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Background: The present study was designed to investigate the evolution and the impact of respiratory muscles function and limb muscles strength on weaning success in prolonged weaning of tracheotomized patients. The primary objective was to determine whether the change in respiratory muscles function and limb muscles strength over the time is or is not associated with weaning success., Methods: Tracheotomized patients who were ventilator dependent upon admission at a weaning center were eligible. Diaphragm function was assessed with the phrenic nerve stimulation technique and with ultrasound to measure the diaphragm thickening fraction (TFdi) and diaphragm excursion (EXdi). Global respiratory muscle function was assessed with the maximal inspiratory pressure (MIP) and the forced vital capacity (FVC). Limb muscle strength was measured with the Medical Research Council Score (MRC). Measurements were made on a weekly basis. Patients were compared according to their outcome at discharge: complete weaning, partial weaning or death., Results: Among the 60 patients who were enrolled, 30 patients finally achieved complete weaning, 20 had partial weaning and 10 died. At 6 months, 6 patients were lost of follow-up, 33 achieved complete weaning, 10 had partial weaning and 11 died. In median, 2 (1-9) assessments were performed per patient. Diaphragm dysfunction was present in all patients with a median Ptr,stim of 5.5 cmH 2 O (3.0-7.5). Ptr,stim, MIP, TFdi and EXdi at admission were not different between patients who achieved complete weaning and their counterparts. At discharge of the weaning center, MIP, Ptr,stim and EXdi significantly increased in patients who achieved complete weaning. The MRC score significantly increased only in patients with complete weaning. At discharge, diaphragm dysfunction was highly prevalent even in patients with complete weaning (Ptr,stim < 11 cmH 2 O in n = 11 (37%))., Conclusion: Respiratory muscle function and limb muscles strength are severely impaired in patients with prolonged weaning from mechanical ventilation. Significant improvement of diaphragm ultrasound indices was associated with successful weaning from mechanical ventilation and ICU-acquired weakness upon admission was significantly associated with good outcome suggesting that it was an amendable determinant of weaning failure in this population., Competing Interests: Declarations. Ethics approval and consent to participate: The Research Ethics Committee of Sorbonne University approved the study (CER 2020-36). Oral information about the study was given to patients or relatives. Consent for publication: Not applicable. Competing interests: Martin Dres received fees from Lungpacer (expertise, lectures). A Demoule reports personal fees from Medtronic, grants, personal fees and non-financial support from Philips, personal fees from Baxter, personal fees from Hamilton, personal fees and non-financial support from Fisher & Paykel, grants from French Ministry of Health, personal fees from Getinge, grants and personal fees from Respinor, grants and non-financial support from Lungpacer, outside the submitted work. The other authors have no conflicts of interest to declare., (© 2024. The Author(s).)

Background: In mechanically ventilated patients, diaphragm ultrasound can identify diaphragm weakness and predict weaning failure. We evaluated whether a novel operator-independent ultrasound-based medical device allowing continuous monitoring of the diaphragm (CUSdi) could reliably (1) measure diaphragm excursion (EXdi) and peak contraction velocity (PCVdi), (2) predict weaning outcome, and (3) approximate transdiaphragmatic pressure (Pdi)., Methods: In 49 mechanically ventilated patients, CUSdi was recorded during a 30-min spontaneous breathing trial (SBT), and EXdi and PCVdi were measured. In subgroups of patients, standard ultrasound measurement of EXdi and PCVdi was performed (n = 36), and Pdi derived parameters (peak and pressure time product, n = 30) were measured simultaneously., Results: The agreement bias between standard ultrasound and CUSdi for EXdi was 0.1 cm (95% confidence interval -0.7-0.9 cm). The regression of Passing-Bablok indicated a lack of systematic difference between EXdi measured with standard ultrasound and CUSdi, which were positively correlated (Rho = 0.84, p < 0.001). Weaning failure was observed in 54% of patients. One, two and three minutes after the onset of the SBT, EXdi was higher in the weaning success group than in the failure group. Two minutes after the onset of the SBT, an EXdi < 1.1 cm predicted weaning failure with a sensitivity of 0.83, a specificity of 0.68, a positive predictive value of 0.76, and a negative predictive value of 0.24. There was a weak correlation between EXdi and both peak Pdi (r = 0.22, 95% confidence interval 0.15 - 0.28) and pressure time product (r = 0.13, 95% confidence interval 0.06 - 0.20). Similar results were observed with PCVdi., Conclusions: Operator-independent continuous diaphragm monitoring quantifies EXdi reliably and can predict weaning failure with an identified cut-off value of 1.1 cm. Trial registration clinicaltrial.gov, NCT04008875 (submitted 12 April 2019, posted 5 July 2019) and NCT03896048 (submitted 27 March 2019, posted 29 March 2019)., (© 2024. The Author(s).)

