Pegli, Italy

Nasal Intermittent Positive Pressure Ventilation(NIPPV) vs Continuous Positive Airway Pressure for Respiratory Distress Syndrome

To this day, early use of noninvasive respiratory support strategies has been suggested to be the most effective pathway to reduce those risks. Nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) are two widely used ways of noninvasive ventilation strategies in preterm infant. As compared with invasive ventilation, NCPAP reduces the risks abnormal neurodevelopment. However, there is only 60% success rate of avoiding intubation in the preterm neonate supported with NCPAP. Supplying with an intermittent peak pressure on NCPAP, NIPPV is considered as a strengthened version of NCPAP with increased flow delivery in the upper airway, increased minute volume and functional residual capacity and recruitment of collapsed alveoli, improved stability of the chest wall and reduced asynchrony of thoraco-abdominal movement,which have been proven to be crucial to decrease the incidences of invasive ventilation and death. However, studies have compared the effects between nasal intermittent positive pressure ventilation(NIPPV) and nasal continuous positive airway pressure(NCPAP) on the incidence of intubation in preterm infants, and the results were inconsistent.

Diaphragmatic Electrical Activity in Preterm Infants on Non-Invasive Ventilation

Continuous Positive Airway Pressure is one of the most researched and accepted methods of delivering NIV to term and preterm infants. Non-invasive high frequency ventilation is a relatively new method of delivering NIV respiratory support in preterm infants. Preliminary studies suggest superiority over CPAP, and NHFOV is being increasingly utilized in clinical practice in an attempt to prevent intubation and minimize ventilation-induced lung injury in preterm infants. However, little is known about its mechanism of action and its effect on respiratory mechanics in the newborn. The objective of this study is to compare the effects of non-invasive ventilation (NIV) delivered by nasal Continuous Positive Airway Pressure (CPAP) versus Non-Invasive High Frequency Ventilation (NHFOV) on respiratory pattern as assessed by the electrical activity of the diaphragm (EAdi) in very low birth weight (VLBW) preterm infants. The investigators hypothesize that in VLBW preterm infants with relative pulmonary insufficiency, NHFOV will reduce respiratory drive and improve ventilation, subsequently resulting in decreased patient diaphragm energy expenditure. This would be demonstrated by decreased neural respiratory rates and/or decreased peak electrical activity of the diaphragm while breathing on NHFOV compared to CPAP. Clinicians are seeking alternative methods for providing non-invasive respiratory support to preterm infants. NHFOV is a relatively new modality that is being increasingly utilized in clinical practice but has not been well studied. This study will help the investigators determine how non-invasive high frequency ventilation affects breathing in preterm infants, as compared to the more traditional modality of nasal CPAP. Therefore, clinicians will not only be able to better understand how NHFOV works, but also utilize this information to decide on the most appropriate respiratory support modality for preterm patients

