Association Between Abdominal Muscle Weakness and Weaning Failure in Mechanically Ventilated Critically Ill Patients: An Ultrasound Assessment

Association Between Abdominal Muscle Weakness and Weaning Failure in Mechanically Ventilated Critically Ill Patients: An Ultrasound Assessment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association Between Abdominal Muscle Weakness and Weaning Failure in Mechanically Ventilated Critically Ill Patients: An Ultrasound Assessment Michele Bertoni, S. Giovanazzi, S. Renzetti, F. Murgolo, L. Ceresoli, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8593236/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Assessing cough effectiveness and abdominal muscle strength in critically ill patients is difficult, despite their significant impact on weaning outcomes. Ultrasound evaluation of abdominal muscle activity during a cough may help identify patients at risk of weaning failure. We investigated how abdominal muscle weakness (AMW), assessed via ultrasound during coughing, relates to weaning failure at 48 hours and 7 days, and explored its links with diaphragm dysfunction (DD) and ICU-acquired weakness (ICUAW). Methods Patients at high risk for weaning failure, who were intubated or tracheostomized and had been ventilated for at least 48 hours, successfully completed the spontaneous breathing trial (SBT), and were attempting their first disconnection, were included. Before the disconnection attempt, all patients were tested for AMW, defined as the overall thickening fraction of the abdominal muscles during cough (TF abs ). DD was explored using ultrasound, and ICUAW was assessed using the Medical Research Council scale or the peripheral nerve test in uncooperative patients. Results Among the 46 patients, weaning was successful at 48 hours in 30 (65.2%) and failed in 16 (34.7%). Nine (20.5%) patients had AMW, ICUAW, and DD simultaneously, whereas 10 (22.9%) patients developed isolated AMW. Pearson's chi-square test confirmed that AMW was not associated with ICUAW (p = 0.28) or DD (p = 0.97). The multivariable logistic regression analysis revealed a greater probability of weaning failure at 48 hours (OR 9.4, CI 1.1–75.2, p = 0.03) and 7 days (OR 14.8, CI 1.6–136.1, p = 0.02) for patients with AMW than for patients without AMW. ICUAW was also associated with weaning failure at 48 hours (OR 8.5, CI 1.5–46.8, p = 0.01) and 7 days (OR 20.4, CI 2.7–155.0, p < 0.01), whereas the presence of DD was not related to either weaning failure at 48 hours or 7 days. Conclusions An ultrasound evaluation of abdominal muscle function during cough, together with an assessment of ICUAW, could help assess ventilator disconnection readiness. abdominal muscle diaphragm dysfunction intensive care unit-acquired weakness muscle weakness weaning failure Figures Figure 1 Figure 2 Figure 3 Background Weaning patients from mechanical ventilation (MV) is a complex and time-consuming process. Approximately 40% of the time spent on MV involves screening and testing the patient's ability to breathe spontaneously to predict successful weaning up to 48 hours after the MV disconnection attempt. The spontaneous breathing trial (SBT) is a well-established method for predicting a patient’s ability to breathe independently at the time of the disconnection attempt. ( 1 ) Controversially, the decision to initiate a weaning trial is still influenced by subjective clinical considerations and nonrespiratory factors, and the concept of "readiness for disconnection" remains widely debated in the literature. ( 2 , 3 ) Determining disconnection readiness remains a more subjective aspect of the weaning process, as it involves several criteria that can be difficult to assess. ( 4 – 6 ) In fact, while ICU-acquired weakness (ICUAW) and diaphragmatic dysfunction (DD) are well-established factors associated with weaning failure in critically ill patients, abdominal muscle weakness (AMW) remains an overlooked condition that could also impede the weaning process through various mechanisms. ( 4 , 7 , 8 ) During expiratory efforts, contraction of the abdominal muscles generates high expiratory pressures, which are essential for effective coughing and secretion clearance. Weak abdominal muscles can reduce peak flow and the effectiveness of coughing, which may raise the risk of alveolar collapse and secretion buildup.( 9 , 10 ) In addition, abdominal muscle tonic activity, maintaining the diaphragm cranially, optimizes the diaphragm’s length‒tension relationship, enhancing its pressure-generating capacity and overall performance, in collaboration with the inspiratory muscles. ( 9 , 11 – 14 ) Furthermore, their force activity during expiration may lead to more effective expiration, reducing volume at the end of expiration and increasing elastic recoil that supports the next inspiration. ( 15 , 16 ) To confirm it, lower maximal expiratory pressure (MEP) and impaired cough seem to be associated with poor extubation outcomes ( 17 ), and recently, Jansen and colleagues demonstrated that recruitment of abdominal muscles is evident during ventilator weaning, particularly in patients more prone to weaning failure. ( 18 ) Indeed, while abdominal muscle activity seems to be one indicator of weaning outcome, some uncertainty remains. First, assessing abdominal muscle function and cough effectiveness is difficult, making it hard to confirm any assumptions. ( 19 ) This is due to the lack of objective, validated measures in uncooperative patients: MEP requires patient cooperation, and cough evaluation is often based on qualitative scales. ( 5 , 15 , 16 , 19 , 20 ) A recent study highlighted the potential of ultrasound (US)-based measurement of total abdominal muscle activity during cough as a tool for identifying patients at high risk of weaning failure, highlighting its high reliability. ( 21 ) Second, AMW has not been studied for its association with other forms of weakness, such as the diaphragm and limbs. Their link may be important at different stages of the weaning process and its outcomes. The present study explored the associations between AMW, as detected by US during cough, and weaning failure 48 hours and 7 days after the ventilator disconnection attempt. Additionally, we examined the relationships among AMW, ICUAW, and DD and their overall impact on weaning outcome. Study design and methods This prospective cohort study was conducted between October 2021 and June 2023 at the intensive care unit of Brescia. The local ethics committee approved the study (no. 3369), and informed consent was obtained from all patients. Study population We screened all patients on MV for at least 48 hours, including both those who were intubated and those who were tracheostomized. Patients were recruited after they had successfully completed an SBT and were scheduled for their first attempt at ventilator disconnection (extubation for intubated patients or disconnection for tracheostomized patients). We included only patients at high risk of weaning failure according to the current definition. ( 22 ) The presence of at least one of the following factors was considered to define high risk ( 22 ): age older than 65 years; heart failure as the primary indication for mechanical ventilation; moderate to severe chronic obstructive pulmonary disease (COPD); acute physiology and chronic health evaluation II (APACHE II) score greater than 12 on extubation day; body mass index of more than 30; inadequate cough reflex or suctioning > 2 times within 8 hours before extubation; prolonged use of invasive ventilation (≥ 7 days from the first SBT); and two comorbidities categorized based on the Charlson Comorbidity Index. The exclusion criteria were as follows: age < 18 years; preexisting neuromuscular disorder that could affect the diagnosis of abdominal, limb and diaphragm muscle weakness; inability to perform an ultrasound of the diaphragm or abdominal muscles; and failure to assess the presence of ICUAW using either the Medical Research Council scale sum score (MRCss) ( 23 ) or simplified peroneal nerve test (PENT). ( 24 – 26 ) Study protocol Tests for AMW, ICUAW, and DD diagnoses were conducted cross-sectionally on the day of the first ventilator disconnection attempt, 120 minutes after the patient had just successfully passed the SBT for the first time. A group of expert researchers conducted all ultrasound measurements and performed the ICUAW assessment, whereas the clinicians taking care of the patient did not consider muscle weakness in their clinical decisions regarding disconnection from MV attempts. According to the center’s weaning protocol,( 27 ) all patients were assessed for disconnection readiness on the basis of the criteria defined by Boles et al.( 28 ) Disconnection readiness was considered when all the following criteria were met: recovery from the precipitating illness; no sedation, with a Richmond Agitation-Sedation Scale (RASS) score ≥ -1; only clinically demonstrated adequate cough with minimal or no tracheobronchial secretions and stable cardiovascular status (heart rate ≤ 140 beats per minute, systolic blood pressure between 90 and 160 mmHg); and minimal (excluding dobutamine and/or dopamine infusion lower than 5 µg/kg/min and 3 µg/kg/min, respectively) or no use of vasopressors. Additionally, the patient needed to have a stable metabolic status, adequate oxygenation (with a PaO 2 /FIO 2 ratio > 150 or SpO 2 > 90% with FIO2 ≤ 0.4, PEEP 7.35), and adequate pulmonary function, as evidenced by a tidal volume (TV) > 5 mL·kg⁻¹ and a rapid shallow breathing index (RSBI; calculated as the ratio of respiratory rate to tidal volume) < 105 breaths·min⁻¹·L⁻¹ in the contextual pressure support setting. Once these clinical criteria were met, an SBT was performed using pressure support ventilation (PSV) with an inspiratory pressure of 6 cmH 2 O and a PEEP level of 6 cmH 2 O for 30 minutes.( 29 ) On the basis of current guidelines and previous research, we considered the criteria for readiness, the criteria for SBT, and the success of weaning to be equivalent for both intubated and tracheostomized patients. ( 27 , 28 , 30 ) According to the SBT success criteria described by Boles et al.( 28 ), patients who passed the SBT were temporarily reconnected to their previous ventilator settings for rest, after which they were disconnected from the ventilator. The clinicians performed disconnections, unaware of the results of the muscle evaluation. We included all patients in the study who passed the SBT and were extubated or disconnected from the ventilator. After disconnection, all enrolled patients received high-flow oxygen or noninvasive ventilation based on immediate clinical judgment, while all tracheostomized patients received high-flow oxygen. Post-ventilator disconnection respiratory failure was based on current recommendations ( 27 ) , and reconnection to MV was guided by the clinical team's judgment without considering the measures used to diagnose muscle weakness. The study protocol is summarized in Fig. 1 . Data collection According to the WIND (Weaning according to a New Definition) classification, ( 31 ) patients were categorized into groups according to the time of weaning: group NW (patients in whom no disconnection or weaning attempt was made; excluded from study); group 1 (patients in whom the weaning process was terminated within 1 day from the first attempt; short weaning); group 2 (patients in whom the weaning process was completed after 1 day but within 1 week from the first SBT; difficult weaning); group 3a (patients who required more than 7 days to be separated from the ventilator with success; prolonged weaning); and group 3b (patients who required more than 7 days to be separated from the ventilator without success; weaning failure). We used the WIND classification because it provides better classification when including both tracheostomized and intubated patients. ( 31 ) The following variables were recorded at ICU admission: demographic data, ICU admission severity (Sequential Organ Failure Assessment, SOFA) score, reason for ICU admission, and comorbidities. ICU and hospital