An algorithm for discontinuing mechanical ventilation in boys with x-linked myotubular myopathy after positive response to gene therapy: the ASPIRO experience.

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy. Most (80%) children with XLMTM have profound muscle weakness and hypotonia at birth resulting in severe respiratory insufficiency, the inability to sit up, stand or walk, and early mortality. At birth, 85-90% of children with XLMTM require mechanical ventilation, with more than half requiring invasive ventilator support. Historically, ventilator-dependent children with neuromuscular-derived respiratory failure of this degree and nature, static or progressive, are not expected to achieve complete independence from mechanical ventilator support. In the ASPIRO clinical trial (NCT03199469), participants receiving a single intravenous dose of an investigational gene therapy (resamirigene bilparvovec) started showing significant improvements in daily hours of ventilation support compared with controls by 24 weeks post-dosing, and 16 of 24 dosed participants achieved ventilator independence between 14 and 97 weeks after dosing. At the time, there was no precedent or published guidance for weaning chronically ventilated children with congenital neuromuscular diseases off mechanical ventilation. When the first ASPIRO participants started showing dramatically improved respiratory function, the investigators initiated efforts to safely wean them off ventilator support, in parallel with primary protocol respiratory outcome measures. A group of experts in respiratory care and physiology and management of children with XLMTM developed an algorithm to safely wean children in the ASPIRO trial off mechanical ventilation as their respiratory muscle strength increased. The algorithm developed for this trial provides recommendations for assessing weaning readiness, a stepwise approach to weaning, and monitoring of children during and after the weaning process.

Outcomes of different pulmonary rehabilitation protocols in patients under mechanical ventilation with difficult weaning: a retrospective cohort study.

BACKGROUND: The endeavor of liberating patients from ventilator dependence within respiratory care centers (RCCs) poses considerable challenges. Multiple factors contribute to this process, yet establishing an effective regimen for pulmonary rehabilitation (PR) remains uncertain. This retrospective study aimed to evaluate existing rehabilitation protocols, ascertain associations between clinical factors and patient outcomes, and explore the influence of these protocols on the outcomes of the patients to shape suitable rehabilitation programs. METHODS: Conducted at a medical center in northern Taiwan, the retrospective study examined 320 newly admitted RCC patients between January 1, 2015, and December 31, 2017. Each patient received a tailored PR protocol, following which researchers evaluated weaning rates, RCC survival, and 3-month survival as outcome variables. Analyses scrutinized differences in baseline characteristics and prognoses among three PR protocols: protocol 1 (routine care), protocol 2 (routine care plus breathing training), and protocol 3 (routine care plus breathing and limb muscle training). RESULTS: Among the patients, 28.75% followed protocol 1, 59.37% protocol 2, and 11.88% protocol 3. Variances in age, body-mass index, pneumonia diagnosis, do-not-resuscitate orders, Glasgow Coma Scale scores (≤ 14), and Acute Physiology and Chronic Health Evaluation II (APACHE) scores were notable across these protocols. Age, APACHE scores, and abnormal blood urea nitrogen levels (> 20 mg/dL) significantly correlated with outcomes-such as weaning, RCC survival, and 3-month survival. Elevated mean hemoglobin levels linked to increased weaning rates (p = 0.0065) and 3-month survival (p = 0.0102). Four adjusted models clarified the impact of rehabilitation protocols. Notably, the PR protocol 3 group exhibited significantly higher 3-month survival rates compared to protocol 1, with odds ratios (ORs) ranging from 3.87 to 3.97 across models. This association persisted when comparing with protocol 2, with ORs between 3.92 and 4.22. CONCLUSION: Our study showed that distinct PR protocols significantly affected the outcomes of ventilator-dependent patients within RCCs. The study underlines the importance of tailored rehabilitation programs and identifies key clinical factors influencing patient outcomes. Recommendations advocate prospective studies with larger cohorts to comprehensively assess PR effects on RCC patients.

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.

Volatile anesthetics for lung- and diaphragm-protective sedation.

