Clinical Research Directory

Vela Generation II: Usability and Performance of a Non-Invasive Ventilation Mask.

Study Overview The goal of this clinical trial is to learn whether an improved non invasive ventilation mask with airway washout can reduce how often people need to breathe and perform as well as standard NIV masks when used with different ventilators, in people receiving NIV therapy for respiratory distress or respiratory insufficiency. The main question(s) it aims to answer are: * Does the new mask reduce breathing rate compared with a standard NIV mask? * Does the ventilator perform as expected when used with the new mask, including pressure delivery and leak? * Do clinicians and participants find the new mask fits and functions well? Three iterations of the new mask (vented, non-vented, dual limb) will be compared to standard of care to see if the mask reduces the need to breathe and performs consistently across ventilators compared with usual NIV masks. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ What Participants Will Do Participants will wear two different NIV masks, each for one hour, during a single study session lasting approximately 2.5 hours. Participants will be asked to: * Wear a small, stick on carbon dioxide (CO₂) sensor on the skin. * Use their usual NIV mask for one hour while ventilator data are collected. * Switch to the investigational mask for one hour while ventilator data are collected. * Choose whether to return to their original mask or remain on the investigational mask after the study period. * Caregiver opinion on the mask will be collected. Participants may also choose (optional): * To have three small blood samples taken (These samples are optional, and participants can still take part in the study if they decline them.) * One when they agree to take part in the study * One when the investigational mask is fitted * One after wearing the investigational mask for one hour * To provide feedback on how the two masks felt and performed. During the study, researchers will collect data from the ventilator, including: * Breathing rate and depth * NIV pressure settings * Amount of air leak Research staff will also complete a short form assessing how well the mask fit and functioned. Participants will remain in the study until the investigational mask is removed.

INSPIRatory Efforts Estimation Under High-flow Nasal Oxygen

High-flow nasal oxygen (HFNO) is recommended as first-line treatment to prevent intubation in acute hypoxemic respiratory failure and to prevent reintubation after extubation. Accumulating data suggest that strong inspiratory efforts and their persistence are associated with HFNO failure. However, tools to monitor continuously and noninvasively inspiratory efforts are lacking. The investigators have developed an algorithm estimating noninvasively inspiratory efforts under HFNO. This pilot study aims at testing the feasibility of estimating inspiratory efforts in patients treated with HNFO.

Platform of Randomized Adaptive Clinical Trials in Critical Illness

PRACTICAL is a randomized multifactorial adaptive platform trial for acute hypoxemic respiratory failure (AHRF). This platform trial will evaluate novel interventions for patients with AHRF across a range of severity states (i.e., not intubated, intubated with lower or higher respiratory system elastance, requiring extracorporeal life support) and across a range of investigational phases (i.e., preliminary mechanistic trials, full-scale clinical trials). AHRF is a common and life-threatening clinical syndrome affecting millions globally every year. Patients with AHRF are at high risk of death and long-term morbidity. Patients who require invasive mechanical ventilation are at risk of ventilator-induced lung injury and ventilator-induced diaphragm dysfunction. New treatments and treatment strategies are needed to improve outcomes for these very ill patients. Utilizing advances in Bayesian adaptive trial design, the platform will facilitate efficient yet rigorous testing of new treatments for AHRF, with a particular focus on mechanical ventilation strategies and extracorporeal life support techniques as well as pharmacological agents and new medical devices. The platform is designed to enable evaluation of novel interventions at a variety of stages of investigation, including pilot and feasibility trials, trials focused on mechanistic surrogate endpoints for preliminary clinical evaluation, and full-scale clinical trials assessing the impact of interventions on patient-centered outcomes. Interventions will be evaluated within therapeutic domains. A domain is defined as a set of interventions that are intended to act on specific mechanisms of injury using different variations of a common therapeutic strategy. Domains are intended to function independently of each other, allowing independent evaluation of multiple therapies within the same patient. Once feasibility is established, Bayesian adaptive statistical modelling will be used to evaluate treatment efficacy at regular interim adaptive analyses of the pre-specified outcomes for each intervention in each domain. These adaptive analyses will compute the posterior probabilities of superiority, futility, inferiority, or equivalence for pre-specified comparisons within domains. Each of these potential conclusions will be pre-defined prior to commencing the intervention trial. Decisions about trial results (e.g., concluding superiority or equivalence) will be based on pre-specified threshold values for posterior probability. The primary outcome of interest, the definitions for superiority, futility, etc. (i.e., the magnitude of treatment effect) and the threshold values of posterior probability required to reach conclusions for superiority, futility etc., will vary from intervention to intervention depending on the phase of investigation and the nature of the intervention being evaluated. All of these parameters will be pre-specified as part of the statistical design for each intervention trial. In general, domains will be designed to evaluate treatment effect within four discrete clinical states: non-intubated patients, intubated patients with low respiratory system elastance (\<2.5 cm H2O/(mL/kg)), intubated patients with high respiratory system elastance (≥2.5 cm H2O/(mL/kg)), and patients requiring extracorporeal life support. Where appropriate, the model will specify dynamic borrowing between states to maximize statistical information available for trial conclusions. In this perpetual trial design, different interventions may be added or dropped over time. Where possible, the platform will be embedded within existing data collection repositories to enable greater efficiency in outcome ascertainment. Standardized systems for acquiring both physiological and biological measurements are embedded in the platform, to be acquired at sites with appropriate training, expertise, and facilities to collect those measurements.

