Rationale: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes. Objectives: To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support. Methods: In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. Measurements and Main Results: Rocuronium titration resulted in significant declines of Vt (mean ± SEM, 9.3 ± 0.6 to 5.6 ± 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 ± 2.5 to 10.7 ± 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 ± 2.3 to 4.5 ± 0.7 μV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 ± 0.02 to 7.35 ± 0.02; P < 0.0001), and mean arterial blood pressure increased (84 ± 6 to 99 ± 6 mm Hg; P = 0.0004), as did heart rate (83 ± 7 to 93 ± 8 beats/min; P = 0.0004). Conclusions: Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.

Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure. The neuromuscular efficiency index (NME) can be used to estimate inspiratory effort, however its repeatability has not been investigated yet. Our goal is to evaluate NME repeatability during an end-expiratory occlusion (NMEoccl) and its use to estimate the pressure generated by the inspiratory muscles (Pmus). This is a prospective cohort study, performed in a medical-surgical ICU. A total of 31 adult patients were included, all ventilated in neurally adjusted ventilator assist (NAVA) mode with an electrical activity of the diaphragm (EAdi) catheter in situ. At four time points within 72 h five repeated end-expiratory occlusion maneuvers were performed. NMEoccl was calculated by delta airway pressure (ΔPaw)/ΔEAdi and was used to estimate Pmus. The repeatability coefficient (RC) was calculated to investigate the NMEoccl variability. A total number of 459 maneuvers were obtained. At time T = 0 mean NMEoccl was 1.22 ± 0.86 cmH2O/μV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH2O/μV, it is expected with a probability of 95% that the subsequent measured NMEoccl will be between 2.22 and 0.22 cmH2O/μV. Additional EAdi waveform analysis to correct for non-physiological appearing waveforms, did not improve NMEoccl variability. Selecting three out of five occlusions with the lowest variability reduced the RC to 29.8%. Repeated measurements of NMEoccl exhibit high variability, limiting the ability of a single NMEoccl maneuver to estimate neuromuscular efficiency and therefore the pressure generated by the inspiratory muscles based on EAdi.

Background: High respiratory drive in mechanically ventilated patients with spontaneous breathing effort may cause excessive lung stress and strain and muscle loading. Therefore, it is important to have a reliable estimate of respiratory effort to guarantee lung and diaphragm protective mechanical ventilation. Recently, a novel non-invasive method was found to detect excessive dynamic transpulmonary driving pressure (∆ P _L ) and respiratory muscle pressure ( P _mus ) with reasonable accuracy. During the Coronavirus disease 2019 (COVID-19) pandemic, it was impossible to obtain the gold standard for respiratory effort, esophageal manometry, in every patient. Therefore, we investigated whether this novel non-invasive method could also be applied in COVID-19 patients. Methods: ∆ P _L and P _mus were derived from esophageal manometry in COVID-19 patients. In addition, ∆ P _L and P _mus were computed from the occlusion pressure (∆ P _occ ) obtained during an expiratory occlusion maneuver. Measured and computed ∆ P _L and P _mus were compared and discriminative performance for excessive ∆ P _L and P _mus was assessed. The relation between occlusion pressure and respiratory effort was also assessed. Results: Thirteen patients were included. Patients had a low dynamic lung compliance [24 (20–31) mL/cmH ₂ O], high ∆ P _L (25 ± 6 cmH ₂ O) and high P _mus (16 ± 7 cmH ₂ O). Low agreement was found between measured and computed ∆ P _L and P _mus . Excessive ∆ P _L > 20 cmH ₂ O and P _mus > 15 cmH ₂ O were accurately detected (area under the receiver operating curve (AUROC) 1.00 [95% confidence interval (CI), 1.00–1.00], sensitivity 100% (95% CI, 72–100%) and specificity 100% (95% CI, 16–100%) and AUROC 0.98 (95% CI, 0.90–1.00), sensitivity 100% (95% CI, 54–100%) and specificity 86% (95% CI, 42–100%), respectively). Respiratory effort calculated per minute was highly correlated with ∆ P _occ (for esophageal pressure time product per minute (PTP _es/min ) r ² = 0.73; P = 0.0002 and work of breathing (WOB) r ² = 0.85; P < 0.0001). Conclusions: ∆ P _L and P _mus can be computed from an expiratory occlusion maneuver and can predict excessive ∆ P _L and P _mus in patients with COVID-19 with high accuracy.

Dynamic pulmonary hyperinflation may develop in patients with chronic obstructive pulmonary disease (COPD) due to dynamic airway collapse and/or increased airway resistance, increasing the risk of volutrauma and hemodynamic compromise. The reference standard to quantify dynamic pulmonary hyperinflation is the measurement of the volume at end-inspiration (Vei). As this is cumbersome, the aim of this study was to evaluate if methods that are easier to perform at the bedside can accurately reflect Vei. Vei was assessed in COPD patients under controlled protective mechanical ventilation (7 ± mL/kg) on zero end-expiratory pressure, using three techniques in a fixed order: (1) reference standard (Veireference): passive exhalation to atmosphere from end-inspiration in a calibrated glass burette; (2) ventilator maneuver (Veimaneuver): measuring the expired volume during a passive exhalation of 45s using the ventilator flow sensor; (3) formula (Veiformula): (Vt × Pplateau)/(Pplateau − PEEPi), with Vt tidal volume, Pplateau is plateau pressure after an end-inspiratory occlusion, and PEEPi is intrinsic positive end-expiratory pressure after an end-expiratory occlusion. A convenience sample of 17 patients was recruited. Veireference was 1030 ± 380 mL and had no significant correlation with Pplateau (r2 = 0.06; P = 0.3710) or PEEPi (r2 = 0.11; P = 0.2156), and was inversely related with Pdrive (calculated as Pplateau −PEEPi) (r2 = 0.49; P = 0.0024). A low bias but rather wide limits of agreement and fairly good correlations were found when comparing Veimaneuver and Veiformula to Veireference. Vei remained stable during the study period (low bias 15 mL with high agreement (95% limits of agreement from − 100 to 130 mL) and high correlation (r2 = 0.98; P < 0.0001) between both measurements of Veireference). In patients with COPD, airway pressures are not a valid representation of Vei. The three techniques to quantify Vei show low bias, but wide limits of agreement.

Non-invasive ventilation (NIV) provides ventilatory support for patients with respiratory failure. However, the glottis can act as a closing valve, limiting effectiveness of NIV. This study investigates the patency of the glottis during NIV in patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Electrical activity of the diaphragm, flow, pressure and videolaryngoscopy were acquired. NIV was randomly applied in pressure support (PSV) and neurally adjusted ventilatory assist (NAVA) mode with two levels of support. The angle formed by the vocal cords represented glottis patency. Eight COPD patients with acute exacerbation requiring NIV were included. No differences were found in median glottis angle during inspiration or peak inspiratory effort between PSV and NAVA at low and high support levels. The present study showed that glottis patency during inspiration in patients with an acute exacerbation of COPD is not affected by mode (PSV or NAVA) or level of assist (5 or 15 cm H2O) during NIV.