This review explores the complex interactions between sedation and invasive ventilation and examines the potential of volatile anesthetics for lung- and diaphragm-protective sedation. In the early stages of invasive ventilation, many critically ill patients experience insufficient respiratory drive and effort, leading to compromised diaphragm function. Compared with common intravenous agents, inhaled sedation with volatile anesthetics better preserves respiratory drive, potentially helping to maintain diaphragm function during prolonged periods of invasive ventilation. In turn, higher concentrations of volatile anesthetics reduce the size of spontaneously generated tidal volumes, potentially reducing lung stress and strain and with that the risk of self-inflicted lung injury. Taken together, inhaled sedation may allow titration of respiratory drive to maintain inspiratory efforts within lung- and diaphragm-protective ranges. Particularly in patients who are expected to require prolonged invasive ventilation, in whom the restoration of adequate but safe inspiratory effort is crucial for successful weaning, inhaled sedation represents an attractive option for lung- and diaphragm-protective sedation. A technical limitation is ventilatory dead space introduced by volatile anesthetic reflectors, although this impact is minimal and comparable to ventilation with heat and moisture exchangers. Further studies are imperative for a comprehensive understanding of the specific effects of inhaled sedation on respiratory drive and effort and, ultimately, how this translates into patient-centered outcomes in critically ill patients.

Impact of sleep disturbances on outcomes in intensive care units.

BACKGROUND: Sleep deprivation is common in intensive care units (ICUs) and may alter respiratory performance. Few studies have assessed the role of sleep disturbances on outcomes in critically ill patients. OBJECTIVES: We hypothesized that sleep disturbances may be associated with poor outcomes in ICUs. METHODS: Post-hoc analysis pooling three observational studies assessing sleep by complete polysomnography in 131 conscious and non-sedated patients included at different times of their ICU stay. Sleep was assessed early in a group of patients admitted for acute respiratory failure while breathing spontaneously (n = 34), or under mechanical ventilation in patients with weaning difficulties (n = 45), or immediately after extubation (n = 52). Patients admitted for acute respiratory failure who required intubation, those under mechanical ventilation who had prolonged weaning, and those who required reintubation after extubation were considered as having poor clinical outcomes. Durations of deep sleep, rapid eye movement (REM) sleep, and atypical sleep were compared according to the timing of polysomnography and the clinical outcomes. RESULTS: Whereas deep sleep remained preserved in patients admitted for acute respiratory failure, it was markedly reduced under mechanical ventilation and after extubation (p < 0.01). Atypical sleep was significantly more frequent in patients under mechanical ventilation than in those breathing spontaneously (p < 0.01). REM sleep was uncommon at any time of their ICU stay. Patients with complete disappearance of REM sleep (50% of patients) were more likely to have poor clinical outcomes than those with persistent REM sleep (24% vs. 9%, p = 0.03). CONCLUSION: Complete disappearance of REM sleep was significantly associated with poor clinical outcomes in critically ill patients.

Pressure Support Ventilation Versus T-piece as Spontaneous Breathing Trials for Extubation of Patients with Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Weaning patients with COPD from mechanical ventilation (MV) presents a challenge, as literature on this topic is limited. This study compares PSV and T-piece during spontaneous breathing trials (SBT) in this specific population. METHODS: A search of PubMed, EMBASE, and Cochrane in September 2023 yielded four randomized controlled trials (RCTs) encompassing 560 patients. Among these, 287 (51%) used T-piece during SBTs. RESULTS: The PSV group demonstrated a significant improvement in the successful extubation rate compared to the T-piece (risk ratio [RR] 1.14; 95% confidence interval [CI] 1.03-1.26; p = 0.02). Otherwise, there was no statistically significant difference in the reintubation (RR 1.07; 95% CI 0.79-1.45; p = 0.67) or the ICU mortality rates (RR 0.99; 95% CI 0.63-1.55; p = 0.95). CONCLUSION: Although PSV in SBTs exhibits superior extubation success, consistent weaning protocols warrant further exploration through additional studies.

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

The diaphragmatic electrical activity during spontaneous breathing trial in patients with mechanical ventilation: physiological description and potential clinical utility.

