Respiratory Therapy

Study Objective This observational study aims to prospectively investigate to what extent tracheostomy-related complications in children are asymptomatic or associated with symptoms when detected through surveillance airway endoscopy. We also aim at investigating how reliable caregiver reports and investigations by pediatriscians are in identifying symptoms associated with severe tracheostomy-related airway complications. Background Children with airway obstruction due to congenital malformations, trauma, or chronic respiratory or neuromuscular conditions may require a tracheostomy. The Long-Term Intensive Care Unit (LIVA), part of the Pediatric Perioperative Medicine and Intensive Care (BPMI) at Karolinska University Hospital, has been providing specialized care for children with tracheostomies across Sweden since 1998. The care at LIVA involves assessements by a multidisciplinary team, including pediatricians, ENT specialists, pediatric anesthesiologists, nurses, physiotherapists, dietitians, speech therapists, counselors, and play therapists. Follow-up at LIVA includes regular multidisciplinary assessments and one to two surveillance airway endoscopies under anesthesia annually, aimed at early detection of airway complications related to the tracheostomy tube. Complications such as granulomas, infections, or bleeding are often asymptomatic but can be potentially life-threatening. There is currently no national or international consensus on the optimal frequency of surveillance endoscopies, and the potential for individualizing surveillance based on risk factors, including the presentation of symptoms, remains unexplored. Given the risks associated with anesthesia, minimizing unnecessary procedures is critical. Currently, a retrospective study is underway to examine the incidence of tracheostomy-related complications, their correlation with risk and demographic factors, and preoperative symptoms. Preliminary results indicate that 72% of patients experienced at least one tracheostomy-related complication, while only 19% exhibited symptoms prior to surveillance endoscopy according to patient records. Suprastomal granuloma was the most frequent complication observed. Interventions were required for all symptomatic patients and 71% of asymptomatic patients with identified complications. Patients using ventilators and/or cuffed cannulas had a higher incidence of complications compared to those without (88% vs. 61%, p\<0.05). Study Population The study population comprises children under 18 years of age undergoing follow-up at the Long-Term Intensive Care Unit (LIVA) at Karolinska University Hospital in Stockholm, Sweden. Research Questions 1. To what extent are tracheostomy-related complications in children asymptomatic when detected through surveillance airway endoscopy? 2. How reliable are caregiver reports in identifying symptoms associated with tracheostomy-related airway complications? Methods Children scheduled for surveillance airway endoscopy are admitted to LIVA. Upon admission, the caregiver is asked to complete a short questionnaire regarding symptoms that may indicate a tracheostomy-related complication. After the questionnaire has been completed, the child will be examined by the responsible paediatrician, with the aim of identifying any signs or symptoms that could indicate an airway complication. The examination includes physical examination and medical history conducted according to a predefined protocol. The airway endoscopy is performed by an ENT surgeon who has not examined the patient beforehand and is not informed of the caregiver's responses nor the result of the examination by the pediatrician. However, there is no strict protocol in place to blind the surgeon to any visibly apparent symptoms or to information that may be spontaneously reported by the caregiver or paediatrician. Ethical Approval Ethical approval for the study has been obtained (Ref. No: 2023-07493-01).

