Publications by authors named "Caio C A Morais"

16 Publications

  • Page 1 of 1

Diminishing Efficacy of Prone Positioning With Late Application in Evolving Lung Injury.

Crit Care Med 2021 Apr 28. Epub 2021 Apr 28.

1 Department of Radiology, University of Pennsylvania, Philadelphia, PA. 2 Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, PA. 3 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 4 Department of Radiology, University of Iowa, Iowa City, IA. 5 Department of Biomedical Engineering, Boston University, Boston, MA. 6 Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA. 7 Department of Physiology, University of Pennsylvania, Philadelphia, PA.

Objectives: It is not known how lung injury progression during mechanical ventilation modifies pulmonary responses to prone positioning. We compared the effects of prone positioning on regional lung aeration in late versus early stages of lung injury.

Design: Prospective, longitudinal imaging study.

Setting: Research imaging facility at The University of Pennsylvania (Philadelphia, PA) and Medical and Surgical ICUs at Massachusetts General Hospital (Boston, MA).

Subjects: Anesthetized swine and patients with acute respiratory distress syndrome (acute respiratory distress syndrome).

Interventions: Lung injury was induced by bronchial hydrochloric acid (3.5 mL/kg) in 10 ventilated Yorkshire pigs and worsened by supine nonprotective ventilation for 24 hours. Whole-lung CT was performed 2 hours after hydrochloric acid (Day 1) in both prone and supine positions and repeated at 24 hours (Day 2). Prone and supine images were registered (superimposed) in pairs to measure the effects of positioning on the aeration of each tissue unit. Two patients with early acute respiratory distress syndrome were compared with two patients with late acute respiratory distress syndrome, using electrical impedance tomography to measure the effects of body position on regional lung mechanics.

Measurements And Main Results: Gas exchange and respiratory mechanics worsened over 24 hours, indicating lung injury progression. On Day 1, prone positioning reinflated 18.9% ± 5.2% of lung mass in the posterior lung regions. On Day 2, position-associated dorsal reinflation was reduced to 7.3% ± 1.5% (p < 0.05 vs Day 1). Prone positioning decreased aeration in the anterior lungs on both days. Although prone positioning improved posterior lung compliance in the early acute respiratory distress syndrome patients, it had no effect in late acute respiratory distress syndrome subjects.

Conclusions: The effects of prone positioning on lung aeration may depend on the stage of lung injury and duration of prior ventilation; this may limit the clinical efficacy of this treatment if applied late.
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April 2021

Ventilatory Variables and Mechanical Power in Patients with Acute Respiratory Distress Syndrome.

Am J Respir Crit Care Med 2021 Mar 30. Epub 2021 Mar 30.

Universidade de São Paulo, 28133, Laboratório de Pneumologia LIM-09, Disciplina de Pneumologia, Heart Institute (Incor), Hospital das Clínicas da Faculdade de Medicina , Sao Paulo, Brazil.

Rationale: Mortality in Acute Respiratory Distress Syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower tidal-volumes, lower driving pressures, lower respiratory rates, and higher end-expiratory pressures have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from ventilator to the patient, calculated from a combination of several ventilator variables.

Objectives: We aimed to assess the impact of mechanical power on mortality in patients with ARDS as compared to that of primary ventilator variables such as driving pressure, tidal volume, and respiratory rate.

Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of ARDS patients who had participated in six randomized clinical trials of protective mechanical ventilation, and one large observational cohort of ARDS patients. The primary outcome was mortality at 28 or 60 days.

Measurements And Main Results: We included 4,549 patients (38% women; mean age, 55±23 years). Average mechanical power was 0.32±0.14 J.min-1.Kg-1 predicted body weight, driving pressure was 15.0±5.8 cmH2O, and respiratory rate was 25.7±7.4 breaths/minute. Driving pressure, respiratory rate, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of driving pressure on mortality was four times as large as that of respiratory rate.

Conclusion: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS but a simpler model using only driving pressure and respiratory rate was equivalent.
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March 2021

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

Acta Anaesthesiol Scand 2021 02 26;65(2):228-235. Epub 2020 Oct 26.

Unidad de Pacientes Críticos, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile.