BACKGROUNDS: Increased respiratory drive has been demonstrated to correlate with weaning failure, which could be quantified by electrical activity of the diaphragm (EAdi). We described the physiological process of EAdi-based parameters during the spontaneous breathing trial (SBT) and evaluated the change of EAdi-based parameters as potential predictors of weaning failure. METHODS: We conducted a prospective study in 35 mechanically ventilated patients who underwent a 2-hour SBT. EAdi and ventilatory parameters were continuously measured during the SBT. Diaphragm ultrasound was performed before the SBT and at the 30 min of the SBT. Three EAdi-based parameters were calculated: neuro-ventilatory efficiency, neuro-excursion efficiency and neuro-discharge per min. RESULTS: Of the thirty 35 patients studied, 25 patients were defined as SBT success, including 22 patients weaning successfully and 3 patients reintubated. Before the SBT, neuro-excursion efficiency differed significantly between two groups and had the highest predictive value for SBT failure (AUROC 0.875, p < 0.01). Early increases in EAdi were observed in SBT, which are more prominent in SBT failure group. One minute, changes in EAdi and neuro-discharge per min also predicted weaning outcome (AUROCs 0.944 and 0.918, respectively). CONCLUSIONS: EAdi-based parameters, especially neuro-excursion efficiency and changes in neuro-discharge per min, may detect impending weaning failure earlier than conventional indices. EAdi monitoring provides physiological insights and a more tailored approach to facilitate successful weaning. Further research should validate these findings and explore the utility of combined EAdi and diaphragm ultrasound assessment in weaning ICU patients from mechanical ventilation. TRIAL REGISTRATION: Registered at ClinicalTrials.gov on 20 September 2022 (Identifier: NCT05632822).

Ultrasonography to Access Diaphragm Dysfunction and Predict the Success of Mechanical Ventilation Weaning in Critical Care: A Narrative Review.

INTRODUCTION: Weaning failure is common in mechanically ventilated patients, and whether ultrasound (US) can predict weaning outcome remains controversial. This review aims to evaluate the diaphragmatic function measured by US as a predictor of weaning outcome. METHODS: PubMed was searched to identify original articles about the use of diaphragmatic US in ICU patients. A total of 61 citations were retrieved initially; available data of 26 studies were included in this review. RESULTS: To assess diaphragmatic dysfunction in adults, six studies evaluated excursion, five evaluated thickening fraction, and both in nine. Despite heterogeneity in the diagnostic accuracy of diaphragm US among the studies, the sonographic indices showed good diagnostic performance for predicting weaning outcome. CONCLUSIONS: Diaphragmatic US can be a useful and accurate tool to detect diaphragmatic dysfunction in critically ill patients and predict weaning outcome.

Predictive Value of Diaphragm Muscle Ultrasound for Ventilator Weaning Outcomes After Cervical Spinal Cord Injury: A Retrospective Case Series.

OBJECTIVES: Neuromuscular respiratory failure after cervical spinal cord injury (cSCI) can lead to dependence on an invasive mechanical ventilator. Ventilator-free breathing after cSCI is associated with improved morbidity, mortality, and quality of life. We investigated the use of diaphragm muscle ultrasound to predict ventilator weaning outcomes after cSCI. METHODS: This is a retrospective case series conducted at a university-affiliated freestanding inpatient rehabilitation facility. We identified patients with cSCI who had a tracheostomy and were dependent on an invasive mechanical ventilator at the time of admission to inpatient rehabilitation. A diaphragm muscle ultrasound was performed, which included measurements of the thickness of the diaphragm and a calculation of the thickening ratio (TR), which reflects diaphragm muscle contraction. The primary outcome measure was the need for mechanical ventilation at time of discharge from the inpatient rehabilitation facility. Successful ventilator weaning was defined as either daytime or full 24-hour ventilator-free breathing. RESULTS: Of the 21 patients enrolled, 11 (52%) were able to wean successfully (partially or fully) from the ventilator. Of the ultrasound measurements that were taken, the TR was the optimal predictor for ventilator weaning outcomes. A threshold of TR ≥ 1.2 as the maximum hemidiaphragm measurement had a sensitivity of 1.0 and specificity of 0.90 for predicting ventilator weaning. CONCLUSION: Normal diaphragm contractility (TR ≥ 1.2) as determined by diaphragm muscle ultrasound is a strong positive predictor for successful ventilator weaning in patients with cSCI. Utilizing diaphragm ultrasound, rehabilitation physicians can set precision rehabilitation goals regarding ventilator weaning for inpatients with respiratory failure after cSCI, potentially improving both outcomes and quality of life.

Comparative impact of COVID-19 infection on tracheostomy patients.

