Clinical Research Directory

Improving Our Understanding of Respiratory Muscle Training to Facilitate Weaning From Mechanical Ventilation in the ICU

Mechanical ventilation is a life-saving treatment frequently applied in intensive care unit (ICU). Nonetheless, by putting at rest the respiratory muscles, it can lead to respiratory muscle weakness and atrophy, which are accompanied by prolonged duration of mechanical ventilation, difficult weaning and increased ICU mortality. Despite a strong theoretical rationale and some evidence supporting the use of inspiratory muscle training (IMT) to address respiratory muscle weakness and atrophy, the optimal approach to IMT remains largely uncertain. In fact, mechanistic studies evaluating physiological adaptations that occur in respiratory muscles of mechanically ventilated patients in response to different training regimens have not been conducted so far. The aim of this study is to comprehensively investigate changes in respiratory muscle function in response to three different conditions that patients will be exposed to during their period of weaning from mechanical ventilation.

Characterization of Weaning Practices in ICUs of Global South Countries

This is a prospective observational study to be conducted in intensive care units of Global South countries. Patients on mechanical ventilation for more than 12 hours who have initiated the weaning process and for whom the attending team plans extubation within the next 6 hours will be included. Data will be collected for each patient during the first 7 days after extubation, with follow-up until hospital discharge or death. We plan to conduct the study in intensive care units from Global South countries (low- and middle-income countries predominantly located in the Southern Hemisphere, though some in the Northern Hemisphere are also considered).

Evaluation of heepSync, a Novel Algorithm for Transcutaneous Electrical Stimulation of Respiratory Muscles in Mechanically Ventilated Patients.

Up to 76% of ICU patients on mechanical ventilation develop significant respiratory muscle atrophy within the first 24 hours, contributing to prolonged ventilation, increased morbidity, and higher healthcare costs. To date, there is no practical, non-invasive technology that offers synchronized, personalized electrostimulation for both inspiratory and expiratory muscles during mechanical ventilation. Heecap is a medical product designed to provide transcutaneous electrical stimulation of the respiratory muscles (TERM) that are involved in inspiration and expiration, detecting those in which it is clinically relevant and safe to provide such stimulation in assisted respiration. The following study aims to evaluate the safety and preliminary performance of the stimulation algorithm in mechanically ventilated patients in the ICU. This evaluation will specifically focus on the algorithm's ability to synchronize stimulation with the patient's breathing patterns, and on evaluating the safety and feasibility of the TERM in activating respiratory muscles.

Quantification of Systemic Congestion by Ultrasound As a Predictor of Weaning Failure From Mechanical Ventilation

Mechanical ventilation is an essential, life-saving therapy in the ICU, allowing critically ill patients to rest and recover. Transitioning patients back to spontaneous breathing-known as weaning-is clinically challenging. The first attempt, the Spontaneous Breathing Trial (SBT), fails in 10-30% of cases. Identifying the mechanisms behind failure is crucial, as unsuccessful weaning prolongs ICU stay and increases the risk of reintubation, which worsens prognosis. The SCOUT study aims to improve prediction and management of weaning failure. The main objective of the study is to evaluate whether a specific ultrasound-based method, the Venous Excess Ultrasound Score (VExUS), can predict failure of weaning from mechanical ventilation. A key pathophysiological factor is systemic venous congestion. When a patient initiates an SBT, the increased respiratory effort shifts venous return and may precipitate cardiovascular decompensation with pulmonary fluid accumulation, termed weaning-induced pulmonary edema (WIPO). Notably, this may occur even in patients without known cardiac disease. Detecting clinically relevant congestion before SBT is difficult. Fluid balance and body weight are imprecise, physical examination lacks sensitivity, and biomarkers such as NT-proBNP have limited predictive capacity. VExUS offers a promising, non-invasive approach by directly assessing venous flow patterns in major veins (inferior vena cava, hepatic, portal, and renal veins), providing an estimation of systemic venous pressure and congestion. The central hypothesis is that elevated VExUS grades prior to SBT will identify patients at high risk of failure, enabling proactive optimization and potentially improving outcomes. SCOUT is designed as a prospective, multicenter, observational study. Standard clinical management of mechanical ventilation and weaning remains unchanged. After informed consent, baseline data will be obtained immediately before SBT, including vital signs, ventilator parameters, blood sampling, and three non-invasive ultrasound assessments: cardiac, pulmonary, and VExUS. During the 30-120-minute SBT, the patient breathes with reduced ventilatory support while their clinical tolerance is evaluated. At the end of the SBT, selected measurements are repeated. Weaning failure is defined as: early termination of SBT due to intolerance, need for invasive or non-invasive ventilation within 48 h after extubation, or death within 48 h. Data are anonymized and stored securely (REDCap) in compliance with Spanish and EU data protection regulations. The study is low-risk and provides no direct individual benefit, but may benefit future ICU patients by improving weaning strategies and prognostication.