Compliance-Guided Abdominal Wall Closure Strategy in Large Ventral Hernia Repair

People undergoing repair of large ventral hernias can develop breathing problems after surgery, especially around the time when the abdominal wall is closed. During closure, pressure inside the abdomen may increase and lung mechanics can worsen. This study will evaluate a structured intraoperative decision approach that uses standard anesthesia measurements of static respiratory system compliance at predefined timepoints to support the choice of abdominal wall closure technique. The main goal is to assess the rate of early postoperative respiratory failure within 72 hours after surgery.

Non-inferiority of Continuing Oral Intake Versus Fasting in Patients With Acute Respiratory Failure

Fasting in intensive care is mainly studied in mechanically ventilated patients or those in the weaning phase. Recent research challenge the common assumption of fasting and suggests that continuing enteral nutrition before extubation may be beneficial. Fasting is also practiced before procedures (e.g., tracheostomy, endoscopy) or surgeries, based on anesthetic guidelines. Yet, no data address fasting in non-intubated ICU patients with acute respiratory failure, despite frequent caloric deficits and inadequate nutritional intake. Aspiration risk often justifies fasting, but studies indicate that swallowing reflexes remain intact in patients receiving high-flow nasal oxygen or non-invasive ventilation. Moreover, although intubation carries a 2-5.9% aspiration risk, rapid sequence induction mitigates this, questioning the necessity of preventive fasting. Despite its prevalence, this practice lacks scientific validation and guideline support. Patient discomfort is also significant. Hunger and thirst are major sources of distress, and evidence from anesthesiology suggests that allowing fluid intake pre-anesthesia reduces discomfort. Extrapolating these findings to ICU patients could improve well-being. In conclusion, fasting in ICU patients may contribute to discomfort, dehydration, and malnutrition, while its protective benefits remain uncertain. We hypothesize that maintaining oral intake does not increase the risk of intubation or aspiration-related complications.

Percutaneous Cryoablation of Intercostal Nerves for the Treatment of Rib Fractures

The goal of this double blinded randomized control trial is to learn if percutaneous cryoablation of traumatic rib fractures improves outcomes. The main questions it aims to answer are: Does percutaneous cryoablation improve short and long term pain scores? Does percutaneous cryoablation improve short and long term respiratory mechanics? Does percutaneous cryoablation improve long term quality of life? Does percutaneous cryoablation decrease delirium? Researchers will compare cryoablation to standard multimodal pain therapy to see if this impacts respiratory recovery. Participants will undergo randomization, percutaneous cryoablative procedure, and participate in tests at pre-determined intervals to evaluate their pulmonary recovery.