PURPOSE: We study outcomes after tracheostomy in COVID-19 positive patients versus COVID-19 negative patients who underwent tracheostomy during the same time frame in an effort to better understand the influence of COVID-19 despite variances in virus strain and treatment practices. MATERIALS AND METHODS: This is a retrospective cohort study of all Veterans Affairs centers nationwide, using data provided by the Veterans Affairs Informatics and Computing Infrastructure. Our cohort consisted of veteran patients who underwent tracheostomy between March 2020 and September 2022. Patients who tested positive for COVID-19 within three months prior to tracheostomy were compared to patients who had never tested positive for COVID-19. RESULTS: 956 patients were included in the analysis, and nearly 96 % of these patients were male. The COVID-19 positive group spent one more week on the ventilator and experienced lower rates of successful ventilator weaning (hazard ratio 0.74, 95 % confidence interval [0.62, 0.88], P < 0.001). Survival curves were non-proportional, and while the COVID-19 positive group had higher 30-day mortality (relative risk 1.37, 95 % confidence interval [1.09, 1.73], P = 0.007), the COVID-19 negative group had higher long-term mortality. CONCLUSIONS: Our findings suggest that while infection with COVID-19 has a significant effect on short-term outcomes after tracheostomy, chronic comorbidities seem to have the more enduring impact. In spite of prolonged ventilation and higher short-term mortality, tracheostomy in COVID-19 can be a positive intervention that does not necessarily predestine patients to the same level of long-term morbidity and mortality of typical tracheostomies.

Ultrasonographic evaluation of diaphragm thickness and excursion: correlation with weaning success in trauma patients: prospective cohort study.

PURPOSE: Prolonged mechanical ventilation (MV) subjects multiple trauma patients to ventilator-induced diaphragmatic dysfunction. There is limited evidence on the predictive role of diaphragm ultrasound (DUS) for weaning success in multiple trauma patients. Therefore, we evaluated Ultrasound of the diaphragm as a valuable indicator of weaning outcomes, in trauma patients. MATERIAL AND METHODS: This prospective cohort study included 50 trauma patients from September 2018 to February 2019. DUS was performed twice: upon ICU admission and the first weaning attempt. The diagnostic accuracy of indexes was evaluated by ROC curves. RESULTS: The study included patients with a mean age of 35.4 ± 17.37, and 78% being male. The median injury severity score was 75 (42-75). The failure group exhibited significantly lower right diaphragmatic excursion (DE) compared to the success group (P = 0.006). In addition, the failure group experienced a significant decrease in both right and left DE from admission to the first attempt of weaning from MV (P < 0.001). Both groups showed a significant decrease in inspiratory and expiratory thickness on both sides during weaning from MV compared to the admission time (P < 0.001). The findings from the ROC analysis indicated that the Rapid shallow breathing index (RSBI) (Sensitivity = 91.67, Specificity = 100), respiratory rate (RR)/DE (Right: Sensitivity = 87.5, Specificity = 92.31), and RR/TF (Thickening Fraction) (Right: Sensitivity = 83.33, Specificity = 80.77) demonstrated high sensitivity and specificity in predicting weaning outcome. CONCLUSION: In the context of patients with multiple trauma, employing DUC and assessing diaphragmatic excursion, thickness, RR/DE index, RR/TF index, and RSBI can aid in determining successful ventilator weaning.

Weaning-associated interventions for ventilated intensive care patients: A scoping review.

BACKGROUND: Mechanical ventilation is a core intervention in critical care, but may also lead to negative consequences. Therefore, ventilator weaning is crucial for patient recovery. Numerous weaning interventions have been investigated, but an overview of interventions to evaluate different foci on weaning research is still missing. AIM: To provide an overview of interventions associated with ventilator weaning. STUDY DESIGN: We conducted a scoping review. A systematic search of the Medline, CINAHL and Cochrane Library databases was carried out in May 2023. Interventions from studies or reviews that aimed to extubate or decannulate mechanically ventilated patients in intensive care units were included. Studies concerning children, outpatients or non-invasive ventilation were excluded. Screening and data extraction were conducted independently by three reviewers. Identified interventions were thematically analysed and clustered. RESULTS: Of the 7175 records identified, 193 studies were included. A total of six clusters were formed: entitled enteral nutrition (three studies), tracheostomy (17 studies), physical treatment (13 studies), ventilation modes and settings (47 studies), intervention bundles (42 studies), and pharmacological interventions including analgesic agents (8 studies), sedative agents (53 studies) and other agents (15 studies). CONCLUSIONS: Ventilator weaning is widely researched with a special focus on ventilation modes and pharmacological agents. Some aspects remain poorly researched or unaddressed (e.g. nutrition, delirium treatment, sleep promotion). RELEVANCE TO CLINICAL PRACTICE: This review compiles studies on ventilator weaning interventions in thematic clusters, highlighting the need for multidisciplinary care and consideration of various interventions. Future research should combine different interventions and investigate their interconnection.

Inspiratory muscle training for mechanically ventilated patients in the intensive care unit: Obstacles and facilitators for implementation. A mixed method quality improvement study.

