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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.

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BACKGROUND: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. METHODS: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. RESULTS: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. CONCLUSIONS: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

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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.

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Rationale: Hypoxemia during mechanical ventilation might be worsened by expiratory muscle activity, which reduces end-expiratory lung volume through lung collapse. A proposed mechanism of benefit of neuromuscular blockade in acute respiratory distress syndrome (ARDS) is the abolition of expiratory efforts. This may contribute to the restoration of lung volumes. The prevalence of this phenomenon, however, is unknown. Objectives: To investigate the incidence and amount of end-expiratory lung impedance (EELI) increase after the administration of neuromuscular blocking agents (NMBAs), clinical factors associated with this phenomenon, its impact on regional lung ventilation, and any association with changes in pleural pressure. Methods: We included mechanically ventilated patients with ARDS monitored with electrical impedance tomography (EIT) who received NMBAs in one of two centers. We measured changes in EELI, a surrogate for end-expiratory lung volume, before and after NMBA administration. In an additional 10 patients, we investigated the characteristic signatures of expiratory muscle activity depicted by EIT and esophageal catheters simultaneously. Clinical factors associated with EELI changes were assessed. Measurements and Main Results: We included 46 patients, half of whom showed an increase in EELI of >10% of the corresponding Vt (46.2%; IQR, 23.9-60.9%). The degree of EELI increase correlated positively with fentanyl dosage and negatively with changes in end-expiratory pleural pressures. This suggests that expiratory muscle activity might exert strong counter-effects against positive end-expiratory pressure that are possibly aggravated by fentanyl. Conclusions: Administration of NMBAs during EIT monitoring revealed activity of expiratory muscles in half of patients with ARDS. The resultant increase in EELI had a dose-response relationship with fentanyl dosage. This suggests a potential side effect of fentanyl during protective ventilation.

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BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

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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.

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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.

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BACKGROUND: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS). METHODS: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes 100 ms]) and inspiratory effort (as the esophageal pressure-time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models. RESULTS: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of -2.8 [-3.8--1.9] cm H2O, -3.6 [-3.9--2.4] cm H2O and -2.1 [-2.5--1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118-209] cm H2O s/min, 197 [145-269] cm H2O s/min, and 134 [93-169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (ß = -2.771, p-value < 0.001) and inspiratory effort (ß = 0.026, p < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (ß = 2.606, p = 0.010 for NAVA, and ß = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (ß = 2.643, p = 0.009 for PAV +). CONCLUSIONS: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.