First real-time imaging of bronchoscopic lung volume reduction by electrical impedance tomography.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) with one-way endobronchial valves (EBV) has better outcomes when the target lobe has poor collateral ventilation, resulting in complete lobe atelectasis. High-inspired oxygen fraction (FIO2) promotes atelectasis through faster gas absorption after airway occlusion, but its application during BLVR with EBV has been poorly understood. We aimed to investigate the real-time effects of FIO2 on regional lung volumes and regional ventilation/perfusion by electrical impedance tomography (EIT) during BLVR with EBV. METHODS: Six piglets were submitted to left lower lobe occlusion by a balloon-catheter and EBV valves with FIO2 0.5 and 1.0. Regional end-expiratory lung impedances (EELI) and regional ventilation/perfusion were monitored. Local pocket pressure measurements were obtained (balloon occlusion method). One animal underwent simultaneous acquisitions of computed tomography (CT) and EIT. Regions-of-interest (ROIs) were right and left hemithoraces. RESULTS: Following balloon occlusion, a steep decrease in left ROI-EELI with FIO2 1.0 occurred, 3-fold greater than with 0.5 (p < 0.001). Higher FIO2 also enhanced the final volume reduction (ROI-EELI) achieved by each valve (p < 0.01). CT analysis confirmed the denser atelectasis and greater volume reduction achieved by higher FIO2 (1.0) during balloon occlusion or during valve placement. CT and pocket pressure data agreed well with EIT findings, indicating greater strain redistribution with higher FIO2. CONCLUSIONS: EIT demonstrated in real-time a faster and more complete volume reduction in the occluded lung regions under high FIO2 (1.0), as compared to 0.5. Immediate changes in the ventilation and perfusion of ipsilateral non-target lung regions were also detected, providing better estimates of the full impact of each valve in place. TRIAL REGISTRATION: Not applicable.

Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

OBJECTIVE: It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. DESIGN: Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. SETTING: University animal research laboratory. SUBJECTS: Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. MEASUREMENTS AND MAIN RESULTS: The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. CONCLUSION: In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial.

Importance: Perioperative lung-protective ventilation has been recommended to reduce pulmonary complications after cardiac surgery. The protective role of a small tidal volume (VT) has been established, whereas the added protection afforded by alveolar recruiting strategies remains controversial. Objective: To determine whether an intensive alveolar recruitment strategy could reduce postoperative pulmonary complications, when added to a protective ventilation with small VT. Design, Setting, and Participants: Randomized clinical trial of patients with hypoxemia after cardiac surgery at a single ICU in Brazil (December 2011-2014). Interventions: Intensive recruitment strategy (n=157) or moderate recruitment strategy (n=163) plus protective ventilation with small VT. Main Outcomes and Measures: Severity of postoperative pulmonary complications computed until hospital discharge, analyzed with a common odds ratio (OR) to detect ordinal shift in distribution of pulmonary complication severity score (0-to-5 scale, 0, no complications; 5, death). Prespecified secondary outcomes were length of stay in the ICU and hospital, incidence of barotrauma, and hospital mortality. Results: All 320 patients (median age, 62 years; IQR, 56-69 years; 125 women [39%]) completed the trial. The intensive recruitment strategy group had a mean 1.8 (95% CI, 1.7 to 2.0) and a median 1.7 (IQR, 1.0-2.0) pulmonary complications score vs 2.1 (95% CI, 2.0-2.3) and 2.0 (IQR, 1.5-3.0) for the moderate strategy group. Overall, the distribution of primary outcome scores shifted consistently in favor of the intensive strategy, with a common OR for lower scores of 1.86 (95% CI, 1.22 to 2.83; P = .003). The mean hospital stay for the moderate group was 12.4 days vs 10.9 days in the intensive group (absolute difference, -1.5 days; 95% CI, -3.1 to -0.3; P = .04). The mean ICU stay for the moderate group was 4.8 days vs 3.8 days for the intensive group (absolute difference, -1.0 days; 95% CI, -1.6 to -0.2; P = .01). Hospital mortality (2.5% in the intensive group vs 4.9% in the moderate group; absolute difference, -2.4%, 95% CI, -7.1% to 2.2%) and barotrauma incidence (0% in the intensive group vs 0.6% in the moderate group; absolute difference, -0.6%; 95% CI, -1.8% to 0.6%; P = .51) did not differ significantly between groups. Conclusions and Relevance: Among patients with hypoxemia after cardiac surgery, the use of an intensive vs a moderate alveolar recruitment strategy resulted in less severe pulmonary complications while in the hospital. Trial Registration: clinicaltrials.gov Identifier: NCT01502332.