Background: Acute lung failure requiring respiratory treatment is the most common cause of intensive care in Sweden and the condition has a high mortality rate; approximately 40%. To a large extent, the high mortality rate is due to the patient's underlying disease, e.g. sepsis or trauma but the respiratory treatment itself can also cause mechanical damage to the lungs with the risk of secondary development of acute lung failure and failure in other organ systems such as the liver, kidneys, heart and brain. In order to reduce the risk and damage of ventilator treatment, it is necessary to improve monitoring of lung function and to develop and evaluate methods for more gentle respiratory treatment. The studies aim to map the elastic properties of the lungs (pulmonary elastance and transpulmonary drive pressure) in different patient groups, lung healthy and patients with acute lung failure, using the non-invasive PEEP step method. Since the method is non-invasive and is based only on a change in the end expiratory pressure in the ventilator, it can be easily applied during clinical conditions, thus allowing a significant improvement in monitoring and setting of ventilator therapy in both patients under general anesthesia in "major surgery" and patients with acute pulmonary failure in intensive care units. During general anesthesia, patients lung elasticity will be measured immediately after starting the anesthesia and during surgery and before emergence. In intensive care, the measurement procedure will be applied immediately after the patient has been placed on a ventilator and then during respiratory care when normal intensive care measures take place, such as changing the ventilator setting in terms of breath volume, respiratory rate, end expiratory pressure (PEEP) and similar measures, as well as respiratory suction and inhalations to identify elastic properties within the range normally present in intensive care patients. Aim: The aim of the studies is to be able to evaluate lung function during intensive care with new noninvasive measurement methods such as measuring transpulmonary pressure and calculating lung drive pressure, to evaluate lung function during intensive care in order to try to find optimal methods for gentle but effective ventilation of critically ill patients. Studies have previously shown that more gentle respiratory treatment can reduce mortality in respiratory-treated intensive care patients. The development and adaptation of new methods for respiratory treatment and monitoring, can offer better decision support when adjusting airway pressure and volumes, which may ultimately lead to improvements in the form of shorter respiratory time and reduced mortality in respiratory patients. An additional aim is to map normal values of the elastance of the lung ("stiffness") on a population of normal lungs in lung-healthy patients who are sedated for planned surgery. Main issues: 1. Is the measurement with the PEEP step up and down procedure sufficient to accurately present the lung pressure/volume curve and the transpulmonary drive pressure in respiratory-treated patient populations in surgery and ICU? 2. Is it possible to collect data on a normal population of lung-healthy patients who are sedated for operative surgery as well as in intensive care patients with different degrees of lung failure with the intention of mapping pulmonary elastance/transpulmonary drive pressure and changes in these parameters at initiation of and during respiratory treatment? Methods: The PEEP-step method for determining lung elastane: The elastic properties of the lung are measured by increasing PEEP from the clinical baseline level and then lowering the measurement procedure by setting the breath volume to correspond to the lung volume increase that occurs during the PEEP increase. PEEP and tidal volume changes are very common routine measures in both general anesthesia and intensive care. So far, all analysis has been done through manual calculations off-line, but now the measurement procedure and calculations must be automated as far as possible and the transpulmonal drive pressure is presented breath by breath in order to be used for the individualization of the ventilator treatment bedside. This automation is performed in the form of software development. This work is ongoing and expected to be completed in August 2020. Then the PEEP-step method can be implemented and tested in the clinic. During ten years, in two doctoral theses and four validation studies and additional lung model studies, the investigators have developed an alternative method for measuring the transpulmonary drive pressure, which does not require oesophageal pressure measurement, but only to make a change in the end expiratory pressure (PEEP) in the ventilator and determine the resulting lung volume increase (DEELV) using the ventilator's volume measurement. The elastic properties of the lung (lung elastane, EL) are calculated as DPEEP/DEELV and then the transpulmonary drive pressure is calculated as the volume of breath of the lung elastance, EL x VT. The above additional measurement methods have been evaluated during the last 15 years. Measurement methods collects data from standard monitoring equipment used in clinical anesthesiological practice since the 1980s. Protocol: The study is a longitudinal observational study. Measurements will be performed before, during and after respiratory treatment in patients in intensive care units and in surgical units. The measurements take place during the respiratory care period with focus on variations in lung mechanics before and after the procedures included in the clinical routine regarding respiratory settings and other care. Noninvasive measurement methods will be used (see above) of which no one has a negative impact on the patient. Physiological data will be collected from blood gas analyses and monitoring equipment. The monitoring equipment will be connected to a laptop with software that collects continuous clinical data for analysis. Informed consent: 1) Adult patients who are about to undergo surgery will be consulted at the preoperative assessment approximately 1-2 weeks before surgery about their participation. 2) In adult intensive care patients treated with respiratory therapy, surrogate consent will be prompted. Since it is not previously predicted which patients will be treated on a ventilator in the intensive care unit, the patient's relatives will be asked for informed consent. For key-references, se References

