Modulation of pulmonary blood flow in patients with acute respiratory failure.

BACKGROUND: Impairment of ventilation and perfusion (V/Q) matching is a common mechanism leading to hypoxemia in patients with acute respiratory failure requiring intensive care unit (ICU) admission. While ventilation has been thoroughly investigated, little progress has been made to monitor pulmonary perfusion at the bedside and treat impaired blood distribution. The study aimed to assess real-time changes in regional pulmonary perfusion in response to a therapeutic intervention. METHODS: Single-center prospective study that enrolled adult patients with ARDS caused by SARS-Cov-2 who were sedated, paralyzed, and mechanically ventilated. The distribution of pulmonary perfusion was assessed through electrical impedance tomography (EIT) after the injection of a 10-ml bolus of hypertonic saline. The therapeutic intervention consisted in the administration of inhaled nitric oxide (iNO), as rescue therapy for refractory hypoxemia. Each patient underwent two 15-min steps at 0 and 20 ppm iNO, respectively. At each step, respiratory, gas exchange, and hemodynamic parameters were recorded, and V/Q distribution was measured, with unchanged ventilatory settings. RESULTS: Ten 65 [56-75] years old patients with moderate (40%) and severe (60%) ARDS were studied 10 [4-20] days after intubation. Gas exchange improved at 20 ppm iNO (PaO2/FiO2 from 86 ± 16 to 110 ± 30 mmHg, p = 0.001; venous admixture from 51 ± 8 to 45 ± 7%, p = 0.0045; dead space from 29 ± 8 to 25 ± 6%, p = 0.008). The respiratory system's elastic properties and ventilation distribution were unaltered by iNO. Hemodynamics did not change after gas initiation (cardiac output 7.6 ± 1.9 vs. 7.7 ± 1.9 L/min, p = 0.66). The EIT pixel perfusion maps showed a variety of patterns of changes in pulmonary blood flow, whose increase positively correlated with PaO2/FiO2 increase (R2 = 0.50, p = 0.049). CONCLUSIONS: The assessment of lung perfusion is feasible at the bedside and blood distribution can be modulated with effects that are visualized in vivo. These findings might lay the foundations for testing new therapies aimed at optimizing the regional perfusion in the lungs.

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Prone positioning may increase lung overdistension in COVID-19-induced ARDS.

Real-time effects of changing body position and positive end-expiratory pressure (PEEP) on regional lung overdistension and collapse in individual patients remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP in supine and prone body positions seeking to reduce lung collapse and overdistension in mechanically ventilated patients with coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS). We hypothesized that prone positioning with bedside titrated PEEP would provide attenuation of both overdistension and collapse. In this prospective observational study, patients with COVID-19-induced ARDS under mechanical ventilation were included. We used electrical impedance tomography (EIT) with decremental PEEP titration algorithm (PEEPEIT-titration), which provides information on regional lung overdistension and collapse, along with global respiratory system compliance, to individualize PEEP and body position. PEEPEIT-titration in supine position followed by PEEPEIT-titration in prone position were performed. Immediately before each PEEPEIT-titration, the same lung recruitment maneuver was performed: 2 min of PEEP 24 cmH2O and driving pressure of 15 cmH2O. Forty-two PEEPEIT-titration were performed in ten patients (21 pairs supine and prone positions). We have found larger % of overdistension along the PEEP titration in prone than supine position (P = 0.042). A larger % of collapse along the PEEP titration was found in supine than prone position (P = 0.037). A smaller respiratory system compliance was found in prone than supine position (P < 0.0005). In patients with COVID-19-induced ARDS, prone body position, when compared with supine body position, decreased lung collapse at low PEEP levels, but increased lung overdistension at PEEP levels greater than 10 cm H2O.Trial registration number: NCT04460859.

Neurological Manifestations of SARS-CoV-2 Infection: Protocol for a Sub-analysis of the COVID-19 Critical Care Consortium Observational Study.

Introduction: Neurological manifestations and complications in coronavirus disease-2019 (COVID-19) patients are frequent. Prior studies suggested a possible association between neurological complications and fatal outcome, as well as the existence of potential modifiable risk factors associated to their occurrence. Therefore, more information is needed regarding the incidence and type of neurological complications, risk factors, and associated outcomes in COVID-19. Methods: This is a pre-planned secondary analysis of the international multicenter observational study of the COVID-19 Critical Care Consortium (which collected data both retrospectively and prospectively from the beginning of COVID-19 pandemic) with the aim to describe neurological complications in critically ill COVID-19 patients and to assess the associated risk factors, and outcomes. Adult patients with confirmed COVID-19, admitted to Intensive Care Unit (ICU) will be considered for this analysis. Data collected in the COVID-19 Critical Care Consortium study includes patients' pre-admission characteristics, comorbidities, severity status, and type and severity of neurological complications. In-hospital mortality and neurological outcome were collected at discharge from ICU, and at 28-days. Ethics and Dissemination: The COVID-19 Critical Care Consortium main study and its amendments have been approved by the Regional Ethics Committee of participating sites. No further approval is required for this secondary analysis. Trial Registration Number: ACTRN12620000421932.