Predictors of Intracranial Hemorrhage in ARDS Patients on ECMO

Dexmedetomidine Infusion and Postoperative Lung Aeration After Thoracic Surgery

Dexmedetomidine is an opioid-sparing anesthetic with minimal effect on adaptive physiologic processes such as respiratory drive and hypoxic pulmonary vasoconstriction (HPV). Recent translational research has demonstrated that dexmedetomidine is associated with less alveolar inflammation and better respiratory mechanics in thoracic surgery under one-lung ventilation (OLV). However, it is unclear whether such results translate into better postoperative lung aeration and superior pulmonary outcomes. Several biological mechanisms have been postulated to explain the lung protective effects of dexmedetomidine. Based on experimental models under OLV, dexmedetomidine has been shown to minimize mechanical ventilation-induced lung injury through the inhibition of inflammatory pathways, thus enhancing pulmonary function recovery, improving respiratory mechanics, and potentially preventing postoperative pulmonary complications (PPCs). There is also clinical evidence to suggest dexmedetomidine may improve respiratory mechanics as well as prevents non-cardiopulmonary complications such as acute kidney injury (AKI) in adult cardiac surgical patients, as well as delirium in both cardiac and non-cardiac patients. The research group from the BWH anesthesia department recently conducted a meta-analysis about the current evidence on dexmedetomidine in thoracic surgery, demonstrating beneficial effects in atelectasis and hypoxemia with low to moderate certainty. Unfortunately, current trials on this topic have limited sample size, and do not provide accurate and standardized outcome measurements. Dexmedetomidine has been shown to have organ protection properties, but there is no conclusive evidence to support its use for pulmonary protection in thoracic surgery. This trial would be the first to demonstrate an effect of dexmedetomidine on the trajectory of postoperative lung aeration and diaphragmatic excursion measured by ultrasound. Furthermore, the feasibility of a large, randomized controlled trial on dexmedetomidine for the prevention of pulmonary complications in thoracic surgery will be assessed. It is important to note that all the trials conducted on this topic have been conducted in Asia (limiting its generalizability), are relatively small (sample size of 30-50 patients) and have studied mainly respiratory mechanics. Postoperative pulmonary complications are relatively common among patients undergoing thoracic surgery. The development of PPCs raises hospital costs (5,000-10,000 USD), prolong length of hospital stay (2-3 days), and affects quality of recovery. Similarly, lung aeration loss is considered a subclinical characteristic of lung injury induced by OLV, which can persist for several days after thoracic surgery. Several protective ventilatory strategies have been proposed to prevent PPCs, such as low tidal volume (TV) (i.e., TV [< 6mL/kg] and alveolar recruitment), yet the literature shows conflicting results, and the incidence of pulmonary complications continues to occur. Therefore, it is imperative to study and implement novel, pharmacologic lung protective interventions in thoracic surgery for the prevention of lung aeration loss and subsequent pulmonary complications. In this study protocol, dexmedetomidine is postulated as an adjunct with possible pulmonary clinical benefits. Previous evidence suggests a possible effect on atelectasis, hypoxemia, and pneumonia, but the certainty of the evidence is low to moderate. Undertaking a pilot trial on dexmedetomidine and lung aeration in thoracic surgery would be useful to assess the feasibility for a large, randomized trial. 2. Specific Aims and Objectives Objective #1: To determine the feasibility of a trial assessing the effect of dexmedetomidine administration on postoperative lung aeration after thoracic surgery. Objective #2: To compare the effect of dexmedetomidine administration protocol versus placebo on postoperative lung aeration and diaphragmatic excursion measured by lung ultrasound. Objective #3: To evaluate the adherence to a protocol of dexmedetomidine administration during thoracic surgery under one-lung ventilation. 3. General Description of Study Design This will be a randomized, placebo-controlled, double-blinded, pilot trial with two parallel groups (1:1 ratio) receiving either dexmedetomidine (initial bolus of 1 mcg/kg over 30 min after induction, followed by an infusion rate of 0.3 mcg/kg/hr that will be stopped 30-45 minutes before the end of the surgery or once a maximum dose of 2mcg/kg has been achieved, whichever comes first) or placebo (normal saline as a bolus followed by maintenance infusion at the same rate of the intervention group). Dexmedetomidine is frequently administered in thoracic surgery. Using local data from the Brigham and Women's Hospital, dexmedetomidine was used in a third of the thoracic procedures performed over the past three years. However, there is no consensus as to the optimal protocol of administration, therefore clinical practice is highly heterogeneous (bolus versus continuous infusion) and mostly depends on the preferences of anesthesia providers. At the Brigham and Women's Hospital, the dose of dexmedetomidine is typically 0.5 mcg/kg but varies based on attending preferences and experience. Given the heterogenous practices in dexmedetomidine administration, one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcg/kg over 30 minutes after induction followed by a continuous infusion of 0.3 mcg/kg/hr. The infusion will be stopped 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcg/kg has been achieved, whichever comes first. The control group will receive normal saline (similar bolus followed by maintenance infusion at the same rate of the intervention group). 4. Subject Selection Inclusion criteria: • Adult patients (Age >18 years until 80 years) undergoing lobectomy and/or segmentectomy. Exclusion Criteria: - Urgent or emergency thoracic surgery. - Other concomitant non-pulmonary procedures (pleurectomy, diaphragmatic procedures, pericardiocentesis, esophageal procedures, thymectomy). - Prior lung resection surgery. - Epidural block for intraoperative or postoperative analgesia. - Preoperative arrhythmia (first or second degree AV block without pacemaker) or significant bradycardia (heart rate < 50). - Preoperative hypotension (mean arterial blood pressure < 65 mmHg). - Severe functional liver or kidney disease. - Non-English speakers - Consent withdrawal. Identification of individuals will be completed every day through Epic. The list of thoracic surgeries will be reviewed each day by one of the co-investigators. Individuals will be contacted via phone 24-48 hours prior to the surgery for pre-screening questions and to determine their interest in participating in the study. Individuals will be consented on the day of surgery at the preoperative area by one of the co-investigators. Women and minorities will be represented in this study and will reflect the thoracic surgery population at Brigham and Women's Hospital (BWH) undergoing the eligible procedures. Based on prior studies conducted on this patient population, we estimate that the sample population will be 57% women, approximately 6% African American, 5% Asian, and 11% Latino. Patients over 65 years old comprise 52%, and low-income population is 4%. The investigators will make every effort to ensure proportional representation by sex/gender, race, and ethnicity (subjects are a sample of thoracic surgical patients), so the investigators do not expect significant deviations from these estimates. 