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

Importance: The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. Objective: To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. Design, Setting, and Participants: Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. Interventions: An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501; experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. Main Outcomes and Measures: The primary outcome was all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day 28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU, in-hospital, and 6-month mortality. Results: A total of 1010 patients (37.5% female; mean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95% CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%; HR, 1.18; 95% CI, 1.01 to 1.38; P = .04), decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, -1.1; 95% CI, -2.1 to -0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%; difference, 2.0%; 95% CI, 0.0% to 4.0%; P = .03), and the risk of barotrauma (5.6% vs 1.6%; difference, 4.0%; 95% CI, 1.5% to 6.5%; P = .001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. Conclusions and Relevance: In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT01374022.

Esophageal balloon catheter system identification to improve respiratory effort time features and amplitude determination.

Objective. Understanding a patient's respiratory effort and mechanics is essential for the provision of individualized care during mechanical ventilation. However, measurement of transpulmonary pressure (the difference between airway and pleural pressures) is not easily performed in practice. While airway pressures are available on most mechanical ventilators, pleural pressures are measured indirectly by an esophageal balloon catheter. In many cases, esophageal pressure readings take other phenomena into account and are not a reliable measure of pleural pressure.Approach.A system identification approach was applied to provide accurate pleural measures from esophageal pressure readings. First, we used a closed pressurized chamber to stimulate an esophageal balloon and model its dynamics. Second, we created a simplified version of an artificial lung and tried the model with different ventilation configurations. For validation, data from 11 patients (five male and six female) were used to estimate respiratory effort profile and patient mechanics.Main results.After correcting the dynamic response of the balloon catheter, the estimates of resistance and compliance and the corresponding respiratory effort waveform were improved when compared with the adjusted quantities in the test bench. The performance of the estimated model was evaluated using the respiratory pause/occlusion maneuver, demonstrating improved agreement between the airway and esophageal pressure waveforms when using the normalized mean squared error metric. Using the corrected muscle pressure waveform, we detected start and peak times 130 ± 50 ms earlier and a peak amplitude 2.04 ± 1.46 cmH2O higher than the corresponding estimates from esophageal catheter readings.Significance.Compensating the acquired measurements with system identification techniques makes the readings more accurate, possibly better portraying the patient's situation for individualization of ventilation therapy.

A comprehensive physical functional assessment of survivors of critical care unit stay due to COVID-19.

OBJECTIVE: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. METHODS: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). RESULTS: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. CONCLUSION: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.

Quantitative analysis of pulmonary perfusion with dual-energy CT angiography: comparison of two quantification methods in patients with pulmonary embolism.

The study aimed to evaluate a quantification method of pulmonary perfusion with Dual-Energy CT Angiography (DE-CTA) normalized by lung density in the prediction of outcome in acute pulmonary embolism (PE). In this prospective study with CTA scans acquired with different breathing protocols, two perfusion parameters were calculated: %PBV (relative value of PBV, expressed per unit volume) and PBVm (PBV normalized by lung density, expressed per unit mass). DE-CTA parameters were correlated with simplified pulmonary embolism severity index (sPESI) and with outcome groups, alone and in combinationwith tomographic right-to-left ventricular ratios (RV/LV). PBVm showed significant correlation with sPESI. PBVm presented higher accuracy than %PBV In the prediction of ICU admission or death in patients with PE, with the best performance when combined with RV/LV volumetric ratio.

Lobar pulmonary perfusion quantification with dual-energy CT angiography: Interlobar variability and relationship with regional clot burden in pulmonary embolism.

