Clinical implications of frailty assessed in hospitalized patients with acute-exacerbation of interstitial lung disease.

BACKGROUND: Approximately 50% of patients with interstitial lung disease (ILD) experience frailty, which remains unexplored in acute exacerbations of ILD (AE-ILD). A better understanding may help with prognostication and resource planning. We evaluated the association of frailty with clinical characteristics, physical function, hospital outcomes, and post-AE-ILD recovery. METHODS: Retrospective cohort study of AE-ILD patients (01/2015-10/2019) with frailty (proportion ≥0.25) on a 30-item cumulative-deficits index. Frail and non-frail patients were compared for pre- and post-hospitalization clinical characteristics, adjusted for age, sex, and ILD diagnosis. One-year mortality, considering transplantation as a competing risk, was analysed adjusting for age, frailty, and Charlson Comorbidity Index (CCI). RESULTS: 89 AE-ILD patients were admitted (median: 67 years, 63% idiopathic pulmonary fibrosis). 31 were frail, which was associated with older age, greater CCI, lower 6-min walk distance, and decreased independence pre-hospitalization. Frail patients had more major complications (32% vs 10%, p = .01) and required more multidisciplinary support during hospitalization. Frailty was not associated with 1-year mortality (HR: 0.97, 95%CI: [0.45-2.10]) factoring transplantation as a competing risk. CONCLUSIONS: Frailty was associated with reduced exercise capacity, increased comorbidities and hospital complications. Identifying frailty may highlight those requiring additional multidisciplinary support, but further study is needed to explore whether frailty is modifiable with AE-ILD.

Accuracy of respiratory muscle assessments to predict weaning outcomes: a systematic review and comparative meta-analysis.

BACKGROUND: Several bedside assessments are used to evaluate respiratory muscle function and to predict weaning from mechanical ventilation in patients on the intensive care unit. It remains unclear which assessments perform best in predicting weaning success. The primary aim of this systematic review and meta-analysis was to summarize and compare the accuracy of the following assessments to predict weaning success: maximal inspiratory (PImax) and expiratory pressures, diaphragm thickening fraction and excursion (DTF and DE), end-expiratory (Tdiee) and end-inspiratory (Tdiei) diaphragm thickness, airway occlusion pressure (P0.1), electrical activity of respiratory muscles, and volitional and non-volitional assessments of transdiaphragmatic and airway opening pressures. METHODS: Medline (via Pubmed), EMBASE, Web of Science, Cochrane Library and CINAHL were comprehensively searched from inception to 04/05/2023. Studies including adult mechanically ventilated patients reporting data on predictive accuracy were included. Hierarchical summary receiver operating characteristic (HSROC) models were used to estimate the SROC curves of each assessment method. Meta-regression was used to compare SROC curves. Sensitivity analyses were conducted by excluding studies with high risk of bias, as assessed with QUADAS-2. Direct comparisons were performed using studies comparing each pair of assessments within the same sample of patients. RESULTS: Ninety-four studies were identified of which 88 studies (n = 6296) reporting on either PImax, DTF, DE, Tdiee, Tdiei and P0.1 were included in the meta-analyses. The sensitivity to predict weaning success was 63% (95% CI 47-77%) for PImax, 75% (95% CI 67-82%) for DE, 77% (95% CI 61-87%) for DTF, 74% (95% CI 40-93%) for P0.1, 69% (95% CI 13-97%) for Tdiei, 37% (95% CI 13-70%) for Tdiee, at fixed 80% specificity. Accuracy of DE and DTF to predict weaning success was significantly higher when compared to PImax (p = 0.04 and p < 0.01, respectively). Sensitivity and direct comparisons analyses showed that the accuracy of DTF to predict weaning success was significantly higher when compared to DE (p < 0.01). CONCLUSIONS: DTF and DE are superior to PImax and DTF seems to have the highest accuracy among all included respiratory muscle assessments for predicting weaning success. Further studies aiming at identifying the optimal threshold of DTF to predict weaning success are warranted. TRIAL REGISTRATION: PROSPERO CRD42020209295, October 15, 2020.

Effects of inspiratory muscle training on exertional breathlessness in patients with unilateral diaphragm dysfunction: a randomised trial.