5. Subject Enrollment Allocation of individuals to the groups will be performed using a predetermined randomized sequence, which will be generated using the asymptotic maximal procedure (https://ctrandomization.cancer.gov/about/). Eligible patients will be contacted via phone call within 24-48 hours prior to surgery for pre-screening questions and assess possible participation in the study. On the day of surgery, the participant will be approached by one of the investigators who will explain further details of the trial and provide an electronic informed consent (e-Consent) on a tablet. 6. STUDY PROCEDURES Pharmacy will be contacted the day before to start processing the study drug based on the randomization list. A research collaborator will collect intraoperative information prospectively, including time to start study drug, time of lung isolation, time of two lung ventilation, respiratory mechanics, and compliance with administration protocol. In the postoperative period, patients will be followed up for 2 days. In the PACU, an investigator will scan anterior, lateral, and posterior quadrants of both lungs, estimate the lung ultrasound score (see Appendix), and save the images. A second independent investigator will estimate the scores independently. Serial assessments will be performed preoperatively (in the preoperative area), immediately after surgery in the recovery area, and at postoperative days 1 and 2. The assessment of complications will end at post-operative day 30. Safety outcomes and pulmonary complications will be collected by another blinded investigator. Primary outcome: • Lung aeration score measured by ultrasound at the post-anesthesia care unit (PACU) as described by Monastesse et al. Serial assessments will be performed at postoperative days 1 and 2 (POD1 and POD2): time frame of measurements 2 days. Secondary outcomes: - Diaphragmatic dysfunction: defined as a diaphragmatic excursion < 1cm - Intraoperative hypoxemia (SpO2 < 90%) - Postoperative atelectasis (radiographic evidence of lung collapse: descriptive parameter) - Pneumonia - radiologic evidence of consolidation (descriptive parameter), - fever (temperature T>38.5C) - white cell count (WBC) > 10G/L. - Acute respiratory distress syndrome (ARDS) - PaO2/FiO2 <200 - acute onset - bilateral lung infiltrates on chest radiograph - absence of heart failure - Pulmonary edema (clinical description from chest radiograph - Reintubation. - Timeframe for assessment of complications: 30 days. 7. Risks and Discomforts Protection Of Human Subjects - Human Subject Involvement and Characteristics There is a risk of breach of confidentiality with individually identifiable health information. The database will have de-identified data using an assigned ID on all study related documents. Once the patient consents to the protocol, he or she will be assigned a unique patient identifier number. As a result, the study database will hold strictly de-identified data using an arbitrary participant ID; paper forms will be stored in a secure location and referenced only for scheduling contacts; and a bridging table associating the two entities will be stored in yet another secure location. Upon initiating the study, all data will be collected and processed using rigorous quality-control methods. As the data forms are completed, they will be entered by the research staff into the secure access de-identified database. All paper forms will be stored in a locked cabinet in a locked room in a secure building. Neither the name of the patient nor any other personally identifying information will be used in any reports or publications that result from this study. Potential Risks: The study will not alter the surgeon's or patient's plan for surgery. A participant may be at risk if they have an adverse reaction to the medication (dexmedetomidine). Dexmedetomidine has been reported to have the following clinical side effects: - Bradycardia - Hypotension - Somnolence 8. Benefits Increasing understanding of the possible lung protective mechanisms of dexmedetomidine. Patients in the dexmedetomidine group may also benefit from better pain control given the long-acting analgesic effects of dexmedetomidine. 9. Statistical Analysis An exploratory analysis of baseline demographic and clinical characteristics will be performed. Compliance with the protocol of dexmedetomidine and/or placebo will be calculated as a percentage of complete adherence to the administration of either solution as stated above. Feasibility will be defined as a compliance greater than 80%. Both groups will be compared in terms of lung ultrasound score in each side (operative vs non-operative) of the thorax at PACU, and postoperative days 1 and 2. Similarly, secondary outcomes (diaphragmatic dysfunction, pulmonary complications) will be compared between both groups. Our analysis will be adjusted for multiple testing hypothesis. The estimated sample size is 100 patients (50 patients in each group) assuming a mean LUS of 14 vs 11 between the control and intervention groups, respectively, with a standard deviation of 5, a missing follow-up of 10%, an alpha error of 0.05, and 80% power. All statistical analyses will be performed in Stata v14.0 (College Station, TX, USA). Analysis: Continuous variables will be reported as means ± standard deviation (SD) or median with their corresponding interquartile ranges based on the distribution of the data, which will be determine using Kolmogorov test. Dichotomous variables will be reported as numbers (percentages). Between-group comparisons of continuous variables will be performed using the independent Student t test. P values < 0.05 will be considered statistically significant. Descriptive statistics will be used to report patient demographics and baseline characteristics. Proportion of participants with postoperative pulmonary complications during admission will be reported (units: percentage). This will be extracted from the patient's electronic medical health records by a co-investigator.