length of stay (LOS) and mortality outcomes were also recorded. Muscle weakness assessment was defined as follows: to define the presence of AMW , we assessed the thickening fraction during cough (TF cough ) of the rectus abdominis (TF cough, RA ), transversus abdominis (TF cough, TrA ), and internal oblique (TF cough, IO ) muscles by ultrasound (US). US was performed on the patient's right side in the recumbent position during voluntary or, in the case of uncooperative patients, stimulated cough. According to a previous study, to better standardize cough in all uncooperative patients, we evoke the reflex by stimulating with tubotracheal aspiration, while in cooperative patients, we ask them to produce the maximal response. ( 21 ) As described elsewhere, ( 19 , 21 , 32 ) we placed a high-frequency linear-array transducer on previously identified landmarks midway between the costal margin and the iliac crest along the right anterior axillary line to measure TF cough, TrA and TF cough, IO and 2–3 cm above the umbilicus and 2–3 cm to the right of the midline to measure TF cough, RA . With the ultrasound set in M mode, the thickness of each abdominal muscle was evaluated at end inspiration (Tpi) and peak expiration (Tpe) during coughing. The distance between the two internal layers (excluding the aponeurosis) of each muscle was measured offline using a DICOM image viewer (RadiAnt DICOM Viewer, version 2021). An example of the measurement has been included in the supplementary material to provide further clarification (e-Figure 1). Thus, the thickening fraction was calculated using the following equation: TF= (Tpe-Tpi)/Tpi × 100. Therefore, we examined the overall thickening fraction of the transversus abdominis, internal oblique, and rectus abdominis during cough (TF abs ) and defined AMW as TF abs less than 127%.( 9 , 21 ) TF abs was computed as follows: $$\:{TF}_{abs}={TF}_{cough,\:\:RA}\:+\:{TF}_{cough,\:TrA}\:+{\:TF}_{cough,\:IO}$$ The values used to analyze each muscle were the average of three consecutive measurements. ICUAW was defined as an MRCss < 48. ( 33 ) In uncooperative patients, ICUAW was investigated at the bedside by a bilateral simplified peroneal nerve test (PENT), which has been validated as a screening test for ICUAW and has a sensitivity of 100% and a specificity of 85%.( 24 – 26 ) Diaphragm function was assessed in the right hemidiaphragm, and TFdi was obtained as described elsewhere. ( 34 ) The thickening fraction was computed as the percentage change in thickness between end expiration (i.e., minimum muscle thickness, Tee) and peak inspiration (i.e., maximal muscle thickness, Tpi) visualized in M mode (TFdi: Tpi-Tee/Tee). DD was defined as the average of three measurements of diaphragm thickening fraction (TFdi) less than 29%( 35 ) taken in the two hours following the SBT. All muscle measurements were conducted by a researcher specialized in ultrasound. Post-analyses of all images were conducted using a DICOM viewer (RadiAnt DICOM Viewer, version 2021). The three operators—MB, SG, and LC—performed measurements independently. When uncertainty arose, two operators analyzed the images separately, and if there was a disagreement, the third determined the final measurement. Outcomes The primary outcome was weaning failure at 48 hours , defined as reintubation (or reconnection to the ventilator in the case of a patient with a tracheostomy) within 48 hours after the first MV liberation attempt. The secondary outcomes were weaning failure at 7 days , defined as the need to return to mechanical ventilation within 7 days after attempted extubation or disconnection, and 28-day ventilator-free days (VFDs) , defined as 28 days – days on mechanical ventilation or as zero if the subject either died within 28 days of MV or was on MV for more than 28 days. We also investigated the association of the AMW with the weaning class (WIND class). Finally, we examined the associations among AMW, ICUAW, and DD and their overall impact on weaning failure at 48 hours and 7 days, VFDs , and the WIND class. Statistical analysis Continuous variables are presented as the mean and standard deviation (SD) or the median and interquartile range (IQR), as appropriate. Categorical variables are presented as counts and percentages. The distribution of the data was assessed graphically. All variables of interest (AMW, DD, and ICUAWI) were examined in terms of weaning failure at 48 hours and 7 days. A sample size of 40 patients was calculated to achieve 80% power (error rate of 0.05) in detecting the association between AMW and weaning failure at 48 hours. The sample size was calculated by considering a proportion of weaning failure among those with 50% AMW and weaning failure among those with no AMW of 10% on the basis of previous studies. ICU admission baseline characteristics were compared between patients with weaning failure and those without weaning failure via t-test or the Wilcoxon test for continuous variables and Pearson's chi-square test for categorical variables. The difference in the prevalence of AMW between the ICUAW and DD groups was evaluated using Pearson’s chi-square test. We used multivariable logistic regression to determine the associations between weaning failure at 48 hours and 7 days (dependent variable) and AMW, DD and ICUAW (independent variables). We used competing risk regression to explore the associations between AMW and VFDs. This analysis provides a subdistribution hazard ratio (SHR) that links an intervention to extubation while accounting for the competing risk of death. ( 36 ) Finally, we utilized multinomial logistic regression to examine the association with WIND. All regressions were adjusted for age, body mass index (BMI), and SOFA score. Given the sample size, we limited the regressions to these variables as a clinically reasonable choice to avoid underpowering. All statistical tests were two-sided, and the significance level was set to 5%. Data were analyzed using R (version 4.4.2). The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Results Forty-six patients were included in the study; details of inclusion and exclusion, as well as the reasons, are outlined in e-Figure 2. Table 1 presents the distribution of patient characteristics according to weaning success at 48 hours. The weaning process at 48 hours was successful in 30 (65.2%) patients and failed in 16 (34.7%). At the 7-day follow-up, weaning failed in only 3 of 30 (10.0%) patients who had successfully weaned at 48 hours. Only one of the patients who failed at 48 hrs was successfully disconnected at 7 days of follow-up. No other causes besides respiratory failure were identified as the reason for reconnection in all cases. The severity of illness (SOFA) score was greater in those who were not weaned. There was no statistically significant difference in the number of days on MV before the first disconnection attempt between patients who experienced weaning failure at 48 hours and those who did not. Compared with intubated patients, tracheostomized patients had a greater probability of weaning failure at 48 hours (9, 56.2% vs. 7, 21.2%). For a better understanding of the study population, e-Table one (e-Table 1 ) highlights and cross-tabulates the characteristics of patients across the two groups: intubated and tracheostomized. Table 1 Patient characteristics according to weaning failure at 48 hours. No WF at 48 hrs (N = 30, 65.2%) WF at 48 hrs (N = 16, 34.7%) p Age (years), mean (DS) 61.8 (10.6) 64.2 (13.0) 0.49 1 BMI (kg/m 2 ), median (IQR) 27.6 (24.0-32.7) 28.2 (24.1–32.1) 0.89 2 Male (N, %), mean (DS) 22 (73.3) 8 (50.0) 0.11 3 ICU admission SOFA score, median (IQR) 4 ( 4 – 8 ) 6 ( 4 – 9 ) 0.05 2 Tracheostomy (N, %) 4 (13.3) 9 (56.2) < 0.01 Comorbidities (N, %) No comorbidity 8 (26.7) 2 (12.5) 0.51 1 One comorbidity 9 (30.0) 5 (31.2) Two comorbidities 7 (23.3) 3 (18.8) Three comorbidities 6 (20.0) 6 (37.5) TF abs (%), median (IQR) 0.9 (0.7–1.3) 0.9 (0.5-1.0) 0.21 2 Reason for admission (N, %) Trauma 2 (6.7) 1 (6.2) 0.70 1 Respiratory failure 5 (16.7) 2 (12.5) Sepsis 2 (6.7) 2 (6.7) Brain injury 1 (3.3) 2 (12.5) COVID-19 ARDS 18 (60.0) 9 (56.2) Other 2 (6.7) 0 (0.0) Presence of ICUAW (N, %) 13 (43.3) 13 (81.2) 0.01 1 Presence of DD (N, %) 13 (43.3) 8 (50.0) 0.67 1 Presence of AMW (N, %) 19 (63.3) 14 (87.5) 0.08 1 WIND class (N, %) 7 days (before disconnection) 2 (6.6) 6 (38.0) 0.01 1 Duration of MV (before disconnection) 5.0 (3.0-8.1) 7.0 (4.0-15.2) 0.13 2 WF at 7 days (N, %) 3 (10.0) 15 (93.8) < 0.01 1 ICU LOS (days), median (IQR) 10.0 (5.9–12.1) 14.5 (13.0–22.0) 0.01 2 H LOS (days), median (IQR) 29.0 (18.8–45.2) 26.5 (22.0–35.0) 0.91 2 ICU mortality (N, %) 3 (10.0) 9 (56.2) < 0.01 1 H mortality (N, %) 2 (6.7) 0 (0.0) < 0.01 1 Abbreviations: WF: weaning failure; BMI: body mass index; ICU: intensive care unit; SOFA: sequential organ failure assessment; TF abs : the sum of the thickening fraction during cough of the rectus abdominis, transversus abdominis and internal oblique; ARDS: acute respiratory distress syndrome; ICUAW: intensive care unit acquired weakness; DD: diaphragm dysfunction; AMW: Abdominal Muscle Weakness; WIND definition: Weaning according to a New Definition; Weaning > 7 days: more than 7 days of mechanical ventilation from the first SBT to the disconnection attempt; Duration of MV: duration of ventilation before the first disconnection attempt; ICU LOS: ICU length of stay; H LOS: hospital length stay; N: number of non-missing values. Based on their distribution and types of variables, the data are presented as the median (interquartile range, IQR), mean (standard deviation, DS) or number (percentage). 1 Pearson’s chi-square test; 2 Wilcoxon rank-sum test; 3 t-test. Figure 2 shows the distributions of AMW, ICUAW, and DD. Only 9 (20.5%) patients had all three conditions simultaneously; 10 (22.9%) patients were affected by isolated AMW, while 8 patients (18.2%) had AMW combined with ICUAW, and 6 (13.6%) patients had DD. Pearson's chi-square test confirmed that AMW was not associated with ICUAW (p = 0.28) or DD (p = 0.97) (e-Table 2). AMW vs. no AMW TF abs did not significantly differ by weaning failure at 48 hours, as it was 0.9 [0.8–1.3] for weaned patients and 0.8 [0.5-1.0] for nonweaned patients. This trend continued at 7 days, with 0.9 [0.8–1.3] for weaned patients and 0.8 [0.5-1.0] for nonweaned patients. The multivariable logistic regression analysis revealed an independent greater probability of weaning failure at 48 hours (OR 9.4, CI 1.1–75.2, p = 0.03) and 7 days (OR 14.8, CI 1.6–136.1, p = 0.02) for patients with AMW compared to those without AMW (Table 2 , Fig. 3 ). Patients with AMW had a lower but not significant risk of being disconnected within 28 days (estimated 50% lower risk, p = 0.18) (e-Table 3). The presence of AMW was not related to the WIND class, and the short weaning group was used as a reference group (e-Table 4). Table 2 Multivariable logistic regression analysis of weaning failure at 48 hours and 7 days. Failure at 48 hrs Failure at 7 days Predictor Odds ratio CI p Odds ratio CI p Presence of AMW 9.4 1.1–75.2 0.03 14.8 1.6-136.1 0.02 Presence of DD 1.2 0.2–5.6 0.74 1.8 0.3–9.7 0.47 Presence of ICUAW 8.5 1.5–46.8 0.01 20.4 2.7–155.0 < 0.01 Age (years) 1.0 0.9–1.1 0.27 0.9 0.7-1.0 0.03 BMI (kg/m 2 ) 0.9 0.8–1.1 0.98 1.0 0.8–1.3 0.34 Admission SOFA score 1.1 0.8–1.4 0.40 1.0 1.0–1.1 0.67 Abbreviations : AMW: abdominal muscle weakness; ICUAW: intensive care unit acquired weakness; DD: diaphragm dysfunction; BMI: body mass index; SOFA: sequential organ failure assessment; CI: 95% confidence interval. ICUAW vs. no ICUAW The presence of ICUAW was independently associated with weaning failure at 48 hours (OR 8.5, CI 1.5–46.8, p = 0.01) and 7 days (OR 20.4, CI 2.7–155.0, p < 0.01) (Table 2 , Fig. 3 ) and with a lower risk of being disconnected within 28 days (estimated 77% lower risk, p < 0.01) (e-Table 4). The presence of ICUAW was not related to the WIND class (e-Table 4). DD vs. no DD The presence of DD was not related to either 48-hour or 7-day weaning failure (Table 2 , Fig. 3 ). No significant difference in extubation risk or WIND class was found (e-Tables 3 and 4). Discussion In this study, we found that ultrasound measurements of the abdominal muscle thickening fraction and ICUAW, but not DD, were strongly and independently associated with weaning failure at both 48 hours and 7 days in a population of patients ready to be liberated from ventilation and who had already passed the SBT. In addition, we confirmed that weakness of the abdominal, limb and diaphragm muscles is highly prevalent in general ICU patients and that these three entities are not directly related to each other. It is well known that accurately assessing the likelihood of weaning failure is crucial, but assessing abdominal muscle strength and cough efficacy remains a primary unanswered question in the "disconnection readiness" concept. Our results suggest that abdominal muscle ultrasound may be valuable for assessing abdominal muscle function in critically ill patients who are ready to wean. In fact, ultrasound-defined AMW during coughing, i.e., when TF abs is less than 127%, was significantly associated with failed weaning from the ventilator. Weaning failure at 48 hours and at 7 days was substantially more likely in patients with AMW and fewer VFDs at 28 days than in patients without AMW. These findings hold greater clinical significance than the commonly referenced failure at 48 hours, particularly considering that a recent study has shown that being ventilated for 7 days after the first weaning attempt significantly impacts the mortality rate, increasing it from 6% to nearly 30%.