Intensive Care Units (ICUs) are stressful places fraught with grief for family members who witness dying loved ones, often in pain, struggling to breathe and/or maintain consciousness. Compounding their distress, family members are often thrust into the position of patient "surrogate," needing to make life-and-death decisions on the patient's behalf. Researchers have shown that end-of-life (EoL) decision-making is undermined by grief, which interferes with acceptance of the patient's impending death and leads to care choices that adversely affect patients' quality of care and death.1-3 These circumstances heighten surrogates' risk of meeting criteria for Prolonged Grief Disorder (PGD), Posttraumatic Stress Disorder (PTSD), and decisional regret about the EoL care that the patient received, each associated with poor bereavement outcomes.4-7 Nearly 60% of ICU surrogates report moderate to extreme grief; 34% report extreme levels of peritraumatic stress symptoms.1 The coronavirus (COVID-19) pandemic has made an already bad situation worse. At the start of the pandemic, social distancing policies forced millions of families to confront obstacles to communication, medical decision-making, and care.8-10 Surrogates were left struggling with severe pre-loss grief and peritraumatic stress -- intensely longing to be near to the patient, confused about their roles, lonely, horrified, angry, disoriented and emotionally numb.10,11 Now, as the Delta variant creates a new "wave" of mortality and infection, bereaved family members may have remorse about vaccine refusal,12 feel guilty for transmitting the virus to the patient, or regret decisions about EoL care. With over 35 million cases and 600,000 deaths in the United States from COVID-19,13 the need for psychosocial interventions to support surrogates in the ICU is clear. Prior efforts to address the plight of family surrogates of critically ill patients have proved disappointing14-20 - with one ICU intervention significantly increasing the surrogate's severity of PTSD symptoms.14 A key limitation of these interventions is that while they targeted psychological outcomes, they were not psychological interventions. To address this, the investigators developed a brief, flexibly administered cognitive-behavioral, acceptance-based psychological intervention called EMPOWER (Enhancing \& Mobilizing the POtential for Wellness \& Emotional Resilience).21,22 Our pilot NIH-R21 (N=39) showed that EMPOWER had superior efficacy to enhanced usual care for reducing symptoms of PGD (d=1.20) and PTSD (d=.99). Consistent with mediation, EMPOWER reduced experiential avoidance (d=1.20); these reductions were correlated with PGD and PTSD change scores (p\<0.01). Large reductions in decisional regret (d=1.57) were observed, with no notable differences by surrogate race or delivery format (telehealth vs. in-person). Investigators propose to conduct a Phase II mixed methods randomized controlled trial (RCT) to further evaluate the efficacy of EMPOWER for reducing surrogate symptoms of PTSD and PGD. Surrogates (N=172) will be randomized to EMPOWER (n=86) or a standardized supportive conversation (SC; n=86). Effects of the intervention will be assessed via measures administered pre-intervention (T1), immediately post-intervention (T2), and at 3 months (T3), and 12 months (T4) following the T2 assessment. Investigators will also conduct semi-structured interviews with surrogates (n≈48) to probe intervention effects on mental health and explore contextual factors (e.g., medical mistrust, visitation restrictions) likely to affect surrogates during the pandemic.

Cystic fibrosis (CF) is a rare autosomal recessive disease involving multiple organs, especially the lungs and digestive organs. It is most commonly seen in Caucasians. Only a few Chinese CF patients have been described in literature, taking into account the large population of China. The main objectives of this study are to accurately evaluate the prevalence of CF, the status of disease, the diagnosis and treatment, the quality of care, and the health related outcomes in China.

Pulmonary lymphangioleiomyomatosis (LAM), a disease characterized by diffuse cystic changes in the lung, is a rare disorder that affects almost exclusively women. The main objectives of this study are to accurately evaluate the prevalence of LAM, the status of disease, the diagnosis and treatment, the quality of care, and the health related outcomes in China. This is a register study lasting 4 years, aims to raise 800 subjects. Primary endpoint is the annual change of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in pulmonary function tests.

Background: Liberation from mechanical ventilation (MV) involves a three-step process; weaning, readiness testing, and extubation. Readiness testing uses objective clinical criteria to determine whether a patient is ready to begin weaning from MV. These criteria include improvement of the underlying indication for MV, hemodynamic stability, and the ability to initiate and sustain both adequate inspiration and expiration. Successfully extubation from invasive MV is a critical milestone in the recovery from severe respiratory failure and and is a clinical challenge for clinicians. Spontaneous breathing trials (SBT) are conducted to evaluate a patient's readiness for ventilator liberation in the intensive care unit (ICU). Extubation is considered successful if invasive mechanical support is not required within 48 hours after the removal of the endotracheal tube. As the final step of the weaning process, the decision to extubate is typically guided by objective criteria demonstrating the patient's ability to sustain respiratory function without mechanical assistance. Considering the complex pathologies of intensive care patients, besides