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Background and Objectives: The present study was designed to explore the utility of ultrasound-guided diaphragmatic thickness in the preoperative period in healthy controls scheduled for live-related donor hepatectomy and patients suffering from chronic liver disease scheduled for liver transplantation (LT) and its use as a predictor of postoperative weaning failure. Materials and Methods: This prospective observational study was conducted in a tertiary health care center and 65 adult (18-70 years) participants (30 healthy liver donors and 35 liver transplant recipients) were enrolled for this study. Right diaphragmatic thickness of both donors and recipients was measured by B-mode ultrasound using a 10 MHz linear array transducer in the supine position in the operation theater just before induction of anesthesia. For subgroup analysis of the recipients, we further divided them into two groups - Group 1 (diaphragmatic thickness < 2 mm) and Group 2 (diaphragmatic thickness > 2 mm), and comparison was done for duration of mechanical ventilation. Intergroup comparison was made for duration of mechanical ventilation and various other parameters. Results: The sonographic measurement of diaphragm revealed that its thickness is decreased in patients with chronic liver disease patients (2.12 ± 0.54 mm) as compared to healthy donors (3.70 ± 0. 58 mm). On multiple logistic regression, higher duration of mechanical ventilation was associated with diaphragmatic thickness < 2 mm (Group 1 of recipients) (adjusted odds ratio 0.86; 95% confidence interval: 0.75-0.99; P = 0.013) after adjusting for age, gender, and body mass index. Conclusions: Diaphragmatic thickness is decreased in patients with chronic liver disease as compared to healthy liver donors. Preoperative measurement of ultrasound-guided right hemidiaphragm thickness can be used to predict weaning failure in patients undergoing LT. Other studies are needed to confirm these finding on different group of patients.

Background Ventilator weaning is of great importance for intensive care patients in order to avoid complications caused by prolonged ventilation. However, not all patients succeed in weaning immediately. Their spontaneous breathing may be insufficient, resulting in extubation failure and the subsequent need for reintubation. To identify patients at high risk for weaning failure, a variety of potential predictors has already been examined in individual studies and meta-analyses over the last decades. However, an overview of all the predictors investigated is missing. Aim To provide an overview of empirically investigated predictors for weaning failure. Methods A systematic evidence map was developed. To this end, we conducted a systematic search in the Medline, Cochrane, and CINAHL databases in December 2023 and added a citation search and a manual search in June 2024. Studies on predictors for weaning failure in adults ventilated in the intensive care unit were included. Studies on children, outpatients, non-invasive ventilation, or explanatory factors of weaning failure were excluded. Two reviewers performed the screening and data extraction independently. Data synthesis followed an inductive approach in which the predictors were thematically analyzed, sorted, and clustered. Results Of the 1388 records obtained, 140 studies were included in the analysis. The 112 prospective and 28 retrospective studies investigated a total of 145 predictors. These were assigned to the four central clusters ‘Imaging procedures’ (n = 22), ‘Physiological parameters’ (n = 61), ‘Scores and indices’ (n = 53), and ‘Machine learning models’ (n = 9). The most frequently investigated predictors are the rapid shallow breathing index, the diaphragm thickening fraction, the respiratory rate, the P/F ratio, and the diaphragm excursion. Conclusion Predictors for weaning failure are widely researched. To date, 145 predictors have been investigated with varying intensity in 140 studies that are in line with the current weaning definition. It is no longer just individual predictors that are investigated, but more comprehensive assessments, indices and machine learning models in the last decade. Future research should be conducted in line with international weaning definitions and further investigate poorly researched predictors. Registration, Protocol : https://doi.org/10.17605/OSF.IO/2KDYU

