[Prolonged weaning after long-term ventilation due to SARS-CoV-2 infection: a multicenter retrospective analysis]. / Prolongierte Entwöhnung nach Langzeitbeatmung aufgrund einer SARS-CoV-2-Infektion ­ eine multizentrische retrospektive Analyse.

Some of the patients with SARS-CoV-2 infection (COVID-19) received invasive ventilation during inpatient care. Weaning from ventilation was difficult for some patients (so-called prolonged weaning). PATIENTS: Patients (n=751) with prolonged weaning (reason for ventilation "pneumonia" and "acute respiratory failure") from four centers for the period 2011-23 from the "WeanNet" registry were used as a matched group. RESULTS: The median duration of intensive medical care was 39 (25-68) days. In 19% (37/193) of patients, ECMO support was necessary for a median of 27 (18-51) days. In-hospital mortality was 8.3% (2.7% with vs. 9.6% without ECMO) and 6.8% died in the comparison group. At discharge, 84% (vs. 77% in the control group) were completely weaned and 2.6% (vs. 17.6% in the control group) of patients received non-invasive treatment. Invasive ventilation was still necessary in 7.8% (control group 15.7%). In the observation period of 6 months after discharge, 22.4% of patients required inpatient care and a further 14.1% after 12 months. The overall mortality at 12-month follow-up was 20,6% (5.6% with vs. 24.6% without ECMO). DISCUSSION: The mortality rate of ventilated patients with COVID-19 was very low at 8.3% in the four weaning centers studied. The mortality rate of patients with ECMO treatment was only 2.7%. The mortality rate in the control group was 7.3%. The lower mortality of patients with ECMO treatment was also evident at follow-up of up to 12 months.Patients with prolonged weaning who received invasive ventilation due to COVID-19 showed comparable results in terms of successful weaning and mortality compared to a control group from the WeanNet registry. The long-term results with a survival of more than 80% for the first year after discharge were encouraging.

Diaphragm ultrasound in patients with prolonged weaning from mechanical ventilation.

Background: Several publications have examined diaphragmatic ultrasound using two-dimensional (2D) parameters in the context of weaning from mechanical ventilation (MV) and extubation. However, the studied cohorts had rather short duration of ventilation. Examinations on patients with prolonged weaning after long-term ventilation were missing. It was the aim of this study to assess of the diaphragm and peripheral musculature of patients undergoing prolonged weaning creating a chronological sequence of ultrasonic parameters during the course of weaning. Methods: This study was carried out as a monocentric, prospective observational cross-sectional study. Patients in prolonged weaning who were transferred to a specialized weaning unit were eligible for inclusion if they were ventilated invasively by means of an endotracheal tube or tracheal cannula and if their expected treatment period was at least 5 days. Diaphragmatic function and one representative peripheral muscle were examined in 50 patients between March 2020 and April 2021. The 2D sonographic parameters of diaphragm and diaphragmatic function consisted of diaphragmatic thickness (Tdi) at the end of inspiration and expiration, the fractional thickening (FT) and the diaphragmatic excursion. Additionally, the M. quadriceps femoris was sonographically assessed at two locations. The difference of measurements between the first and the last measuring timepoint were examined using the Wilcoxon signed-rank test. For a longer chronological sequence, the Friedman's rank sum test with subsequent Wilcoxon-Nemenyi-McDonald-Thompson test for multiple comparisons was carried out. Results: Fifty patients with prolonged weaning were included. The median duration of MV before transfer to the weaning unit was 11.5 [interquartile range (IQR) 10] days. Forty-one patients could be assessed over the full course of weaning, with 38 successfully weaned. Within these 41 patients, the sonographic parameters of the diaphragm slightly increased over the course of weaning indicating an increase in thickness and mobility. Especially parameters which represented an active movement reached statistical significance, i.e., inspiratory Tdi when assessed under spontaneous breathing [begin 3.41 (0.99) vs. end 3.43 (1.31) mm; P=0.01] and diaphragmatic excursion [begin 0.7 (0.8) vs. end 0.9 (0.6) cm; P=0.01]. The presence of positive end-expiratory pressure (PEEP) and pressure support did not influence the sonographic parameters significantly. The M. quadriceps femoris, in contrast, decreased slightly but constantly over the time [lower third: begin 1.36 (0.48) vs. end 1.28 (0.36) cm; P=0.054]. Conclusions: The present study is the first one to longitudinally analyse diaphragmatic ultrasound in patients with prolonged weaning. Sonographic assessment showed that Tdi and excursion increased over the course of prolonged weaning, while the diameter of a representative peripheral muscle decreased. However, the changes are rather small, and data show a wide dispersion. To allow a potential, standardized use of diaphragm ultrasound for diagnostic decision support in prolonged weaning, further studies in this specific patient group are required.