Pulmonary and Inflammatory Responses Following Exposure to a Low Concentration of Ozone or Clean Air

Potential health effects of ozone have been extensively studied over decades at various levels of exposure concentration and for varying time periods in young healthy adult subjects. Effects of ozone have been well documented particularly for decrements of lung function and an influx of neutrophils and other markers of pulmonary inflammation. The majority of those studies were done at ozone concentrations between 0.12 and 0.40 ppm, considerably higher than the current EPA NAAQS ozone standard of 0.070 ppm, and at exposure durations of two hours, even though the current standard is an 8-hour standard. However, a small number of studies have assessed changes in lung function following exposure to low levels of ozone for several hours. These latter studies have shown that exposure to ozone for 6.6 hours at concentrations between 0.06 and 0.08 ppm causes mild reversible decrements in lung function (1.7-10%) as measured by forced vital capacity (FVC) and forced expired volume at 1 s (FEV1) immediately after exposure in healthy young adults. In addition, in one study an increase in ozone-induced neutrophils was seen in induced sputum following exposure to 0.06 ppm ozone (8) and in bronchoalveolar lavage fluid) following exposure to 0.08 ppm ozone (9). The EPA is considering whether the current ozone NAAQS standard at 0.070 is protective and has asked EPA researchers to conduct a study similar to those done at 0.06 and 0.08 ppm.

