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BACKGROUND: High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. METHODS: NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO(2)) concentration. RESULTS: Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO(2) concentrations remained between 0.70 ppm (0.63–0.79) and 0.75 ppm (0.67–0.83) in the INO group and between 0.74 ppm (0.68–0.78) and 0.88 ppm (0.70–0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. CONCLUSIONS: This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension. Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6). Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7–10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and V./Q. matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13–4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2–0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15–6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the V./Q. ratio. Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure. Clinical trial registered with www.clinicaltrials.gov (NCT 02503241).

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 (StrainCT). Objectives: To compare the global StrainCT with the change in electrical impedance (ΔZ). Methods: Acute respiratory distress syndrome patients under mechanical ventilation (VT 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 StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. Main results: StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT. Conclusions: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., 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.

Secretion management in mechanically ventilated patients is a paramount task for clinicians. A better understanding of the mechanisms of flow bias and airway dynamic compression during airway clearance therapy may enable a more effective approach for this population. Ventilator hyperinflation, expiratory rib cage compression, a PEEP-ZEEP maneuver, and mechanical insufflation-exsufflation are examples of techniques that can be optimized according to such mechanisms. In addition, novel technologies, such as electric impedance tomography, may help improve airway clearance therapy by monitoring the consequences of regional secretion displacement on lung aeration and regional lung mechanics.

Background Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. Methods An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. Results Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. Conclusions Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Introduction General anesthesia is associated with the development of atelectasis, which may affect lung ventilation. Electrical impedance tomography (EIT) is a noninvasive imaging tool that allows monitoring in real time the topographical changes in aeration and ventilation. Objective To evaluate the pattern of distribution of pulmonary ventilation through EIT before and after anesthesia induction in pediatric patients without lung disease undergoing nonthoracic surgery. Methods This was a prospective observational study including healthy children younger than 5 years who underwent nonthoracic surgery. Monitoring was performed continuously before and throughout the surgical period. Data analysis was divided into 5 periods: induction (spontaneous breathing, SB), ventilation-5min, ventilation-30min, ventilation-late and recovery-SB. In addition to demographic data, mechanical ventilation parameters were also collected. Ventilation impedance (Delta Z) and pulmonary ventilation distribution were analyzed cycle by cycle at the 5 periods. Results Twenty patients were included, and redistribution of ventilation from the posterior to the anterior region was observed with the beginning of mechanical ventilation: on average, the percentage ventilation distribution in the dorsal region decreased from 54%(IC95%:49–60%) to 49%(IC95%:44–54%). With the restoration of spontaneous breathing, ventilation in the posterior region was restored. Conclusion There were significant pulmonary changes observed during anesthesia and controlled mechanical ventilation in children younger than 5 years, mirroring the findings previously described adults. Monitoring these changes may contribute to guiding the individualized settings of the mechanical ventilator with the goal to prevent postoperative complications.

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.

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower VT, lower driving pressure (DP), lower respiratory rates (RR), and higher end-expiratory pressure 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 the ventilator to the patient, calculated froma combination of several ventilator variables. Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the DP, VT, and RR. Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days. Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55623 yr). The average mechanical power was 0.3260.14 J _ min21 _ kg21 of predicted body weight, the DP was 15.065.8 cm H2O, and the RR was 25.767.4 breaths/ min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the DP on mortality was four times as large as that of the RR. Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the DP and RR was equivalent.

Nitric Oxide (NO) is administered as gas for inhalation to induce selective pulmonary vasodilation. It is a safe therapy, with few potential risks even if administered at high concentration. Inhaled NO gas is routinely used to increase systemic oxygenation in different disease conditions. The administration of high concentrations of NO also exerts a virucidal effect in vitro. Owing to its favorable pharmacodynamic and safety profiles, the familiarity in its use by critical care providers, and the potential for a direct virucidal effect, NO is clinically used in patients with coronavirus disease-2019 (COVID-19). Nevertheless, no device is currently available to easily administer inhaled NO at concentrations higher than 80 parts per million (ppm) at various inspired oxygen fractions, without the need for dedicated, heavy, and costly equipment. The development of a reliable, safe, inexpensive, lightweight, and ventilator-free solution is crucial, particularly for the early treatment of non-intubated patients outside of the intensive care unit (ICU) and in a limited-resource scenario. To overcome such a barrier, a simple system for the non-invasive NO gas administration up to 250 ppm was developed using standard consumables and a scavenging chamber. The method has been proven safe and reliable in delivering a specified NO concentration while limiting nitrogen dioxide levels. This paper aims to provide clinicians and researchers with the necessary information on how to assemble or adapt such a system for research purposes or clinical use in COVID-19 or other diseases in which NO administration might be beneficial.

