Background: A large proportion of patients with a SARS-Cov-2-associated respiratory failure develop an acute respiratory distress syndrome (ARDS). It has been recently suggested that SARS-Cov-2-associated ARDS may differ from usual non-SARS-Cov-2-associated ARDS by higher respiratory system compliance (C RS ), lower potential for recruitment with positive end-expiratory pressure (PEEP) contrasting with severe shunt fraction. The purpose of the study was to systematically assess respiratory mechanics and recruitability in SARS-Cov-2-associated ARDS. Methods:Gas exchanges, C RS and hemodynamics were assessed at 2 levels of PEEP (15 cmH 2 O and 5 cmH 2 O) within 36 h (day1) and from 4 to 6 days (day 5) after intubation. The recruited volume was computed as the difference between the volume expired from PEEP 15 to 5 cmH 2 O and the volume predicted by compliance at PEEP 5 cmH 2 O (or above airway opening pressure). The recruitment-to-inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and C RS at PEEP 5 cmH 2 O) was used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruitable patients. Results:The R/I ratio was calculated in 25 of the 26 enrolled patients at day 1 and in 15 patients at day 5. At day 1, 16 (64%) were considered as highly recruitable (R/I ratio median [interquartile range] 0.7 [0.55-0.94]) and 9 (36%) were considered as poorly recruitable (R/I ratio 0.41 [0.31-0.48]). The PaO 2 /FiO 2 ratio at PEEP 15 cmH 2 O was higher compared to PEEP 5 cmH 2 O only in highly recruitable patients (173 [139-236] vs 135 [89-167] mmHg; p < 0.01). Neither PaO 2 /FiO 2 or C RS measured at PEEP 15 cmH 2 O or at PEEP 5 cmH 2 O nor changes in PaO 2 /FiO 2 or C RS in response to PEEP changes allowed to identify highly or poorly recruitable patients. Conclusion:In this series of 25 patients with SARS-Cov-2 associated ARDS, 64% were considered as highly recruitable and only 36% as poorly recruitable based on the R/I ratio performed on the day of intubation. This observation suggests that a systematic R/I ratio assessment may help to guide initial PEEP titration to limit harmful effect of unnecessary high PEEP in the context of Covid-19 crisis.

Impact of the research: Although bilateral phrenic nerve stimulation did not increase the proportion of successful weaning from mechanical ventilation compared to the standard of care, it resulted in substantial improvements in inspiratory pressure generation capacity without major safety issues. In the absence of previous clinical data, these findings suggest that diaphragm pacing could be effective in mitigating diaphragm dysfunction in patients difficult to wean from mechanical ventilation. Author contributions:The academic authors (MD, MGDA, TS) wrote the first draft of the manuscript and verified the underlying data. All authors critically reviewed and approved the manuscript and are accountable its accuracy and integrity. Dr Martin Dres had full access to all the data in the study and takes full responsibility for the integrity of the data and the accuracy of the data analysis. Teresa Nelson conducted and is responsible for the data analysis. Support:The study was funded by Lungpacer Medical Inc, PA, USA.

Baclofen, a gamma-aminobutyric acid-B agonist with muscle-relaxant properties, is widely used in patients with severe spasticity. In animals, baclofen has been shown to decrease respiratory drive. In humans, however, use of baclofen at the standard dose did not significantly impair sleep-disordered breathing in a susceptible population of snorers. Recently, there has been increasing interest in the role of baclofen for the treatment of alcohol dependence. We describe severe central sleep apnea (CSA) in four patients with none of the conditions commonly associated with CSA who were receiving chronic baclofen therapy for alcohol withdrawal. In one patient, baclofen withdrawal was associated with a complete resolution of CSA. Three patients were treated by adaptive servo-ventilation while continuing their treatment with baclofen. Given the increasing number of patients receiving baclofen for alcohol withdrawal treatment, physicians should be aware that these patients might be affected by severe CSA. Future studies are required to determine the mechanisms, prevalence, and treatment modalities of sleep-disordered breathing associated with baclofen usage.