BACKGROUND: Mechanically ventilated patients are at risk of developing inspiratory muscle weakness (IMW), which is associated with failure to wean and poor outcomes. Inspiratory muscle training (IMT) is a recommended intervention during and after extubation but has not been widely adopted in Dutch intensive care units (ICUs). OBJECTIVES: The objective of this study was to explore the potential, barriers, and facilitators for implementing IMT as treatment modality for mechanically ventilated patients. METHODS: This mixed-method, proof-of-concept study was conducted in a large academic hospital in the Netherlands. An evidence-based protocol for assessing IMW and training was applied to patients ventilated for ≥24 h in the ICU during an 8-month period in 2021. Quantitative data on completed measurements and interventions during and after ICU-stay were collected retrospectively and were analysed descriptively. Qualitative data were collected through semistructured interviews with physiotherapists executing the new protocol. Interview data were transcribed and thematically analysed. FINDINGS: Of the 301 screened patients, 11.6% (n = 35) met the inclusion criteria. Measurements were possible in 94.3% of the participants, and IMW was found in 78.8% of the participants. Ninety-six percent started training in the ICU, and 88.5% continued training after transfer to the ward. Follow-up measurements were achieved in 73.1% of the patients with respiratory muscle weakness. Twelve therapists were interviewed, of whom 41.7% regularly worked in the ICU. When exploring reasons for protocol deviation, three themes emerged: "professional barriers", "external factors", and "patient barriers". CONCLUSIONS: Implementation of measurements of and interventions for IMW showed to be challenging in this single centre study. Clinicians' willingness to change their handling was related to beliefs regarding usefulness, effectiveness, and availability of time and material. We recommend that hospitals aiming to implement IMT during or after ventilator weaning consider these professional and organisational barriers for implementation of novel, evidence-based interventions into daily clinical practice.

Physicians' decision making when weaning patients from mechanical ventilation: A qualitative content analysis.

BACKGROUND: Weaning from mechanical ventilation is a complex and central intensive care process. This complexity indicates that the challenges of weaning must be explored from different perspectives. Furthermore, physicians' experiences and the factors influencing their decision-making regarding weaning are unclear. OBJECTIVES: This study aimed to explore and describe the factors influencing physicians' decision-making when weaning patients from invasive mechanical ventilation in Swedish intensive care units (ICUs). METHODS: This qualitative study used an exploratory and descriptive design with qualitative content analysis. Sixteen physicians from five ICUs across Sweden were purposively included and interviewed regarding their weaning experiences. FINDINGS: The physicians expressed that prioritising the patient's well-being was evident, and there was agreement that both the physical and mental condition of the patient had a substantial impact on decision-making. Furthermore, there was a lack of agreement on whether patients should be involved in the weaning process and how their resources, needs, and wishes should be included in decision-making. In addition, there were factors not directly linked to the patient but which still influenced decision-making, such as the available resources and teamwork. Sometimes, it was difficult to point out the basis for decisions; in that decisions were made by gut feeling, intuition, or clinical experience. CONCLUSION: Physicians' decision-making regarding weaning was a dynamic process influenced by several factors. These factors were related to the patient's condition and the structure for weaning. Increased understanding of weaning from the physicians' and ICU teams' perspectives may improve the weaning process by broadening the knowledge about the aspects influencing the decision-making.

Mechanical Power Density Predicts Prolonged Ventilation Following Double Lung Transplantation.

Prolonged mechanical ventilation (PMV) after lung transplantation poses several risks, including higher tracheostomy rates and increased in-hospital mortality. Mechanical power (MP) of artificial ventilation unifies the ventilatory variables that determine gas exchange and may be related to allograft function following transplant, affecting ventilator weaning. We retrospectively analyzed consecutive double lung transplant recipients at a national transplant center, ventilated through endotracheal tubes upon ICU admission, excluding those receiving extracorporeal support. MP and derived indexes assessed up to 36 h after transplant were correlated with invasive ventilation duration using Spearman's coefficient, and we conducted receiver operating characteristic (ROC) curve analysis to evaluate the accuracy in predicting PMV (>72 h), expressed as area under the ROC curve (AUROC). PMV occurred in 82 (35%) out of 237 cases. MP was significantly correlated with invasive ventilation duration (Spearman's ρ = 0.252 [95% CI 0.129-0.369], p < 0.01), with power density (MP normalized to lung-thorax compliance) demonstrating the strongest correlation (ρ = 0.452 [0.345-0.548], p < 0.01) and enhancing PMV prediction (AUROC 0.78 [95% CI 0.72-0.83], p < 0.01) compared to MP (AUROC 0.66 [0.60-0.72], p < 0.01). Mechanical power density may help identify patients at risk for PMV after double lung transplantation.