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD. Methods: 15 people with UDD (73% male, 61±8 years) were randomised to 6 months of IMT (50% maximal inspiratory mouth pressure (PI,max), n=10) or sham training (10% PI,max, n=5) (30 breaths twice per day). UDD was confirmed by phrenic nerve stimulation and persisted throughout the training period. Symptoms were assessed by the transitional dyspnoea index (TDI) and exercise tolerance by constant-load cycle tests performed pre- and post-training. Oesophageal (Pes) and gastric (Pga) pressures were measured with a dual-balloon catheter. Electromyography (EMG) and oxygenation (near-infrared spectroscopy) of respiratory muscles were assessed continuously during exercise. Results: The IMT group (from 45±6 to 62±23% PI,max) and sham group (no progression) completed 92 and 86% of prescribed sessions, respectively. PI,max, TDI scores and cycle endurance time improved significantly more after IMT versus sham (mean between-group differences: 28 (95% CI 13-28) cmH2O, 3.0 (95% CI 0.9-5.1) points and 6.0 (95% CI 0.4-11.5) min, respectively). During exercise at iso-time, Pes, Pga and EMG of the scalene muscles were reduced and the oxygen saturation indices of the scalene and abdominal muscles were higher post- versus pre-training only in the IMT group (all p<0.05). Conclusion: The effects of IMT on dyspnoea and exercise tolerance in UDD were not mediated by an improvement in isolated diaphragm function, but may reflect improvements in strength, coordination and/or oxygenation of the extra-diaphragmatic respiratory muscles.

Managing respiratory muscle weakness during weaning from invasive ventilation.

Weaning is a critical stage of an intensive care unit (ICU) stay, in which the respiratory muscles play a major role. Weakness of the respiratory muscles, which is associated with significant morbidity in the ICU, is not limited to atrophy and subsequent dysfunction of the diaphragm; the extradiaphragmatic inspiratory and expiratory muscles also play important parts. In addition to the well-established deleterious effect of mechanical ventilation on the respiratory muscles, other risk factors such as sepsis may be involved. Weakness of the respiratory muscles can be suspected visually in a patient with paradoxical movement of the abdominal compartment. Measurement of maximal inspiratory pressure is the simplest way to assess respiratory muscle function, but it does not specifically take the diaphragm into account. A cut-off value of -30 cmH2O could identify patients at risk for prolonged ventilatory weaning; however, ultrasound may be better for assessing respiratory muscle function in the ICU. Although diaphragm dysfunction has been associated with weaning failure, this diagnosis should not discourage clinicians from performing spontaneous breathing trials and considering extubation. Recent therapeutic developments aimed at preserving or restoring respiratory muscle function are promising.

Occurrence Rate and Outcomes of Weaning Groups According to a Refined Weaning Classification: A Retrospective Observational Study.

OBJECTIVES: The weaning according to a new definition (WIND) classification groups mechanically ventilated (MV) patients into "short weaning," "difficult weaning," "prolonged weaning," and "no weaning." The aims of the study were: 1) to describe the weaning group distribution, 2) to evaluate if "short weaning" patients can be divided into groups with distinct characteristics and outcomes depending on the MV duration, and 3) to study 1-year outcomes related to weaning groups. DESIGN: Retrospective observational study. SETTING: Tertiary center with a mixed, mainly surgical ICU population. PATIENTS: MV patients admitted between April 11, 2018, and April 10, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A refined WIND classification was used, dividing "short weaning" patients into patients MV less than or equal to 24 hours, "short weaning a," and those MV greater than 24 hours, "short weaning b." Data were collected from electronic medical records. Of 1,801 MV patients, 65% were categorized as "short weaning a," 13% "short weaning b," 8% "difficult weaning," 6% "prolonged weaning," and 8% "no weaning." "Short weaning a" patients were older, more frequently male, and had lower disease severity compared with "short weaning b." Weaning duration (days: 0 [0-0] to 14 [10-21]), weaning success rate (99-69%), ICU length of stay (days: 2 [1-4] to 28 [19-48]), ICU mortality (1-37%), and hospital length of stay (days: 10 [7-18] to 48 [27-89]) and hospital mortality (4-42%; all p < 0.01) increasingly worsened from "short weaning a" to "prolonged weaning." One-year mortality increased from "short weaning a" (9%) to "short weaning b" (27%), "difficult weaning" (39%), and "prolonged weaning" (49%). In adjusted analyses, weaning groups remained independently associated with 1-year mortality. CONCLUSIONS: The high proportion of "short weaning" patients in this mainly surgical ICU population could be divided into two groups with distinct characteristics. This refined WIND classification allowed to enhance prognostication, also beyond hospitalization, highlighting the need to further optimize the weaning process.