Abstract Background: Established structured weaning approaches, which are effective for patients in simple and difficult weaning, are often not appropriate for patients undergoing prolonged weaning. Addressing the complexity of weaning failure requires personalized precision medicine. The therapeutic concept of treatable traits (TTs) has been proposed as a new paradigm for the management of chronic respiratory diseases. It is based on a multidimensional assessment of specific characteristics, which can be addressed by specific interventions that go beyond traditional diagnostic criteria. The concept is increasingly adopted for other complex diseases. Summary: This is a narrative review and an expert opinion on the development of a concept of TTs for patients undergoing prolonged weaning. The proposed TTs are based on a systematic review of risk factors for prolonged weaning, an analysis of claims data to assess risk factors within 96 h of IMV onset and data from the WEAN SAFE study. A multidisciplinary team identified clinically important TTs and determined appropriate interventions. The following TTs have been identified: airway disorders and complications associated with tracheostomy or intubation, such as airway obstruction, strictures or tracheomalacia, infectious aspects, anxiety, depression, delirium, post-traumatic stress disorder, anemia, pulmonary and cardio-renal disease. The multidimensional holistic approach also includes tailored sedation and pain management, nutritional therapy, early mobilization, and physiotherapy. Key Message: We propose a framework of relevant considerations for a multidimensional approach to the management of patients undergoing prolonged weaning that supports the regain of respiratory capacity, reduces the respiratory load, and thus could resolve the respiratory workload imbalance.

Background Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation. Methods This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure. Results Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7–22). Median DTF within 24 h since the start of weaning was 28% (IQR 22–39%), RASS score (− 2 vs − 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO 2 /FiO 2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 10 27 ; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO 2 /FiO 2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004). Conclusions DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used over the last decade in patients with refractory cardiogenic shock. ECMO weaning can, however, be challenging and lead to circulatory failure and death. Recent data suggest a potential benefit of levosimendan for ECMO weaning. We sought to further investigate whether the use of levosimendan could decrease the rate of ECMO weaning failure in adult patients with refractory cardiogenic shock. METHODS: We performed an observational single-center cohort study. All patients undergoing VA-ECMO from January 2012 to December 2018 were eligible and divided into two groups: group levosimendan and group control (without levosimendan). The primary endpoint was VA-ECMO weaning failure defined as death during VA-ECMO treatment or within 24 h after VA-ECMO removal. Secondary outcomes were mortality at day 28 and at 6 months. The two groups were compared after propensity score matching. P \\textless 0.05 was considered statistically significant. RESULTS: Two hundred patients were analyzed (levosimendan group: n = 53 and control group: n = 147). No significant difference was found between groups on baseline characteristics except for ECMO duration, which was longer in the levosimendan group (10.6 ± 4.8 vs. 6.5 ± 4.7 days, p \\textless 0.001). Levosimendan administration started 6.6 ± 5.4 days on average following ECMO implantation. After matching of 48 levosimendan patients to 78 control patients, the duration of ECMO was similar in both groups. The rate of weaning failure was 29.1% and 35.4% in levosimendan and control groups, respectively (OR: 0.69, 95%CI: 0.25-1.88). No significant difference was found between groups for all secondary outcomes. CONCLUSION: Levosimendan did not improve the rate of successful VA-ECMO weaning in patients with refractory cardiogenic shock. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04323709 .