Features of Regional Perfusion of Lung Consolidation

Lung consolidation is one of the most causes of hypoxia in intensive care unit(ICU) settings. A quantitative measurement of consolidation would be extremely benefit for the clinical management in hypoxemia, both as an index of severity and to predict outcomes.In order to quantify the lung consolidation and its effect on clinical outcomes, a simple and quantitative scoring system of the size and perfusion of lung consolidation was proposed by lung ultrasound. Subjects with respiratory failure and lung consolidation proved by chest imaging underwent lung ultrasound examination. The size of consolidation and the richness of blood flow was computed upon lung ultrasound. The sensitivity, specificity and accuracy of the scoring system were calculated and compared to evaluate the diagnostic efficacy.

Prevalence, Impact and Reversibility of Acute Diaprhagmatic Dysfunction in Acute Respiratory Detresse

A Modified Mathematical Model to Calculate Power Received by Mechanically Ventilated Patients With Different Etiologies

Mesenchymal Stem Cell for Acute Respiratory Distress Syndrome Due for COVID-19

Acute Respiratory Distress Syndrome (ARDS) is the main cause of death from COVID-19. One of the main mechanisms for ARDS is the storm of cytokines and chemokines, which cause uncontrolled fatal systemic inflammation. The SARS-CoV-2 virus infects cells that express the angiotensin II converting enzyme receptor (ACE2). This receptor is widely distributed on the surface of type II alveolar cells (AT2) and on the capillary endothelium. This is why the cytokine storm will trigger a violent attack by the immune system on the body, cause ARDS and multiple organ failure, and can ultimately lead to death. Mortality in cases of severe SIRA caused by COVID 19 varies significantly between 50 and 90%, basically depending on the age of the patient and the presence of comorbidities. The plasticity of Mesenchymal Stem Cell (MSC) regulates inflammation and immunity. MSC can promote and inhibit an immune response, depending on the dynamics of inflammation and depending on the activation force of the immune system, the types of inflammatory cytokines present, and the effects of immunosuppressants. Essentially, the state of inflammation determines the immunoregulatory fate of MSC. Thus, IV application of MSC has been shown to control the inflammatory response in various diseases, such as the graft-versus-host reaction and the ARDS caused by H5NI. MSC are negative for ACE2, therefore they have been used to decrease the cytokine storm present in COVID-19. Two recent studies in China have used human allogeneic MSC to treat COVID-19 pneumonia. Both studies reveal a marked reversal of symptoms, even in critically serious cases. Lung function improved two days after MSC application and 10 days later they were discharged. Lymphocytes increased, PCR decreased, and cytokine-producing immune cells disappeared within 3 to 6 days. Regulatory immune cells increased. TNF alpha factor decreased and IL10 increased. Taking into account the previous concepts together with the current global pandemic, and the high mortality existing among patients with bilateral pneumonia caused by COVID-19 and severe ARDS, the investigators propose intravenous infusion of mesenchymal stem cells from bank laboratory, with the purpose partially proven to decrease the systemic inflammatory process, offering it as a salvage treatment. Five patients, of either sex, over 18 years of age, with bilateral pneumonia caused by COVID-19 and severe ARDS that has not improved in relation to the following parameters: a) Persistent PaO2 / FiO2 less than 150, b) persistent fever, c ) D-dimer increase of at least 50% of baseline and / or ferritin greater than 1000, after 48 h of hospital stay receiving the standard management measures used at that time in the care center, will be included in the study. Covid pneumonia should be confirmed by chest CT and RNA detection by positive SARS-Cov2 PCR. This treatment will be administered after discussing it with the relatives that it is a procedure considered as rescue and will be carried out with informed consent. Their follow-up will be daily while they are hospitalized in the Intensive Care Unit and / or hospitalized, until their discharge from