of PEEP; 480 [430–540] vs 510 [430–590] mL at 15 cmH2O) in patients with intrinsic PEEP, while the respiratory rate was significantly higher (18 [15–20] vs 15 [13–19] bpm at 5 cmH2O of PEEP; 18 [15–20] vs 15 [13–19] bpm at 15 cmH2O). At both PEEP levels, the total airway resistance and compliance of the respiratory system were not different in patients with and without intrinsic PEEP. The total lung gas volume and lung recruitability were also not different between patients with and without intrinsic PEEP (respectively 961 [701–1535] vs 973 [659–1433] mL and 15 [0–32] % vs 22 [0–36] %). Conclusions In sedated, paralyzed ARDS patients without a known obstructive disease, the amount of intrinsic PEEP during lung-protective ventilation is negligible and does not influence respiratory mechanical properties.

Dynamic Hyperinflation and Intrinsic Positive End-Expiratory Pressure

Dynamic hyperinflation and intrinsic PEEP almost always occur in patients with severe obstructive lung disease, in whom slowing of expiratory flow prevents complete exhalation. Occasionally, patients without airflow obstruction develop dynamic hyperinflation when expiratory time, is excessively shortened by a rapid respiratory rate, a long set inspiratory time (TI), or both. Dynamic Hyperinflation and Intrinsic Positive End-Expiratory Pressure describes the causes of dynamic hyperinflation and the mechanisms of its adverse effects, including reduced cardiac output and blood pressure, pulmonary barotrauma, and ineffective ventilator triggering. The chapter also describes how to screen for and measure intrinsic PEEP, and how to reduce or eliminate its adverse effects.