SBT many clinical parameters have been used as predictors of weaning and extubation. For this reason, different multi-component scales and scores have been developed. The study protocol is designed and will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. The aim of this study is to develop a multi-component Readiness for EXtubation score (REXs) that can predict extubation readiness and to analyze this score that can be applied to patients under invasive MV in the ICU. Sample Size: The sample size was calculated as 427 using the Area Under ROC Curve in the ExPreS study. The total targeted sample size was accepted 470 patients with estimating that there would be a 10% dropout. Screening and Admission: The daily screen will be performed between 8:00 and 10:00 a.m. by the clinician assigned to the unit each morning that the patient was on invasive mechanical ventilation. Patients meeting the criteria will be included in the study. Data Collection and Anonymization: The data collected are part of routine clinical care, and the data will be anonymized. Clinicians will add anonymously the data they obtain to a created electronic case report form (e-CRF). Clinicians will be allowed to assign numbers to patients so that they can be distinguished by the clinicians who add them. The dataset that constitute the e-CRF for each patient are; demographics (country, age, sex, BMI), ICU type, cause of ICU admission, number of comorbidities, weaning/extubation type, SBT duration, arterial blood gases (ABG: pH, PaCO2, PaO2), ventilation parameters (brand/model, FiO2, PEEP, ventilation index, RSBI, MVspont/MVtotal, PCF, P0.1, vital capacity, NIF, Cdyn), secretion type, agitation and sedation score (RASS), heart rate, hemoglobin, nutrition target percentage, ventilatory support after extubation, extubation failure (24,48 and 72 hrs), duration of invasive MV, ICU and hospital length of stay and mortality. pH: It measures the acidity or alkalinity of blood and is crucial for assessing acid-base balance. Normal arterial pH is 7.35-7.45. A pH lower than 7.35 indicates acidosis, while a pH higher than 7.45 indicates alkalosis. Abnormal pH can indicate metabolic or respiratory disorders. The pH of the blood is crucial when assessing the success of weaning. The pH outside the normal range can indicate an imbalance in acid-base homeostasis, which may suggest inadequate respiratory function or metabolic disturbances that would make weaning unsafe. Maintaining a normal pH ensures that the patient's respiratory and metabolic systems can function without requiring excessive ventilatory support. PaCO2: PaCO2 is a direct measure of ventilation. During weaning, a PaCO2 level within normal limits is needed for extubation success. Persistent hypercapnia during weaning suggests that the patient may be unable to sustain adequate ventilation on their own, leading to potential failure. PaO2/FiO2: This ratio is a measure of the severity of hypoxemia. During weaning, a higher PaO2/FiO2 ratio suggests that the lungs are functioning well enough to support breathing without mechanical assistance. A low ratio suggests the need for continued mechanical ventilation. PEEP: PEEP is used to prevent alveolar collapse and improve oxygenation. When weaning, reducing PEEP gradually helps assess whether the patient can maintain oxygenation without it. High levels of PEEP might be detrimental when reducing ventilatory support, as it can affect weaning success. Ventilation Index (VI): The ventilation index (VI) combines respiratory rate and tidal volume, giving an overall assessment of ventilation efficiency. A low VI is favorable during weaning because it indicates that the patient is able to achieve adequate ventilation with minimal support. VI is calculated as VI="(PIP\* PaCO2\*RR)/1000". Rapid Shallow Breathing Index (RSBI): The rapid shallow breathing index (RSBI), also known as the ratio of respiratory rate to tidal volume (RR/VT), is the most commonly used predictor of weaning success due to its simplicity and ease of interpretation. The clinical utility of the RSBI is emphasized in the 2007 international consensus guidelines for weaning from mechanical ventilation, the 2007 Brazilian consensus guidelines, and the 2013 Brazilian guidelines for mechanical ventilation, all of which recommend its use. MVspont/MVtotal: This ratio reflects the proportion of ventilation that is spontaneous versus mechanical in one minute. A higher spontaneous ventilation (MVspont) relative to total ventilation (MVtotal) indicates that the patient is relying less on mechanical support, which may be reflect favorable for weaning. Peak Cough Flow (PCF): PCF is an indicator of a patient's ability to clear secretions. Secretion retention is a key factor in weaning failure, as it increases respiratory load and is often linked to an ineffective cough. Evaluating cough strength in ICU patients can help predict weaning outcomes, as insufficient cough strength appears to be associated with higher in-hospital mortality. Consequently, assessing cough strength in intubated patients is increasingly being integrated into ICU extubation protocols. The subject is instructed to take a deep breath and cough as forcefully as possible. The clinician then freezes the ventilator screen and measures the maximal expiratory flow (L/min) from the flow curve. Clinicians can use the mechanical ventilator's algorithm if available. The average of three successful measurements will be taken. P0.1: In a study on healthy subjects, Whitelaw et al. conducted random, brief end-expiratory occlusions using a specialized circuit during both resting and CO2 rebreathing. They observed that the decrease in airway pressure (Paw) within the first 100 milliseconds (0.1 s) of an occluded breath remained relatively constant, was consistent for each subject under different conditions, and correlated more strongly with end-tidal CO2 than with minute ventilation. They introduced this parameter as airway occlusion pressure Pocc, or P0.1. P0.1 reflects the inspiratory effort of the patient. It is used to assess the respiratory drive. Normal P0.1 suggests that the patient has adequate respiratory