NIV Mask and Headgear Evaluation

Non-invasive ventilation (NIV) is the delivery of breathing support via a facemask. It is used to treat people whose natural breathing is ineffective. Evidence shows that, when used long-term, it improves both quality of life and life expectancy. Ventilation is delivered in the home through a mask covering the nose or the nose and mouth. A good fit between the mask and the patient's face is essential to deliver the treatment effectively. Mass-produced masks are available for the adult market but in children it is often difficult to find a mask that provides an adequate fit. A particularly disadvantaged group is children with facial deformities or facial asymmetry. In these groups NIV may not be possible due to unavailability of an adequate mask. Currently the options for these groups of children are to ventilate invasively via a breathing tube (tracheostomy) which can lead to serious complications and costly care-packages or to abandon ventilation, eventually leading to respiratory failure and premature death. Persevering with an inadequately fitting mask leads to pressure sores, impairment of facial bone growth and significant disturbance to the sleep of the child and family due to noise from air leakage from the mask and alarms from the ventilator. These problems lead to an increased burden on nursing and hospital resources as well as harm and suffering to patients. The COMFORT study was funded by the NIHR in 2015 to develop novel mask-face interfaces to optimise mask fit to the needs of individual patients using 3D assessment and manufacturing technologies. Since then, we have developed a mask prototype and a modular headgear prototype that straps the mask onto the face. We have already demonstrated that our proposed method is more effective than a standard mass-produced mask/headgear in the laboratory setting with adult volunteers. In the first part of this project, we will carry out a proof-of-concept study to test the prototype mask/headgear system with children and young people that currently use NIV but have a poorly-fitting mask. We will compare our new system with their current mask by asking them to rate them in terms of comfort and fit as well as measuring the effectiveness of their ventilation. In the second part, we will work with Imperial University, who have developed software to automate and speed up the manufacturing process. We will scan 120 children to help develop the software to be suitable for children and then repeat the proof-of-concept study with a mask manufactured using the automated process. Following these studies we will apply for funding to carry out a multicentre UK-wide clinical trial.

A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)

Amyotrophic lateral sclerosis (ALS) is a disease that causes weakness of the muscles of the body. The disease can eventually lead to severe breathing problems, which is the most common cause of death from ALS. The treatment for breathing is non-invasive ventilation (NIV). It is a machine that helps a person breathe by pushing air in and out of their lungs through a mask worn over the face. Research has shown that NIV can improve the quality of life and survival of someone with ALS. Unfortunately, NIV is not equally beneficial for everyone. The investigators do not yet know the best time or method for starting NIV in ALS. Europe and Canada allow starting NIV much earlier in ALS than the United States. Current recommendations for starting NIV are based on the opinion of experts rather than large research studies. Medical insurance companies will not cover NIV until significant breathing weakness occurs. After NIV is started, there is no evidence-based guidance on the best way to adjust NIV to benefit patients as much as possible. Some patients have difficulty tolerating NIV, but it is not clear how to identify these individuals ahead of time. The investigators have created a new prediction tool that can identify patients at high risk of breathing problems within the next 6 months. This may help the study team identify who is more likely to benefit from starting NIV early. The investigators have published a paper that shows that NIV helps people with ALS live longer. This paper also showed that patients get more benefit with use NIV for at least 4 hours per day. The investigators published another paper that measured a gas called carbon dioxide (CO2), which goes high if someone's breathing is weakened. This paper showed that patients with ALS may live longer when CO2 levels are lowered using NIV. The investigators also have data suggesting that certain characteristics may predict who is less likely to use NIV at least 4 hours per day. In this study, the investigators will collect pilot data on starting early NIV in individuals with ALS who do not yet meet insurance criteria for covering NIV. The research team will first use their previously published prediction tool to identify patient risk. Then, subjects would be randomized to start early NIV or to usual care. The usual care group would eventually start NIV as would occur if the participants were not in the study. The purpose of this study is to collect data to help the investigators plan a larger randomized clinical trial. This study has 4 objectives. First, the project aims to identify individuals who would benefit from earlier NIV. The research team will use the original prediction tool to identify risk of severe breathing problems within the next 6 months. Second, the project aims to show that it is feasible to start NIV early. Third, the project aims to gather data on the effect of randomization on symptoms, CO2 levels, and outcomes. Fourth, the project aims to identify traits that may make someone less likely to use NIV.