Purpose: Semi-automated lobar segmentation tools enable an anatomical assessment of regional pulmonary perfusion with Dual-Energy CTA (DE-CTA). We aimed to quantify lobar pulmonary perfusion with DE-CTA, analyze the perfusion distribution among the pulmonary lobes in subjects without cardiopulmonary diseases and assess the correlation between lobar perfusion and regional endoluminal clots in patients with acute pulmonary embolism (PE). Methods: We evaluated 151 consecutive subjects with suspected PE and without cardiopulmonary comorbidities. DE-CTA derived perfused blood volume (PBV) of each pulmonary lobe was measured applying a semi-automated lobar segmentation technique. In patients with PE, blood clot location was assessed, and CT-based vascular obstruction index of each lobe (CTOIlobe) was calculated and classified into three groups: CTOIlobe= 0, low CTOIlobe (1-50%) and high CTOIlobe (>50%). Results: Among patients without PE (103/151, 68.2%), median lobar PBV was 13.7% (IQR 10.2-18.0%); the right middle lobe presented lower PBV when compared to all the other lobes (p < .001). In patients with PE (48/151, 31.8%), lobar PBV was 12.6% (IQR 9.6-15.7%), 13.7% (IQR 10.1-16.7%) and 6.5% (IQR 5.1-10.2%) in the lobes with CTOIlobe= 0, low CTOIlobe and high CTOIlobe scores, respectively, with a significantly decreased PBV in the lobes with high CTOIlobe score (p < .001). ROC analysis of lobar PBV for prediction of high CTOIlobe score revealed AUC of 0.847 (95%CI 0.785-0.908). Conclusion: Pulmonary perfusion was heterogeneously distributed along the pulmonary lobes in patients without cardiopulmonary diseases. In patients with PE, the lobes with high vascular obstruction score (CTOIlobe> 50%) presented a decreased lobar perfusion.

Pleural Pressure Targeted Positive Airway Pressure Improves Cardiopulmonary Function in Spontaneously Breathing Patients With Obesity.

BACKGROUND: Increased pleural pressure affects the mechanics of breathing of people with class III obesity (BMI > 40 kg/m2). RESEARCH QUESTION: What are the acute effects of CPAP titrated to match pleural pressure on cardiopulmonary function in spontaneously breathing patients with class III obesity? STUDY DESIGN AND METHODS: We enrolled six participants with BMI within normal range (control participants, group I) and 12 patients with class III obesity (group II) divided into subgroups: IIa, BMI of 40 to 50 kg/m2; and IIb, BMI of ≥ 50 kg/m2. The study was performed in two phases: in phase 1, participants were supine and breathing spontaneously at atmospheric pressure, and in phase 2, participants were supine and breathing with CPAP titrated to match their end-expiratory esophageal pressure in the absence of CPAP. Respiratory mechanics, esophageal pressure, and hemodynamic data were collected, and right heart function was evaluated by transthoracic echocardiography. RESULTS: The levels of CPAP titrated to match pleural pressure in group I, subgroup IIa, and subgroup IIb were 6 ± 2 cmH2O, 12 ± 3 cmH2O, and 18 ± 4 cmH2O, respectively. In both subgroups IIa and IIb, CPAP titrated to match pleural pressure decreased minute ventilation (IIa, P = .03; IIb, P = .03), improved peripheral oxygen saturation (IIa, P = .04; IIb, P = .02), improved homogeneity of tidal volume distribution between ventral and dorsal lung regions (IIa, P = .22; IIb, P = .03), and decreased work of breathing (IIa, P < .001; IIb, P = .003) with a reduction in both the work spent to initiate inspiratory flow as well as tidal ventilation. In five hypertensive participants with obesity, BP decreased to normal range, without impairment of right heart function. INTERPRETATION: In ambulatory patients with class III obesity, CPAP titrated to match pleural pressure decreased work of breathing and improved respiratory mechanics while maintaining hemodynamic stability, without impairing right heart function. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02523352; URL: www.clinicaltrials.gov.

Protective mechanical ventilation in suspected influenza infection.

INTRODUCTION: Patients with acute respiratory failure due to influenza require ventilatory support. However, mechanical ventilation itself can exacerbate lung damage and increase mortality. METHODS: The aim of this study was to describe a feasible and protective ventilation protocol, with limitation of the tidal volume to ≤6 mL/kg of the predicted weight and a driving pressure ≤15 cmH2O after application of the alveolar recruitment maneuver and PEEP titration. RESULTS: Initial improvement in oxygenation and respiratory mechanics were observed in the four cases submitted to the proposed protocol. CONCLUSIONS: Our results indicate that the mechanical ventilation strategy applied could be optimized.

Driving Pressure-limited Strategy for Patients with Acute Respiratory Distress Syndrome. A Pilot Randomized Clinical Trial.