Do Cerebral Cortex Perfusion, Oxygen Delivery, and Oxygen Saturation Responses Measured by Near-Infrared Spectroscopy Differ Between Patients Who Fail or Succeed in a Spontaneous Breathing Trial? A Prospective Observational Study.

BACKGROUND: Alterations in perfusion to the brain during the transition from mechanical ventilation (MV) to a spontaneous breathing trial (SBT) remain poorly understood. The aim of the study was to determine whether changes in cerebral cortex perfusion, oxygen delivery (DO2), and oxygen saturation (%StiO2) during the transition from MV to an SBT differ between patients who succeed or fail an SBT. METHODS: This was a single-center prospective observational study conducted in a 16-bed medical intensive care unit of the University Hospital Leuven, Belgium. Measurements were performed in 24 patients receiving MV immediately before and at the end of a 30-min SBT. Blood flow index (BFI), DO2, and %StiO2 in the prefrontal cortex, scalene, rectus abdominis, and thenar muscle were simultaneously assessed by near-infrared spectroscopy using the tracer indocyanine green dye. Cardiac output, arterial blood gases, and systemic oxygenation were also recorded. RESULTS: During the SBT, prefrontal cortex BFI and DO2 responses did not differ between SBT-failure and SBT-success groups (p > 0.05). However, prefrontal cortex %StiO2 decreased in six of eight patients (75%) in the SBT-failure group (median [interquartile range 25-75%]: MV = 57.2% [49.1-61.7] vs. SBT = 51.0% [41.5-62.5]) compared to 3 of 16 patients (19%) in the SBT-success group (median [interquartile range 25-75%]: MV = 65.0% [58.6-68.5] vs. SBT = 65.1% [59.5-71.1]), resulting in a significant differential %StiO2 response between groups (p = 0.031). Similarly, a significant differential response in thenar muscle %StiO2 (p = 0.018) was observed between groups. A receiver operating characteristic analysis identified a decrease in prefrontal cortex %StiO2 > 1.6% during the SBT as an optimal cutoff, with a sensitivity of 94% and a specificity of 75% to predict SBT failure and an area under the curve of 0.79 (95% CI: 0.55-1.00). Cardiac output, systemic oxygenation, scalene, and rectus abdominis BFI, DO2, and %StiO2 responses did not differ between groups (p > 0.05); however, during the SBT, a significant positive association in prefrontal cortex BFI and partial pressure of arterial carbon dioxide was observed only in the SBT-success group (SBT success: Spearman's ρ = 0.728, p = 0.002 vs. SBT failure: ρ = 0.048, p = 0.934). CONCLUSIONS: This study demonstrated a reduced differential response in prefrontal cortex %StiO2 in the SBT-failure group compared with the SBT-success group possibly due to the insufficient increase in prefrontal cortex perfusion in SBT-failure patients. A > 1.6% drop in prefrontal cortex %StiO2 during SBT was sensitive in predicting SBT failure. Further research is needed to validate these findings in a larger population and to evaluate whether cerebral cortex %StiO2 measurements by near-infrared spectroscopy can assist in the decision-making process on liberation from MV.

Comparing two types of loading during inspiratory muscle training in patients with weaning difficulties: An exploratory study.

BACKGROUND: Inspiratory muscle training improves respiratory muscle function and may improve weaning outcomes in patients with weaning difficulties. Compared to the commonly used pressure threshold loading, tapered flow resistive loading better accommodates pressure-volume relationships of the respiratory muscles, which might help to facilitate application of external loads and optimise training responses. OBJECTIVE: The objective of this study was to compare acute breathing pattern responses and perceived symptoms during an inspiratory muscle training session performed against identical external loading provided as pressure threshold loading or as tapered flow resistive loading. We hypothesised that for a given loading, tapered flow resistive loading would allow larger volume expansion and higher inspiratory flow responses and consequently higher external work of breathing and power than pressure threshold loading and that subsequently patients perceived fewer symptoms during tapered flow resistive loading than during pressure threshold loading. METHODS: In this exploratory study, 21 patients (maximal inspiratory pressure: 35 ± 14 cmH2O and vital capacity:0.85 L±0.37 L) performed two training sessions against external loads equalling 42 ± 15% of maximal inspiratory pressure provided either as pressure threshold loading or as tapered flow resistive loading. During these training sessions, breath-by-breath data of breathing parameters were collected, and patients rated their perceived breathing effort, dyspnoea, and unpleasantness. RESULTS: Compared to pressure threshold loading, tapered flow resistive loading allowed significantly larger volume expansion (0.53 ± 0.28 L versus 0.41 ± 0.20 L, p < 0.01) and inspiratory flow responses (0.43 ± 0.20 L/s versus 0.33 ± 0.16 L/s, p = 0.01). Tapered flow resistive loading was perceived as less unpleasant (3.1 ± 1.9 versus 3.8 ± 2.4, p = 0.048). No significant differences in breathing effort, dyspnoea, work of breathing, and power were observed. CONCLUSIONS: For a given loading, inspiratory muscle training with tapered flow resistive loading allowed larger volume expansion and higher inspiratory flow responses than pressure threshold loading, which led patients to perceive tapered flow resistive loading as less unpleasant. This might help us to facilitate early implementation of inspiratory muscle training in patients with weaning difficulties. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov identifier: NCT03240263.

