ABSTRACT
Objectives:To provide an update to the 1999 French guidelines on " Muscle relaxants and reversal in anaesthesia" , a consensus committee of sixteen experts was convened.A formal policy of declaration and monitoring of conflicts of interest (COI) was developed at the outset of the process and enforced throughout.The entire guidelines process was conducted independently of any industrial funding (i.e.pharmaceutical, medical devices). The authors were required to follow the rules of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE ?) system to assess the quality of the evidence on which the recommendations were based.The potential drawbacks of making strong recommendations based on low-quality evidence were stressed.Few of the recommendations remained ungraded. Methods:The panel focused on eight questions: (1) In the absence of difficult mask ventilation criteria, is it necessary to check the possibility of ventilation via a facemask before muscle relaxant injection? Is it necessary to use muscle relaxants to facilitate facemask ventilation? (2) Is the use of muscle relaxants necessary to facilitate tracheal intubation? (3) Is the use of muscle relaxants necessary to facilitate the insertion of a supraglottic device and management of related complications? (4) Is it necessary to monitor neuromuscular blockade for airway management? (5) Is the use of muscle relaxants necessary to facilitate interventional procedures, and if so, which procedures? (6) Is intraoperative monitoring of neuromuscular blockade necessary? (7) What are the strategies for preventing and treating residual neuromuscular blockade? (8) What are the indications and precautions for use of both muscle relaxants and reversal agents in special populations (e.g.electroconvulsive therapy, obese patients, children, neuromuscular diseases, renal/hepatic failure, elderly patients)? All questions were formulated using the Population, Intervention, Comparison and Outcome (PICO) model for clinical questions and evidence profiles were generated.The results of the literature analysis and the recommendations were then assessed using the GRADE ? system. Results:The summaries prepared by the SFAR Guideline panel resulted in thirty-one recommendations on muscle relaxants and reversal agents in anaesthesia.Of these recommendations, eleven have a high level of evidence (GRADE 1±) while twenty have a low level of evidence (GRADE 2±). No recommendations could be provided using the GRADE ? system for five of the questions, and for two of these questions expert opinions were given.After two rounds of discussion and an amendment, a strong agreement was reached for all the recommendations. Conclusion:Substantial agreement exists among experts regarding many strong recommendations for the improvement of practice concerning the use of muscle relaxants and reversal agents during anaesthesia.In particular, the French Society of Anaesthesia and Intensive Care (SFAR) recommends the use of a device to monitor neuromuscular blockade throughout anaesthesia.
ABSTRACT
The biological determinants of the wide spectrum of COVID-19 clinical manifestations are not fully understood. Here, over 1400 plasma proteins and 2600 single-cell immune features comprising cell phenotype, basal signaling activity, and signaling responses to inflammatory ligands were assessed in peripheral blood from patients with mild, moderate, and severe COVID-19, at the time of diagnosis. Using an integrated computational approach to analyze the combined plasma and single-cell proteomic data, we identified and independently validated a multivariate model classifying COVID-19 severity (multi-class AUCtraining = 0.799, p-value = 4.2e-6; multi-class AUCvalidation = 0.773, p-value = 7.7e-6). Features of this high-dimensional model recapitulated recent COVID-19 related observations of immune perturbations, and revealed novel biological signatures of severity, including the mobilization of elements of the renin-angiotensin system and primary hemostasis, as well as dysregulation of JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks. These results provide a set of early determinants of COVID-19 severity that may point to therapeutic targets for the prevention of COVID-19 progression. SummaryFeyaerts et al. demonstrate that an integrated analysis of plasma and single-cell proteomics differentiates COVID-19 severity and reveals severity-specific biological signatures associated with the dysregulation of the JAK/STAT, MAPK/mTOR, and NF-{kappa}B immune signaling networks and the mobilization of the renin-angiotensin and hemostasis systems.