Rationale: Evidence from observational studies suggests that driving pressure is strongly associated with pulmonary injury and mortality, regardless of positive end-expiratory pressure (PEEP) levels, tidal volume, or plateau pressure. Therefore, it is possible that targeting driving pressure may improve the safety of ventilation strategies for patients with acute respiratory distress syndrome (ARDS). However, the clinical effects of a driving pressure-limited strategy for ARDS has not been assessed in randomized controlled trials.Objectives: To evaluate the feasibility of testing a driving pressure-limited strategy in comparison with a conventional lung-protective ventilation strategy in patients with ARDS and a baseline driving pressure of ≥13 cm H2O.Methods: This was a randomized, controlled, nonblinded trial that included 31 patients with ARDS who were on invasive mechanical ventilation and had a driving pressure of ≥13 cm H2O. Patients allocated to the driving pressure-limited strategy were ventilated with volume-controlled or pressure-support ventilation modes, with tidal volume titrated to 4-8 ml/kg of predicted body weight (PBW), aiming at a driving pressure of 10 cm H2O, or the lowest possible. Patients in the control group were ventilated according to the ARDSNet (Acute Respiratory Distress Syndrome Network) protocol, using a tidal volume of 6 ml/kg PBW, which was allowed to be set down to 4 ml/kg PBW if the plateau pressure was >30 cm H2O. The primary endpoint was the driving pressure on Days 1-3.Results: Sixteen patients were randomized to the driving pressure-limited group and 15 were randomized to the conventional strategy group. All patients were considered in analyses. Most of the patients had mild ARDS with a mean arterial oxygen tension/fraction of inspired oxygen ratio of 215 (standard deviation [SD] = 95). The baseline driving pressure was 15.0 cm H2O (SD = 2.6) in both groups. In comparison with the conventional strategy, driving pressure from the first hour to the third day was 4.6 cm H2O lower in the driving pressure-limited group (95% confidence interval [CI], 6.5 to 2.8; P < 0.001). From the first hour up to the third day, tidal volume in the driving pressure-limited strategy group was kept lower than in the control group (mean difference [ml/kg of PBW], 1.3; 95% CI, 1.7 to 0.9; P < 0.001). We did not find statistically significant differences in the incidence of severe acidosis (pH < 7.10) within 7 days (absolute difference -12.1; 95% CI, -41.5 to -17.3) or any clinical secondary endpoint.Conclusions: In patients with ARDS, a trial assessing the effects of a driving pressure-limited strategy using very low tidal volumes versus a conventional ventilation strategy on clinical outcomes is feasible.Clinical trial registered with ClinicalTrials.gov (NCT02365038).

A comprehensive physical functional assessment of survivors of critical care unit stay due to COVID-19 / Avaliação físico-funcional abrangente de sobreviventes de internação em unidade de terapia intensiva devido à COVID-19

ABSTRACT Objective: To examine the physical function and respiratory muscle strength of patients - who recovered from critical COVID-19 - after intensive care unit discharge to the ward on Days one (D1) and seven (D7), and to investigate variables associated with functional impairment. Methods: This was a prospective cohort study of adult patients with COVID-19 who needed invasive mechanical ventilation, non-invasive ventilation or high-flow nasal cannula and were discharged from the intensive care unit to the ward. Participants were submitted to Medical Research Council sum-score, handgrip strength, maximal inspiratory pressure, maximal expiratory pressure, and short physical performance battery tests. Participants were grouped into two groups according to their need for invasive ventilation: the Invasive Mechanical Ventilation Group (IMV Group) and the Non-Invasive Mechanical Ventilation Group (Non-IMV Group). Results: Patients in the IMV Group (n = 31) were younger and had higher Sequential Organ Failure Assessment scores than those in the Non-IMV Group (n = 33). The short physical performance battery scores (range 0 - 12) on D1 and D7 were 6.1 ± 4.3 and 7.3 ± 3.8, respectively for the Non-Invasive Mechanical Ventilation Group, and 1.3 ± 2.5 and 2.6 ± 3.7, respectively for the IMV Group. The prevalence of intensive care unit-acquired weakness on D7 was 13% for the Non-IMV Group and 72% for the IMV Group. The maximal inspiratory pressure, maximal expiratory pressure, and handgrip strength increased on D7 in both groups, but the maximal expiratory pressure and handgrip strength were still weak. Only maximal inspiratory pressure was recovered (i.e., > 80% of the predicted value) in the Non-IMV Group. Female sex, and the need and duration of invasive mechanical were independently and negatively associated with the short physical performance battery score and handgrip strength. Conclusion: Patients who recovered from critical COVID-19 and who received invasive mechanical ventilation presented greater disability than those who were not invasively ventilated. However, they both showed marginal functional improvement during early recovery, regardless of the need for invasive mechanical ventilation. This might highlight the severity of disability caused by SARS-CoV-2.