High-Intensity Inspiratory Muscle Training Improves Scalene and Sternocleidomastoid Muscle Oxygenation Parameters in Patients With Weaning Difficulties: A Randomized Controlled Trial.

BACKGROUND: Critically ill patients who have difficulties weaning from the mechanical ventilator are prone to develop respiratory muscle weakness. Inspiratory muscle training (IMT) can improve respiratory muscle strength. Whether IMT can improve scalene and sternocleidomastoid muscle oxygenation parameters is unknown. AIM: To compare changes in muscle oxygenation parameters of scalene and sternocleidomastoid inspiratory muscles during a standardized task between patients with weaning difficulties who received either high-intensity IMT (intervention) or sham low-intensity IMT (control). METHOD: Forty-one patients performed daily IMT sessions (4 sets, 6-10 breaths) until weaning success or for 28 consecutive days. The training load was progressively adjusted in the intervention group (n = 22) to the highest tolerable load, whilst the control group (n = 19) kept training at 10% of their baseline maximal inspiratory pressure (PImax). Breathing characteristics (i.e., work and power of breathing, PoB), respiratory muscle function [i.e., PImax and forced vital capacity (FVC)] were measured during a standardized loaded breathing task against a load of 30% of baseline PImax before and after the IMT period. In addition, during the same loaded breathing task, absolute mean and nadir changes from baseline in local scalene and sternocleidomastoid muscle oxygen saturation index (Δ%StiO2) (an index of oxygen extraction) and nadir Δ%StiO2 normalized for the PoB were measured by near-infrared spectroscopy. RESULTS: At post measures, only the intervention group improved mean PoB compared to pre measures (Pre: 0.42 ± 0.33 watts, Post: 0.63 ± 0.51watts, p-value < 0.01). At post measures, both groups significantly improved nadir scalene muscles StiO2% normalized for the mean PoB (ΔStiO nadir %/watt) compared to pre measurements and the improvement was not significant different between groups (p-value = 0.40). However, at post measures, nadir sternocleidomastoid muscle StiO2% normalized for the mean PoB (ΔStiO nadir %/watt) was significantly greater improved in the intervention group (mean difference: +18.4, 95%CI: -1.4; 38.1) compared to the control group (mean difference: +3.7, 95%CI: -18.7; 26.0, between group p-value < 0.01). Both groups significantly improved PImax (Intervention: +15 ± 13 cmH2O p-value < 0.01, Control: +13 ± 15 cmH2O p-value < 0.01). FVC only significantly improved in the intervention group (+0.33 ± 0.31 L p < 0.01) report also change in control group. CONCLUSION: This exploratory study suggests that high-intensity IMT induces greater improvements in scalene and sternocleidomastoid muscle oxygenation parameters attributed for oxygen delivery, utilization and oxygen saturation index compared to low-intensity IMT in patients with weaning difficulties.

Early mobilization in clinical practice: the reliability and feasibility of the 'Start To Move' Protocol.