Shorter Weaning From Invasive Ventilation With Levosimendan

Prolonged weaning from mechanical ventilation is a common and serious challenge in the ICU, associated with increased morbidity, mortality, and length of stay. Diaphragm dysfunction plays a key role in weaning failure, and current strategies to support respiratory muscle function are limited. Levosimendan is a calcium sensitizer that enhances cardiac and skeletal muscle contractility, including the diaphragm, without increasing oxygen demand. The investigators hypothesize that treatment with Levosimendan in difficult-to-wean ICU patients will improve diaphragm function and thereby shorten the duration of mechanical ventilation compared to placebo.

The Value of Repeated BIOMarker Measurements During an SBT to Predict EXtubation Failure in ICU Patients

The Value of Repeated BIOMarker Measurements During an SBT to Predict EXtubation Failure in Mechanically Ventilated ICU Patients

Surface Electrical Myography, Oxygen Consumption, Effort, and Weaning in the Mechanically Ventilated Patient in the Intensive Care Unit

The goal of this observational study is to measure effort using esophageal pressure measurements, oxygen consumption and diaphragm activity in mechanically ventilated Intensive Care Unit patients during a Spontaneous Breathing Trial. The main question aims to answer whether the sEMG signal derived from the SERA device, effort parameters and oxygen consumption have an association with weaning failure. Participants will be measured while performing a spontaneous breathing trial.

Role of Regional Lung Compliance and Dynamic Transpulmonary Driving Pressure in the Liberation Difficulty in Tracheostomized Patients Receiving Prolonged Mechanical Ventilation

This project focuses on the analysis of the correlation between transpulmonary driving pressure and uneven lung ventilation and regional lung compliance in patients using prolonged mechanical ventilation (PMV), in order to understand the clinical occurrence of failure of the final spontaneous breathing test and inability to breathe. Respiratory physiology impairments in patients successfully discharged from respirators.

Effect of Hypophosphatemia on Neuro-excursion Efficiency During Mechanical Ventilator Weaning

Hypophosphatemia is a common phenomenon in the ICU, and several retrospective studies have shown that hypophosphatemia is associated with prolonged mechanical ventilation in ICU patients. However, the specific mechanism and causal relationship are not clear. Previous studies have shown that phosphate infusion improves the contraction of the diaphragm induced by exogenous electrical stimulation, but the effect of hypophosphatemia and phosphate supplementation on the pathophysiology in decannulated patients on mechanical ventilation has not been confirmed. The study group hypothesized that hypophosphatemia affects neural conduction function and muscle contraction by affecting ATP synthesis. Correcting hypophosphatemia may improve respiratory muscle strength and potentially improve diaphragmatic neural conduction, ultimately improving the patient's neuromuscular conversion efficiency and facilitating discharge. 1. The attending physician evaluates the patient's ventilator condition daily and meets the disconnection criteria (spontaneous breathing, RSBI \< 105 (min\*ml)-1, stable hemodynamics: norepinephrine or epinephrine ≤ 0.1μg/kg/min, PEEP ≤ 8cmH2O, FiO2 ≤ 50%, no increase in ventilator support conditions in the past 24 hours, PS 10cmH2O, MAAS score 2-4, pH ≥ 7.30, discontinuation of all sedative medications). After signing an informed consent form, a diaphragm electromyography (EEG) catheter is placed. (The diaphragm EEG catheter is a gastric tube with diaphragm electromyography monitoring function, with the same placement process and risks as a regular gastric tube. There is a small probability of complications such as nasal mucosal damage.) 2. Start CPAP disconnection: Adjust the ventilator PS 10 → 0 cmH2O, and keep the other conditions unchanged. Collect ventilator parameters, diaphragm electromyography (EAdi) parameters, and diaphragm ultrasound parameters at 0, 1, 3, 5, 10, 20, and 30 minutes after the trial begins, and collect the maximum EAdi and diaphragm ultrasound during quiet state. 3. Simultaneously monitor blood inorganic phosphorus, and divide the patients into two groups: the low phosphorus group (\<0.8mmol/L) and the control group (0.8-1.4 mmol/L). Low phosphorus patients receive intravenous phosphate supplementation according to the clinical phosphate supplementation protocol at our center \[1-5\]: patients with blood phosphorus \< 0.4mmol/L receive 40mmol of glycerol phosphate sodium intravenously via infusion or injection over 4-6 hours; patients with blood phosphorus 0.4-0.8mmol/L receive 30mmol of glycerol phosphate sodium intravenously via infusion or injection; Normal phosphorus patients do not require any special treatment. 4. 24h after the first CPAP offline, patients in both groups repeated the CPAP offline process, collected related parameters, and measured blood inorganic phosphorus.

