Clinical Research Directory

Physiological Effects of Controlled vs. Assisted Ventilation During Moderate-to-severe ARDS (PEARL Study)

Background: In patients with acute hypoxemic respiratory failure or ARDS, mechanical ventilation is often required. Two common strategies are pressure support ventilation (PSV), which allows spontaneous breathing, and volume-controlled ventilation (VCV), which delivers fixed tidal volumes. Although PSV can improve comfort, strong inspiratory efforts may cause excessive lung inflation and increase the risk of ventilator-induced lung injury (VILI). In contrast, VCV with muscle paralysis ensures full control over tidal volume and driving pressure, potentially offering better lung protection. Hypothesis: The study will help determine whether a controlled ventilation strategy - with or without volume adjustments and with or without muscle paralysis - provides superior lung protection compared to PSV in hypoxemic patients with intense inspiratory effort. Methods: This prospective physiological study will be performed in the ICU of Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) and will include 20 moderate to severe ARDS patients. Each patient will undergo four 30-minute ventilation phases: PSV with clinical PEEP; VCV at 6 ml/kg predicted body weight (PBW); VCV with muscle paralysis and Vt equal to PSV; VCV with muscle paralysis and Vt adjusted to keep driving pressure ≤14 cmH₂O. During each phase, data on gas exchange, respiratory mechanics, inspiratory effort, and regional ventilation (via electrical impedance tomography) will be collected. Endpoints: Primary: Regional tidal volume distribution during VCV vs. PSV. Secondary: Transpulmonary driving pressure, dorsal ventilation fraction, and pendelluft occurrence. Expected Impact: By comparing assisted and controlled ventilation under different conditions, the study aims to clarify which strategy better balances patient comfort, effective ventilation, and lung protection in ARDS patients with high respiratory drive.

Dynamic Compliance-Guided Ventilation in Lumbar Surgery

Postoperative pulmonary complications are a frequent cause of morbidity following lumbar stabilization surgery. Conventional ventilation strategies may not adequately reflect intraoperative changes in respiratory mechanics, potentially leading to impaired postoperative pulmonary function. Dynamic compliance-guided ventilation provides a real-time, individualized approach by adjusting ventilatory parameters according to lung compliance. This prospective randomized controlled study aims to evaluate the effects of dynamic compliance-guided ventilation compared with standard ventilation strategies on postoperative pulmonary function in patients undergoing lumbar stabilization surgery. Eligible patients will be randomly assigned to either the compliance-guided group or the conventional ventilation group. In this study, the investigators aim to prospectively compare ventilation with the dynamic compliance (Cdyn) approach-one of the lung-protective ventilation strategies-with conventional ventilation methods in patients undergoing surgery in the prone position. The primary outcome will be evaluated using a modified lung ultrasound scoring system based on the most severely affected regions of aeration loss. Secondary objectives include the assessment of intraoperative hemodynamics, respiratory mechanics, and the effects on postoperative pulmonary function.

Inspiratory Effort-Targeted Pressure Support Ventilation (IT-PSV) Trial

The Inspiratory effort-Targeted Pressure Support Ventilation (IT-PSV) is a cluster randomized controlled trial. Its main aim is to determine whether an inspiratory effort-targeted pressure support setting strategy, compared to the traditional tidal volume and respiratory rate target, can improve clinical outcomes in adult participants undergoing pressure support ventilation. The investigators propose a physiological-oriented assisted ventilation management that, if found effective, could potentially change the clinical practice for mechanical ventilation.

Open Lung Protective Extubation Following General Anesthesia

Perioperative respiratory complications are a major source of morbidity and mortality. Postoperative atelectasis plays a central role in their development. Protective "open lung" mechanical ventilation aims to minimize the occurrence of atelectasis during the perioperative period. Randomized controlled studies have been performed comparing various "open lung" ventilation protocols, but these studies report varying and conflicting effects. The interpretation of these studies is complicated by the absence of imagery supporting the pulmonary impact associated with the use of different ventilation strategies. Imaging studies suggest that the gain in pulmonary gas content in "open lung" ventilation regimens disappears within minutes after the extubation. Thus, the potential benefits of open-lung ventilation appear to be lost if, at the time of extubation, no measures are used to keep the lungs well aerated. Recent expert recommendations on good mechanical ventilation practices in the operating room conclude that there is actually no quality study on extubation. Extubation is a very common practice for anesthesiologists as part of their daily clinical practice. It is therefore imperative to generate evidence on good clinical practice during anesthetic emergence in order to potentially identify an effective extubation strategy to reduce postoperative pulmonary complications.