Potential Diaphragm Muscle Weakness-related Dyspnea Persists Two Years after COVID-19 and Could Be Improved by Inspiratory Muscle Training: Results of an Observational and an Interventional Trial.

RATIONALE: Diaphragm muscle weakness might underly persistent exertional dyspnea despite normal lung/cardiac function in individuals previously hospitalized for acute COVID-19 illness. OBJECTIVES: Firstly, to determine the persistence and pathophysiological nature of diaphragm muscle weakness and its association with exertional dyspnea two years after hospitalization for COVID-19, and secondly to investigate the impact of inspiratory muscle training (IMT) on diaphragm and inspiratory muscle weakness and exertional dyspnea in individuals with long COVID. METHODS: ~2 years after hospitalization for COVID-19, 30 individuals (11 female, median age 58 [interquartile range (IQR) 51-63] years) underwent comprehensive (invasive) respiratory muscle assessment and evaluation of dyspnea. Eighteen with persistent diaphragm muscle weakness and exertional dyspnea were randomized to 6 weeks of IMT or sham training; assessments were repeated immediately after and 6 weeks after IMT completion. The primary endpoint was change in inspiratory muscle fatiguability immediately after IMT. RESULTS: At median 31 [IQR 23-32] months after hospitalization, 21/30 individuals reported relevant persistent exertional dyspnea. Diaphragm muscle weakness on exertion and reduced diaphragm cortical activation were potentially related to exertional dyspnea. Compared with sham control, IMT improved diaphragm and inspiratory muscle function (sniff transdiaphragmatic pressure 83 [IQR 75-91] vs. 100 [IQR 81-113] cmH2O; p=0.02), inspiratory muscle fatiguability (time to task failure 365 [IQR 284-701] vs. 983 [IQR 551-1494] sec; p=0.05), diaphragm voluntary activation index (79 [IQR 63-92] vs 89 [IQR 75-94]%; p=0.03), and dyspnea (Borg score 7 [IQR 5.5-8] vs. 6 [IQR 4-7]; p=0.03); improvements persisted for 6 weeks after IMT completion. CONCLUSIONS: This study is the first to identify a potential treatment for persisting exertional dyspnea in long COVID, and provide a possible pathophysiological explanation for the treatment benefit. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Persistence of Diffusion Capacity Impairment and Its Relationship with Dyspnea 12 Months after Hospitalization for COVID-19.

