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. Objetivo COVID19 COVID 19 COVID-1 Métodos Tratase Trata sumscore, sumscore sum score, score sum-score . Resultados n 31 33. 33 33) intervalo 12 61 6 6, 43 4 3 4, 73 7, 38 8 3,8 13 1, 25 2 5 2, 26 37 3,7 72 fracas seja 80 previsto feminino Conclusão invasivamente entanto recuperação SARSCoV2. SARSCoV2 SARSCoV SARS CoV 2. SARS-CoV-2 COVID1 COVID- 3, SARS-CoV- SARS-CoV

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. Objective COVID19 COVID 19 COVID-1 D (D1 D7, , (D7) impairment Methods noninvasive non highflow high flow sumscore, sumscore sum score, sum-score tests NonInvasive Non NonIMV . Results n 31 33. 33 33) range 12 61 6 1 6. 43 4 3 4. 73 7 7. 38 8 3.8 13 1. 25 2 5 2. 26 37 3.7 unitacquired acquired 72 weak i.e., ie i e (i.e. 80 value sex Conclusion ventilated However recovery SARSCoV2. SARSCoV2 SARSCoV SARS CoV SARS-CoV-2 COVID1 COVID- (D (D7 3. i.e. (i.e SARS-CoV- i.e SARS-CoV

Abstract 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.

RESUMO 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.

ABSTRACT 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.

Abstract Introduction: This work concerns the assessment of a novel system for mechanical ventilation and a parameter estimation method in a bench test. The tested system was based on a commercial mechanical ventilator and a personal computer. A computational routine was developed do drive the mechanical ventilator and a parameter estimation method was utilized to estimate positive end-expiratory pressure, resistance and compliance of the artificial respiratory system. Methods The computational routine was responsible for establishing connections between devices and controlling them. Parameters such as tidal volume, respiratory rate and others can be set for standard and noisy ventilation regimes. Ventilation tests were performed directly varying parameters in the system. Readings from a calibrated measuring device were the basis for analysis. Adopting a first-order linear model, the parameters could be estimated and the outcomes statistically analysed. Results Data acquisition was effective in terms of sample frequency and low noise content. After filtering, cycle detection and estimation took place. Statistics of median, mean and standard deviation were calculated, showing consistent matching with adjusted values. Changes in positive end-expiratory pressure statistically imply changes in compliance, but not the opposite. Conclusion The developed system was satisfactory in terms of clinical parameters. Statistics exhibited consistent relations between adjusted and estimated values, besides precision of the measurements. The system is expected to be used in animals, with a view to better understand the benefits of noisy ventilation, by evaluating the estimated parameters and performing cross relations among blood gas, ultrasonography and electrical impedance tomography.

A estenose brônquica pode comprometer a ventilação pulmonar regional devido a limitações anormais e assimétricas ao fluxo aéreo. A tomografia de impedância elétrica (TIE) é uma técnica que possibilita a avaliação da ventilação pulmonar regional por imagem e, portanto, pode complementar a avaliação funcional dos pulmões. Relatamos o caso de uma paciente com estenose brônquica unilateral à esquerda, pós-tuberculose, em que se avaliou a ventilação pulmonar regional através da TIE, relacionando-a com a cintilografia de ventilação/perfusão. Foram estudados os efeitos das mudanças posturais e da aplicação de continuous positive airway pressure (CPAP, pressão positiva contínua nas vias aéreas) nasal, uma vez que a paciente usava esse tratamento para síndrome da apneia obstrutiva do sono. A TIE demonstrou distribuição heterogênea da ventilação pulmonar regional com maior ventilação no pulmão direito, sendo essa distribuição influenciada pelas mudanças de decúbitos e pela aplicação de CPAP. A análise da ventilação pulmonar regional pela TIE se mostrou similar aos achados da cintilografia pulmonar de ventilação com a vantagem de possibilitar uma avaliação dinâmica e sem exposição à radiação.

Bronchial stenosis can impair regional lung ventilation by causing abnormal, asymmetric airflow limitation. Electrical impedance tomography (EIT) is an imaging technique that allows the assessment of regional lung ventilation and therefore complements the functional assessment of the lungs. We report the case of a patient with left unilateral bronchial stenosis and a history of tuberculosis, in whom regional lung ventilation was assessed by EIT. The EIT results were compared with those obtained by ventilation/perfusion radionuclide imaging. The patient was using nasal continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea syndrome. Therefore, we studied the effects of postural changes and of the use of nasal CPAP. The EIT revealed heterogeneous distribution of regional lung ventilation, the ventilation being higher in the right lung, and this distribution was influenced by postural changes and CPAP use. The EIT assessment of regional lung ventilation produced results similar to those obtained with the radionuclide imaging technique and had the advantage of providing a dynamic evaluation without radiation exposure.

