Pandemic lockdowns: who feels coerced and why? - a study on perceived coercion, perceived pressures and procedural justice during the UK COVID-19 lockdowns.

BACKGROUND: This study examined perceptions of coercion, pressures and procedural injustice and how such perceptions influenced psychological well-being in those who experienced a UK COVID-19 lockdown, with a view to preparing for the possibility of future lockdowns. METHODS: 40 individuals categorised as perceiving the lockdown(s) as either highly or lowly coercive took part in one of six asynchronous virtual focus groups (AVFGs). RESULTS: Using thematic analysis, the following key themes were identified in participants' discussions: (1) Choice, control and freedom; (2) threats; (3) fairness; (4) circumstantial factors; and (5) psychological factors. CONCLUSIONS: As the first qualitative study to investigate the psychological construct of perceived coercion in relation to COVID-19 lockdowns, its findings suggest that the extent to which individuals perceived pandemic-related lockdowns as coercive may have been linked to their acceptance of restrictions. Preparing for future pandemics should include consideration of perceptions of coercion and efforts to combat this, particularly in relation to differences in equity, in addition to clarity of public health messaging and public engagement.

Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Current knowledge gaps in extracorporeal respiratory support.

Extracorporeal life support (ECLS) for acute respiratory failure encompasses veno-venous extracorporeal membrane oxygenation (V-V ECMO) and extracorporeal carbon dioxide removal (ECCO2R). V-V ECMO is primarily used to treat severe acute respiratory distress syndrome (ARDS), characterized by life-threatening hypoxemia or ventilatory insufficiency with conventional protective settings. It employs an artificial lung with high blood flows, and allows improvement in gas exchange, correction of hypoxemia, and reduction of the workload on the native lung. On the other hand, ECCO2R focuses on carbon dioxide removal and ventilatory load reduction ("ultra-protective ventilation") in moderate ARDS, or in avoiding pump failure in acute exacerbated chronic obstructive pulmonary disease. Clinical indications for V-V ECLS are tailored to individual patients, as there are no absolute contraindications. However, determining the ideal timing for initiating extracorporeal respiratory support remains uncertain. Current ECLS equipment faces issues like size and durability. Innovations include intravascular lung assist devices (ILADs) and pumpless devices, though they come with their own challenges. Efficient gas exchange relies on modern oxygenators using hollow fiber designs, but research is exploring microfluidic technology to improve oxygenator size, thrombogenicity, and blood flow capacity. Coagulation management during V-V ECLS is crucial due to common bleeding and thrombosis complications; indeed, anticoagulation strategies and monitoring systems require improvement, while surface coatings and new materials show promise. Moreover, pharmacokinetics during ECLS significantly impact antibiotic therapy, necessitating therapeutic drug monitoring for precise dosing. Managing native lung ventilation during V-V ECMO remains complex, requiring a careful balance between benefits and potential risks for spontaneously breathing patients. Moreover, weaning from V-V ECMO is recognized as an area of relevant uncertainty, requiring further research. In the last decade, the concept of Extracorporeal Organ Support (ECOS) for patients with multiple organ dysfunction has emerged, combining ECLS with other organ support therapies to provide a more holistic approach for critically ill patients. In this review, we aim at providing an in-depth overview of V-V ECMO and ECCO2R, addressing various aspects of their use, challenges, and potential future directions in research and development.

Environmental Contamination by SARS-CoV-2 During Noninvasive Ventilation in COVID-19.

BACKGROUND: Environmental contamination by SARS-CoV-2 from patients with COVID-19 undergoing noninvasive ventilation (NIV) in the ICU is still under investigation. This study set out to investigate the presence of SARS-CoV-2 on surfaces near subjects receiving NIV in the ICU under controlled conditions (ie, use of dual-limb circuits, filters, adequate room ventilation). METHODS: This was a single-center, prospective, observational study in the ICU of a tertiary teaching hospital. Four surface sampling areas, at increasing distance from subject's face, were identified; and each one was sampled at fixed intervals: 6, 12, and 24 h. The presence of SARS-CoV-2 was detected with real-time reverse transcriptase-polymerase-chain-reaction (RT-PCR) test on environmental swabs; the RT-PCR assay targeted the SARS-CoV-2 virus nucleocapsid N1 and N2 genes and the human RNase P gene as internal control. RESULTS: In a total of 256 collected samples, none were positive for SARS-CoV-2 genetic material, whereas 21 samples (8.2%) tested positive for RNase P, thus demonstrating the presence of genetic material unrelated to SARS-CoV-2. CONCLUSIONS: Our data show that application of NIV in an appropriate environment and with correct precautions leads to no sign of surface environmental contamination. Accordingly, our data support the idea that use of NIV in the ICU is safe both for health care workers and for other patients.