CT for Personalized Mechanical Ventilation

The goal of this study is to compare two different ways of helping patients with a condition called sepsis who need help breathing using a machine called a ventilator. The investigators want to study which way of setting the ventilator is better for the lungs. Here are the main questions the investigators want to answer: 1. How does the amount of air in the lungs and the way it moves differ between the two ways? 2. How does the way air spreads out in different parts of the lungs differ between the two ways? In this study, the investigators will take special pictures of the lungs using a machine called a CT scan. The pictures will show us how much the lungs stretch and how much air is in different parts of the lungs. The investigators will compare two different ways of using the ventilator: one personalized for each patient based on their breathing, and another way that is commonly used. By comparing these two ways, the investigators hope to learn which one is better for helping patients with sepsis who need the ventilator. This information can help doctors make better decisions about how to care for these patients and improve their breathing.

A New Ultrasonographic Tool to Assess Pulmonary Strain in the ICU

The primary objective of the study is to create a small dataset of regional pulmonary strain values in patients suffering from pulmonary diseases under mechanical ventilation in an intensive care setting. Hypothesis: The analysis of lung ultrasonographic sequences using speckle-tracking allows the determination of local pleural strain in 4 predetermined pulmonary areas in mechanically ventilated patients suffering from pulmonary diseases.

Electrical Activity of the Diaphragm and Respiratory Mechanics During NAVA

Protective ventilatory strategy should be applied to reduce ventilator-induced lung injury (VILI) after Lung Transplantation (LTx) or in case of acute respiratory failure requiring invasive mechanical ventilation. Neurally Adjusted Ventilatory Assist (NAVA) is an assisted ventilation mode in which respiratory support is coordinated by the electrical activity of the diaphragm (EAdi). Aim of the study is to assess the physiological relationship between neural respiratory drive, as assessed by EAdi, and tidal volume, driving pressure, and mechanical power, at different levels of ventilatory assist, in the absence of pulmonary vagal afferent feedback or during acute respiratory failure. Additional parameters will be collected: Pmus, Pocc, transpulmonary pressure etc.

Inspiratory Work of Breathing Before and After Extubation

Critically ill patients who (1) are not able to maintain their airway, (2) cannot breathe on their own, or (3) both, are ones who often require tracheal intubation and support from a breathing machine (mechanical ventilator). When the patient is ready to be liberated from the mechanical ventilator because the initial insult for intubation has been resolved, the patient is screened using the readiness to wean test in preparation for extubation. As the patient passes this screening, a spontaneous breathing test (SBT) is initiated. Currently, there are many debates surrounding which SBT technique is most favorable. At Toronto General Hospital, the clinical team uses a zero-end expiratory pressure (ZEEP) trial. Once the patient successfully passes their SBT they are then extubated. The patient will undergo a spontaneous breathing trial of continuous positive airway pressure (CPAP) of 5 cmH2O and ZEEP, in which time the investigators will be using a new technology called electrical impedance tomography (EIT), to study and compare the end expiratory lung volume (EELV); investigators will use an esophageal catheter to measure and monitor pressures in the lung, and also assess the patient's work of breathing. This will be repeated once the patient has been extubated safely.

Phrenic Identification in the ICU

This will be a prospective observational study where the investigator will scan patients' necks with an ultrasound and look for anatomical landmarks that may help identify the phrenic nerve.