Electrical impedance tomography in pediatric patients with COVID-19, the first reports.

INTRODUCTION: Electrical impedance tomography (EIT) is a noninvasive, radiation-free, bedside tool to monitor ventilation distribution in real time. OBJECTIVE: To evaluate, in pediatric COVID-19 patients, the ventilation distribution using EIT and compare it to thoracic computed tomography (TCT) or chest radiograph results obtained in these patients. METHODS: This was a prospective, observational clinical study including pediatric patients admitted to the intensive care unit of a private hospital. The patients monitored with EIT tested positive for COVID-19 and were submitted to the previously mentioned radiation exams. EIT monitoring lasted 15 min and no sedation was used. RESULTS: Six patients were included in this study. The main differences observed in the EIT were in the right-left distribution and were compatible with the morphological changes found in the TCT or radiograph images due to COVID-19 infection. CONCLUSION: We conclude that EIT is ready to investigate the ventilatory profile present at different lung diseases, including COVID-19, and might postpone or mitigate the need of repeated ionizing radiation exams in the pediatric population, although larger pediatric cohorts comparing to standard radiological imaging are needed.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

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 [Formula: see text]/[Formula: see text] 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 [Formula: see text]/[Formula: see text] 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 (NCT02503241).

Targeted lateral positioning decreases lung collapse and overdistension in COVID-19-associated ARDS.

BACKGROUND: Among the challenges for personalizing the management of mechanically ventilated patients with coronavirus disease (COVID-19)-associated acute respiratory distress syndrome (ARDS) are the effects of different positive end-expiratory pressure (PEEP) levels and body positions in regional lung mechanics. Right-left lung aeration asymmetry and poorly recruitable lungs with increased recruitability with alternating body position between supine and prone have been reported. However, real-time effects of changing body position and PEEP on regional overdistension and collapse, in individual patients, remain largely unknown and not timely monitored. The aim of this study was to individualize PEEP and body positioning in order to reduce the mechanisms of ventilator-induced lung injury: collapse and overdistension. METHODS: We here report a series of five consecutive mechanically ventilated patients with COVID-19-associated ARDS in which sixteen decremental PEEP titrations were performed in the first days of mechanical ventilation (8 titration pairs: supine position immediately followed by 30° targeted lateral position). The choice of lateral tilt was based on X-Ray. This targeted lateral position strategy was defined by selecting the less aerated lung to be positioned up and the more aerated lung to be positioned down. For each PEEP level, global and regional collapse and overdistension maps and percentages were measured by electrical impedance tomography. Additionally, we present the incidence of lateral asymmetry in a cohort of forty-four patients. RESULTS: The targeted lateral position strategy resulted in significantly smaller amounts of overdistension and collapse when compared with the supine one: less collapse along the PEEP titration was found within the left lung in targeted lateral (P = 0.014); and less overdistension along the PEEP titration was found within the right lung in targeted lateral (P = 0.005). Regarding collapse within the right lung and overdistension within the left lung: no differences were found for position. In the cohort of forty-four patients, ventilation inequality of > 65/35% was observed in 15% of cases. CONCLUSIONS: Targeted lateral positioning with bedside personalized PEEP provided a selective attenuation of overdistension and collapse in mechanically ventilated patients with COVID-19-associated ARDS and right-left lung aeration/ventilation asymmetry. TRIAL REGISTRATION: Trial registration number: NCT04460859.

Electrical impedance tomography to titrate positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome.

RATIONALE: Patients with coronavirus disease-19-related acute respiratory distress syndrome (C-ARDS) could have a specific physiological phenotype as compared with those affected by ARDS from other causes (NC-ARDS). OBJECTIVES: To describe the effect of positive end-expiratory pressure (PEEP) on respiratory mechanics in C-ARDS patients in supine and prone position, and as compared to NC-ARDS. The primary endpoint was the best PEEP defined as the smallest sum of hyperdistension and collapse. METHODS: Seventeen patients with moderate-to-severe C-ARDS were monitored by electrical impedance tomography (EIT) and evaluated during PEEP titration in supine (n = 17) and prone (n = 14) position and compared with 13 NC-ARDS patients investigated by EIT in our department before the COVID-19 pandemic. RESULTS: As compared with NC-ARDS, C-ARDS exhibited a higher median best PEEP (defined using EIT as the smallest sum of hyperdistension and collapse, 12 [9, 12] vs. 9 [6, 9] cmH2O, p < 0.01), more collapse at low PEEP, and less hyperdistension at high PEEP. The median value of the best PEEP was similar in C-ARDS in supine and prone position: 12 [9, 12] vs. 12 [10, 15] cmH2O, p = 0.59. The response to PEEP was also similar in C-ARDS patients with higher vs. lower respiratory system compliance. CONCLUSION: An intermediate PEEP level seems appropriate in half of our C-ARDS patients. There is no solid evidence that compliance at low PEEP could predict the response to PEEP.