drive to maintain spontaneous breathing. Clinicians can use the mechanical ventilator's algorithm if available. The average of three successful measurements will be taken. Vital Capacity (VC): Vital capacity (VC) reflects the total volume of air a person can exhale after a maximal inhalation. During weaning, a VC of at least 10-15 mL/kg is generally considered adequate for successful extubation. Vital capacity is measured by instructing patients to inhale deeply to their maximum capacity, followed by a forceful exhalation. The clinician then freezes the ventilator screen and measures maximal volume (mL) from the volume curve. Clinicians can use the mechanical ventilator's algorithm if available. The maximum of three successful measurements will be taken. Negative Inspiratory Force (NIF): Negative inspiratory force (NIF), also referred to as maximum inspiratory pressure, reflects the maximal effort of the inspiratory muscles during inhalation against an obstructed airway. This index is used to evaluate respiratory muscle strength, with a value greater than - 30 cm H2O serving as a criterion for initiating the mechanical ventilator weaning process. After exhaling, the patient is given the command to take a deep breath. The clinician freezes the screen when the patient perform the fastest inhalation during expiratory hold maneuver. The clinician measures the minimum pressure from the pressure curve. Clinicians can use the mechanical ventilator's algorithm if available. The minimum of three successful measurements will be taken. Cdyn: Dynamic compliance is a measure of lung and chest wall compliance during mechanical ventilation. High compliance typically indicates less stiff lungs, which is favorable during weaning. It is obtained by dividing the VT by the difference between PIP and PEEP. Secretion: In mechanically ventilated patients, the primary mechanisms of secretion clearance-mucociliary transport and cough-are impaired. Major contributing factors to pulmonary secretion retention include the presence of an artificial airway, insufficient humidification of inspired gases, and limited mobility. Ineffective secretion clearance increases the risk of ventilator dependency and reintubation due to airway obstruction, aspiration, or infection. Agitation/Sedation: Effective management of agitation and sedation is essential for successful weaning in mechanically ventilated patients, as both excessive sedation and agitation can impede the process. Over-sedation reduces respiratory drive, weakens respiratory muscles, prolongs ventilation, and increases the risk of ventilator-associated pneumonia. In contrast, agitation can heighten the work of breathing, increase the risk of self-extubation, and cause cardiovascular strain. The Richmond Agitation-Sedation Scale (RASS) is a 10-point tool that categorizes patient states, ranging from severe agitation (+4, combative) to deep sedation and unresponsiveness (-5), with 0 indicating a calm and alert state. Heart rate: Heart rate is an important indicator of cardiovascular stability during weaning. A significant increase in heart rate during mechanical ventilation or SBTs can signal distress, leading to the suspension of the weaning attempt. Hemoglobin: The impact of hemoglobin levels on weaning outcomes in mechanically ventilated patients remains controversial, with limited data, particularly for those experiencing difficult weaning. Patients with weaning difficulties may benefit more from higher hemoglobin levels than those in the early stages of respiratory failure, as sufficient hemoglobin is essential for adequate oxygen delivery during the weaning process. Lower hemoglobin levels reduce arterial oxygen content, impair oxygen delivery, and increase respiratory muscle workload, potentially hindering successful weaning. %Nutrition Target: Adequate nutrition is essential for survival and reducing hospital stay in critically ill patients, as it supports muscle strength, including respiratory muscles, which is crucial for successful weaning from mechanical ventilation. Malnutrition can impair weaning by weakening respiratory function. To guide evidence-based nutritional therapy, several global guidelines have been published. The American Society for Parenteral and Enteral Nutrition (ASPEN) and the Society of Critical Care Medicine (SCCM) recommend energy intake of 25-30 kcal/kg/day and protein intake of 1.2-2.0 g/kg/day, while the European Society for Parenteral and Enteral Nutrition (ESPEN) suggests 20-25 kcal/kg/day with 1.3 g/kg of protein equivalents per day. Statistical Analysis: Statistical analysis will be performed using IBM SPSS Statistics 26 (IBM Corp., Armonk, NY, USA). Categorical variables will be summarized as numbers (n) and frequencies (%). The Fisher's exact test will be applied for 2×2 contingency tables, and the Chi-square test will be used for all other contingencies to evaluate associations between clinical/demographic characteristics and extubation success or failure. For continuous variables, the Shapiro-Wilk test will be used to assess normality of distribution. Normally distributed variables will be summarized as means (± standard deviation), while non-normally distributed variables will be expressed as medians (with interquartile range). The independent samples Student's t-test will be employed to compare groups for normally distributed variables, and the Mann-Whitney U test will be used for non-normally distributed variables. All parameters with a p-value \< 0.4 in group comparisons (extubation success vs. failure) will be further investigated using univariable logistic regression analysis to assess their association with extubation outcome; odds ratios (OR) and 95% confidence intervals (CI) will be calculated. Receiver operating characteristic (ROC) analysis will be performed to evaluate the predictive value of each parameter. The cutoff values optimizing sensitivity and specificity will be determined using the Youden Index. The REXs cutoffs used in comparisons will be established based on the Youden Index. Finally, REXs cutoff values indicating low, moderate, and high probability of extubation risk will be determined.