( 31 ) Importantly, our patients met the criteria typically used in clinical practice to confirm disconnection readiness and successfully passed the SBT. In addition, these results highlight the critical role of expiratory muscles in generating adequate cough pressure to facilitate airway clearance, avoid atelectasis and improve diaphragmatic contractile efficiency, thus supporting the ability of the patient to wean from mechanical ventilation.( 5 , 37 ) As reviewed by Shi et al.( 9 ), severe expiratory muscle weakness commonly develops in critically ill patients and is associated with worse outcomes. However, the underlying pathophysiological relationship between abdominal muscle weakness and weaning failure remains unclear, and their association from a clinical perspective has been rarely demonstrated. ( 12 ) This uncertainty may be due to the challenge of assessing abdominal muscle function using high-skill methods such as expiratory flow measurement. ( 4 ) Our study obtained reliable results using ultrasound, an easily repeatable, noninvasive bedside method validated in a previous study.( 21 ) This is the first study to investigate the overlap between AMW, ICUAW, and DD in both cooperative and uncooperative patients, contributing to a better understanding of the impact of global muscle weakness on weaning failure. Despite the high prevalence of AMW, DD, and ICUAW in our cohort, only nine patients presented all three conditions simultaneously. These findings align with the literature and reflect the variable involvement of the abdominal muscles, limb muscles and diaphragm during critical illness. Although DD and ICUAW have historically been described as having common risk factors and pathophysiological mechanisms, ( 38 ), more recent data suggest that they should be considered two distinct entities. ( 39 , 40 ) Similarly, AMW may not necessarily recognize the same mechanisms that cause ICUAW or DD. The absence of correlation suggests a complex interaction between different muscle groups with distinct biological characteristics, which may respond differently and at different times to the critical condition. Further studies with larger sample sizes and with a more representative ICU population are needed to clarify the pathophysiology of AMW, its influence on overall respiratory muscle performance, its properties and its overlap with ICUAW and DD. From a clinical perspective, our data confirm the well-known impact of ICUAW on weaning outcomes. ( 41 , 42 ) Patients with ICUAW had a significantly greater probability of weaning failure at both 48 hours and 7 days and fewer VFDs at 28 days, comparable in magnitude but independent of that of AMW. This emphasizes the relevance of assessing limb muscle weakness in clinical practice. ( 33 ) Conversely, DD did not emerge as a predictor of weaning failure, as it showed no significant correlation with any of the three weaning outcome indicator parameters (including VFDs at 28 days and the WIND class). The role of DD in predicting weaning failure remains a topic of debate. While some recent studies have highlighted its relationship with weaning outcomes, others have reported conflicting results. ( 21 , 39 , 40 , 42 – 44 ) In our study, we did not examine the typical impact of DD on SBT failure. Instead, we focused on patients at high risk of weaning failure who successfully passed the SBT, sometimes despite having DD. We hypothesize that delayed weaning failure, occurring at 48 hours and especially at 7 days, may be more related to abdominal and peripheral muscle function rather than diaphragm performance, and is strongly linked to cough effectiveness. For instance, measuring diaphragm function can help predict SBT success but might not identify long-term disconnection failure, which could be more influenced by the strength of abdominal muscles than by the diaphragm itself. Our study has limitations. First, we analyzed a relatively small population with a high prevalence of ICUAW and AMW, although this is consistent with the literature. The small sample size and the inclusion of tracheostomized patients, who are often more impaired and prone to weaning failure, may have contributed to the high rates of weaning failure in our population. However, when considering only intubated patients, the extubation failure rate was 20%, which aligns with the definition of high-risk patients. Further studies must confirm these results by separating the tracheostomized and intubated populations. Second, we select a population at high risk of muscle weakness, which may have led to a high rate of TFabs values less than 100%. However, the prevalence of ICUAW and DD in our population is consistent with the current evidence. In Schreiber et al ( 21 ), the threshold value for defining AMW was 127%, which was estimated from the 2.5th percentile of TFabs in healthy subjects. In the mechanically ventilated population, a lower cough TFabs was strongly associated with a greater risk of weaning failure for every 10% decrease in cough TFabs (OR 2.1 [95% CI 1.1–4.4]). Additionally, TFabs demonstrated stronger predictive ability for liberation failure, with an area under the ROC curve of 82% [95% CI, 59–100]. Nevertheless, our findings suggest that the threshold of 127% might not be optimal for ventilated patients, in contrast to its applicability in healthy subjects. ( 21 ) Unfortunately, the number of patients enrolled and the weaning failure rate did not allow predictive analysis, and we could not consider a new threshold. Our data did not verify the interaction between AMW, ICUAW, and DD, nor their association with weaning outcomes; we considered them as independent variables and conducted a multivariate analysis, accounting for their effects. Unfortunately, the sample size did not allow us to consider the coexistence of two or three of these factors in our population or their overall impact on outcomes. Third, we did not assess ultrasound diaphragm excursion as a method for diagnosing DD. However, we chose this approach because, although it is a validated tool for predicting weaning failure, it does not directly reflect diaphragm performance, and respiratory support can lead to overestimation. ( 45 ) Finally, ultrasound is an operator-dependent technique. A recent study ( 21 ) demonstrated moderate reproducibility in assessing and monitoring the structure and activity of abdominal muscles in mechanically ventilated patients. Indeed, future studies involving larger populations are needed to confirm our results and further support the use of this easily repeatable method to assist clinicians in optimizing weaning readiness. Conclusion An ultrasound evaluation of abdominal muscle activity during coughing may help determine readiness for disconnection. Our findings emphasize the importance of assessing overall muscle weakness, including the abdominal muscles, limb muscles, and diaphragm, due to their varying prevalence in critically ill, ventilated patients and their distinct effects on the weaning process. A comprehensive assessment of muscle weakness can help identify patients at risk of challenging weaning and support the development of targeted interventions to enhance outcomes. Abbreviations DD diaphragm dysfunction AMW abdominal muscle weakness ICUAW Intensive Care Unit Acquired Weakness TF abs the sum of the thickening fraction during cough of the rectus abdominis, transversus abdominis and internal oblique MV Mechanical Ventilation ARDS acute respiratory distress syndrome ICUAW intensive care unit acquired weakness WIND definition Weaning according to a New Definition Weaning > 7 days more than 7 days of mechanical ventilation from the first SBT to the disconnection attempt ICU LOS ICU length of stay H LOS hospital length stay FC cardiac frequency; BP:blood pressure SpO2 arterial oxygen saturation FiO2 inspiratory oxygen fraction PaO2 arterial oxygen tension PEEP positive end-expiratory pressure FR respiratory frequency VT tidal volume RSBI Rapid Shallow Breathing Index WF weaning failure BMI body mass index SOFA sequential organ failure assessment Declarations Human Ethics and Consent to Participate : The local ethics committee (Fondazione IRCCS Policlinico San Matteo; https://www.sanmatteo.org) approved the study (no. 3369), and informed consent was obtained from all participants. Consent for publication : I had full access to all the study data and have approved the final version of the manuscript for submission. Availability of data and material : I, Michele Bertoni, am the guarantor for this manuscript. I accept full responsibility for the integrity of the work, including the accuracy of the data and analysis. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest. Funding : The authors declare that the study received no funding, and no external funding or sponsorship was obtained. No financial or non-financial support is claimed. Authors' contributions: MB, SP, and NL conceptualized the study. MB, SG, FM, and LC collected the data. SR and MB conducted statistical analysis. MB and SP drafted the manuscript. 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Epidemiology of weaning outcome according to a new definition. The WIND study. Am J Respir Crit Care Med. 2017;195(6):772–83. Tuinman PR, Jonkman AH, Dres M, Shi Z-H, Goligher EC, Goffi A, et al. Respiratory muscle ultrasonography: methodology, basic and advanced principles and clinical applications in ICU and ED patients-a narrative review. Intensive Care Med. 2020;46(4):594–605. Latronico N, Rasulo FA, Eikermann M, Piva S. Publisher Correction to: Critical Illness Weakness, Polyneuropathy and Myopathy: Diagnosis, treatment, and long–term outcomes. Crit Care. 2023;27(1):469. Goligher EC, Laghi F, Detsky ME, Farias P, Murray A, Brace D, et al. Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity. Intensive Care Med. 2015;41(4):734. Dres M, Goligher EC, Heunks LMA, Brochard LJ. Critical illness-associated diaphragm weakness. Intensive Care Med. 2017;43(10):1441–52. Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of ventilator-free days in critical care research. Am J Respir Crit Care Med. 2019;200(7):828–36. Jiang C, Esquinas A, Mina B. Evaluation of cough peak expiratory flow as a predictor of successful mechanical ventilation discontinuation: a narrative review of the literature. J Intensive Care. 2017 June 2;5(1):33. Puthucheary ZA, Rawal J, Mcphail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. Surv Anesthesiol. 