Background: Dyspnea is a common persistent symptom after acute coronavirus disease 2019 illness (COVID-19). One potential explanation for post-COVID-19 dyspnea is a reduction in diffusion capacity. This longitudinal study investigated diffusion capacity and its relationship with dyspnea on exertion in individuals previously hospitalized with COVID-19. Methods: Eligible participants had been hospitalized for the treatment of acute COVID-19 and were assessed at 6 weeks, 6 months, and 12 months after discharge. Pulmonary function testing, diffusion capacity of carbon monoxide (DLCO), blood gas analysis and the level of dyspnea (Borg scale; before and after a 6 min walk test [6 MWT]) were performed. Participants were divided into subgroups based on the presence or absence of dyspnea during the 6 MWT at 12 months after hospitalization. Results: Seventy-two participants (twenty-two female, mean age 59.8 ± 13.5 years) were included. At 12 months after discharge, 41/72 participants (57%) had DLCO below the lower limit of normal and 56/72 (78%) had DLCO < 80% of the predicted value. Individuals with exertional dyspnea had significantly lower DLCO than those without exertional dyspnea (p = 0.001). In participants with DLCO data being available at three timepoints over 12 months (baseline, 6 months, and 12 months) after discharge (n = 25), DLCO improved between 6 weeks and 6 months after hospital discharge, but not thereafter (p = 0.017). Conclusions: About 2/3 of the post-COVID individuals in this study had impaired diffusion capacity at 12 months after hospital discharge. There was an association between persisting dyspnea on exertion and significantly reduced DLCO. Impaired diffusion capacity improved over the first 6 months after hospitalization but not thereafter.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

Effective non-invasive ventilation reduces muscle sympathetic nerve activity in patients with stable hypercapnic COPD.

Increased sympathetic drive is of prognostic significance in chronic obstructive pulmonary disease (COPD) but its determinants remain poorly understood. One potential mechanism may be chemoreflex-mediated adrenergic stimulation caused by sustained hypercapnia. This study determined the impact of non-invasive ventilation (NIV) on muscle sympathetic nerve activity (MSNA) in patients with stable hypercapnic COPD. Ten patients (age 70 ± 7 years, GOLD stage 3-4) receiving long-term NIV (mean inspiratory positive airway pressure 21 ± 7 cmH2O) underwent invasive MSNA measurement via the peroneal nerve during spontaneous breathing and NIV. Compared with spontaneous breathing, NIV significantly reduced hypercapnia (PaCO2 51.5 ± 6.9 vs 42.6 ± 6.1 mmHg, p < 0.0001) along with the burst rate (64.4 ± 20.9 vs 59.2 ± 19.9 bursts/min, p = 0.03) and burst incidence (81.7 ± 29.3 vs 74.1 ± 26.9 bursts/100 heartbeats, p = 0.04) of MSNA. This shows for the first time that correcting hypercapnia with NIV decreases MSNA in COPD.

GLI-12 Reference Values versus Fixed 0.7 Ratio for the Detection of Airflow Obstruction in the Presence of Lung Hyperinflation.

Introduction: Airflow obstruction (AO) is evidenced by reduced forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) with the threshold for diagnosis often being set at <0.7. However, currently the ATS/ERS standards for interpretation of lung function tests recommend the lower limit of normal (LLN), calculated by reference equations of the Global Lung Initiative from 2012 (GLI-12), as a threshold for AO diagnosis. The present study aims to investigate phenotypes, with focus on hyperinflation, which influence AO prevalence defined by FEV1/FVC < LLN when compared to the fixed 0.7 threshold. Methods: Data from 3,875 lung function tests (56.4% men, aged 18-95) including 3,824 body plethysmography recordings performed from July 2021 to June 2022 were analysed. The difference between both classifiers was quantified, before and after stratification by sex, age, and hyperinflation. Results: AO diagnosis was significantly less frequent with the LLN threshold (18.2%) compared to the fixed threshold (28.0%) (p < 0.001) with discordance rate of 10.5%. In the presence of mild or moderate hyperinflation, there was substantial agreement (Cohen's kappa: 0.616, 0.718) between the classifiers compared to near perfect agreement in the presence of severe hyperinflation (Cohen's kappa: 0.896). In addition, subgroup analysis after stratification for sex, age, and hyperinflation showed significant differences between both classifiers. Conclusion: The importance of using the LLN threshold instead of the fixed 0.7 threshold for the diagnosis of AO is highlighted. When using the fixed threshold AO, misdiagnosis was more common in the presence of mild to moderate hyperinflation.