PREdicting Failure of Non-inVasIve Ventilatory Support Using Non-invaSIve mONitoring in Non-intubated Patients With Acute Hypoxemic Respiratory Failure or Post-extubation Failure. The PREVISION Study

The goal of this observational study is to assess the potential non-invasive tools (e.g. regional ventilation, respiratory muscle response, lung mechanic's parameters) to identify the risk of failure when using high flow nasal cannula (HFNC) or non-invasive ventilation (NIV). The main question, it aims to answer is: Does abnormal regional ventilation could predict HFNC or NIV failure?

Ventilatory Settings and Monitoring Variables Associated With Weaning Failure in Critically Ill Patients

Mechanical ventilation (MV) is essential in managing acute respiratory failure. Its duration is a crucial aspect since both, unnecessary prolongation and premature withdrawal have deleterious effects on patient outcomes in the ICU. The process of weaning refers to the set of procedures and evaluations carried out to discontinue MV. Regardless of the definition used, within the population undergoing weaning, there is a group of patients who successfully pass the daily screening but fail the spontaneous breathing trial (SBT) or the separate attempt (SA). In Argentina, this figure is 39.5%, and 31.4% in patients with COVID-19. On the other hand, another group of patients successfully passes the SA, is extubated, but fails in post-extubation. This failure rate varies in the literature, ranging from approximately 10 to 20%. In our country, this figure is 16% in the general population and rises to 29.7% in COVID-19 patients. Additionally, this population is divided into those who cannot tolerate ventilation without an artificial airway due to upper airway patency issues (such as laryngeal edema), i.e., "airway failure," and those who experience acute respiratory failure. In 2023, the WEAN SAFE study reported novel findings regarding variables associated with weaning failure. In multivariable analysis, it was found that the MV settings and monitoring variables at the time of the first SBT - respiratory rate, positive end-expiratory pressure (PEEP), dynamic airway pressure difference (peak pressure (Ppeak) minus PEEP) on the day of the SA - were associated with weaning failure. In this context, the investigators will conduct a retrospective cohort study, whose primary objective will be to assess which MV settings and monitoring variables are associated with weaning failure. \*\*Primary Objective\*\* To determine if there are any MV settings or monitoring variables that are associated with extubation failure. \*\*Secondary Objective\*\* To determine if there are any MV settings or monitoring variables that are associated with failure in the first SBT.

TESTO-TRIAL: Use of Testosterone in Critically Ill Patients

The objective of this study is to evaluate whether the use of the anabolic agent testosterone cypionate in critically ill patients, compared to placebo, increases the number of ventilator-free days

Estimation of the Diaphragm Electrical Activity and Intercostal Thickening Fraction During Different Pattern of Mechanical Ventilation: PSV Versus NAVA

the introduction of new MV modalities has shown promising results in reducing the incidence of weaning failure, mainly due to a more physiologic approach which allows respiratory muscle preservation. Among them, the Neurally Adjust Ventilatory Assist (NAVA) seemed to be associated with lower incidence of weaning failure and subsequent duration of mechanical ventilation, compared to standard modalities like the Pressure Support Ventilation (PSV) . Moreover, NAVA allows the evaluation of the diaphragm electrical activity (EAdi), an index of diaphragmatic neural respiratory drive. However, no study has compared TFic values during PSV and NAVA modalities in patients with difficult weaning from MV admitted in ICU.

Predictive Value of Airway Occlusion Pressure, Maximal Inspiratory Pressure and Their Ratio for Successful Extubation in Patients With Traumatic Brain Injury

The aim of this study will be to measure the predictive power of the respiratory muscle determinants including The maximal inspiratory pressure, and central drive determinant including Airway occlusion pressure and ratio between them in weaning outcome of traumatic brain injury patients undergoing invasive mechanical ventilation.