2014;58(4):159–60. Dres M, Dubé B-P, Mayaux J, Delemazure J, Reuter D, Brochard L, et al. Coexistence and impact of limb muscle and diaphragm weakness at time of liberation from mechanical ventilation in medical intensive care unit patients. Am J Respir Crit Care Med. 2017;195(1):57–66. Bertoni M, Piva S, Beretta A, Bongiovanni F, Contarino R, Artigas RM, et al. Occurrence and Effects on Weaning From Mechanical Ventilation of Intensive Care Unit Acquired and Diaphragm Weakness: A Pilot Study. Front Med. 2022 July 22;9:930262. De Jonghe B, Bastuji-Garin S, Durand M-C, Malissin I, Rodrigues P, Cerf C, et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. Crit Care Med. 2007 Sept;35(9):2007–15. Dres M, Jung B, Molinari N, Manna F, Dubé B-P, Chanques G, et al. Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts. Crit Care. 2019;23(1):370. Vetrugno L, Orso D, Corradi F, Zani G, Spadaro S, Meroi F, et al. Diaphragm ultrasound evaluation during weaning from mechanical ventilation in COVID-19 patients: a pragmatic, cross-section, multicenter study. Respir Res. 2022;23(1):210. Boscolo A, Sella N, Pettenuzzo T, Pistollato E, Calabrese F, Gregori D, et al. Diaphragm dysfunction predicts weaning outcome after bilateral lung transplant. Anesthesiology [Internet]. 2023; Available from: http://dx.doi.org/10.1097/ALN.0000000000004729 Sabourin E, Carpentier C, Lai C, Monnet X, Pham T. “Under pressure”: should we use diaphragm excursion to predict weaning success in patients receiving pressure support ventilation? Crit Care. 2023 June 15;27(1):238. Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialfinal.docx SupplementaryTables.docx SupplementaryFigure1.jpg Supfig2.tiff Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 11 Mar, 2026 Reviews received at journal 11 Mar, 2026 Reviews received at journal 03 Mar, 2026 Reviewers agreed at journal 02 Mar, 2026 Reviewers agreed at journal 23 Feb, 2026 Reviewers agreed at journal 08 Feb, 2026 Reviewers invited by journal 07 Feb, 2026 Editor assigned by journal 02 Feb, 2026 Submission checks completed at journal 02 Feb, 2026 First submitted to journal 13 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8593236","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":588785223,"identity":"43e22e79-0e9c-42c3-889b-a1972a0582ff","order_by":0,"name":"Michele Bertoni","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+klEQVRIiWNgGAWjYDACZgY2BoYCBgYDCFdCjoGBsQ3EIKDFAIwYG4AqjWFa8OhB1cKQ2AAWwWONbjvzswcfDGwYzNl7nz/4uMMifcPt5raHPxgs6nBpMTvMZm44wyCNwbLnuGHjzDMSuRvuHGw35sHjMLPDPGzSPAaHGQxupDE287YBtdxIbJPG5xewlj8G/xkM7j8Da0k3AGqR/EFIC4PBAaAtbGAtCSAtEvgdxmYm2WOQzGPZk8Y4c2abhOHMG4lAvxhISDbg0nL+8DOJHxV2cubsxxg+fGyrk+e7kf7s4Y+KOn5ctsAADxrfgJCGUTAKRsEoGAX4AABTG00YUJ+puAAAAABJRU5ErkJggg==","orcid":"","institution":"Università di Brescia","correspondingAuthor":true,"prefix":"","firstName":"Michele","middleName":"","lastName":"Bertoni","suffix":""},{"id":588785224,"identity":"23a687a7-384f-4cfd-80f8-74ddfebbaeee","order_by":1,"name":"S. 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Ceresoli","email":"","orcid":"","institution":"Università di Brescia","correspondingAuthor":false,"prefix":"","firstName":"L.","middleName":"","lastName":"Ceresoli","suffix":""},{"id":588785228,"identity":"30ef9d7f-1321-4a59-b241-ecb5c560e4da","order_by":5,"name":"F. Magri","email":"","orcid":"","institution":"ASST Spedali Civili University Hospital","correspondingAuthor":false,"prefix":"","firstName":"F.","middleName":"","lastName":"Magri","suffix":""},{"id":588785229,"identity":"d92cad1d-22a5-44ac-a3fd-98d5c37d47c3","order_by":6,"name":"C. Ferrando Ortola","email":"","orcid":"","institution":"University of Barcelona","correspondingAuthor":false,"prefix":"","firstName":"C.","middleName":"Ferrando","lastName":"Ortola","suffix":""},{"id":588785230,"identity":"13d6f2ae-7158-4438-860f-238de4e368cf","order_by":7,"name":"S. Spadaro","email":"","orcid":"","institution":"azienda ospedaliera universitaria di Ferrara, Università di Ferrara","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Spadaro","suffix":""},{"id":588785231,"identity":"378d31d5-5cb3-4055-9535-bbbdea143a78","order_by":8,"name":"E. C. Goligher","email":"","orcid":"","institution":"University of Toronto","correspondingAuthor":false,"prefix":"","firstName":"E.","middleName":"C.","lastName":"Goligher","suffix":""},{"id":588785232,"identity":"a58301cf-adec-4cbc-bb22-e0ae2294b690","order_by":9,"name":"N. Latronico","email":"","orcid":"","institution":"Università di Brescia","correspondingAuthor":false,"prefix":"","firstName":"N.","middleName":"","lastName":"Latronico","suffix":""},{"id":588785233,"identity":"c4a7208c-ea0c-4400-a54c-f2f5d25dee57","order_by":10,"name":"S. Piva","email":"","orcid":"","institution":"Università di Brescia","correspondingAuthor":false,"prefix":"","firstName":"S.","middleName":"","lastName":"Piva","suffix":""}],"badges":[],"createdAt":"2026-01-13 14:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8593236/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8593236/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102620659,"identity":"980f3285-aeee-4c6e-b70b-a37a3535fd9d","added_by":"auto","created_at":"2026-02-13 16:44:51","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":52709,"visible":true,"origin":"","legend":"\u003cp\u003eStudy protocol. Critically ill patients tracheostomized or intubated and mechanically ventilated for at least 48 hours were screened daily for weaning from mechanical ventilation. On the day of the first extubation or disconnection attempt, muscle weakness was assessed and defined as follows: DD with diaphragm thickening fraction (TFdi) \u0026lt;29%, ICUAW with Medical Research Council scale (MRC) \u0026lt; 48 in cooperative patients or simplified peroneal nerve test (PENT) \u0026lt;5.26 mV in uncooperative ones, AMW with the sum of thickening fraction during cough of rectus abdominis, transversus abdominis and internal oblique (TFabs) \u0026lt;127%. Criteria for readiness to wean are modified from Boles et al.\u003csup\u003e22\u003c/sup\u003e \u003cem\u003eAbbreviations\u003c/em\u003e: SBT: spontaneous breathing trial; DD: diaphragm dysfunction; AMW: abdominal muscle weakness; ICUAW: Intensive Care Unit Acquired Weakness; MV: Mechanical Ventilation; FC: cardiac frequency; BP: blood pressure; SpO2 : arterial oxygen saturation; FiO2 : inspiratory oxygen fraction; PaO2 : arterial oxygen tension; PEEP: positive end-expiratory pressure; FR: respiratory frequency; VT: tidal volume; RSBI: Rapid Shallow Breathing Index.\u003c/p\u003e","description":"","filename":"Figure1AMW.png","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/6a5ff0864b21f2a0efe86583.png"},{"id":102747537,"identity":"b209abc5-f5fa-4a28-9d30-bcdcc3c95aaa","added_by":"auto","created_at":"2026-02-16 09:04:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":42076,"visible":true,"origin":"","legend":"\u003cp\u003eVenn diagram illustrating the prevalence of AMW based on the presence of ICUAW, DD, or both. Abbreviations: AMW: abdominal muscles acquired weakness; ICUAW: Intensive Care Unit Acquired Weakness; DD: diaphragm dysfunction.\u003c/p\u003e","description":"","filename":"Figure2AMW.png","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/7ffe613687bb64da07d02dd1.png"},{"id":102620660,"identity":"e60d2cbd-b4b7-457b-afaf-7076308ad7a0","added_by":"auto","created_at":"2026-02-13 16:44:51","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":102518,"visible":true,"origin":"","legend":"\u003cp\u003eThe forest plot displays the results of the multivariable logistic regression analysis, showing that AMW and ICUAW are independently associated with weaning failure at 48 hours (A) and 7 days (B). \u003cem\u003eAbbreviations\u003c/em\u003e: AMW: abdominal muscle weakness; ICUAW: intensive care unit acquired weakness; DD: diaphragm dysfunction; BMI: body mass index; SOFA: sequential organ failure assessment; CI: 95% confidence interval.\u003c/p\u003e","description":"","filename":"Figure3AMW.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/b35a5844bccf07fcdd008594.jpg"},{"id":102751212,"identity":"79271e87-62e2-437a-9e37-302d169dabfd","added_by":"auto","created_at":"2026-02-16 09:24:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1038840,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/4b7fec6b-8632-4cf9-be78-e3d96a1c82b5.pdf"},{"id":102620665,"identity":"1539c417-2652-46e7-a620-73b296ded253","added_by":"auto","created_at":"2026-02-13 16:44:51","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":7119863,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialfinal.docx","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/f7e3a6d546767c09c34e3b3d.docx"},{"id":102620662,"identity":"42b011d6-44fd-4c0d-8db3-272e9d573bfc","added_by":"auto","created_at":"2026-02-13 16:44:51","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":22638,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/682f7d01c57674b8033ae0c3.docx"},{"id":102748547,"identity":"3d8259da-fcda-40c3-a941-e7812f60f003","added_by":"auto","created_at":"2026-02-16 09:11:09","extension":"jpg","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":73632,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/a8436f0b0c5b2e3f4c2a1e06.jpg"},{"id":102620664,"identity":"76cf7d59-d815-4932-94fd-5a1c0a6cf20f","added_by":"auto","created_at":"2026-02-13 16:44:51","extension":"tiff","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":106146,"visible":true,"origin":"","legend":"","description":"","filename":"Supfig2.tiff","url":"https://assets-eu.researchsquare.com/files/rs-8593236/v1/12f43e6579b3bf781ba18872.tiff"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eAssociation Between Abdominal Muscle Weakness and Weaning Failure in Mechanically Ventilated Critically Ill Patients: An Ultrasound Assessment\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eWeaning patients from mechanical ventilation (MV) is a complex and time-consuming process. Approximately 40% of the time spent on MV involves screening and testing the patient's ability to breathe spontaneously to predict successful weaning up to 48 hours after the MV disconnection attempt. The spontaneous breathing trial (SBT) is a well-established method for predicting a patient\u0026rsquo;s ability to breathe independently at the time of the disconnection attempt. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Controversially, the decision to initiate a weaning trial is still influenced by subjective clinical considerations and nonrespiratory factors, and the concept of \"readiness for disconnection\" remains widely debated in the literature. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Determining disconnection readiness remains a more subjective aspect of the weaning process, as it involves several criteria that can be difficult to assess. (\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn fact, while ICU-acquired weakness (ICUAW) and diaphragmatic dysfunction (DD) are well-established factors associated with weaning failure in critically ill patients, abdominal muscle weakness (AMW) remains an overlooked condition that could also impede the weaning process through various mechanisms. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) During expiratory efforts, contraction of the abdominal muscles generates high expiratory pressures, which are essential for effective coughing and secretion clearance. Weak abdominal muscles can reduce peak flow and the effectiveness of coughing, which may raise the risk of alveolar collapse and secretion buildup.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn addition, abdominal muscle tonic activity, maintaining the diaphragm cranially, optimizes the diaphragm\u0026rsquo;s length‒tension relationship, enhancing its pressure-generating capacity and overall performance, in collaboration with the inspiratory muscles. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Furthermore, their force activity during expiration may lead to more effective expiration, reducing volume at the end of expiration and increasing elastic recoil that supports the next inspiration. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) To confirm it, lower maximal expiratory pressure (MEP) and impaired cough seem to be associated with poor extubation outcomes (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), and recently, Jansen and colleagues demonstrated that recruitment of abdominal muscles is evident during ventilator weaning, particularly in patients more prone to weaning failure. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIndeed, while abdominal muscle activity seems to be one indicator of weaning outcome, some uncertainty remains. First, assessing abdominal muscle function and cough effectiveness is difficult, making it hard to confirm any assumptions. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) This is due to the lack of objective, validated measures in uncooperative patients: MEP requires patient cooperation, and cough evaluation is often based on qualitative scales. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) A recent study highlighted the potential of ultrasound (US)-based measurement of total abdominal muscle activity during cough as a tool for identifying patients at high risk of weaning failure, highlighting its high reliability. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Second, AMW has not been studied for its association with other forms of weakness, such as the diaphragm and limbs. Their link may be important at different stages of the weaning process and its outcomes.\u003c/p\u003e \u003cp\u003eThe present study explored the associations between AMW, as detected by US during cough, and weaning failure 48 hours and 7 days after the ventilator disconnection attempt. Additionally, we examined the relationships among AMW, ICUAW, and DD and their overall impact on weaning outcome.\u003c/p\u003e"},{"header":"Study design and methods","content":"\u003cp\u003eThis prospective cohort study was conducted between October 2021 and June 2023 at the intensive care unit of Brescia. The local ethics committee approved the study (no. 3369), and informed consent was obtained from all patients.\u003c/p\u003e\n\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy population\u003c/h2\u003e\n\u003cp\u003eWe screened all patients on MV for at least 48 hours, including both those who were intubated and those who were tracheostomized. Patients were recruited after they had successfully completed an SBT and were scheduled for their first attempt at ventilator disconnection (extubation for intubated patients or disconnection for tracheostomized patients). We included only patients at high risk of weaning failure according to the current definition. (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e) The presence of at least one of the following factors was considered to define high risk (\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e): age older than 65 years; heart failure as the primary indication for mechanical ventilation; moderate to severe chronic obstructive pulmonary disease (COPD); acute physiology and chronic health evaluation II (APACHE II) score greater than 12 on extubation day; body mass index of more than 30; inadequate cough reflex or suctioning\u0026thinsp;\u0026gt;\u0026thinsp;2 times within 8 hours before extubation; prolonged use of invasive ventilation (\u0026ge;\u0026thinsp;7 days from the first SBT); and two comorbidities categorized based on the Charlson Comorbidity Index.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows: age\u0026thinsp;\u0026lt;\u0026thinsp;18 years; preexisting neuromuscular disorder that could affect the diagnosis of abdominal, limb and diaphragm muscle weakness; inability to perform an ultrasound of the diaphragm or abdominal muscles; and failure to assess the presence of ICUAW using either the Medical Research Council scale sum score (MRCss) (\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e) or simplified peroneal nerve test (PENT). (\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eStudy protocol\u003c/h3\u003e\n\u003cp\u003eTests for AMW, ICUAW, and DD diagnoses were conducted cross-sectionally on the day of the first ventilator disconnection attempt, 120 minutes after the patient had just successfully passed the SBT for the first time. A group of expert researchers conducted all ultrasound measurements and performed the ICUAW assessment, whereas the clinicians taking care of the patient did not consider muscle weakness in their clinical decisions regarding disconnection from MV attempts.\u003c/p\u003e\n\u003cp\u003eAccording to the center\u0026rsquo;s weaning protocol,(\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e) all patients were assessed for disconnection readiness on the basis of the criteria defined by Boles et al.(\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e) Disconnection readiness was considered when all the following criteria were met: recovery from the precipitating illness; no sedation, with a Richmond Agitation-Sedation Scale (RASS) score \u0026ge; -1; only clinically demonstrated adequate cough with minimal or no tracheobronchial secretions and stable cardiovascular status (heart rate\u0026thinsp;\u0026le;\u0026thinsp;140 beats per minute, systolic blood pressure between 90 and 160 mmHg); and minimal (excluding dobutamine and/or dopamine infusion lower than 5 \u0026micro;g/kg/min and 3 \u0026micro;g/kg/min, respectively) or no use of vasopressors. Additionally, the patient needed to have a stable metabolic status, adequate oxygenation (with a PaO\u003csub\u003e2\u003c/sub\u003e/FIO\u003csub\u003e2\u003c/sub\u003e ratio\u0026thinsp;\u0026gt;\u0026thinsp;150 or SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026gt;\u0026thinsp;90% with FIO2\u0026thinsp;\u0026le;\u0026thinsp;0.4, PEEP\u0026thinsp;\u0026lt;\u0026thinsp;8 cmH\u003csub\u003e2\u003c/sub\u003eO, and arterial pH\u0026thinsp;\u0026gt;\u0026thinsp;7.35), and adequate pulmonary function, as evidenced by a tidal volume (TV)\u0026thinsp;\u0026gt;\u0026thinsp;5 mL\u0026middot;kg⁻\u0026sup1; and a rapid shallow breathing index (RSBI; calculated as the ratio of respiratory rate to tidal volume)\u0026thinsp;\u0026lt;\u0026thinsp;105 breaths\u0026middot;min⁻\u0026sup1;\u0026middot;L⁻\u0026sup1; in the contextual pressure support setting.\u003c/p\u003e\n\u003cp\u003eOnce these clinical criteria were met, an SBT was performed using pressure support ventilation (PSV) with an inspiratory pressure of 6 cmH\u003csub\u003e2\u003c/sub\u003eO and a PEEP level of 6 cmH\u003csub\u003e2\u003c/sub\u003eO for 30 minutes.(\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eOn the basis of current guidelines and previous research, we considered the criteria for readiness, the criteria for SBT, and the success of weaning to be equivalent for both intubated and tracheostomized patients. (\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eAccording to the SBT success criteria described by Boles et al.(\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e), patients who passed the SBT were temporarily reconnected to their previous ventilator settings for rest, after which they were disconnected from the ventilator. The clinicians performed disconnections, unaware of the results of the muscle evaluation. We included all patients in the study who passed the SBT and were extubated or disconnected from the ventilator.\u003c/p\u003e\n\u003cp\u003eAfter disconnection, all enrolled patients received high-flow oxygen or noninvasive ventilation based on immediate clinical judgment, while all tracheostomized patients received high-flow oxygen. Post-ventilator disconnection respiratory failure was based on current recommendations (\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e)\u003csup\u003e,\u003c/sup\u003e and reconnection to MV was guided by the clinical team's judgment without considering the measures used to diagnose muscle weakness.\u003c/p\u003e\n\u003cp\u003eThe study protocol is summarized in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eAccording to the WIND (Weaning according to a New Definition) classification, (\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e) patients were categorized into groups according to the time of weaning: group NW (patients in whom no disconnection or weaning attempt was made; excluded from study); group 1 (patients in whom the weaning process was terminated within 1 day from the first attempt; short weaning); group 2 (patients in whom the weaning process was completed after 1 day but within 1 week from the first SBT; difficult weaning); group 3a (patients who required more than 7 days to be separated from the ventilator with success; prolonged weaning); and group 3b (patients who required more than 7 days to be separated from the ventilator without success; weaning failure). We used the WIND classification because it provides better classification when including both tracheostomized and intubated patients. (\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eThe following variables were recorded at ICU admission: demographic data, ICU admission severity (Sequential Organ Failure Assessment, SOFA) score, reason for ICU admission, and comorbidities. ICU and hospital length of stay (LOS) and mortality outcomes were also recorded.\u003c/p\u003e\n\u003cp\u003eMuscle weakness assessment was defined as follows: to define the presence of \u003cem\u003eAMW\u003c/em\u003e, we assessed the thickening fraction during cough (TF\u003csub\u003ecough\u003c/sub\u003e) of the rectus abdominis (TF\u003csub\u003ecough, RA\u003c/sub\u003e), transversus abdominis (TF\u003csub\u003ecough, TrA\u003c/sub\u003e), and internal oblique (TF\u003csub\u003ecough, IO\u003c/sub\u003e) muscles by ultrasound (US). US was performed on the patient's right side in the recumbent position during voluntary or, in the case of uncooperative patients, stimulated cough. According to a previous study, to better standardize cough in all uncooperative patients, we evoke the reflex by stimulating with tubotracheal aspiration, while in cooperative patients, we ask them to produce the maximal response. (\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e) As described elsewhere, (\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e) we placed a high-frequency linear-array transducer on previously identified landmarks midway between the costal margin and the iliac crest along the right anterior axillary line to measure TF\u003csub\u003ecough, TrA\u003c/sub\u003e and TF\u003csub\u003ecough, IO\u003c/sub\u003e and 2\u0026ndash;3 cm above the umbilicus and 2\u0026ndash;3 cm to the right of the midline to measure TF\u003csub\u003ecough, RA\u003c/sub\u003e. With the ultrasound set in M mode, the thickness of each abdominal muscle was evaluated at end inspiration (Tpi) and peak expiration (Tpe) during coughing. The distance between the two internal layers (excluding the aponeurosis) of each muscle was measured offline using a DICOM image viewer (RadiAnt DICOM Viewer, version 2021). An example of the measurement has been included in the supplementary material to provide further clarification (e-Figure 1). Thus, the thickening fraction was calculated using the following equation: TF= (Tpe-Tpi)/Tpi \u0026times; 100.\u003c/p\u003e\n\u003cp\u003eTherefore, we examined the overall thickening fraction of the transversus abdominis, internal oblique, and rectus abdominis during cough (TF\u003csub\u003eabs\u003c/sub\u003e) and defined AMW as TF\u003csub\u003eabs\u003c/sub\u003e less than 127%.(\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eTF\u003csub\u003eabs\u003c/sub\u003e was computed as follows:\u003c/p\u003e\n\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\n\u003cdiv id=\"FileID_Equa\" class=\"mathdisplay\"\u003e$$\\:{TF}_{abs}={TF}_{cough,\\:\\:RA}\\:+\\:{TF}_{cough,\\:TrA}\\:+{\\:TF}_{cough,\\:IO}$$\u003c/div\u003e\n\u003c/div\u003e\n\u003cp\u003eThe values used to analyze each muscle were the average of three consecutive measurements.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eICUAW\u003c/em\u003e was defined as an MRCss\u0026thinsp;\u0026lt;\u0026thinsp;48. (\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e) In uncooperative patients, ICUAW was investigated at the bedside by a bilateral simplified peroneal nerve test (PENT), which has been validated as a screening test for ICUAW and has a sensitivity of 100% and a specificity of 85%.