Subjective Assessment of Motor Function by the Bedside Nurses in Mechanically Ventilated Surgical Intensive Care Unit Patients Predicts Tracheostomy.

OBJECTIVE: In many institutions, intensive care unit (ICU) nurses assess their patients' muscle function as part of their routine bedside examination. We tested the research hypothesis that this subjective examination of muscle function prior to extubation predicts tracheostomy requirement. METHODS: Adult, mechanically ventilated patients admitted to 7 ICUs at Beth Israel Deaconess Medical Center (BIDMC) between 2008 and 2019 were included in this observational study. Assessment of motor function was performed every four hours by ICU nurses. Multivariable logistic regression analysis controlled for acute disease severity, delirium risk assessment through the confusion assessment method for the ICU (CAM-ICU), and pre-defined predictors of extubation failure was applied to examine the association of motor function and tracheostomy within 30 days after extubation. RESULTS: Within 30 days after extubation, 891 of 9609 (9.3%) included patients required a tracheostomy. The inability to spontaneously move and hold extremities against gravity within 24 h prior to extubation was associated with significantly higher odds of 30-day tracheostomy (adjusted OR 1.56, 95% CI 1.27-1.91, p < 0.001, adjusted absolute risk difference (aARD) 2.8% (p < 0.001)). The effect was magnified among patients who were mechanically ventilated for >7 days (aARD 21.8%, 95% CI 12.4-31.2%, p-for-interaction = 0.015). CONCLUSIONS: ICU nurses' subjective assessment of motor function is associated with 30-day tracheostomy risk, independent of known risk factors. Muscle function measurements by nursing staff in the ICU should be discussed during interprofessional rounds.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

Modifiable risk factors for ventilator associated diaphragmatic dysfunction: a multicenter observational study.

BACKGROUND: Diaphragmatic dysfunction is known to be associated with difficulties weaning from invasive mechanical ventilation and is related to worse patient outcomes yet our understanding of how to prevent diaphragmatic dysfunction remains incomplete. We examined potentially modifiable risk factors for diaphragmatic dysfunction and attempted to estimate benefits attributable to altering these modifiable risk factors. METHODS: This prospective multicenter observational study was undertaken in the general ICUs of two tertiary care teaching hospitals. Critically ill adults expected to receive invasive mechanical ventilation for at least 48 h were enrolled. Diaphragm function was assessed by ultrasound each study day, with dysfunction defined as thickening fraction less than 20%. RESULTS: From January to December 2019, 856 patients were screened and 126 patients were enrolled. Overall, 40.5% (51/126) of patients experienced diaphragmatic dysfunction during invasive mechanical ventilation. Patients with diaphragmatic dysfunction were more likely to develop ventilator associated pneumonia (risk difference [RD] + 12.9%, 95% Confidence Interval [CI] 1.4 to 24.4%, P = 0.028), were more likely to experience extubation failure (RD + 8.5%, 95% CI 0.4 to 16.6%, P = 0.039) and required a longer duration of invasive mechanical ventilation (RD + 1.3 days, 95% CI 0.1 to 2.5 days, P = 0.035). They also required a longer hospital stay (RD + 1.2 days, 95% CI 0.04 to 2.4 days, P = 0.041) and were more likely to die before hospital discharge (RD + 18.1%, 95% CI 3.7 to 32.5%, P = 0.014). Multivariable analysis considered the impact of age, sex, pre-existing nutritional status, caloric intake, amino acid intake, acute disease severity, modes of mechanical ventilation, measures of respiratory status, sedation, pain control and baseline diaphragm thickness. Only SOFA score (P = 0.008) and early amino acid intake (P = 0.001) remained significant independent risk factors for the onset of diaphragmatic dysfunction. Causal path modeling suggested early amino acid intake may significantly reduce diaphragmatic dysfunction (RRR 29%, 95% CI 10% to 48%, P = 0.003) and may also reduce mortality (RRR 49%, 95% CI 25% to 73%, P < 0.0001). CONCLUSIONS: Amino acid intake during the first 24 h of ICU stay may represent an important, modifiable risk factor for diaphragmatic dysfunction and may have a direct causal effect on mortality. We recommend additional research on this topic.

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.