the hospital or until the third week after surgery. If the patient has already been discharged from the hospital, his last evaluation will be in the third week. The main objective of this protocol is: To describe the clinical changes secondary to IV administration of MSC, in patients with bilateral COVID-19 pneumonia complicated by severe ARDS, with the evaluation of the PaO2 / FiO2 ratio, heart rate and respiratory rate, as well as of the fever curve daily. The secondary objectives are: a) To assess the effect of the proposed treatment on the general biochemical indicators (Leukocytes, absolute lymphocytes, absolute neutrophils, absolute monocytes, absolute eosinophils, absolute basophils, erythrocytes, hemoglobin, platelets, total bilirubin, albumin, amino-aspartate transferase, fibrinogen, procalcitonin, glomerular filtration, myoglobin, troponin, ferritin and D-dimer. Daily. b. To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of cytokines, and C-reactive protein, TNFa, IL10, IL1, IL6, IL17, VEGF in plasma. These variables will be evaluated before treatment, upon discharge from the ICU, and / or from the Hospital. c. Assess the radiological evolution of the proposed treatment through simple chest CT. These variables will be evaluated before treatment, upon discharge from the ICU, and / or from the Hospital. d. Evaluate immune system improvement with mass cytometry to analyze patients' immune cells: regulatory T cells (CXCR3-), dendritic cells (DC, CXCR3-), CXCR3 + CD4 + T, CXCR3 + CD + T, and CXCRT3 + NK. These variables will be evaluated before treatment, upon discharge from the ICU, and / or from the Hospital. e) Assess the safety of the proposed treatment (allergic reactions and / or infection) F. To assess the negativization of the RNA detection test by SARS-Cov2 PCR. These variables will be evaluated before treatment, upon discharge from the ICU, and / or from the Hospital. The inclusion criteria are: 1. Comply with the informed consent procedure and sign the informed consent form. 2. Over 18 years 3. Of any gender 4. With SARS-Cov2 PCR RNA detection test, positive 5. With bilateral pneumonia caused by COVID-19 6. Severe ARDS with PaO2 / FiO2 less than 150 7. That it has not improved in relation to: a) Persistent PaO2 / FiO2 less than 150, b) persistent fever, c) increase in D-dimer at least 50% of the baseline and / or ferritin greater than 1000, after 48 hrs hospital stay receiving the standard management measures used at that time in the care center. 8. Lymphopenia less than 800 total lymphocytes 9. Increased D-dimer (> 1200 mg / dl) 10. CT compatible with bilateral pneumonia 11. SOFA under 11 With knowledge of the patient and / or their responsible relatives that it is a rescue treatment, in an experimental phase. The bank mesenchymal cells will be donated by the CBCells Bio Technology Laboratory, at no cost to the patient or INCMNSZ. 1x106 x Kg of weight, diluted in 100 ml of saline, will be infused intravenously, to pass in 40 minutes. It will be monitored with monitors, Pao2 / Fio2, FC, FR, ECG. Additionally, fever and muscle contractures will be monitored, which will be recorded every hour for 24 hours and every 24 hours thereafter, up to three weeks after the application of MSC. The patient should continue with their indicated medical treatments, such as antibiotics and specific treatments in case of comorbidities. The results will be compared with the historical controls attended at INCMNSZ Thus, the results obtained will give information to calculate the sample size in subsequent studies in which the usefulness of the procedure will be evaluated.

Effect of PEEP Titration on the EELV Measured by the Nitrogen Dilution Technique in ARDS

The application of positive end expiratory pressure is recommended but the question remains "How to set the best positive end-expiratory pressure (PEEP) level for each patient? ". Different titration techniques have been studied on oxygenation and respiratory mechanics parameters without reaching a consensus. Currently we have a module that is connected to the ventilator to collect the patient's lung volume. It will therefore allow us to optimize the settings of the ventilator and to set the best level of positive end-expiratory pressure "best peep" in order to individualize our treatment for each patient.