(\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e)\u003c/p\u003e\n\u003cp\u003eDiaphragm function was assessed in the right hemidiaphragm, and TFdi was obtained as described elsewhere. (\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e) The thickening fraction was computed as the percentage change in thickness between end expiration (i.e., minimum muscle thickness, Tee) and peak inspiration (i.e., maximal muscle thickness, Tpi) visualized in M mode (TFdi: Tpi-Tee/Tee). \u003cem\u003eDD\u003c/em\u003e was defined as the average of three measurements of diaphragm thickening fraction (TFdi) less than 29%(\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e) taken in the two hours following the SBT.\u003c/p\u003e\n\u003cp\u003eAll muscle measurements were conducted by a researcher specialized in ultrasound. Post-analyses of all images were conducted using a DICOM viewer (RadiAnt DICOM Viewer, version 2021). The three operators\u0026mdash;MB, SG, and LC\u0026mdash;performed measurements independently. When uncertainty arose, two operators analyzed the images separately, and if there was a disagreement, the third determined the final measurement.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was \u003cem\u003eweaning failure at 48 hours\u003c/em\u003e, defined as reintubation (or reconnection to the ventilator in the case of a patient with a tracheostomy) within 48 hours after the first MV liberation attempt.\u003c/p\u003e\n\u003cp\u003eThe secondary outcomes were \u003cem\u003eweaning failure at 7 days\u003c/em\u003e, defined as the need to return to mechanical ventilation within 7 days after attempted extubation or disconnection, and \u003cem\u003e28-day ventilator-free days (VFDs)\u003c/em\u003e, defined as 28 days \u0026ndash; days on mechanical ventilation or as zero if the subject either died within 28 days of MV or was on MV for more than 28 days. We also investigated the association of the AMW with the \u003cem\u003eweaning class (WIND class).\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFinally, we examined the associations among AMW, ICUAW, and DD and their overall impact on \u003cem\u003eweaning failure at 48 hours\u003c/em\u003e and \u003cem\u003e7 days, VFDs\u003c/em\u003e, and the \u003cem\u003eWIND class.\u003c/em\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analysis\u003c/h2\u003e\n\u003cp\u003eContinuous variables are presented as the mean and standard deviation (SD) or the median and interquartile range (IQR), as appropriate. Categorical variables are presented as counts and percentages. The distribution of the data was assessed graphically.\u003c/p\u003e\n\u003cp\u003eAll variables of interest (AMW, DD, and ICUAWI) were examined in terms of weaning failure at 48 hours and 7 days. A sample size of 40 patients was calculated to achieve 80% power (error rate of 0.05) in detecting the association between AMW and weaning failure at 48 hours. The sample size was calculated by considering a proportion of weaning failure among those with 50% AMW and weaning failure among those with no AMW of 10% on the basis of previous studies.\u003c/p\u003e\n\u003cp\u003eICU admission baseline characteristics were compared between patients with weaning failure and those without weaning failure via t-test or the Wilcoxon test for continuous variables and Pearson's chi-square test for categorical variables. The difference in the prevalence of AMW between the ICUAW and DD groups was evaluated using Pearson\u0026rsquo;s chi-square test.\u003c/p\u003e\n\u003cp\u003eWe used multivariable logistic regression to determine the associations between weaning failure at 48 hours and 7 days (dependent variable) and AMW, DD and ICUAW (independent variables). We used competing risk regression to explore the associations between AMW and VFDs. This analysis provides a subdistribution hazard ratio (SHR) that links an intervention to extubation while accounting for the competing risk of death. (\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e) Finally, we utilized multinomial logistic regression to examine the association with WIND. All regressions were adjusted for age, body mass index (BMI), and SOFA score. Given the sample size, we limited the regressions to these variables as a clinically reasonable choice to avoid underpowering.\u003c/p\u003e\n\u003cp\u003eAll statistical tests were two-sided, and the significance level was set to 5%. Data were analyzed using R (version 4.4.2). The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eForty-six patients were included in the study; details of inclusion and exclusion, as well as the reasons, are outlined in e-Figure 2. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the distribution of patient characteristics according to weaning success at 48 hours. The weaning process at 48 hours was successful in 30 (65.2%) patients and failed in 16 (34.7%). At the 7-day follow-up, weaning failed in only 3 of 30 (10.0%) patients who had successfully weaned at 48 hours. Only one of the patients who failed at 48 hrs was successfully disconnected at 7 days of follow-up. No other causes besides respiratory failure were identified as the reason for reconnection in all cases. The severity of illness (SOFA) score was greater in those who were not weaned. There was no statistically significant difference in the number of days on MV before the first disconnection attempt between patients who experienced weaning failure at 48 hours and those who did not. Compared with intubated patients, tracheostomized patients had a greater probability of weaning failure at 48 hours (9, 56.2% vs. 7, 21.2%). For a better understanding of the study population, e-Table one (e-Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) highlights and cross-tabulates the characteristics of patients across the two groups: intubated and tracheostomized.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics according to weaning failure at 48 hours.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo WF at 48 hrs\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;30, 65.2%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWF at 48 hrs\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;16, 34.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), mean (DS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.8 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.2 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.49\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.6 (24.0-32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.2 (24.1\u0026ndash;32.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.89\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale (N, %), mean (DS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (73.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.11\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU admission SOFA score, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTracheostomy (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (56.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (26.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.51\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOne comorbidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (30.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTwo comorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThree comorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTF\u003csub\u003eabs\u003c/sub\u003e (%), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9 (0.7\u0026ndash;1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9 (0.5-1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.21\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReason for admission (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrauma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.70\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSepsis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrain injury\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 ARDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (56.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of ICUAW (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (81.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of DD (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.67\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of AMW (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (63.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (87.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWIND class (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eShort weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifficult weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlonged weaning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeaning failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (50.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeaning\u0026thinsp;\u0026gt;\u0026thinsp;7 days (before disconnection)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (38.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of MV (before disconnection)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.0 (3.0-8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.0 (4.0-15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWF at 7 days (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU LOS (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (5.9\u0026ndash;12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.5 (13.0\u0026ndash;22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH LOS (days), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.0 (18.8\u0026ndash;45.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.5 (22.0\u0026ndash;35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.91\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU mortality (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (56.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH mortality (N, %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: WF: weaning failure; BMI: body mass index; ICU: intensive care unit; SOFA: sequential organ failure assessment; TF\u003csub\u003eabs\u003c/sub\u003e: the sum of the thickening fraction during cough of the rectus abdominis, transversus abdominis and internal oblique; ARDS: acute respiratory distress syndrome; ICUAW: intensive care unit acquired weakness; DD: diaphragm dysfunction; AMW: Abdominal Muscle Weakness; WIND definition: Weaning according to a New Definition; Weaning\u0026thinsp;\u0026gt;\u0026thinsp;7 days: more than 7 days of mechanical ventilation from the first SBT to the disconnection attempt; Duration of MV: duration of ventilation before the first disconnection attempt; ICU LOS: ICU length of stay; H LOS: hospital length stay; N: number of non-missing values. Based on their distribution and types of variables, the data are presented as the median (interquartile range, IQR), mean (standard deviation, DS) or number (percentage). \u003csup\u003e1\u003c/sup\u003ePearson\u0026rsquo;s chi-square test; \u003csup\u003e2\u003c/sup\u003eWilcoxon rank-sum test; \u003csup\u003e3\u003c/sup\u003et-test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the distributions of AMW, ICUAW, and DD. Only 9 (20.5%) patients had all three conditions simultaneously; 10 (22.9%) patients were affected by isolated AMW, while 8 patients (18.2%) had AMW combined with ICUAW, and 6 (13.6%) patients had DD. Pearson's chi-square test confirmed that AMW was not associated with ICUAW (p\u0026thinsp;=\u0026thinsp;0.28) or DD (p\u0026thinsp;=\u0026thinsp;0.97) (e-Table\u0026nbsp;2).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAMW\u003c/b\u003e \u003cb\u003evs.\u003c/b\u003e \u003cb\u003eno AMW\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTF\u003csub\u003eabs\u003c/sub\u003e did not significantly differ by weaning failure at 48 hours, as it was 0.9 [0.8\u0026ndash;1.3] for weaned patients and 0.8 [0.5-1.0] for nonweaned patients. This trend continued at 7 days, with 0.9 [0.8\u0026ndash;1.3] for weaned patients and 0.8 [0.5-1.0] for nonweaned patients.