RESUMO Objetivo: Examinar a função física e a força muscular respiratória de pacientes que se recuperaram da COVID-19 grave após a alta da unidade de terapia intensiva para a enfermaria nos Dias 1 e 7 e investigar as variáveis associadas ao comprometimento funcional. Métodos: Trata-se de estudo de coorte prospectivo de pacientes adultos com COVID-19 que necessitaram de ventilação mecânica invasiva, ventilação mecânica não invasiva ou cânula nasal de alto fluxo e tiveram alta da unidade de terapia intensiva para a enfermaria. Os participantes foram submetidos aos testes Medical Research Council sum-score, força de preensão manual, pressão inspiratória máxima, pressão expiratória máxima e short physical performance battery. Os participantes foram agrupados em dois grupos conforme a necessidade de ventilação mecânica invasiva: o Grupo Ventilação Mecânica Invasiva (Grupo VMI) e o Grupo Não Ventilação Mecânica Invasiva (Grupo Não VMI). Resultados: Os pacientes do Grupo VMI (n = 31) eram mais jovens e tinham pontuações do Sequential Organ Failure Assessment mais altas do que os do Grupo VMI (n = 33). As pontuações do short physical performance battery (intervalo de zero a 12) nos Dias 1 e 7 foram 6,1 ± 4,3 e 7,3 ± 3,8, respectivamente para o Grupo Não VMI, e 1,3 ± 2,5 e 2,6 ± 3,7, respectivamente para o Grupo VMI. A prevalência de fraqueza adquirida na unidade de terapia intensiva no Dia 7 foi de 13% para o Grupo Não VMI e de 72% para o Grupo VMI. A pressão inspiratória máxima, a pressão expiratória máxima e a força de preensão manual aumentaram no Dia 7 em ambos os grupos, porém a pressão expiratória máxima e a força de preensão manual ainda eram fracas. Apenas a pressão inspiratória máxima foi recuperada (ou seja, > 80% do valor previsto) no Grupo Não VMI. As variáveis sexo feminino, e necessidade e duração da ventilação mecânica invasiva foram associadas de forma independente e negativa à pontuação do short physical performance battery e à força de preensão manual. Conclusão: Os pacientes que se recuperaram da COVID-19 grave e receberam ventilação mecânica invasiva apresentaram maior incapacidade do que aqueles que não foram ventilados invasivamente. No entanto, os dois grupos de pacientes apresentaram melhora funcional marginal durante a fase inicial de recuperação, independentemente da necessidade de ventilação mecânica invasiva. Esse resultado pode evidenciar a gravidade da incapacidade causada pelo SARS-CoV-2.

Fuzzy modeling of electrical impedance tomography images of the lungs.

OBJECTIVES: Aiming to improve the anatomical resolution of electrical impedance tomography images, we developed a fuzzy model based on electrical impedance tomography's high temporal resolution and on the functional pulmonary signals of perfusion and ventilation. INTRODUCTION: Electrical impedance tomography images carry information about both ventilation and perfusion. However, these images are difficult to interpret because of insufficient anatomical resolution, such that it becomes almost impossible to distinguish the heart from the lungs. METHODS: Electrical impedance tomography data from an experimental animal model were collected during normal ventilation and apnea while an injection of hypertonic saline was administered. The fuzzy model was elaborated in three parts: a modeling of the heart, the pulmonary ventilation map and the pulmonary perfusion map. Image segmentation was performed using a threshold method, and a ventilation/perfusion map was generated. RESULTS: Electrical impedance tomography images treated by the fuzzy model were compared with the hypertonic saline injection method and computed tomography scan images, presenting good results. The average accuracy index was 0.80 when comparing the fuzzy modeled lung maps and the computed tomography scan lung mask. The average ROC curve area comparing a saline injection image and a fuzzy modeled pulmonary perfusion image was 0.77. DISCUSSION: The innovative aspects of our work are the use of temporal information for the delineation of the heart structure and the use of two pulmonary functions for lung structure delineation. However, robustness of the method should be tested for the imaging of abnormal lung conditions. CONCLUSIONS: These results showed the adequacy of the fuzzy approach in treating the anatomical resolution uncertainties in electrical impedance tomography images.

Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial. / Plano de análise estatística para o Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). Ensaio controlado randomizado.