Background Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). Methods This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. Results Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4–8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. Conclusions In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Made available in DSpace on 2021-06-25T11:13:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-28 Introduction and aim: Studies regarding asynchrony in patiients in the cardiac postoperative period are still only a few. The main objective of our study was to compare asynchronies incidence and its index (AI) in 3 different modes of ventilation (volume-controlled ventilation [VCV], pressure-controlled ventilation [PCV] and pressure-support ventilation [PSV]) after ICU admission for postoperative care. Methods: A prospective parallel randomised trialin the setting of a non-profitable hospital in Brazil. The participants were patients scheduled for cardiac surgery. Patients were randomly allocated to VCV or PCV modes of ventilation and later both groups were transitioned to PSV mode. Results: All data were recorded for 5 minutes in each of the three different phases: T1) in assisted breath, T2) initial spontaneous breath and T3) final spontaneous breath, a marking point prior to extubation. Asynchronies were detected and counted by visual inspection method by two independent investigators. Reliability, inter-rater agreement of asynchronies, asynchronies incidence, total and specific asynchrony indexes (AIt and AIspecific) and odds of AI ≥10% weighted by total asynchrony were analysed. A total of 17 patients randomly allocated to the VCV (n= 9) or PCV (n=8) group completed the study. High inter-rated agreement for AIt (ICC 0.978; IC95%, 0,963-0.987) and good reliability (r=0.945; p

Editor’s Perspective 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.

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.

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 (NO2) levels in the delivered NO gas. Lastly, we measured the inspired and expired NO and NO2 of this system in 5 healthy subjects during a 15-minute 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 NO2 concentration on average 0.9 ppm (95% CI -1.58, -0.22; p=0.01). 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 NO2 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., Highlights • We conceived and tested a NO delivery system for spontaneously breathing subjects. • A scavenger containing calcium hydroxide reduces the inspired NO2 concentration. • A reservoir bag reduces variations of NO concentration during breathing. • In five healthy subjects breathing 164.8±10.74ppm of NO, inspired NO2 was 0.7±0.13ppm. • In a healthy subject breathing 153 ppm of NO, the exhaled NO2 was 0.03 ppm.

Purpose. To assess the potential effectiveness or efficacy of early mobilization on respiratory and peripheral muscle strengths and functionality in nonintubated patients. Methods. For 40 nonintubated patients over 18 years of age with over 24-hour intensive care unit (ICU) stay allocated to a single intervention, an incremental mobilization protocol was initiated. Maximal inspiratory and expiratory pressures (MIP and MEP), peripheral muscle strength (handgrip strength (HGS) and Medical Research Council scale (MRC-s)), and functionality (FIM, ICF-BMS, PFIT-s, and FSS-ICU scales) were evaluated at ICU admission and discharge. Results. All outcomes were significantly improved (pre vs. post values): MIP (43.93 ± 21.95 vs. 54.12 ± 21.68 cmH2O; P<0.001), MEP (50.32 ± 28.65 vs. 60.30 ± 21.23; P=0.002), HGS (25.5 (9.58) vs. 27.5 (9.48); P=0.046), MRC-s (58.52 ± 2.84 vs. 59.47 ± 1.81; P=0.023), FIM (54.4 ± 22.79 vs. 69.48 ± 12.74), ICF-BMS (28.63 ± 16.19 vs. 14.03 ± 11.15), PFIT-s (9.55 ± 2.34 vs. 11.18 ± 1.32) (P<0.001), and FSS-ICU (28.7 ± 9.1 vs. 32.6 ± 5.0; P=0.001). The ceiling effect at admission/discharge was in MRC-s (60/82.5%), FSS-ICU (50/70%), and FIM (35/62.5%). The floor effect occurred at discharge in ICF-BMS (7.5/52.5%). Conclusions. The early mobilization protocol seemed effective at maintaining/increasing the respiratory muscle strength and functionality of nonintubated patients in critical care. Ceiling effect was high for MRC-s, FSS-ICU, and FIM scales.

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 JAMA, “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 et al. 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.