Background Tracheostomized critically ill patients weaning from invasive mechanical ventilation (IMV) are at risk for dyspnea. This study aimed to assess the prevalence and severity of dyspnea during tracheostomized weaning, its impact on weaning outcomes, and its association with psychological outcome and health-related quality of life (HR-QoL) after Intensive Care unit (ICU)-discharge. Methods A prospective observational study in tracheostomized patients weaning from mechanical ventilation was performed in 13 hospitals in the Netherlands. Main exclusion criteria were tracheostomy for airway obstruction and neuromuscular disease. Dyspnea was assessed daily during mechanical ventilation and weaning. The primary endpoint was the number of weaning days with dyspnea. Main secondary endpoints were dyspnea severity measured using a visual analog scale (D-VAS), weaning success, post-traumatic stress disorder (PTSD) related symptoms and HR-QoL evaluated using IES-R and EQ-5D questionnaires 90 days post- ICU, respectively. Results From April 2023 to June 2024, 156 patients were included; 130 (83%) were successfully weaned. The median weaning duration was 10 [8−15] days, with a median of 3 [2−6] days with dyspnea per patient. Dyspnea affected 58% of patients, with a median D-VAS score of 6 [5–7]. Dyspnea was associated with longer weaning duration and reduced weaning success (hazard ratio 0.37, P < 0.001). The number of days with dyspnea correlated significantly with IES-R (linear regression coefficient (β) 2.42; P = 0.02) and EQ-5D utility score (-0.025; P = 0.03). Conclusion Dyspnea in tracheostomized critically ill patients is common during weaning and associated with prolonged weaning, reduced weaning success, increased PTSD-symptoms and decreased HR-QoL after ICU discharge.

Background In anaesthetized patients scheduled for surgery, tracheal intubation is performed with the expectation of subsequent smooth extubation. In critically ill patients, separation from the ventilator is often gradual and the time chosen for extubation may be either delayed or premature. Thus, weaning is challenging, represents a large part of the ventilation period and concerns all mechanically ventilated patients surviving their stay. Definitions and management Weaning may be stratified in three groups according to its difficulty and duration. In simple weaning the main issue is to detect the soonest time to start separation from the ventilator; this is frequently impeded by poor sedation management and excessive ventilator assistance. A two-step diagnostic approach is the most efficacious: screening for ascertained readiness to wean is confirmed by a diagnostic test simulating the post-extubation period, best performed by unassisted breathing (no PEEP). In case of test failure ( difficult weaning), a structured and thorough diagnostic work-up regarding potentially reversible pathologies is required with a focus on cardiovascular dysfunction or fluid overload at the time of separation from the ventilator, respiratory or global muscle weakness and underlying infection. Prolonged weaning is exceptionally time- and resource-consuming, needs to properly appraise psychological problems, sleep and nutrition, and is probably best performed in specialized units. Conclusions Adequately managing simple and difficult weaning requires one to think about ICU policies in terms of sedation, fluid balance and having a systematic screening strategy; it also needs an individualized approach to understand and treat the failing patients. Prolonged weaning requires a holistic approach.

Background Although multidrug-resistant bacteria (MDR) are common in patients undergoing prolonged weaning, there is little data on their impact on weaning and patient outcomes. Methods This is a retrospective analysis of consecutive patients who underwent prolonged weaning and were at a university weaning centre from January 2018 to December 2020. The influence of MDR colonisation and infection on weaning success (category 3a and 3b), successful prolonged weaning from invasive mechanical ventilation (IMV) with or without the need for non-invasive ventilation (NIV) compared with category 3c (weaning failure 3cI or death 3cII) was investigated. The pathogen groups considered were: multidrug-resistant gram-negative bacteria (MDRGN), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus spp. (VRE). Results A total of 206 patients were studied, of whom 91 (44.2%) showed evidence of MDR bacteria (32% VRE, 1.5% MRSA and 16% MDRGN), with 25 patients also meeting the criteria for MDR infection. 70.9% of the 206 patients were successfully weaned from IMV, 8.7% died. In 72.2% of cases, nosocomial pneumonia and other infections were the main cause of death. Patients with evidence of MDR (infection and colonisation) had a higher incidence of weaning failure than those without evidence of MDR (48% vs. 34.8% vs. 21.7%). In multivariate analyses, MDR infection (OR 4.9, p  = 0.004) was an independent risk factor for weaning failure, along with male sex (OR 2.3, p  = 0.025), Charlson Comorbidity Index (OR 1.2, p  = 0.027), pH (OR 2.7, p  < 0.001) and duration of IMV before admission (OR 1.01, p  < 0.001). In addition, MDR infection was the only independent risk factor for death (category 3cII), (OR 6.66, p  = 0.007). Conclusion Patients with MDR infection are significantly more likely to die during the weaning process. There is an urgent need to develop non-antibiotic approaches for the prevention and treatment of MDR infections as well as clinical research on antibiotic stewardship in prolonged weaning as well as in ICUs.