OBJETIVO: Avaliar o desempenho de reanimadores manuais (RMs) utilizados no Brasil conforme critérios definidos por uma norma internacional. MÉTODOS: Utilizando um simulador do sistema respiratório, oito RMs manuais (cinco produzidos no Brasil e três importados) foram avaliados em relação a resistência inspiratória e expiratória da válvula para o paciente; funcionamento da válvula limitadora de pressão; e volume corrente (VT) gerado por quatro fisioterapeutas voluntários, utilizando uma ou duas mãos. Para a realização e análise dos testes, foram utilizados critérios sugeridos pela norma da American Society for Testing and Materials (ASTM) F920-93. RESULTADOS: A resistência expiratória foi superior a 6 cmH2O . L−1 . s−1 em apenas um dos RMs testados. A válvula limitadora de pressão, presente em cinco RMs, abriu em baixas pressões (< 17 cmH2O), e a pressão máxima variou de 32,0-55,9 cmH2O. Houve grande variação da média de VT obtido pelos diferentes RMs. Os valores médios de VT utilizando uma mão foram inferiores ao sugerido pela ASTM (600 mL). O VT médio, nas situações estudadas, foi geralmente menor nos RMs nacionais com válvula limitadora de pressão. CONCLUSÕES: As resistências impostas pela válvula do paciente estão de acordo com os critérios da ASTM, com exceção de um RM. As válvulas limitadoras de pressão dos RMs nacionais geralmente abrem em baixas pressões, determinando o fornecimento de um menor VT nas situações estudadas, principalmente com o uso de uma mão, o que sugere que a ventilação deva ser feita com as duas mãos e a válvula limitadora de pressão deva ser fechada sempre que possível.

OBJECTIVE: To evaluate the performance of manual resuscitators (MRs) used in Brazil in accordance with international standards. METHODS: Using a respiratory system simulator, four volunteer physiotherapists employed eight MRs (five produced in Brazil and three produced abroad), which were tested for inspiratory and expiratory resistance of the patient valve; functioning of the pressure-limiting valve; and tidal volume (VT) generated when the one-handed and two-handed techniques were used. The tests were performed and analyzed in accordance with the American Society for Testing and Materials (ASTM) F920-93 criteria. RESULTS: Expiratory resistance was greater than 6 cmH2O . L−1 . s−1 in only one MR. The pressure-limiting valve, a feature of five of the MRs, opened at low pressures (< 17 cmH2O), and the maximal pressure was 32.0-55.9 cmH2O. Mean VT varied greatly among the MRs tested. The mean VT values generated with the one-handed technique were lower than the 600 mL recommended by the ASTM. In the situations studied, mean VT was generally lower from the Brazilian-made MRs that had a pressure-limiting valve. CONCLUSIONS: The resistances imposed by the patient valve met the ASTM criteria in all but one of the MRs tested. The pressure-limiting valves of the Brazilian-made MRs usually opened at low pressures, providing lower VT values in the situations studied, especially when the one-handed technique was used, suggesting that both hands should be used and that the pressure-limiting valve should be closed whenever possible.

OBJECTIVES: Hemodynamic support is aimed at providing adequate O2 delivery to the tissues; most interventions target O2 delivery increase. Mixed venous O2 saturation is a frequently used parameter to evaluate the adequacy of O2 delivery. METHODS: We describe a mathematical model to compare the effects of increasing O2 delivery on venous oxygen saturation through increases in the inspired O2 fraction versus increases in cardiac output. The model was created based on the lungs, which were divided into shunted and non-shunted areas, and on seven peripheral compartments, each with normal values of perfusion, optimal oxygen consumption, and critical O2 extraction rate. O2 delivery was increased by changing the inspired fraction of oxygen from 0.21 to 1.0 in steps of 0.1 under conditions of low (2.0 L.min-1) or normal (6.5 L.min-1) cardiac output. The same O2 delivery values were also obtained by maintaining a fixed O2 inspired fraction value of 0.21 while changing cardiac output. RESULTS: Venous oxygen saturation was higher when produced through increases in inspired O2 fraction versus increases in cardiac output, even at the same O2 delivery and consumption values. Specifically, at high inspired O2 fractions, the measured O2 saturation values failed to detect conditions of low oxygen supply. CONCLUSIONS: The mode of O2 delivery optimization, specifically increases in the fraction of inspired oxygen versus increases in cardiac output, can compromise the capability of the "venous O2 saturation" parameter to measure the adequacy of oxygen supply. Consequently, venous saturation at high inspired O2 fractions should be interpreted with caution.