Obesity is a highly prevalent condition worldwide that aggravates symptoms of already existing conditions such as asthma and COPD. The limited effectiveness of inhaled medications in these individuals may be related to anatomic characteristics of their upper airways, mainly due to compressive factors.Controlled clinical trial with obese and nonobese individuals. The following variables were evaluated: anthropometric characteristics, Lung and airway deposition of radiolabeled aerosol (pulmonary scintigraphy), upper airways anatomy (CT scans), and modified Mallampati score.29 subjects (17 nonobese and 12 obese) participated. Obese volunteers presented 30% lower aerosol lung deposition compared to nonobese. Moreover, obese subjects Mallampati classification of 4 presented an aerosol lung deposition two times lower than nonobese subjects (p = 0.021). The cross-sectional area of the retropalatal region and retroglossal region were lower in obese patients (p 0.05), but no correlation to aerosol lung deposition was observed. BMI was associated with 32% of the variance of lung deposition (p 0.001; β -0.28; 95% CI -0.43 to -0.11).High BMI correlated to reduced percentage lung deposition. Also, modified Mallampati class 4 was even more detrimental to aerosol delivery into the lungs. Obese subjects have narrower upper airways, compared to nonobese, but this is not reflected in higher radiolabeled aerosol impaction into their oropharynx and does not predict the percentage of lung deposition in this group.NCT03031093 (clinicaltrials.org).

Introduction: Noninvasive ventilation has been widely used to prevent pulmonary complications after cardiac surgery. Electrical Impedance Tomography(EIT) has been highlighted as a tool to monitor the distribution of regional pulmonary ventilation. However, there are few studies available on the use of this tool in evaluating the effects of noninvasive ventilation(NIV). Objectives: To compare the effects of noninvasive ventilation with oxygen therapy(OT) on pulmonary aeration and ventilation in patients in the immediate postoperative period of cardiac surgery; Hypothesis: the use of non-invasive ventilation in patients in the postoperative period of cardiac surgery results in greater ventilation and greater aeration during and after intervention compared to the control group. Methods: Patients were randomized into two groups: NIV and OT (control). The evaluation was performed through EIT. Results: 16 patients were randomized, 9 in NIV group and 7 in OT group. Greater global end expiratory lung impedance (pulmonary aeration) was observed during NIV when compared to OT group (0,20±0,08 and 0,23±0,10 vs. -0,14±0,01 and -0,21±0,02, p value 0,009 and 0,013 respectively); but there was no maintenance of this improvement after intervention. There was also a greater variation of global impedance (ventilation) change during intervention (7,96 vs. 4,17, p value 0,03). Conclusion: There was increased global aeration and ventilation during noninvasive ventilation in patients in post-operative cardiac surgery, but there was no maintenance of aeration improvement after its interruption. Grants: FACEPE, CNPq and CAPES.

Background: Floor and ceiling effects of functional status (FS) and peripheral muscle strength (PMS) assessment scales are reported in patients under mechanical ventilation at Intensive Care Unit (ICU) (Parry, S.M. et al. Critical Care 2015; 19:127). These effects can influence sensibility and responsiveness of those scales to clinical changes of different health conditions. Objective: To evaluate the frequency of floor and ceiling effects of FS and PMS scales in non-intubated patients during ICU stay. Methods: 40 patients (26 men). Functional Independence Measure (FIM), Functional Status Score for the Intensive Care Unit (FSS-ICU), Physical Function ICU Test Score (PFIT-s), Basic Mobility Scale (ICF-BMS) and Medical Research Council score (MRC-s) were assessed at ICU admission and discharge. Floor and ceiling effects were calculated by percentage frequency of highest and lowest scores, respectively. Results: Mean age was 55.1(19.2) years old and SAPSIII was 41.7(11.0) points. The following results are all in Table 1. Conclusion: High magnitude of ceiling effect for FIM, FSS-ICU, PFIT-s and MRC-s as well as floor effect for ICF-BMS suggest that using these tools may be insufficient to detect changes in the FS and PMS of non-intubated critically ill patients during ICU stay. Table 1. Floor and ceiling effects in FS and PMS scores at ICU admission and discharge.

CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Outra Agência Individuals post-stroke may present restrictive ventilatory pattern generated from changes in the functionality of respiratory system due to muscle spasticity and contractures. Objective was to assess the acute effects after respiratory muscle stretching on the ventilatory pattern and volume distribution of the chest wall in stroke subjects. Ten volunteers with right hemiparesis after stroke and a mean age of 60 ± 5.7 years were randomised into the following interventions: respiratory muscle stretching and at rest (control). The ventilatory pattern and chest wall volume distribution were evaluated through optoelectronic plethysmography before and immediately after each intervention. Respiratory muscle stretching promoted a significant acute increase of 120 mL in tidal volume, with an increase in minute ventilation, mean inspiratory flow and mean expiratory flow compared with the control group. Pulmonary ribcage increased 50 mL after stretching, with 30 mL of contribution to the right pulmonary rib cage (hemiparetic side) in comparison to the control group. Respiratory muscle stretching in patients with right hemiparesis post-stroke demonstrated that acute effects improve the expansion of the respiratory system during tidal breathing.

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.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.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.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.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.