Rationale: Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (Strain ).

Objectives: To compare the global Strain with the change in electrical impedance (ΔZ).

Methods: Acute respiratory distress syndrome patients under mechanical ventilation (V 6 mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine Strain at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between Strain and ΔZ. Linear regression models were used to predict the change in lung Strain between different PEEP levels based on the change in ΔZ.

Main Results: Strain was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in Strain (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R 0.855, P < .001 at global level) with a high agreement between predicted and measured Strain .

Conclusions: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.
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February 2021

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in ARDS with Class III Obesity.

Am J Respir Crit Care Med 2020 Sep 2. Epub 2020 Sep 2.

Massachusetts General Hospital, 2348, Boston, Massachusetts, United States.

Obesity is characterized by elevated pleural pressure (P) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). To determine the effects of lung recruitment maneuver (LRM) in the presence of elevated P on hemodynamics, left and right ventricular pressures and pulmonary vascular resistance. We hypothesized that elevated P protects the cardiovascular system against high airway pressures and prevents lung overdistension. First, an interventional crossover trial in adult subjects with ARDS and BMI ≥35 kg/m (n=21) was performed to explore the hemodynamic consequences of LRM. Second, cardiovascular function was studied during low/high PEEPs in a model of swine with ARDS and high P (n=9) versus healthy swine with normal P (n=6). Subjects with ARDS and obesity (BMI=57±12 kg/m), following LRM, required an increase in PEEP of 8[7, 10] cmHO above traditional ARDSnet settings to improve lung function, oxygenation and ventilation/perfusion matching, without impairment of hemodynamics or right heart function. ARDS swine with high P demonstrated unchanged transmural left ventricle pressure and systemic blood pressure after LRM protocol. Pulmonary artery hypertension decreased 8[13, 4] mmHg, as did vascular resistance 1.5[2.2, 0.9] WU, and transmural right ventricle pressure 10[15, 6] mmHg during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized ventilation/perfusion ratio. High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. Additionally, patients with ARDS and class III obesity tolerate hemodynamically LRM with high airway pressure.
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September 2020

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19).

Obstet Gynecol 2020 12;136(6):1109-1113

Department of Anesthesia, the Department of Pediatrics, the Respiratory Care Department, the Department of Obstetrics and Gynecology, and the Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts; and the Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking.

Method: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160-200 ppm) nitric oxide by mask twice daily and report on their clinical response.

Experience: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission.

Conclusion: Nitric oxide at 160-200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.
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December 2020

Ideation and assessment of a nitric oxide delivery system for spontaneously breathing subjects.

Nitric Oxide 2020 11 21;104-105:29-35. Epub 2020 Aug 21.

Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:

Background: There is an increasing interest in safely delivering high dose of inhaled nitric oxide (NO) as an antimicrobial and antiviral therapeutics for spontaneously breathing patients. A novel NO delivery system is described.

Methods: We developed a gas delivery system that utilizes standard respiratory circuit connectors, a reservoir bag, and a scavenging chamber containing calcium hydroxide. The performance of the system was tested using a mechanical lung, assessing the NO concentration delivered at varying inspiratory flows. Safety was assessed in vitro and in vivo by measuring nitrogen dioxide (NO) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO of this system in 5 healthy subjects during a 15-min administration of high dose NO (160 parts-per-million, ppm) using our delivery system.

Results: The system demonstrated stable delivery of prescribed NO levels at various inspiratory flow rates (0-50 L/min). The reservoir bag and a high flow of entering air minimized the oscillation of NO concentrations during inspiration on average 4.6 ppm for each 10 L/min increment in lung inspiratory flow. The calcium hydroxide scavenger reduced the inhaled NO concentration on average 0.9 ppm (95% CI -1.58, -0.22; p = .01). We performed 49 NO administrations of 160 ppm in 5 subjects. The average concentration of inspired NO was 164.8±10.74 ppm, with inspired NO levels of 0.7±0.13 ppm. The subjects did not experience any adverse events; transcutaneous methemoglobin concentrations increased from 1.05±0.58 to 2.26±0.47%.