BACKGROUND: The Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) is an international multicenter randomized pragmatic controlled trial with allocation concealment involving 120 intensive care units in Brazil, Argentina, Colombia, Italy, Poland, Portugal, Malaysia, Spain, and Uruguay. The primary objective of ART is to determine whether maximum stepwise alveolar recruitment associated with PEEP titration, adjusted according to the static compliance of the respiratory system (ART strategy), is able to increase 28-day survival in patients with acute respiratory distress syndrome compared to conventional treatment (ARDSNet strategy). OBJECTIVE: To describe the data management process and statistical analysis plan. METHODS: The statistical analysis plan was designed by the trial executive committee and reviewed and approved by the trial steering committee. We provide an overview of the trial design with a special focus on describing the primary (28-day survival) and secondary outcomes. We describe our data management process, data monitoring committee, interim analyses, and sample size calculation. We describe our planned statistical analyses for primary and secondary outcomes as well as pre-specified subgroup analyses. We also provide details for presenting results, including mock tables for baseline characteristics, adherence to the protocol and effect on clinical outcomes. CONCLUSION: According to best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and beginning analyses. We anticipate that this document will prevent analysis bias and enhance the utility of the reported results. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01374022.

FUNDAMENTAÇÃO: O estudo Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) é um ensaio clínico internacional, multicêntrico, randomizado, pragmático e controlado com ocultação da alocação que envolve 120 unidades de terapia intensiva no Brasil, Argentina, Colômbia, Espanha, Itália, Polônia, Portugal, Malásia e Uruguai, com o objetivo primário de determinar se o recrutamento alveolar gradual máximo associado com titulação da pressão positiva expiratória final, ajustada segundo a complacência estática do sistema respiratório (estratégia ART), é capaz de aumentar, quando comparada aos resultados do tratamento convencional (estratégia ARDSNet), a sobrevivência em 28 dias de pacientes com síndrome do desconforto respiratório agudo. OBJETIVO: Descrever o processo de gerenciamento dos dados e o plano de análise estatística em um ensaio clínico internacional. MÉTODOS: O plano de análise estatística foi delineado pelo comitê executivo e revisado pelo comitê diretivo do ART. Foi oferecida uma visão geral do delineamento do estudo, com foco especial na descrição de desfechos primário (sobrevivência aos 28 dias) e secundários. Foram descritos o processo de gerenciamento dos dados, o comitê de monitoramento de dados, a análise interina e o cálculo do tamanho da amostra. Também foram registrados o plano de análise estatística para os desfechos primário e secundários, e os subgrupos de análise pré-especificados. Detalhes para apresentação dos resultados, inclusive modelos de tabelas para as características basais, adesão ao protocolo e efeito nos desfechos clínicos, foram fornecidos. CONCLUSÃO: Em acordo com as melhores práticas em ensaios clínicos, submetemos nossos planos de análise estatística e de gerenciamento de dados para publicação antes do fechamento da base de dados e início das análises. Antecipamos que este documento deve prevenir viés em análises e incrementar a utilidade dos resultados a serem relatados. REGISTRO DO ESTUDO: Número no registro ClinicalTrials.gov NCT01374022.

Physiologic effects of alveolar recruitment and inspiratory pauses during moderately-high-frequency ventilation delivered by a conventional ventilator in a severe lung injury model.

BACKGROUND AND AIMS: To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT) during moderately-high-frequency positive pressure ventilation (MHFPPV) delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS). METHODS: Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR) = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57-63 mmHg for 30 minutes. RESULTS: The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O), but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O), higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg), lower shunt (23 [20, 23] vs 32 [27, 49]%), lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%), and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT. CONCLUSIONS: During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space.

Pulmonary capillary pressure in pulmonary hypertension.

INTRODUCTION: Pulmonary capillary pressure (PCP), together with the time constants of the various vascular compartments, define the dynamics of the pulmonary vascular system. Our objective in the present study was to estimate PCPs and time constants of the vascular system in patients with idiopathic pulmonary arterial hypertension (IPAH), and compare them with these measures in patients with acute respiratory distress syndrome (ARDS). METHODS: We conducted the study in two groups of patients with pulmonary hypertension: 12 patients with IPAH and 11 with ARDS. Four methods were used to estimate the PCP based on monoexponential and biexponential fitting of pulmonary artery pressure decay curves. RESULTS: PCPs in the IPAH group were considerably greater than those in the ARDS group. The PCPs measured using the four methods also differed significantly, suggesting that each method measures the pressure at a different site in the pulmonary circulation. The time constant for the slow component of the biexponential fit in the IPAH group was significantly longer than that in the ARDS group. CONCLUSION: The PCP in IPAH patients is greater than normal but methodological limitations related to the occlusion technique may limit interpretation of these data in isolation. Different disease processes may result in different times for arterial emptying, with resulting implications for the methods available for estimating PCP.