Acute respiratory distress syndrome (ARDS) is a clinical entity that acutely affects the lung parenchyma, and is characterized by diffuse alveolar damage and increased pulmonary vascular permeability. Currently, computed tomography (CT) is commonly used for classifying and prognosticating ARDS. However, performing this examination in critically ill patients is complex, due to the need to transfer these patients to the CT room. Fortunately, new technologies have been developed that allow the monitoring of patients at the bedside. Electrical impedance tomography (EIT) is a monitoring tool that allows one to evaluate at the bedside the distribution of pulmonary ventilation continuously, in real time, and which has proven to be useful in optimizing mechanical ventilation parameters in critically ill patients. Several clinical applications of EIT have been developed during the last years and the technique has been generating increasing interest among researchers. However, among clinicians, there is still a lack of knowledge regarding the technical principles of EIT and potential applications in ARDS patients. The aim of this review is to present the characteristics, technical concepts, and clinical applications of EIT, which may allow better monitoring of lung function during ARDS.

Introduction: Upon admission into ICU service not requiring mechanical ventilation, patients are usually considered less serious by the health care staff, which may conceal physical deficits at ICU admission which may worsen due reduced mobility during their stay. Aim: To evaluate respiratory and peripheral muscle strengths and functionality of critically ill non-ventilated patients admitted to the ICU within 48 hours. Methods: An observational study. In 82 patients (47 men), the following parameters were analysed: age, gender, SAPS III, respiratory muscle strength (MIP and MEP), peripheral muscle strength by MRC score, hand grip strength (HGS) and functionality by the functional independence measure scale (FIM), and the scored Physical Function in Intensive Care Test (PFIT-s). Results: The mean age was 57.8±19.54 years and SAPSIII was 44.1±12.6 points. Regarding the status of respiratory muscle strength, values of MIP and MEP below normal occurred in 85.7% and 80% in women and 70.2% and 72.3% in men, respectively. The MRC score was normal in all participants, but for HGS (based on the reference values by Shlussel, MM. et al. Clin Nutri. 2008), 58.5% of the participants presented a reduction; of these, 51.4% were women and 63.8% men. Regarding functionality, the median for FIM was 58 (44-71) points, representing 75.3% of the maximum score, while PFIT-s had a median of 10 (8-11) points, representing 83.3% of the maximum score. Conclusion: In a short stay in an ICU, it is possible to identify already committed changes in either respiratory and peripheral muscle strengths that may compromise functionality evaluated in the first 48 hours of admission.

Objectives Atelectasis develops in critically ill obese patients when undergoing mechanical ventilation due to increased pleural pressure. The current study aimed to determine the relationship between transpulmonary pressure, lung mechanics, and lung morphology and to quantify the benefits of a decremental positive end-expiratory pressure trial preceded by a recruitment maneuver. Design Prospective, crossover, nonrandomized interventional study. Setting Medical and Surgical Intensive Care Units at Massachusetts General Hospital (Boston, MA) and University Animal Research Laboratory (Sao Paulo, Brazil). Patients/subjects Critically ill obese patients with acute respiratory failure and anesthetized swine. Interventions Clinical data from 16 mechanically ventilated critically ill obese patients were analyzed. An animal model of obesity with reversible atelectasis was developed by placing fluid filled bags on the abdomen to describe changes of lung mechanics, lung morphology, and pulmonary hemodynamics in 10 swine. Measurements and main results In obese patients (body mass index, 48 ± 11 kg/m), 21.7 ± 3.7 cm H2O of positive end-expiratory pressure resulted in the lowest elastance of the respiratory system (18.6 ± 6.1 cm H2O/L) after a recruitment maneuver and decremental positive end-expiratory pressure and corresponded to a positive (2.1 ± 2.2 cm H2O) end-expiratory transpulmonary pressure. Ventilation at lowest elastance positive end-expiratory pressure preceded by a recruitment maneuver restored end-expiratory lung volume (30.4 ± 9.1 mL/kg ideal body weight) and oxygenation (273.4 ± 72.1 mm Hg). In the swine model, lung collapse and intratidal recruitment/derecruitment occurred when the positive end-expiratory transpulmonary pressure decreased below 2-4 cm H2O. After the development of atelectasis, a decremental positive end-expiratory pressure trial preceded by lung recruitment identified the positive end-expiratory pressure level (17.4 ± 2.1 cm H2O) needed to restore poorly and nonaerated lung tissue, reestablishing lung elastance and oxygenation while avoiding increased pulmonary vascular resistance. Conclusions In obesity, low-to-negative values of transpulmonary pressure predict lung collapse and intratidal recruitment/derecruitment. A decremental positive end-expiratory pressure trial preceded by a recruitment maneuver reverses atelectasis, improves lung mechanics, distribution of ventilation and oxygenation, and does not increase pulmonary vascular resistance.