PURPOSE: The properties of a local Intensive Care Unit early mobilization protocol ('Start To Move As Soon As Possible') in critically ill patients, consisting of an objective diagnostic assessment linked to six treatment levels were evaluated. This study aimed to investigate whether the protocol can be reliably applied by different health-care providers (reliability), to examine the associations between prescribed and delivered treatments (feasibility) and to explore safety and patient satisfaction with the protocol. METHODS: Cross-sectional observational study evaluating the reliability of the protocol between physiotherapist was evaluated with Cohen's kappa, percentage of agreement, and intraclass correlation coefficients in 61 patients. Feasibility was analyzed as agreement between prescribed and delivered treatments with Spearman's rank correlation coefficients in 60 patients. A satisfaction survey was used to evaluate patient satisfaction with the protocol. RESULTS: Excellent agreement was observed between physiotherapists for diagnostic level assignment (Kappa = 0.92), while the majority of the treatment proposals per level showed moderate to substantial agreement between the physiotherapists (Kappa range: 0.40-0.89). Three hundred and thirteen treatments were prescribed. Perfect agreement was observed between prescribed and delivered treatments in level 0 (Spearman's rho 1.00) and excellent associations for levels 1-5 (0.941, 0.995, 0.951, 0.998, and 0.999), respectively. Unwanted safety events rate was 3%. Most patients (92%) were very satisfied with physiotherapy. CONCLUSION: Excellent inter-rater agreement for diagnostic level assignment and moderate to substantial agreement for proposed treatments support the reliability of the protocol. Perfect to excellent associations between prescribed and delivered treatments supports its feasibility. Complications were rare, and most patients were very positive regarding the care provided by physiotherapists during their stay in the ICU.

Measurement validity of an electronic training device to assess breathing characteristics during inspiratory muscle training in patients with weaning difficulties.

Inspiratory muscle training (IMT) improves respiratory muscle function and might enhance weaning outcomes in patients with weaning difficulties. An electronic inspiratory loading device provides valid, automatically processed information on breathing characteristics during IMT sessions. Adherence to and quality of IMT, as reflected by work of breathing and power generated by inspiratory muscles, are related to improvements in inspiratory muscle function in patients with chronic obstructive pulmonary disease. The aim of this study was to investigate the validity of an electronic training device to assess and provide real-time feedback on breathing characteristics during inspiratory muscle training (IMT) in patient with weaning difficulties. Patients with weaning difficulties performed daily IMT sessions against a tapered flow-resistive load of approximately 30 to 50% of the patient's maximal inspiratory pressure. Airflow and airway pressure measurements were simultaneously collected with the training device (POWERbreatheKH2, POWERbreathe International Ltd, UK) and a portable spirometer (reference device, Pocket-Spiro USB/BT100, M.E.C, Belgium). Breath by breath analysis of 1002 breaths of 27 training sessions (n = 13) against a mean load of 46±16% of the patient's maximal inspiratory pressure were performed. Good to excellent agreement (Intraclass correlation coefficients: 0.73-0.97) was observed for all breathing characteristics. When individual differences were plotted against mean values of breaths recorded by both devices, small average biases were observed for all breathing characteristics. To conclude, the training device provides valid assessments of breathing characteristics to quantify inspiratory muscle effort (e.g. work of breathing and peak power) during IMT in patients with weaning difficulties. Availability of valid real-time data of breathing responses provided to both the physical therapist and the patient, can be clinically usefull to optimize the training stimulus. By adapting the external load based on the visual feedback of the training device, respiratory muscle work and power generation during IMT can be maximized during the training.

Training Specificity of Inspiratory Muscle Training Methods: A Randomized Trial.

INTRODUCTION: Inspiratory muscle training (IMT) protocols are typically performed using pressure threshold loading with inspirations initiated from residual volume (RV). We aimed to compare effects of three different IMT protocols on maximal inspiratory pressures (PImax) and maximal inspiratory flow (V̇Imax) at three different lung volumes. We hypothesized that threshold loading performed from functional residual capacity (FRC) or tapered flow resistive loading (initiated from RV) would improve inspiratory muscle function over a larger range of lung volumes in comparison with the standard protocol. METHODS: 48 healthy volunteers (42% male, age: 48 ± 9 years, PImax: 110 ± 28%pred, [mean ± SD]) were randomly assigned to perform three daily IMT sessions of pressure threshold loading (either initiated from RV or from FRC) or tapered flow resistive loading (initiated from RV) for 4 weeks. Sessions consisted of 30 breaths against the highest tolerable load. Before and after the training period, PImax was measured at RV, FRC, and midway between FRC and total lung capacity (1/2 IC). V̇Imax was measured at the same lung volumes against a range of external threshold loads. RESULTS: While PImax increased significantly at RV and at FRC in the group performing the standard training protocol (pressure threshold loading from RV), it increased significantly at all lung volumes in the two other training groups (all p < 0.05). No significant changes in V̇Imax were observed in the group performing the standard protocol. Increases of V̇Imax were significantly larger at all lung volumes after tapered flow resistive loading, and at higher lung volumes (i.e., FRC and 1/2 IC) after pressure threshold loading from FRC in comparison with the standard protocol (all p < 0.05). CONCLUSION: Only training with tapered flow resistive loading and pressure threshold loading from functional residual capacity resulted in consistent improvements in respiratory muscle function at higher lung volumes, whereas improvements after the standard protocol (pressure threshold loading from residual volume) were restricted to gains in PImax at lower lung volumes. Further research is warranted to investigate whether these results can be confirmed in larger samples of both healthy subjects and patients.