Partial Neuromuscular Blockade in Acute Hypoxemic Respiratory Failure

PNEUMA is a preliminary safety and feasibility trial of a novel approach to the titration of neuromuscular blockade (NMB) to safe spontaneous breathing in patients with moderate to severe acute hypoxemic respiratory failure (AHRF) supported with invasive mechanical ventilation.

Combined Respiratory Training in Persons With ALS

The goal of this interventional trial is to learn about lung volume recruitment (LVR) and expiratory muscle strength training (EMST) in a total of up to 39 patients diagnosed with ALS. The following aims will be addressed: 1. Determine the impact of combined LVR and EMST on cough strength and respiratory function in individuals with ALS. 2. Determine the impact of combined LVR and EMST on patient-reported dyspnea and bulbar impairment. 3. Describe the effect of combined LVR and EMST on patient- and caregiver reported burden and quality of life.

Noninvasive Ventilation Facemasks Favoring Carbon Dioxide Washout

The objective of this randomized cross-over trial is to assess the physiological effects of three different facemasks for noninvasive ventilation (Nivairo, Visairo, Optiniv) in patients with acute hypercapnic respiratory failure

The Impact of Low Versus High Positive End-expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics

The goal of this interventional study is to evaluate the effect of different positive end-expiratory pressures (PEEP) on lung and diaphragm function in patients mechanically ventilated with pressure support ventilation in the intensive care unit. The main questions aim to answer: Does higher PEEP level affect diaphragm contractions and ventilatory efficiency? Does higher PEEP level limit inspiratory efforts? Does higher PEEP level affect lung compliance? The participants will be subjected to three different PEEP levels during pressure support ventilation: Low PEEP (4 cmH2O), Medium PEEP (10 cmH2O), High PEEP (16 cmH2O). The lung and diaphragm function will be evaluated using high-resolution esophageal manometry, electrical activity of the diaphragm, external diaphragm ultrasound and spirometric ventilator data.

Early Sedation With Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients

Sedation remains a ubiquitous and crucial component of intensive care treatments in critically ill mechanically ventilated patients. Sedation relieves anxiety, reduces distress, and promotes tolerance of endotracheal intubation and associated life-sustaining interventions such as mechanical ventilation, cardiovascular assistance, and renal support. Thus, choosing the optimal sedative agent is vital to patient comfort, safety, and survival. Despite more than 20 years of intensive care sedation research, there is still no consensus on what constitutes best sedation practice. The Society of Critical Care Medicine, the premier critical care organisation in North America, published the 2018 Clinical Practice Guidelines on the management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep (PADIS) disruption (chaired by our primary applicant W.A.) and issued weak recommendations to provide analgesia before sedation, to target light sedation whenever clinically feasible, and to use either dexmedetomidine or propofol over midazolam for the sedation of mechanically ventilated critically ill patients. Similarly, the American Thoracic Society produced a set of Clinical Practice Guidelines to promote liberation and weaning from mechanical ventilation in critically ill patients, with weak recommendations for the use of non-benzodiazepines as primary sedatives and to target light sedation when clinically possible. A weak recommendation was issued in an Intensive Care Medicine Rapid Practice Guideline published in 2022 to use dexmedetomidine over propofol for sedation of critically ill adults, if the desired outcome is a reduction in delirium. These guidelines, however, do not consider age-dependent pharmacokinetics and pharmacodynamics, illness severity, timing of sedative administration, operative vs medical reason for admission, or the changing dynamics of sedation practice at different phases of critical illness. The lack of high-level evidence to inform sedation practice in the critically ill has led to approaches that are mainly opinion-based and lack the support of evidence from large multicentre, international randomised clinical trials.

Multicenter HomeVENT: Home Values and Experiences Navigation Track

This is a multicenter study to test a decision-making support process for families and clinicians facing decisions about chronic home ventilation for a child. The investigators hypothesize that the intervention will increase family preparedness for decision-making and will improve clinician-family shared-decision making. Half of families will be assigned to "usual care" arm and half to the "intervention" arm. Intervention families will view the study website with study staff and will answer questions related to website content. All families will be interviewed and surveyed at 1, 6 and 12 months after enrollment. Each family will designate 1-2 physician involved in the decision about home ventilation; each physician will be interviewed and surveyed at 1 month.