Long Term Follow up of Children Enrolled in the REDvent Study

This is a prospective observational follow-up study of children enrolled in a single center randomized controlled trial (REDvent). Nearly 50% of adult Acute Respiratory Distress Syndrome (ARDS) survivors are left with significant abnormalities in pulmonary, physical, neurocognitive function and Health Related Quality of Life (HRQL) which may persist for years.Data in pediatric ARDS (PARDS) survivors is limited. More importantly, there are no data identifying potentially modifiable factors during ICU care which are associated with long term impairments, which may include medication choices, or complications from mechanical ventilator (MV) management in the ICU including ventilator induced lung injury (VILI) or ventilator induced diaphragm dysfunction (VIDD). The Real-time effort driven ventilator (REDvent) trial is testing a ventialtor management algorithm which may prevent VIDD and VILI. VIDD and VILI have strong biologic plausibility to affect the post-ICU health of children with likely sustained effects on lung repair and muscle strength. Moreover, common medication choices (i.e. neuromuscular blockade, corticosteroids) or other complications in the ICU (i.e. delirium) are likely to have independent effects on the long term health of these children. This proposed study will obtain serial follow-up of subjects enrolled in REDvent (intervention and control patients). The central hypothesis is that preventing VIDD, VILI and shortening time on MV will have a measureable impact on longer term function by mitigating abnormalities in pulmonary function (PFTs), neurocognitive function and emotional health, functional status and HRQL after hospital discharge for children with PARDS. For all domains, the investigators will determine the frequency, severity and trajectory of recovery of abnormalities amongst PARDS survivors after ICU discharge, identify risk factors for their development, and determine if they are prevented by REDvent. They will leverage the detailed and study specific respiratory physiology data being obtained in REDvent, and use a variety of multi-variable models for comprehensive analysis. Completion of this study will enable the investigators to identify ICU related therapies associated with poor long term outcome, and determine whether they can be mitigated by REDvent.

"Lung Barometric Measurements in Normal And in Respiratory Distressed Lungs"

Little is known about how lung mechanics are affected during the very early phase after starting mechanical ventilation. Since the conventional method of measuring esophageal pressure is complicated, hard to interpret and expensive, there are no studies on lung mechanics on intensive care patients directly after intubation, during the first hours of ventilator treatment and forward until the ventilator treatment is withdrawn. Published studies have collected data using the standard methods from day 1 to 3 of ventilator treatment for respiratory system mechanics, i.e. the combined mechanics of lung and chest wall. Consequently, information on lung mechanical properties during the first critical hours of ventilator treatment is missing and individualization of ventilator care done on the basis of respiratory system mechanics, which are not representative of lung mechanics on an individual patient basis. We have developed a PEEP-step method based on a change of PEEP up and down in one or two steps, where the change in end-expiratory lung volume ΔEELV) is determined and lung compliance calculated as ΔEELV divided by ΔPEEP (CL = ΔEELV/ΔPEEP). This simple non-invasive method for separating lung and chest wall mechanics provides an opportunity to enhance the knowledge of lung compliance and the transpulmonary pressure. After the two-PEEP-step procedure, the PEEP level where transpulmonary driving pressure is lowest can be calculated for any chosen tidal volume. The aim of the present study in the ICU is to survey lung mechanics from start of mechanical ventilation until extubation and to determine PEEP level with lowest (least injurious) transpulmonary driving pressure during ventilator treatment. The aim of the study during anesthesia in the OR, is to survey lung mechanics in lung healthy and identify patients with lung conditions before anesthesia, which may have an increased risk of postoperative complications.

Ventilation of the Extremely Premature Infants Optimized by Dead Space Washout

The Continuous Tracheal Gas Insufflation (CTGI) is a ventilation option of conventional mechanical ventilation that is used to reduce or even eliminate the dead space caused by respiratory prostheses. This objective is of particular interest in the smallest preterm infants, where the volume of anatomical dead space due to prostheses is little different from the tidal volume. The principle of this option is to continuously blow an additional flow of 0.2 L/minute at the tip of the endotracheal tube to purge expired CO2 trapped in the prostheses, to have a CO2-free volume of gas available for subsequent insufflation. The goal of this clinical trial is to learn if Continuous Tracheal Gas Insufflation (CTGI) works to reduce ventilatory dependence in preterm infants after mechanical ventilation. It will also learn about the safety of CTGI. The main questions it aims to answer are: * Does Continuous Tracheal Gas Insufflation (CTGI) reduce the number of days of non-invasive ventilation in extremely preterm infants who needed mechanical ventilation? * Does Continuous Tracheal Gas Insufflation (CTGI) reduce the age at the weaning of any ventilatory support and/or oxygen supplementation. Researchers will compare the clinical outcome of patients mechanically ventilated with the CTGI-device to the outcome of patients ventilated without the CTGI device, to see if the CTGI ventilation works to reduce ventilation dependence. Participants will: • Be mechanically ventilated using CTGI (if randomly assigned in the CTGI-group), for the entire endotracheal ventilation period during their stay in the neonatal intensive care unit.