Conclusions: The system we developed to administer high-dose NO for inhalation is easy to build, reliable, was well tolerated in healthy subjects.
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November 2020

High PEEP may have reduced injurious transpulmonary pressure swings in the ROSE trial.

Crit Care 2019 12 11;23(1):404. Epub 2019 Dec 11.

Divisao de Pneumologia, Instituto do Coracao, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

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December 2019

Lung Recruitment in Obese Patients with Acute Respiratory Distress Syndrome.

Anesthesiology 2019 05;130(5):791-803

From the Department of Anesthesia, Critical Care and Pain Medicine (J.F., R.R.S.S., M.T.D., C.Z., L.B.) the Respiratory Care Department (R.M.K.) the Department of Radiology (F.J.F., F,M.T.), Massachusetts General Hospital, Boston, Massachusetts the Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (Incor), Hospital Das Clínicas, Faculty of Medicine, University of Sao Paulo, São Paulo, Brazil (C.C.A.M., M.B.P.A.). Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Respiratory Care Department, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Background: Obese patients are characterized by normal chest-wall elastance and high pleural pressure and have been excluded from trials assessing best strategies to set positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). The authors hypothesized that severely obese patients with ARDS present with a high degree of lung collapse, reversible by titrated PEEP preceded by a lung recruitment maneuver.

Methods: Severely obese ARDS patients were enrolled in a physiologic crossover study evaluating the effects of three PEEP titration strategies applied in the following order: (1) PEEPARDSNET: the low PEEP/FIO2 ARDSnet table; (2) PEEPINCREMENTAL: PEEP levels set to determine a positive end-expiratory transpulmonary pressure; and (3) PEEPDECREMENTAL: PEEP levels set to determine the lowest respiratory system elastance during a decremental PEEP trial following a recruitment maneuver on respiratory mechanics, regional lung collapse, and overdistension according to electrical impedance tomography and gas exchange.

Results: Fourteen patients underwent the study procedures. At PEEPARDSNET (13 ± 1 cm H2O) end-expiratory transpulmonary pressure was negative (-5 ± 5 cm H2O), lung elastance was 27 ± 12 cm H2O/L, and PaO2/FIO2 was 194 ± 111 mmHg. Compared to PEEPARDSNET, at PEEPINCREMENTAL level (22 ± 3 cm H2O) lung volume increased (977 ± 708 ml), lung elastance decreased (23 ± 7 cm H2O/l), lung collapse decreased (18 ± 10%), and ventilation homogeneity increased thus rising oxygenation (251 ± 105 mmHg), despite higher overdistension levels (16 ± 12%), all values P < 0.05 versus PEEPARDSnet. Setting PEEP according to a PEEPDECREMENTAL trial after a recruitment maneuver (21 ± 4 cm H2O, P = 0.99 vs. PEEPINCREMENTAL) further lowered lung elastance (19 ± 6 cm H2O/l) and increased oxygenation (329 ± 82 mmHg) while reducing lung collapse (9 ± 2%) and overdistension (11 ± 2%), all values P < 0.05 versus PEEPARDSnet and PEEPINCREMENTAL. All patients were maintained on titrated PEEP levels up to 24 h without hemodynamic or ventilation related complications.

Conclusions: Among the PEEP titration strategies tested, setting PEEP according to a PEEPDECREMENTAL trial preceded by a recruitment maneuver obtained the best lung function by decreasing lung overdistension and collapse, restoring lung elastance, and oxygenation suggesting lung tissue recruitment.
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May 2019

Individual Positive End-expiratory Pressure Settings Optimize Intraoperative Mechanical Ventilation and Reduce Postoperative Atelectasis.

Anesthesiology 2018 12;129(6):1070-1081

From Divisao de Anestesia, Terapia Intensiva e Dor (S.M.P., C.M.S., B.F.F.T., M.S.P., J.E.V.) Divisao de Pneumologia, Instituto do Coracao (S.M.P., M.R.T., C.C.A.M., M.B.P.A.), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil Anesthesia Department, Hospital Sírio-Libanes, Sao Paulo, Brazil (C.M.S., B.F.F.T, ) UT Southwestern Medical Center - Radiology Department, Dallas, Texas (F.U.K.) Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino Policlinico Hospital, University of Genoa, Italy (P.P.).