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.

INTRODUÇÃO: A adenosina é um nucleosídeo com potente ação vasodilatadora. Apesar de seus efeitos sobre o território arterial pulmonar ser conhecido, seu efeito sobre o território capilar/venoso ainda não foi descrito. OBJETIVO: Estudar o comportamento das resistências arterial e venosa da circulação pulmonar de pacientes com hipertensão pulmonar primária antes e depois da administração de adenosina. MÉTODO: Foram estudados sete pacientes com hipertensão pulmonar primária que apresentaram resposta positiva durante o teste agudo com adenosina. Resistência arterial e resistência venosa foram determinadas pela estimativa da pressão capilar pulmonar realizada através da análise da curva de decaimento da pressão arterial pulmonar, antes e depois da administração da adenosina. RESULTADOS: Após a administração da adenosina, houve um aumento do índice cardíaco (1,71 ± 0,23 para 2,72 ± 0,74 L.min-1.m-2) com concomitante diminuição da resistência vascular pulmonar (2.924 ± 1.060 para 1.975 ± 764 dina.s.cm-5.m-2), sem variações significativas da pressão arterial pulmonar média (75,6 ± 16,8 para 78,1 ± 18,8 mmHg), da pressão de oclusão da artéria pulmonar (15,3 ± 1,5 para 15,4 ± 1,9 mmHg) e da pressão capilar pulmonar (43,8 ± 5,8 para 44,5 ± 4,9 mmHg). A proporção entre a resistência arterial e a resistência vascular pulmonar total também apresentou variação não significativa (50 ± 15 para 49 ± 17%). Estes achados sugerem que a adenosina teve ação não somente sobre o território arterial mas também sobre o território capilar/venoso. CONCLUSÃO: Os autores concluem que o mecanismo de ação da adenosina não é restrito ao território arterial da circulação pulmonar e que este tipo de análise, através da determinação da pressão capilar pulmonar, pode ser útil no estudo das diversas drogas que agem sobre a circulação pulmonar.

BACKGROUND: The nucleoside adenosine is a potent vasodilator. Although its effect on the pulmonary arteries is well known, its influence on capillaries and veins has yet to be described. OBJECTIVE: To evaluate the pre- and post-administration effects of adenosine on arterial and venous resistance in the pulmonary circulation of patients with primary pulmonary hypertension. METHOD: The study involved 7 patients with primary pulmonary hypertension and presenting a positive response to adenosine on the acute test. Before and after adenosine administration, arterial and venous resistances were determined by estimating pulmonary capillary pressure through analysis of pulmonary artery pressure decay curves. RESULTS: Following adenosine administration, there was an increase in the cardiac index (from 1.71 ± 0.23 to 2.72 ± 0.74 L/min-1/m-2) and a decrease in pulmonary vascular resistance (from 2924 ± 1060 to 1975 ± 764 dynes/s/cm-5/m-2) with no significant variations in mean pulmonary artery pressure (pre: 75.6 ± 16.8 mmHg; post: 78.1 ± 18.8 mmHg), pulmonary wedge pressure (pre: 15.3 ± 1.5 mmHg; post: 15.4 ± 1.9 mmHg) and pulmonary capillary pressure (pre: 43.8 ± 5.8 mmHg; post: 44.5 ± 4.9 mmHg). The ratio between arterial resistance and total pulmonary vascular resistance also presented a less than significant variation (pre: 50 ± 15%; post: 49 ± 17%). These findings suggest that adenosine affects the capillaries and veins as well as the arteries. CONCLUSION: We can conclude that the adenosine mechanism is not restricted to the arterial aspect of the pulmonary circulation, and that analysis of pulmonary capillary pressure could prove useful in the study of various drugs that affect the pulmonary circulation.