Oxygen Consumption (VO2), Effort, and Weaning in the Mechanically Ventilated Patient in the Intensive Care Unit (ICU)

In patients who are mechanically ventilated for more than 72 hours weaning failure is a common issue. The Spontaneous breathing trial (SBT) is often done to assess if the patient can be extubated with a high chance of success. However, re-intubation rates are between 15 - 20 % after a successful SBT. The rapid shallow breathing index (RSBI) is an important parameter used in an SBT. Because the high incidence of extubation failure (re-intubation within 48 hours) a search for a better parameter than the RSBI is warranted. Using the measured end-tidal oxygen (etO2) of mechanically ventilated patients it is possible to calculate the VO2, which is a measure of patient effort. The VO2 is a parameter with the potential to predict weaning success or failure, together with other parameters of patient effort like the work of breathing (WOB), pressure time product (PTP) and esophageal pressure swings, reflecting muscle strength of the diaphragm. Therefore, the investigators want to investigate if these parameters are associated with an SBT success or failure.

Extremes of Respiratory Effort in Weaning Failure From Mechanical Ventilation: a Prospective Observational Study

The presence of high levels of respiratory effort in patients under mechanical ventilation may worsen the adjacent lung injury even after adapting protective ventilation. Primary outcome: To evaluate the failure rate of weaning from IMV and its relationship with the lower and upper extremes of respiratory effort and the upper extreme of dynamic pulmonary stress during the first 7 days of spontaneous ventilation. Analyze the influence of these extremes based on the thresholds of Pocc, P0.1 and their derivatives Pmus, Ptp, din and MP: in relation to days off MV (in the 28-day interval); Total weaning time; Rate and time for tracheostomy; Length of stay in the ICU and hospital; In-hospital mortality rate. CAAE: 78185823.4.0000.5249. Prospective multicenter observational study, carried out in the ICUs of Glória D'or and Niteroi D'or hospitals, from January 2024 to July 2026, in patients over 18 years old, undergoing orotracheal intubation and IMV, in their first 7 days on spontaneous ventilation. Hypothesis: Extremes of respiratory effort and dynamic pulmonary stress would be associated with a higher rate of weaning from IMV, as well as longer time on IMV and subsequent longer hospital stay.

Exploration of Mechanisms for Weaning Failure

This study is a prospective physiologic study. The primary study population will be adult invasive tracheal intubated patients with COPD, and investigators will collect relevant demographic data, vital signs, and baseline physiologic parameters of the patients prior to the spontaneous breathing test（SBT). The participants will be divided into a successful withdrawal group and a failed withdrawal group according to the SBT outcome, and the changes in the above parameters during SBT will be compared between the two groups .

Preventing Celiac Disease by Weaning With Mediterranean Diet

Background: The introduction of solid foods in alignment with the Mediterranean Diet (MD) post-exclusive milk feeding has been demonstrated to cultivate a lasting affinity for healthy eating during infancy and childhood. Despite this, access to healthy diets remains a challenge for numerous children, particularly in underserved areas. The clinical trial under discussion is set in Scampia, a municipality in Naples, Italy, known for its dense population and socio-economic challenges. This trial, utilizing the Family Pediatrician (FP) system, aims to promote MD nutrition among children in Scampia to potentially prevent or reduce chronic childhood diseases. Study Design: In this pragmatic trial, FPs are utilized as the unit for randomization to administer the intervention. The intervention group will be introduced to an intensified MD-based diet from weaning, incorporating adult-type MD foods, while the control group will follow standard regional dietary guidelines. Dietary adherence and health outcomes are to be periodically monitored, and genetic and microbiome analyses will be conducted using collected saliva and stool samples. Incorporating a Bayesian group sequential design, this trial is structured to conduct interim analyses for efficacy, aligning with local healthcare systems for optimal resource allocation. Conclusion: The study is poised to be methodologically innovative and socially impactful, utilizing existing healthcare frameworks to enhance childhood nutrition in challenging environments. Outcomes from this trial are expected to provide valuable insights into the effects of MD-based nutrition on child health and potentially serve as a model for promoting healthier diets in urban suburbs globally.

The Effect of Quantitative EEG Combined With Ultrasound and Sputum Volume on Predicting Weaning Failure

Neurocritical patients often face the need for removal of endotracheal tubes. However, despite following the extubation criteria for general critical ill patients, neurocritical patients still exhibit a higher rate of weaning failure, significantly higher than that of general critical ill patients. The extubation criteria for general critical patients emphasize the assessment of lung conditions. However, neurological critical patients often have less severe lung damage, but factors such as consciousness level and coughing ability may significantly influence extubation. Quantitative EEG serves as an objective tool to reflect consciousness level status, while bedside ultrasound can assess respiratory muscle function. Additionally, sputum volume may reflect the condition of lung condition. Therefore, we believe that combination of these three indicators can better predict the success of extubation for neurocritical patients.