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Intraoperative lung-protective ventilation has been recommended to reduce postoperative pulmonary complications after abdominal surgery. Although the protective role of a more physiologic tidal volume has been established, the added protection afforded by positive end-expiratory pressure (PEEP) remains uncertain. The authors hypothesized that a low fixed PEEP might not fit all patients and that an individually titrated PEEP during anesthesia might improve lung function during and after surgery.

Methods: Forty patients were studied in the operating room (20 laparoscopic and 20 open-abdominal). They underwent elective abdominal surgery and were randomized to institutional PEEP (4 cm H2O) or electrical impedance tomography-guided PEEP (applied after recruitment maneuvers and targeted at minimizing lung collapse and hyperdistension, simultaneously). Patients were extubated without changing selected PEEP or fractional inspired oxygen tension while under anesthesia and submitted to chest computed tomography after extubation. Our primary goal was to individually identify the electrical impedance tomography-guided PEEP value producing the best compromise of lung collapse and hyperdistention.

Results: Electrical impedance tomography-guided PEEP varied markedly across individuals (median, 12 cm H2O; range, 6 to 16 cm H2O; 95% CI, 10-14). Compared with PEEP of 4 cm H2O, patients randomized to the electrical impedance tomography-guided strategy had less postoperative atelectasis (6.2 ± 4.1 vs. 10.8 ± 7.1% of lung tissue mass; P = 0.017) and lower intraoperative driving pressures (mean values during surgery of 8.0 ± 1.7 vs. 11.6 ± 3.8 cm H2O; P < 0.001). The electrical impedance tomography-guided PEEP arm had higher intraoperative oxygenation (435 ± 62 vs. 266 ± 76 mmHg for laparoscopic group; P < 0.001), while presenting equivalent hemodynamics (mean arterial pressure during surgery of 80 ± 14 vs. 78 ± 15 mmHg; P = 0.821).

Conclusions: PEEP requirements vary widely among patients receiving protective tidal volumes during anesthesia for abdominal surgery. Individualized PEEP settings could reduce postoperative atelectasis (measured by computed tomography) while improving intraoperative oxygenation and driving pressures, causing minimum side effects.
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December 2018

Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.

Am J Respir Crit Care Med 2018 04;197(8):1018-1026

2 Translational Medicine, Departments of Critical Care Medicine and Anesthesia, Hospital for Sick Children, and.

Rationale: Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl.

Objectives: To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl.

Methods: In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure.

Measurements And Main Results: In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values.

Conclusions: These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.
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April 2018

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

Am J Respir Crit Care Med 2018 05;197(10):1285-1296

2 Intensive Care Unit, Osaka University Hospital, Suita, Japan.

Rationale: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious.

Objectives: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP).

Methods: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS.

Measurements And Main Results: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients).

Conclusions: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.
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May 2018

Noninvasive ventilation for acute respiratory distress syndrome: the importance of ventilator settings.

J Thorac Dis 2016 Sep;8(9):E982-E986

Respiratory ICU, Pulmonary Division, Heart Institute (INCOR), Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.

Noninvasive ventilation (NIV) is commonly used to prevent endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Patients with hypoxemic acute respiratory failure who fail an NIV trial carry a worse prognosis as compared to those who succeed. Additional factors are also knowingly associated with worse outcomes: higher values of ICU severity score, presence of severe sepsis, and lower ratio of arterial oxygen tension to fraction of inspired oxygen. However, it is still unclear whether NIV failure is responsible for the worse prognosis or if it is merely a marker of the underlying disease severity. There is therefore an ongoing debate as to whether and which ARDS patients are good candidates to an NIV trial. In a recent paper published in , "Effect of Noninvasive Ventilation Delivered by Helmet vs. Face Mask on the Rate of Endotracheal Intubation in Patients with Acute Respiratory Distress Syndrome: A Randomized Clinical Trial", Patel . evaluated ARDS patients submitted to NIV and drew attention to the importance of the NIV interface. We discussed their interesting findings focusing also on the ventilator settings and on the current barriers to lung protective ventilation in ARDS patients during NIV.
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September 2016