\u003c/p\u003e \u003cp\u003eThe multivariable logistic regression analysis revealed an independent greater probability of weaning failure at 48 hours (OR 9.4, CI 1.1\u0026ndash;75.2, p\u0026thinsp;=\u0026thinsp;0.03) and 7 days (OR 14.8, CI 1.6\u0026ndash;136.1, p\u0026thinsp;=\u0026thinsp;0.02) for patients with AMW compared to those without AMW (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients with AMW had a lower but not significant risk of being disconnected within 28 days (estimated 50% lower risk, p\u0026thinsp;=\u0026thinsp;0.18) (e-Table\u0026nbsp;3). The presence of AMW was not related to the WIND class, and the short weaning group was used as a reference group (e-Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable logistic regression analysis of weaning failure at 48 hours and 7 days.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"20\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c18\" colnum=\"18\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c19\" colnum=\"19\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c20\" colnum=\"20\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"8\" nameend=\"c10\" namest=\"c3\"\u003e \u003cp\u003eFailure at 48 hrs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c15\" namest=\"c12\"\u003e \u003cp\u003eFailure at 7 days\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c17\" namest=\"c16\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c20\" namest=\"c18\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003ePredictor\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c7\" namest=\"c4\"\u003e \u003cp\u003e\u003cem\u003eOdds ratio\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003e\u003cem\u003eCI\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c13\" namest=\"c12\"\u003e \u003cp\u003e\u003cem\u003eOdds ratio\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c15\" namest=\"c14\"\u003e \u003cp\u003e\u003cem\u003eCI\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c17\" namest=\"c16\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c20\" namest=\"c18\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of AMW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.1\u0026ndash;75.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.03\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e1.6-136.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of DD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.2\u0026ndash;5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e0.3\u0026ndash;9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c20\" namest=\"c20\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresence of ICUAW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1.5\u0026ndash;46.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e2.7\u0026ndash;155.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.9\u0026ndash;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e0.7-1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.8\u0026ndash;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e0.8\u0026ndash;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c20\" namest=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission SOFA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.8\u0026ndash;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c12\" namest=\"c10\"\u003e \u003cp\u003e0.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c14\" namest=\"c13\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e1.0\u0026ndash;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c18\" namest=\"c17\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c19\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"1\" nameend=\"c20\" namest=\"c20\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"20\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e: AMW: abdominal muscle weakness; ICUAW: intensive care unit acquired weakness; DD: diaphragm dysfunction; BMI: body mass index; SOFA: sequential organ failure assessment; CI: 95% confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eICUAW\u003c/b\u003e \u003cb\u003evs.\u003c/b\u003e \u003cb\u003eno ICUAW\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe presence of ICUAW was independently associated with weaning failure at 48 hours (OR 8.5, CI 1.5\u0026ndash;46.8, p\u0026thinsp;=\u0026thinsp;0.01) and 7 days (OR 20.4, CI 2.7\u0026ndash;155.0, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) and with a lower risk of being disconnected within 28 days (estimated 77% lower risk, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (e-Table\u0026nbsp;4). The presence of ICUAW was not related to the WIND class (e-Table\u0026nbsp;4).\u003c/p\u003e \u003cp\u003e \u003cb\u003eDD\u003c/b\u003e \u003cb\u003evs.\u003c/b\u003e \u003cb\u003eno DD\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe presence of DD was not related to either 48-hour or 7-day weaning failure (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No significant difference in extubation risk or WIND class was found (e-Tables\u0026nbsp;3 and 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we found that ultrasound measurements of the abdominal muscle thickening fraction and ICUAW, but not DD, were strongly and independently associated with weaning failure at both 48 hours and 7 days in a population of patients ready to be liberated from ventilation and who had already passed the SBT. In addition, we confirmed that weakness of the abdominal, limb and diaphragm muscles is highly prevalent in general ICU patients and that these three entities are not directly related to each other.\u003c/p\u003e \u003cp\u003eIt is well known that accurately assessing the likelihood of weaning failure is crucial, but assessing abdominal muscle strength and cough efficacy remains a primary unanswered question in the \"disconnection readiness\" concept. Our results suggest that abdominal muscle ultrasound may be valuable for assessing abdominal muscle function in critically ill patients who are ready to wean. In fact, ultrasound-defined AMW during coughing, i.e., when TF\u003csub\u003eabs\u003c/sub\u003e is less than 127%, was significantly associated with failed weaning from the ventilator. Weaning failure at 48 hours and at 7 days was substantially more likely in patients with AMW and fewer VFDs at 28 days than in patients without AMW. These findings hold greater clinical significance than the commonly referenced failure at 48 hours, particularly considering that a recent study has shown that being ventilated for 7 days after the first weaning attempt significantly impacts the mortality rate, increasing it from 6% to nearly 30%.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) Importantly, our patients met the criteria typically used in clinical practice to confirm disconnection readiness and successfully passed the SBT.\u003c/p\u003e \u003cp\u003e In addition, these results highlight the critical role of expiratory muscles in generating adequate cough pressure to facilitate airway clearance, avoid atelectasis and improve diaphragmatic contractile efficiency, thus supporting the ability of the patient to wean from mechanical ventilation.(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) As reviewed by Shi et al.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), severe expiratory muscle weakness commonly develops in critically ill patients and is associated with worse outcomes. However, the underlying pathophysiological relationship between abdominal muscle weakness and weaning failure remains unclear, and their association from a clinical perspective has been rarely demonstrated. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) This uncertainty may be due to the challenge of assessing abdominal muscle function using high-skill methods such as expiratory flow measurement. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Our study obtained reliable results using ultrasound, an easily repeatable, noninvasive bedside method validated in a previous study.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThis is the first study to investigate the overlap between AMW, ICUAW, and DD in both cooperative and uncooperative patients, contributing to a better understanding of the impact of global muscle weakness on weaning failure. Despite the high prevalence of AMW, DD, and ICUAW in our cohort, only nine patients presented all three conditions simultaneously. These findings align with the literature and reflect the variable involvement of the abdominal muscles, limb muscles and diaphragm during critical illness.\u003c/p\u003e \u003cp\u003eAlthough DD and ICUAW have historically been described as having common risk factors and pathophysiological mechanisms, (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e), more recent data suggest that they should be considered two distinct entities. (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e) Similarly, AMW may not necessarily recognize the same mechanisms that cause ICUAW or DD. The absence of correlation suggests a complex interaction between different muscle groups with distinct biological characteristics, which may respond differently and at different times to the critical condition. Further studies with larger sample sizes and with a more representative ICU population are needed to clarify the pathophysiology of AMW, its influence on overall respiratory muscle performance, its properties and its overlap with ICUAW and DD.\u003c/p\u003e \u003cp\u003eFrom a clinical perspective, our data confirm the well-known impact of ICUAW on weaning outcomes. (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e) Patients with ICUAW had a significantly greater probability of weaning failure at both 48 hours and 7 days and fewer VFDs at 28 days, comparable in magnitude but independent of that of AMW. This emphasizes the relevance of assessing limb muscle weakness in clinical practice. (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) Conversely, DD did not emerge as a predictor of weaning failure, as it showed no significant correlation with any of the three weaning outcome indicator parameters (including VFDs at 28 days and the WIND class). The role of DD in predicting weaning failure remains a topic of debate. While some recent studies have highlighted its relationship with weaning outcomes, others have reported conflicting results. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our study, we did not examine the typical impact of DD on SBT failure. Instead, we focused on patients at high risk of weaning failure who successfully passed the SBT, sometimes despite having DD. We hypothesize that delayed weaning failure, occurring at 48 hours and especially at 7 days, may be more related to abdominal and peripheral muscle function rather than diaphragm performance, and is strongly linked to cough effectiveness. For instance, measuring diaphragm function can help predict SBT success but might not identify long-term disconnection failure, which could be more influenced by the strength of abdominal muscles than by the diaphragm itself.\u003c/p\u003e \u003cp\u003eOur study has limitations. First, we analyzed a relatively small population with a high prevalence of ICUAW and AMW, although this is consistent with the literature. The small sample size and the inclusion of tracheostomized patients, who are often more impaired and prone to weaning failure, may have contributed to the high rates of weaning failure in our population. However, when considering only intubated patients, the extubation failure rate was 20%, which aligns with the definition of high-risk patients. Further studies must confirm these results by separating the tracheostomized and intubated populations.