Background: In critically ill patients receiving mechanical ventilation, dyspnoea is frequent, severe and associated with an increased risk of neuropsychological sequelae. We evaluated the efficacy of sensory interventions targeting the brain rather than the respiratory system to relieve dyspnoea in mechanically ventilated patients., Methods: Patients receiving mechanical ventilation for ≥48 h and reporting dyspnoea (unidimensional dyspnoea visual analogue scale (Dyspnoea-VAS)) first underwent increased pressure support and then, in random order, auditory stimulation (relaxing music versus pink noise) and air flux stimulation (facial versus lower limb). Treatment responses were assessed using Dyspnoea-VAS, the Multidimensional Dyspnea Profile and measures of the neural drive to breathe (airway occlusion pressure ( P 0.1 ) and electromyography of inspiratory muscles)., Results: We included 46 patients (tracheotomy or intubation n=37; noninvasive ventilation n=9). Increasing pressure support decreased Dyspnoea-VAS by median 40 mm (p<0.001). Exposure to music decreased Dyspnoea-VAS compared with exposure to pink noise by median 40 mm (p<0.001). Exposure to facial air flux decreased Dyspnoea-VAS compared with limb air flux by median 30 mm (p<0.001). Increasing pressure support, but not music exposure and facial air flux, reduced P 0.1 by median 3.3 cmH 2 O (p<0.001)., Conclusions: In mechanically ventilated patients, sensory interventions can modulate the processing of respiratory signals by the brain irrespective of the intensity of the neural drive to breathe. It should therefore be possible to alleviate dyspnoea without resorting to pharmacological interventions or having to infringe the constraints of mechanical ventilation lung protection strategies by increasing ventilatory support., Competing Interests: Conflict of interest: M. Decavèle reports personal fees from Isis Medical, outside the submitted work. M. Dres reports grants and personal fees from Lungpacer Inc., outside the submitted work. T. Similowski reports personal fees from ADEP Assistance, AstraZeneca France, Boehringer Ingelheim France, Chiesi France, GSK France, Lungpacer Inc., Novartis France and Teva France, outside the submitted work; and in addition has a patent for a brain–ventilator interface licensed, and patents for a protection device for intubation and a noncontact thoracic movement imaging system pending. A. Demoule reports personal fees from Medtronic, Baxter, Hamilton and Getinge, grants and personal fees from Philips and Respinor, personal fees and nonfinancial support from Fisher & Paykel, grants from the French Ministry of Health, and grants and nonfinancial support from Lungpacer, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings., Methods: A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson's correlation coefficients (r) were used to investigate within-individual relationships between variables, and repeated measure correlations (R) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation., Results: Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (R = 0.45, 95% CIs [0.35 0.54], p < 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (r = 0.55-0.86, all p < 0.05, versus r = - 0.43-0.52, all p > 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi-ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi-ΔSMdi relationship (median (Q1-Q3), 25 (18-33) vs. 21 (15-26) breaths.min -1 , respectively)., Conclusions: We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients., Trial Registration: NCT03832231 .

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients., Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7., Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7., Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.