Steering committee (chief investigators): Feng-Xue Zhu, Li Weng, Jian-Xin Zhou Aim. Our aim is to explore clinical and implementation factors relevant to a future definitive randomized controlled trial to evaluate PMI - and VT/RR - pressure support level setting strategies. The Inspiratory effort-targeted pressure support ventilation pragmatic pilot trial will test clinician adherence and to explore clinical outcomes. Study design and Work plan. Two centers are included in a pragmatic sequential cluster crossover pilot trial. The pressure support level setting strategy will be assigned according to the epoch. The first trial epoch will be assigned to VTRR - pressure support level setting strategy for 4 weeks, because that is the current standard practice in ICU prior to study initiation. The washout week between the two epochs will be 4 weeks. Then sequentially, it will be crossed over to PMI - pressure support level setting strategy for 4 weeks. Before each epoch, a one-week comprehensive training program will be conducted for all staff in the participating ICUs. Patients Mechanically ventilated patients admitted to the ICU with acute hypoxic respiratory failure (AHRF) will be consecutively screened daily at 08:00-10:00 morning rounds. Patients undergoing PSV are eligible for inclusion. The patients will be enrolled only once during the same hospitalization. Written informed consent will be obtained from the patient or their legal representative. Study Procedures In both PMI-targeted and VT/RR-targeted groups, standard clinical care for mechanical ventilation is followed according to local routine practice, which is formatted based on international clinical guidelines, except for pressure support adjustment during PSV. General standard of care for mechanical ventilation Analgesia is routinely used in mechanically ventilated patients with continuous infusion of fentanyl or remifentanil. Sedation with midazolam, propofol, or dexmedetomidine is used when the patient exhibits agitation and a light sedation level is maintained on RASS of -2 to +1 or Riker's SAS of 3 to 4. In patients with AHRF, mechanical ventilation is usually initiated on protective control ventilation, such as volume or pressure control mode, with VT 6-8 ml/kg predicted body weight (PBW), RR to control arterial partial pressure of carbon dioxide (PaCO2) and pH, and FiO2 and PEEP to maintain pulse arterial oxygen saturation (SpO2) between 90% and 95%. Transition of control modes to PSV During the morning rounds, the responsible ICU physicians check the ventilator mode for each patient. The ventilator mode is recommended to transit from controlled modes to PSV if all the following criteria are met: 1. The patient is able to trigger ventilator breaths; 2. PaO2/FiO2 above 100 mmHg; 3. PEEP below 15 cmH2O; 4. Stable hemodynamic status (none or stable doses of vasopressors); 5. No sedation or light sedation (\[RASS\] of -2 to +1 or \[SAS\] of 3 to 4). PSV setting strategy In both the PMI-targeted and VT/RR-targeted groups, the same principle PSV settings are followed except for the adjustment of pressure support level: 1. The inspiratory trigger sensitivity is set as 1-2 L/min for the flow-trigger or 1.5-3 cmH2O for the pressure-trigger; 2. Inspiration-to-expiration cycle-off is set as 25% of the peak inspiratory flow. Responsible physicians can adjust this parameter in case of suspected cycle-off patient-ventilator asynchrony; 3. FiO2 and PEEP are set to maintain SpO2 between 90% and 95%. Specifically, if SpO2 is lower than 90%, PEEP and then FiO2 will be increased by 2 cmH2O and 0.1, respectively; whereas if SpO2 is higher than 95%, FiO2 and then PEEP will be decreased by 0.1 and 2 cmH2O, respectively. In the VT/RR-targeted group, the pressure support is adjusted to obtain a VT between 6 and 8 ml/kg PBW, RR between 20 and 35 breaths/min, and no signs of respiratory distress, such as prominent use of the accessory respiratory muscles, nose flaring, retractions, etc. In the PMI-targeted group, the pressure support is adjusted according to the PMI between 0 and 2 cmH2O. During PSV, after an end-inspiratory airway occlusion, Paw will reach a plateau. PMI can be measured on the ventilator screen as plateau Paw minus peak Paw by using a sliding marking line when the screen frozen function is initiated. According to our previous studies, a PMI value of 0 to 2 cmH2O will be used as the target for pressure support adjustment. This PMI range represents a well-accepted normal inspiratory effort. During the study period in the two groups, pressure support adjustment will be performed at least twice daily. Rescue backup of controlled ventilation In both groups, PSV can be switched to protective controlled modes when predefined