Cerebral cortex and respiratory muscles perfusion during spontaneous breathing attempts in ventilated patients and its relation to weaning outcomes: a protocol for a prospective observational study.

INTRODUCTION: In addition to the well-documented factors that contribute to weaning failure, increased energy demands of the respiratory muscles during spontaneous breathing trials (SBTs) might not be met by sufficient increases in energy supplies. This discrepancy may deprive blood and oxygen of other tissues. In this context, restrictions in perfusion of splanchnic organs and non-working muscles during SBT have been associated with weaning failure. However, alterations in perfusion of the brain during the weaning process are less well understood. OBJECTIVE AND HYPOTHESIS: To investigate whether cerebral cortex perfusion evolves differentially during the transition from mechanical ventilation (MV) to spontaneous breathing between patients failing or succeeding the SBT. We hypothesise that patients failing the SBT will exhibit reduced cerebral cortex perfusion during the transition from MV to spontaneous breathing as compared with patients succeeding the SBT. METHODS AND ANALYSIS: This single-centre, prospective, observational study will be conducted in a medical Intensive Care unit of University Hospital Leuven, Belgium in ready to wean patients. Blood flow index in the cerebral cortex (prefrontal area), inspiratory (scalene) and expiratory muscle (upper rectus abdominis) and a non-working muscle (thenar eminence) will be simultaneously assessed by near-infrared spectroscopy (NIRS) using the tracer indocyanine green dye. Measurements will be performed on the same day during MV and during SBT. NIRS-derived tissue oxygenation index and cardiac output (by pulse contour analyses) will be recorded continuously. Twenty patients failing an SBT are estimated to be sufficient for detecting a significant difference in the change of cerebral cortex perfusion from MV to SBT (primary outcome) between SBT failure and success patients. ETHICS AND DISSEMINATION: Ethics approval was obtained from the local ethical committee (Ethische Commissie Onderzoek UZ/KU Leuven protocol ID: S60516). Results from this study will be presented at scientific meetings and congresses and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03240263; Pre-results.

Can inspiratory muscle training improve weaning outcomes in difficult to wean patients? A protocol for a randomised controlled trial (IMweanT study).

INTRODUCTION: Respiratory muscle dysfunction has been associated with failure to wean from mechanical ventilation. It has therefore been hypothesised that these patients might benefit from inspiratory muscle training (IMT). Evidence, however, is thus far limited to data from small, single-centre studies with heterogeneity in inclusion criteria, training modalities and outcomes. The aim of this study is to evaluate the effects of a novel IMT method on weaning outcomes in selected patients with weaning difficulties. METHODS: This study is designed as a double-blind, parallel-group, randomised controlled superiority trial with 1:1 allocation ratio. Patients with weaning difficulties will be randomly allocated into either an IMT group (intervention) or a sham-IMT group (control). Ninetypatients (45 in each group) will be needed to detect a 28% difference in the proportion of weaning success between groups (estimated difference in primary outcome based on previous studies) with a risk for type I error (α) of 5% and statistical power (1-ß) of 80%. Patients will perform four sets of 6-10 breaths daily against an external load using a tapered flow resistive loading device (POWERbreathe KH2, HaB International, UK). Training intensity in the intervention group will be adjusted to the highest tolerable load. The control group will train against a low resistance that will not be modified during the training period. Training will becontinued until patients are successfully weaned or for a maximum duration of 28 days. Pulmonary and respiratory muscle function, weaning duration, duration of mechanical ventilation, ventilator-free days and length of stay in the intensive care unit will be evaluated as secondary outcomes. Χ2 tests and analysis of covariance with adjustments for baseline values of respective outcomesas covariates will be used to compare results after the intervention period between groups. ETHICS AND DISSEMINATION: Ethics approval was obtained from the local ethical committee (Ethische Commissie Onderzoek UZ/KU Leuven protocol ID: S60516). Results from this randomised controlled trial will be presented at scientific meetings as abstracts for poster or oral presentations and published in peerreviewed journals. TRIAL STATUS: Enrolment into the study have started in August 2017. Data collection and data analysis are expected to be completed in September 2021. TRIAL REGISTRATION NUMBER: NCT03240263.