Predictors of Long-term Muscle Weakness in Survivors of Covid-19 Acute Respiratory Distress Syndrome (preprint)

Background Long-term weakness is common in survivors of COVID-19–associated acute respiratory distress syndrome (CARDS). We assessed the predictors of muscle weakness in patients evaluated at 3, 6, and 12 months after intensive care unit discharge with in-person visits.Methods Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength, Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for its essential role in ankle control.Results MVC improved at 12 months compared with 3 months. Sex (P < 0.001), age (P = 0.012), duration of mechanical ventilation (P = 0.044), and CMAP-TA-S100 (P < 0.001) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.Conclusions Female sex, increasing age, increased duration of mechanical ventilation, and electrical neuromuscular abnormalities are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.Trial registration : The present study was registered at ClinicalTrial.gov (NCT: ​​NCT04608994). Registered on October 30, 2020. Retrospectively registered.

Excessive sedation as a risk factor for delirium: a comparison between two cohorts of critically-ill patients with and without COVID-19 (preprint)

Background: Excessive sedation has been associated with poor outcome in critically-ill patients with acute respiratory Distress Syndrome (ARDS). The on-going pandemic has seen many critically-ill COVID-19 with ARDS, yet the incidence of excessive sedation and its association to delirium in these patients has to date not been assessed. We aimed at comparing the incidence and outcome of excessive sedation and delirium in two cohorts of critically-ill patients. Methods: This was an international, dual center retrospective analysis of prospectively collected data from two cohorts of critically ill patients, with and without COVID-19 disease, pertaining to two different hospital settings. Depth of sedation was monitored through processed EEG and delirium through the Confusion Assessment Method for the ICU(CAM-ICU). The main outcomes were the incidence of excessive sedation and delirium between the two cohorts, and secondary outcomes were length of ICU and hospital stay and mechanical ventilation duration.Results: Fifty-seven non-COVID-19 and 21 COVID-19 patients were included, 38(49%) of whom had ARDS. Twenty-seven(47.3%) non-COVID-19 and 11(52.3%) COVID-19 patients fulfilled the criteria for excessive sedation. Excessively sedated patients were older(p=0.034) and had delirium more frequently(p<0.001). There was a trend in excessive sedation in ARDS patients, while there was no correlation between excessive sedation and COVID-19 diagnosis. COVID-19 with ARDS was related to delirium at the limit of significance. On adjusted analysis excessive sedation was independently related to delirium(p=0.008). Patients with delirium had longer MV duration, ICU-LOS and H-LOS. In the adjusted analysis, delirium was an independent predictor of ICU-LOS(p=0.005) and MV duration(p=0.039). SAPS II was higher in the non-COVID-19 patients when compared to COVID-19 patients. Despite this, COVID-19 patients remained ventilated for a longer period of time, had a longer ICU and H-LOS. Conclusion: Besides age, excessive sedation might represent an important risk factor for delirium in COVID-19 and non-COVID-19 critically ill patients, which may lead to an increased ICU-LOS, H-LOS and MV duration. The use of continuous EEG-based monitoring for quantification of sedation depth, along with frequent delirium assessment in critically-ill COVID-19 patients is warranted along with larger prospective trials aimed at verifying weather the use of EEG-based monitoring leads to improved outcome.