Effectiveness of Platform-Based Lateralization Therapy in Reducing Interface Pressure Between The Patient And The Support Surface

Pressure injury (PI) is characterized as damage to the skin and/or underlying tissues resulting from sustained pressure or a combination of pressure and shear forces between the patient and the support surface. Prolonged pressure is a well-established risk factor in the development of PIs. Frequent repositioning and routine patient care have been recognized for decades as integral components of PI prevention and treatment protocols. The duration of interface pressure is as critical as its magnitude. When interface pressure exceeds the mean capillary blood pressure, blood flow can be compromised, leading to ischemia in affected areas, which may progress to necrosis if sustained over time. Furthermore, it is widely accepted in the literature that tissue becomes at risk when interface pressure exceeds 30 to 32 mmHg. In this context, continuous lateral rotation therapy (CLRT) offers a potential alternative for managing critically ill patients. CLRT involves continuous mechanical rotation of the patient in the lateral plane. However, its effects on skin integrity remain poorly understood. Despite the rationale behind and widespread recommendation of repositioning, the lack of robust evaluations on how repositioning impacts interface pressure creates uncertainty, underscoring the need for high-quality trials to assess different strategies for implementation. Although lateralization is a pragmatic strategy for preventing pressure injuries, its use in critically ill patients requires an integrated assessment of respiratory, hemodynamic, and gastroesophageal effects. Therefore, this study proposes an innovative approach by evaluating, for the first time, the effectiveness of automated postural change with simultaneous monitoring of tissue integrity, pulmonary function, cardiovascular stability, and gastroesophageal protection. The aim is to optimize pressure injury prevention, improve pulmonary mechanics, ensure hemodynamic stability, and preserve gastroesophageal safety in critically ill patients.

Delayed Cord Clamping With Oxygen In Extremely Low Gestation Infants

This study is being conducted to compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life (MOL) given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC for 90 seconds (LO Group).

Effect of Physiotherapy Methods on Functional and Respiratory Outcomes in ICU Patients With Respiratory Failure

The aim of the biomedical study is to assess the changes in functional and qualitative indicators of critically ill patients with respiratory failure by applying different physiotherapy methods. By conducting this study and developing the "Physiotherapy Protocol for Critically Ill Patients Treated in the ICU," physiotherapists worldwide could be encouraged to work using a unified and adapted method. It is expected that the results, conclusions, and practical clinical recommendations derived from this study will be beneficial not only for rehabilitation specialists and intensivists in Lithuania but also for medical professionals working with respiratory diseases, including COVID-19 patients, at various stages of their treatment and consultation. Implementing an appropriate physiotherapy procedure protocol is anticipated to bring economic benefits, as early physiotherapy is safe and can reduce the incidence of delirium, decrease the duration of patient sedation, shorten the number of days on mechanical ventilation, and minimize hospital stay duration. Additionally, it aims to restore or improve patients' functional and independence levels, help prevent ICU-acquired weakness, and can be easily implemented in intensive care units.

Retrospective Data Analysis With the Aim to Determine the Success Rate of Endotracheal Intubation in the First Attempt in the Zug Rescue Service With Various Airway Devices Already in Everyday Use

Airway management is a critical procedure in emergency medicine, especially endotracheal intubation, which can be life-saving. Various techniques, such as video laryngoscopes and conventional laryngoscopes, are used, with success depending on first-pass success. The aim of this retrospective data analysis is to determine the success rate of endotracheal intubation in the first attempt in the Zug Rescue Service between 01/20 and 01/25 with various airway management devices already used in everyday life. The individual complications should secondary with regard to frequency and category as well as possible risk factors. risk factors. The aim is to examine the data on airway management of patients who had to be intubated due to a critical illness (e.g. impaired oxygenation or ventilation, reduced vigilance, cardiovascular arrest, etc.). The data is continuously collected and evaluated by the RDZ as part of quality assurance.