Background Traditional predictors of weaning outcomes primarily focus on acute illness severity and physiological parameters, while geriatric vulnerability domains such as frailty, functional dependence, and nutritional risk are often overlooked. Evidence regarding the incremental prognostic value of these domains for predicting weaning failure in critically ill older patients remains limited. This study aimed to evaluate the association between pre-admission frailty, functional status, comorbidity burden, and acute organ dysfunction with weaning failure in critically ill patients aged ≥ 65 years, and to compare their prognostic contribution with traditional severity scores. Methods This study is a secondary analysis of a national, multicenter, prospective observational cohort conducted across adult ICUs in Türkiye. Consecutive ICU patients aged ≥ 65 years who required invasive mechanical ventilation for more than 24 h were included. Multivariable logistic regression was used to identify factors independently associated with weaning failure. Weaning failure was defined as the need for reintubation within 7 days after extubation, death during the weaning process, or persistent requirement for invasive mechanical ventilation at day 90. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 647 critically ill older patients were included in the study. Weaning failure occurred in 347 patients (53.6%). There was no significant difference in age between patients with weaning failure and those successfully weaned. Patients with weaning failure had significantly higher frailty scores, greater comorbidity burden, more severe organ dysfunction, higher nutritional risk, and worse functional dependency. In the final multivariable logistic regression model, higher Clinical Frailty Scale (CFS) (aOR = 1.26 per point; 95% CI = 1.16–1.38) and higher Sequential Organ Failure Assessment (SOFA) score (aOR = 1.12 per point; 95% CI = 1.06–1.19) were independently associated with weaning failure. Conclusions In critically ill older patients, frailty and early organ dysfunction were the factors most strongly associated with weaning failure, whereas chronological age alone showed limited prognostic value, supporting a shift from age-based to vulnerability-based risk assessment.

Myasthenic crisis (MC) requiring mechanical ventilation is a serious complication of myasthenia gravis (MG). Here we analyze the frequency and risk factors of weaning- and extubation failure as well as its impact on the clinical course in a large cohort. We performed a retrospective chart review on patients treated for MC in 12 German neurological departments between 2006 and 2015. Weaning failure (WF) was defined as negative spontaneous breathing trial, primary tracheostomy, or extubation failure (EF) (reintubation or death). WF occurred in 138 episodes (64.2%). Older Age (p = 0.039), multiple comorbidities (≥ 3) (p = 0.007, OR = 4.04), late-onset MG (p = 0.004, OR = 2.84), complications like atelectasis (p = 0.008, OR = 3.40), pneumonia (p < 0.0001, OR = 3.45), cardio-pulmonary resuscitation (p = 0.005, OR = 5.00) and sepsis (p = 0.02, OR = 2.57) were associated with WF. WF occurred often in patients treated with intravenous immungloblins (IVIG) (p = 0.002, OR = 2.53), whereas WF was less often under first-line therapy with plasma exchange or immunoadsorption (p = 0.07, OR = 0.57). EF was observed in 58 of 135 episodes (43.0%) after first extubation attempt and was related with prolonged mechanical ventilation, intensive care unit stay and hospital stay (p ≤ 0.0001 for all). Extubation success was most likely in a time window for extubation between day 7 and 12 after intubation (p = 0.06, OR = 2.12). We conclude that WF and EF occur very often in MC and are associated with poor outcome. Older age, multiple comorbidities and development of cardiac and pulmonary complications are associated with a higher risk of WF and EF. Our data suggest that WF occurs less frequently under first-line plasma exchange/immunoadsorption compared with first-line use of IVIG.