Clinical Decision Support Tool in PARDS Pilot Study

Previous clinical trials in adults with acute respiratory distress syndrome (ARDS) have demonstrated that ventilator management choices can improve Intensive Care Unit (ICU) mortality and shorten time on mechanical ventilation. This study seeks to scale an established Clinical Decision Support (CDS) tool to facilitate dissemination and implementation of evidence-based research in mechanical ventilation of infants and children with pediatric ARDS (PARDS). This will be accomplished by using CDS tools developed and deployed in Children's Hospital Los Angeles (CHLA) which are based on the best available pediatric evidence, and are currently being used in an NHLBI funded single center randomized controlled trial (NCT03266016, PI: Khemani). Without CDS, there is significant variability in ventilator management of PARDS patients both between and within Pediatric ICUs (PICUs), but clinicians are willing to accept CDS recommendations. The CDS tool will be deployed in multiple PICUs, targeting enrollment of up to 180 children with PARDS. Study hypotheses: 1. The CDS tool in will be implementable in nearly all participating sites 2. There will be \> 80% compliance with CDS recommendations and 3. The investigators can implement automatic data capture and entry in many of the ICUs Once feasibility of this CDS tool is demonstrated, a multi-center validation study will be designed, which seeks to determine whether the CDS can result in a significant reduction in length of mechanical ventilation (LMV).

Evaluation of Respiratory Mechanics in Supine and PARK-bench Positions (SPARK)

The primary objective of this prospective observational physiological study is to evaluate the variation in regional distribution of intrapulmonary volume in the dependent and non-dependent lung regions in patients undergoing neurosurgical intervention between supine and Park-Bench position.

Non-invasive Phrenic Nerve Stimulation in ARDS Patient

Reduced diaphragmatic activity during mechanical ventilation can lead to diaphragmatic disuse atrophy, atelectasis, increased lung stress and strain, and hemodynamic impairment. This, in turn, may prolong the duration of mechanical ventilation, make weaning more difficult, and even increase mortality. Synchronizing phrenic nerve stimulation to promote diaphragmatic activity may prevent ventilator-induced lung injury and ventilator-induced diaphragm dysfunction, thereby improving patient outcomes. Surgically implanted phrenic nerve stimulation has been used in certain neurological disorders, but the effects of percutaneous non-invasive synchronized phrenic nerve stimulation in patients with ARDS undergoing mechanical ventilation remain unclear and require further investigation.

Optimizing the Assessment of Mechanical Ventilation by Integrating Advanced Monitoring Techniques [AVIM]

The aim of this study is to collect synchronized data from multiple monitoring techniques of mechanical ventilation (pressure/flow waves from the ventilator, electrical impedance tomography - EIT, esophageal pressure, capnography) in patients ventilated either on intensive care units or during anesthesia and evaluate the data by detailed mathematical analysis, to test three hypotheses: 1. Various published methods of calculation of the expiratory time constant provide different results in most cases. 2. Inhomogeneous ventilation (as described by EIT) affects the form of the expiratory flow curve and thus the calculated expiratory time constants. 3. The calculation of mechanical energy transferred to the lungs is affected by the chosen technique and length of the inspiratory pause maneuver. This study does not test any new or non-standard methods and does not in any way interfere with the course of treatment indicated by the clinician, apart from extending the monitoring techniques.

Effect of Vitamin C on Postoperative Pulmonary Complications After Intracranial Tumor Surgery

The goal of this clinical trial is to investigate the effect of perioperative administration of vitamin C on postoperative pulmonary complications, with the aim of providing a safe and effective medication regimen for the prevention and treatment of postoperative pulmonary complications in patients undergoing surgery for craniocerebral tumors. The main questions it aims to answer are: 1. To determine whether vitamin C can reduce pulmonary complications after surgery for intracranial tumors. 2. Does intraoperative vitamin C improve the prognosis of surgical patients Researchers will compare vitamin C to a placebo (saline) to see if vitamin C is effective for postoperative lung complications in patients undergoing surgery for cranial tumors. 1. Participants will be intravenously pumped with vitamin C for two hours after induction of anesthesia. 2. Participants will have intraoperative plasma sampling and recording of ventilator parameters, monitor parameters and perioperative data. 3. Participants will be followed up until discharge from the hospital to record symptoms and adverse events, and will be called at six months to check on their prognosis.

Mechanism Study of Ventilator-Induced Lung Injury in Elderly People.

1. We collect lung tissues from patients with different ages and confirm that KLK8 expression is positively correlated with age. 2. We collect peripheral blood from patients with different ages and duration of mechanical ventilation to explore the correlation between the degree of endothelial/epithelial damage, age and duration of mechanical ventilation.