Home Versus Hospital Based NIV Care in MND

Non-invasive ventilation (NIV) is commonly offered to people with Motor Neurone Disease (MND) who have breathing difficulties. It improves their quality of life and can prolong life by 6 months or more. It is initially used at night and typically set up during a hospital admission. By the time that they develop respiratory failure and need to start NIV, however, most patients require wheelchairs or have other significant health problems. Repeated travel to hospitals is increasingly difficult with increasing disability. It is possible to start and monitor NIV treatment at home. This may be more convenient for selected patients, though starting NIV is quite complex; it is not known if home treatment is as safe and effective as hospital-based treatment. To establish this, 60 patients with MND who have indications for NIV will be recruited. They will be randomly allocated to a home-based treatment (home NIV set up plus home visits supported by telemonitoring) or hospital-based care (inpatient NIV set up plus outpatient NIV monitoring) and followed up at 1, 4 and 7 months. Alongside measures of treatment effectiveness, assessment of patient and carer preferences, quality of life, and cost-effectiveness will be undertaken. In the additional qualitative part on this study, interviews with patients who took part in the main study and their carers will be conducted to understand in more depth their perspective on what makes for a good or bad experience with NIV, how the environment (home vs hospital) influences their NIV experience and what personal factors determine NIV use. Findings from the interviews will inform the design of a truly patient-centred NIV service.

Inhaled Nitric Oxide in Severe Obesity

The goal of this clinical trial is to learn about the effects of inhaled nitric oxide on oxygenation and lung perfusion in participants with severe obesity who have acute hypoxemic respiratory failure and are on mechanical ventilation The main questions it aims to answer are: 1. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on oxygenation in participants with severe obesity compared to participants with normal body weight. 2. In acute hypoxemic respiratory failure, what are the effects of inhaled nitric oxide on lung perfusion and heart function in participants with severe obesity compared to participants with normal body weight. 3. In acute hypoxemic respiratory failure, does severe obesity impact nitric oxide signaling pathways? Participants with acute hypoxemic respiratory failure will be exposed to inhaled nitric oxide (20 ppm) while being clinically monitored.

Diaphragm Dysfunction and Ultrasound Perioperatively

This study aims at determining whether diaphragm ultrasound examining diaphragm thickening fraction, excursion and density before and after surgery can predict respiratory complications in the postoperative period. Patients scheduled for major elective abdominal, pelvic or vascular surgery will be included in the study and diaphragm ultrasound is performed before surgery and after surgery in the postoperative ward. Physiological parameters, laboratory parameters, data on surgery and anesthesia and comorbidities will be registered. Complications such as pneumonia, desaturation, need for intubation and other respiratory events up to 30 days will be registered and later correlated with the diaphragm measurements.

The Evaluation of the Effectiveness and Safety of Nalbuphine Hydrochloride Injection for Analgesia in ICU Patients: A Multicenter, Randomized, Single-blinded, Parallel, Two-step Trial

The analgesic effect of nalbuphine hydrochloride injection will be evaluated in a multicenter, randomized, single-blind, parallel, positive-controlled approach in two steps: step 1, to explore the optimal dosage of nalbuphine hydrochloride injection with 2 experimental arms and 1 positive control and step 2, to evaluate the effectiveness and safety of nalbuphine hydrochloride injection in mechanically ventilated ICU patients at a dosage determined in step 1 with the same positive control.

Respiratory Functions, Thoracoabdominal Movements and Exercise Capacity in Neuromuscular Diseases

The clinical trial titled "Investigation of Respiratory Functions, Thoracoabdominal Movements, and Exercise Capacity in Neuromuscular Diseases" aims to evaluate the respiratory functions, thoracoabdominal movements, and exercise capacity in children with Duchenne Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) compared to healthy controls. The study will use spirometry, structured light plethysmography (SLP), the six-minute walk test, and the six-minute pegboard ring test to assess these functions. This trial will be conducted at the Lokman Hekim University Muscle and Nerve Diseases Application and Research Center from May 2024 to Dec 2025.

Feasibility of Reducing Respiratory Drive Using the Through-flow System

Mechanical ventilation can lead to diaphragm and lung injury. During mechanical ventilation, the diaphragm could be completely rested or it could be overworked, either of which may cause diaphragm injury. Mechanical stress and strain applied by mechanical ventilation or by the patient's own respiratory muscles can also cause injury to the lungs. Diaphragm and lung injury are associated with increased morbidity and mortality. Throughflow is a novel system that can reduce dead space without the need to increase the tidal ventilation, reducing the ventilatory demands and respiratory drive.