Increased duration and similar outcomes of V-V ECLS in patients with COVID-19 ARDS compared to non-COVID ARDS: Single center experience.

BACKGROUND: Veno-venous extracorporeal life support (V-V ECLS or V-V ECMO) has been adopted as a rescue support in severe cases of COVID-19 ARDS. Initial reports on the use of V-V ECLS in COVID-19 patients reported very high mortality rates (57%-94%), but subsequent studies showed much lower rates (30%-40%). The aim of this study is to analyze demographic features, clinical course and outcomes of COVID-19 treated with V-V ECLS during the Italian 'third wave', in which the alpha variant was prevalent in the country. METHODS: Single-center, retrospective observational study conducted at the ECLS referral center of a teaching hospital in Italy from January 1st, 2021 and October 31st, 2021. RESULTS: Between January and October 2021, 18 consecutive adult patients who underwent V-V ECLS for severe ARDS due to COVID-19 were enrolled. Thirteen patients (72.2%) were male, and their median age was 50 years; the median P/F ratio before V-V ECLS initiation was 43 mm Hg (IQR, 40; 56), and the median RESP score was 0.5 (IQR, -2.25; 1.0). The mortality rate at 90 days was 55.6, compared to 55.7% in non-COVID patients in our center (p > 0.05); the median duration of ECLS was 29 days (IQR, 11; 32), compared to 10 days (IQR, 8; 15), in non-COVID patients (p = 0.004). Incidence of complications was high. CONCLUSIONS: In patients with COVID-19 ARDS receiving V-V ECLS, unadjusted mortality was similar to pre-pandemic V-V ECLS cases, while the duration of ECLS was almost three times longer and with frequent complications. This could be partly explained by the selection of very sick patients at the baseline that evolved to multiorgan failure during the course of ECLS.

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome.

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p < 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p < 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits.

Rethinking Acute Respiratory Distress Syndrome after COVID-19: If a "Better" Definition Is the Answer, What Is the Question?

The definition of acute respiratory distress syndrome (ARDS) has a somewhat controversial history, with some even questioning the need for the term "ARDS." This controversy has been amplified by the coronavirus disease (COVID-19) pandemic given the marked increase in the incidence of ARDS, the relatively new treatment modalities that do not fit neatly with the Berlin definition, and the difficulty of making the diagnosis in resource-limited settings. We propose that attempts to revise the definition of ARDS should apply the framework originally developed by psychologists and social scientists and used by other medical disciplines to generate and assess definitions of clinical syndromes that do not have gold standards. This framework is structured around measures of reliability, feasibility, and validity. Future revisions of the definition of ARDS should contain the purpose, the methodology, and the framework for empirically testing any proposed definition. Attempts to revise critical illness syndromes' definitions usually hope to make them "better"; our recommendation is that future attempts use the same criteria used by other fields in defining what "better" means.

High-Flow Versus VenturiMask Oxygen Therapy to Prevent Reintubation in Hypoxemic Patients after Extubation: A Multicenter Randomized Clinical Trial.

Rationale: When compared with VenturiMask after extubation, high-flow nasal oxygen provides physiological advantages. Objectives: To establish whether high-flow oxygen prevents endotracheal reintubation in hypoxemic patients after extubation, compared with VenturiMask. Methods: In this multicenter randomized trial, 494 patients exhibiting PaO2:FiO2 ratio ⩽ 300 mm Hg after extubation were randomly assigned to receive high-flow or VenturiMask oxygen, with the possibility to apply rescue noninvasive ventilation before reintubation. High-flow use in the VenturiMask group was not permitted. Measurements and Main Results: The primary outcome was the rate of reintubation within 72 hours according to predefined criteria, which were validated a posteriori by an independent adjudication committee. Main secondary outcomes included reintubation rate at 28 days and the need for rescue noninvasive ventilation according to predefined criteria. After intubation criteria validation (n = 492 patients), 32 patients (13%) in the high-flow group and 27 patients (11%) in the VenturiMask group required reintubation at 72 hours (unadjusted odds ratio, 1.26 [95% confidence interval (CI), 0.70-2.26]; P = 0.49). At 28 days, the rate of reintubation was 21% in the high-flow group and 23% in the VenturiMask group (adjusted hazard ratio, 0.89 [95% CI, 0.60-1.31]; P = 0.55). The need for rescue noninvasive ventilation was significantly lower in the high-flow group than in the VenturiMask group: at 72 hours, 8% versus 17% (adjusted hazard ratio, 0.39 [95% CI, 0.22-0.71]; P = 0.002) and at 28 days, 12% versus 21% (adjusted hazard ratio, 0.52 [95% CI, 0.32-0.83]; P = 0.007). Conclusions: Reintubation rate did not significantly differ between patients treated with VenturiMask or high-flow oxygen after extubation. High-flow oxygen yielded less frequent use of rescue noninvasive ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT02107183).