criteria are met, which include at least one of the following conditions: 1. Pressure support level above 20 cmH2O; 2. PEEP above 15 cmH2O; 3. pH \< 7.30; 4. PaO2/FiO2 ≤ 100 mmHg; 5. Strong inspiratory effort which cannot be controlled by sedation; 6. Unstable hemodynamic status (systolic blood pressure below 90 mmHg with vasopressors or systolic blood pressure above 180 mmHg); 7. Active cardiac ischemia; 8. Unconsciousness (RASS \< -3 or SAS \< 2); 9. Dangerous agitation that cannot be controlled by sedation (RASS \> +2 or SAS \> 6). Data will be documented in patients whose mechanical ventilation is switched to controlled modes. The patients will be reassessed at least every 12 hours and transited back to PSV as soon as possible according to the abovementioned criteria. The patients will be visited daily until 28 days after randomization. Data will be documented and reported for those patients whose controlled ventilation is not transited back to PSV during the follow-up. Weaning and extubation The weaning and extubation process follows clinical guidelines recommended by the American Thoracic Society and the American College of Chest Physicians. The attending physicians assess readiness to initiate the weaning process during daily morning rounds. If all the following aspects are satisfied, an SBT will be performed: 1. Improvement of the cause of intubation and mechanical ventilation; 2. Hemodynamic stability when the dose of norepinephrine is less than 0.1 μg/kg/min or equivalent and lasts for 6 hours at stable or reduced doses; 3. No agitation or coma; 4. SpO2 higher than 90% with FiO2 less than 0.4 and PEEP less than 5 cmH2O. SBT is conducted by respiratory therapists using the low-level PSV with pressure support of 5 cmH2O and PEEP of 5 cmH2O. The SBT will last at least 30 min, and criteria for failure of SBT include: 1. RR of greater than 35 breaths/min for more than 5 min; 2. SpO2 of less than 90%; 3. Elevated PaCO2 and/or pH of less than 7.3; 4. Heart rate (HR) of greater than 140 beats/min or a sustained change in HR of more than 20%; 5. Systolic blood pressure greater than 180 mmHg or less than 90 mmHg; 6. Signs of cardiac ischemia indicated by dynamic ST changes on ICU monitor or electrocardiogram; 7. Abrupt unconsciousness with RASS below -3 or SAS below 2; 8. Signs of anxiety, agitation, or diaphoresis. Patients with a failure SBT will be mechanically ventilated with PSV following settings and adjustments according to the original grouping. Extubation will be performed in endotracheal intubated patients who pass the SBT, and mechanical ventilation will be discontinued in patients with tracheostomy. PSV will be restored to maintain the grouping in patients with reintubation or reapplication of mechanical ventilation via tracheostomy within seven days. The decision to reintubate and restore mechanical ventilation will be at the discretion of the ICU physician team according to the local standard of care. The duration of mechanical ventilation will be added to the total duration. Data Collection An electronic case report form (eCRF) is designed and available online via Electronic Data Capture System (Yiduoyun medical health corporation, suzhou, china). Data collected at the study entry At baseline, demographics, comorbidities, diagnosis for ICU admission, recent medical history, reasons for mechanical ventilation, duration of ventilation before enrolment, conditions of gas exchange, and mechanical ventilation settings will be documented, as will the Acute Physiological and Chronic Health Evaluation II (APACHE II) score at the ICU admission. Data collection during daily visits All patients will be visited daily between 08:00 and 12:00 until successful weaning or separation of mechanical ventilation, death, hospital discharge, or until 28 days after randomization. Successful weaning or separation of mechanical ventilation is defined as extubation without reintubation or death within the next seven days, whether post-extubation noninvasive ventilation is used or not, or ICU discharge without invasive mechanical ventilation within seven days, whichever comes first. Data collected include: 1. Gas exchange: SpO2 and arterial blood gas analysis; 2. Hemodynamics: blood pressure, HR, vasoactive agents, and cumulative fluid balance during the last day; 3. Analgesia and sedation: RASS or SAS score, visual analog scale or critical care pain observation tool, the use of analgesics and sedatives; 4. Sequential Organ Failure Assessment (SOFA) score; 5. Switch to controlled ventilation: whether switching to controlled mode during the last 24 hours, reasons, and settings; 6. PSV: pressure support level, PEEP, FiO2, VT, and RR; 7. Respiratory drive: the negative airway pressure generated during the first 100 ms against an end-expiratory airway occlusion (airway occlusion pressure, P0.1) (29); 8. SBT: whether performing an SBT during the last 24 hours, methods, and results; 9. Extubation or discontinuation of mechanical ventilation: whether performed during the last 24 hours; 10. Re-intubation or restoration of mechanical ventilation: whether performed during the last 24 hours and reasons; 11. Tracheostomy: whether performed during the last 24 hours; 12. Self-extubation: whether occurring during the last 24 hours; 13. 