\u003c/p\u003e \u003cp\u003eSecond, we select a population at high risk of muscle weakness, which may have led to a high rate of TFabs values less than 100%. However, the prevalence of ICUAW and DD in our population is consistent with the current evidence. In Schreiber et al (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), the threshold value for defining AMW was 127%, which was estimated from the 2.5th percentile of TFabs in healthy subjects. In the mechanically ventilated population, a lower cough TFabs was strongly associated with a greater risk of weaning failure for every 10% decrease in cough TFabs (OR 2.1 [95% CI 1.1\u0026ndash;4.4]). Additionally, TFabs demonstrated stronger predictive ability for liberation failure, with an area under the ROC curve of 82% [95% CI, 59\u0026ndash;100]. Nevertheless, our findings suggest that the threshold of 127% might not be optimal for ventilated patients, in contrast to its applicability in healthy subjects. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Unfortunately, the number of patients enrolled and the weaning failure rate did not allow predictive analysis, and we could not consider a new threshold.\u003c/p\u003e \u003cp\u003eOur data did not verify the interaction between AMW, ICUAW, and DD, nor their association with weaning outcomes; we considered them as independent variables and conducted a multivariate analysis, accounting for their effects. Unfortunately, the sample size did not allow us to consider the coexistence of two or three of these factors in our population or their overall impact on outcomes.\u003c/p\u003e \u003cp\u003eThird, we did not assess ultrasound diaphragm excursion as a method for diagnosing DD. However, we chose this approach because, although it is a validated tool for predicting weaning failure, it does not directly reflect diaphragm performance, and respiratory support can lead to overestimation. (\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eFinally, ultrasound is an operator-dependent technique. A recent study (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) demonstrated moderate reproducibility in assessing and monitoring the structure and activity of abdominal muscles in mechanically ventilated patients. Indeed, future studies involving larger populations are needed to confirm our results and further support the use of this easily repeatable method to assist clinicians in optimizing weaning readiness.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAn ultrasound evaluation of abdominal muscle activity during coughing may help determine readiness for disconnection. Our findings emphasize the importance of assessing overall muscle weakness, including the abdominal muscles, limb muscles, and diaphragm, due to their varying prevalence in critically ill, ventilated patients and their distinct effects on the weaning process. A comprehensive assessment of muscle weakness can help identify patients at risk of challenging weaning and support the development of targeted interventions to enhance outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediaphragm dysfunction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAMW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eabdominal muscle weakness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICUAW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive Care Unit Acquired Weakness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTF\u003csub\u003eabs\u003c/sub\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe sum of the thickening fraction during cough of the rectus abdominis, transversus abdominis and internal oblique\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMechanical Ventilation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eARDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eacute respiratory distress syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICUAW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintensive care unit acquired weakness\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWIND definition\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWeaning according to a New Definition\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWeaning\u0026thinsp;\u0026gt;\u0026thinsp;7 days\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emore than 7 days of mechanical ventilation from the first SBT to the disconnection attempt\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU LOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eICU length of stay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eH LOS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehospital length stay\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiac frequency; BP:blood pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSpO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003earterial oxygen saturation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFiO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einspiratory oxygen fraction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePaO2\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003earterial oxygen tension\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePEEP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003epositive end-expiratory pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erespiratory frequency\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etidal volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRSBI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRapid Shallow Breathing Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eweaning failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOFA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esequential organ failure assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate\u003c/strong\u003e:\u0026nbsp;The local ethics committee (Fondazione IRCCS Policlinico San Matteo; https://www.sanmatteo.org) approved the study (no. 3369), and informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: I had full access to all the study data and have approved the final version of the manuscript for submission.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e: I, Michele Bertoni, am the guarantor for this manuscript. I accept full responsibility for the integrity of the work, including the accuracy of the data and analysis. The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that the research was conducted without any commercial or financial relationships that could be construed as potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: The authors declare that the study received no funding, and no external funding or sponsorship was obtained. No financial or non-financial support is claimed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u0026nbsp;\u003c/strong\u003eMB, SP, and NL conceptualized the study. MB, SG, FM, and LC collected the data. SR and MB conducted statistical analysis. MB and SP drafted the manuscript. All\u0026nbsp;the authors critically revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eThe authors would like to thank the medical and nursing staff for their invaluable support throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePham T, Heunks L, Bellani G, Madotto F, Aragao I, Beduneau G, et al. Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study. Lancet Respir Med. 2023;11(5):465\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePerren A, Brochard L. Managing the apparent and hidden difficulties of weaning from mechanical ventilation. 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Anesthesiology [Internet]. 2023; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dx.doi.org/10.1097/ALN.0000000000004729\u003c/span\u003e\u003cspan address=\"10.1097/ALN.0000000000004729\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSabourin E, Carpentier C, Lai C, Monnet X, Pham T. \u0026ldquo;Under pressure\u0026rdquo;: should we use diaphragm excursion to predict weaning success in patients receiving pressure support ventilation? Crit Care. 2023 June 15;27(1):238.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"abdominal muscle, diaphragm dysfunction, intensive care unit-acquired weakness, muscle weakness, weaning failure","lastPublishedDoi":"10.21203/rs.3.rs-8593236/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8593236/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAssessing cough effectiveness and abdominal muscle strength in critically ill patients is difficult, despite their significant impact on weaning outcomes. Ultrasound evaluation of abdominal muscle activity during a cough may help identify patients at risk of weaning failure. We investigated how abdominal muscle weakness (AMW), assessed via ultrasound during coughing, relates to weaning failure at 48 hours and 7 days, and explored its links with diaphragm dysfunction (DD) and ICU-acquired weakness (ICUAW).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients at high risk for weaning failure, who were intubated or tracheostomized and had been ventilated for at least 48 hours, successfully completed the spontaneous breathing trial (SBT), and were attempting their first disconnection, were included. Before the disconnection attempt, all patients were tested for AMW, defined as the overall thickening fraction of the abdominal muscles during cough (TF\u003csub\u003eabs\u003c/sub\u003e). DD was explored using ultrasound, and ICUAW was assessed using the Medical Research Council scale or the peripheral nerve test in uncooperative patients.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 46 patients, weaning was successful at 48 hours in 30 (65.2%) and failed in 16 (34.7%). Nine (20.5%) patients had AMW, ICUAW, and DD simultaneously, whereas 10 (22.9%) patients developed isolated AMW. Pearson's chi-square test confirmed that AMW was not associated with ICUAW (p\u0026thinsp;=\u0026thinsp;0.28) or DD (p\u0026thinsp;=\u0026thinsp;0.97). The multivariable logistic regression analysis revealed a greater probability of weaning failure at 48 hours (OR 9.4, CI 1.1\u0026ndash;75.2, p\u0026thinsp;=\u0026thinsp;0.03) and 7 days (OR 14.8, CI 1.6\u0026ndash;136.1, p\u0026thinsp;=\u0026thinsp;0.02) for patients with AMW than for patients without AMW. ICUAW was also associated with weaning failure at 48 hours (OR 8.5, CI 1.5\u0026ndash;46.8, p\u0026thinsp;=\u0026thinsp;0.01) and 7 days (OR 20.4, CI 2.7\u0026ndash;155.0, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), whereas the presence of DD was not related to either weaning failure at 48 hours or 7 days.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAn ultrasound evaluation of abdominal muscle function during cough, together with an assessment of ICUAW, could help assess ventilator disconnection readiness.\u003c/p\u003e","manuscriptTitle":"Association Between Abdominal Muscle Weakness and Weaning Failure in Mechanically Ventilated Critically Ill Patients: An Ultrasound Assessment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-13 16:44:46","doi":"10.21203/rs.3.rs-8593236/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-11T15:52:52+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-11T10:10:57+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-03T15:23:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"236253224593908696077693939779142337750","date":"2026-03-02T16:46:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"164603514875270282733378870943546280996","date":"2026-02-23T21:24:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15574839074059852180907910260887270496","date":"2026-02-08T20:41:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-07T21:49:27+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-02T10:15:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-02T10:09:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Anesthesia, Analgesia and Critical Care","date":"2026-01-13T14:17:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bf25c281-a150-4c78-9b0c-e924c286caf7","owner":[],"postedDate":"February 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-27T12:55:18+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-13 16:44:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8593236","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8593236","identity":"rs-8593236","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}