28-day follow-up: duration of mechanical ventilation, length of stay in the ICU and hospital, and death. After the study, a questionnaire survey will be conducted involving all staff members in the participating ICUs. The survey mainly includes Likert scales to assess the PMI - pressure support level setting strategy acceptability and also assessed feasibility of conducting a full RCT. Additionally, we also have open-ended questions to understand the difficulties in implementation and ways to improve compliance.

Many newborn infants have breathing difficulty after birth, particularly when they are born prematurely. Many of these infants are supported with nasal continuous positive airway pressure (NCPAP). Some of the infants deteriorate despite treatment with NCPAP and have a thin catheter inserted into their trachea for the administration of surfactant, which is then immediately removed (often referred to as "less-invasive surfactant administration" or LISA). Insertion of a thin catheter is usually performed by doctors who are experienced at intubation (i.e. inserting endotracheal tubes, ETTs). They look directly into the the infants mouth using a standard laryngoscope to identify the opening of the airway (i.e. perform direct laryngoscopy). More recently video laryngoscopes have been developed. These devices display a magnified image of the airway on a screen that can be viewed indirectly by the doctor attempting to insert the ETT or thin catheter, and also by others. A single centre study reported that more infants were successfully intubated at the first attempt when doctors performed indirect video laryngoscopy compared to direct laryngoscopy. It is possible to independently verify when a doctor has correctly inserted and ETT, for example by detecting carbon dioxide coming out of the tube or seeing condensation in the tube during exhalation, or by hearing breath sounds by listening to the chest during positive pressure inflations. It is not possible to independently verify whether a doctor has correctly inserted a thin catheter under direct laryngoscopy, by these or other means. The standard (and to date only) way of confirming that a thin catheter has been correctly inserted is to rely on the report of the operator. Video laryngoscopy, in contrast, allows the independent verification of the tip of a thin catheter by one or more people observing the screen. The investigators are performing NEU-VODE, a stepped wedge cluster randomised study of the introduction of video laryngoscopy versus direct laryngoscopy for the intubation of newborn infants. Alongside this study, the investigators are performing a study of infants who have a thin endotracheal catheter inserted under video laryngoscopy versus direct laryngoscopy. As it is not possible to measure the outcome of successful insertion of the thin catheter equally in both groups, this is a prospective observational cohort study. The investigators will record information on infants who have a thin catheter inserted into the trachea for the purpose of surfactant administration at centres participating in the NEU-VODE study. The type of laryngoscope used for thin catheter insertion attempts will not be mandated; instead, the investigators will compare the information of groups within the cohort who have their first attempt made using the video laryngoscope to the group who have their first attempt made with direct laryngoscopy.

This randomized con aims to enroll patients at high risk of developing post-operative pulmonary complications after gynecological surgery, the eligible patients will be randomly assigned to receive oxygen therapy via high-flow nasal cannula or conventional nasal cannula. The study primary outcome is the incidence of post-operative pulmonary complications, including postoperative hypoxemia, atelectasis, pneumonia, etc. Secondary outcomes are the improvement of postoperative oxygenation, antibiotic use, length of hospital stay, adverse events related to oxygen therapy, etc.

The purpose of this study is to assess the immediate and long-term effects of structured breathing on clinical symptoms related to mental health including anxiety, depression, perceived stress, and sleep quality.