Modulation of LTCC Pathways by a Melusin Mimetic Increases Ventricular Contractility During LPS-Induced Cardiomyopathy.

AIM: Sepsis-induced cardiomyopathy is commonplace and carries an increased risk of death. Melusin, a cardiac muscle-specific chaperone, exerts cardioprotective function under varied stressful conditions through activation of the AKT pathway. The objective of this study was to determine the role of melusin in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction and to explore its signaling pathway for the identification of putative therapeutic targets. METHODS AND RESULTS: Prospective, randomized, controlled experimental study in a research laboratory. Melusin overexpressing (MelOV) and wild-type (MelWT) mice were used. MelOV and MelWT mice were injected intraperitoneally with LPS. Cardiac function was assessed using trans-thoracic echocardiography. Myocardial expression of L-type calcium channel (LTCC), phospho-Akt and phospho-Gsk3-b were also measured. In separate experiments, wild-type mice were treated post-LPS challenge with the allosteric Akt inhibitor Arq092 and a mimetic peptide (R7W-MP) targeting the LTCC. The impact of these therapies on protein-protein interactions, cardiac function, and survival was assessed. MelOV mice had limited derangement in cardiac function after LPS challenge. Protection was associated with higher Akt and Gsk3-b phosphorylation and restored LTCC density. Pharmacological inhibition of Akt activity reversed melusin-dependent cardiac protection. Treatment with R7W-MP preserved cardiac function in wild-type mice after LPS challenge and significantly improved survival. CONCLUSIONS: This study identifies AKT / Melusin as a key pathway for preserving cardiac function following LPS challenge. The cell-permeable mimetic peptide (R7W-MP) represents a putative therapeutic for sepsis-induced cardiomyopathy.

Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial.

BACKGROUND: In acute respiratory distress syndrome (ARDS), response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP based on patients' individual response is warranted. End-expiratory lung volume (EELV) assessment by nitrogen washing-washout aids bedside estimation of PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual recruitability. We designed a randomized trial to test whether an individualized PEEP setting protocol driven by EELV measurement may improve a composite clinical outcome in patients with moderate-to-severe ARDS (IPERPEEP trial). METHODS: IPERPEEP is an open-label, multicenter, randomized trial that will be conducted in 10 intensive care units in Italy and will enroll 132 ARDS patients showing PaO2/FiO2 ratio ≤ 150 mmHg within 24 h from endotracheal intubation while on mechanical ventilation with PEEP 5 cmH2O. To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume of 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for 30 min (EXPRESS PEEP). Afterwards, a 5-step decremental PEEP trial will be conducted (EXPRESS PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. Recruitment-to-inflation ratio will be calculated for each PEEP range from EELV difference. Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or to achieve a plateau pressure of 28-30 cmH2O (control arm, EXPRESS strategy). In both groups, tidal volume size, use of prone positioning and neuromuscular blocking agents, and weaning from PEEP and from mechanical ventilation will be standardized. The primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator-free days, and serum interleukin-6 concentration over the course of the initial 72 h of treatment. DISCUSSION: The IPERPEEP study is a randomized trial powered to elucidate whether an individualized PEEP setting protocol based on bedside assessment of lung recruitability can improve a composite clinical outcome during moderate-to-severe ARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04012073 . Registered 9 July 2019.

High-Flow Nasal Oxygen for Severe Hypoxemia: Oxygenation Response and Outcome in Patients with COVID-19.

Rationale: The "Berlin definition" of acute respiratory distress syndrome (ARDS) does not allow inclusion of patients receiving high-flow nasal oxygen (HFNO). However, several articles have proposed that criteria for defining ARDS should be broadened to allow inclusion of patients receiving HFNO. Objectives: To compare the proportion of patients fulfilling ARDS criteria during HFNO and soon after intubation, and 28-day mortality between patients treated exclusively with HFNO and patients transitioned from HFNO to invasive mechanical ventilation (IMV). Methods: From previously published studies, we analyzed patients with coronavirus disease (COVID-19) who had PaO2/FiO2 of ⩽300 while treated with ⩾40 L/min HFNO, or noninvasive ventilation (NIV) with positive end-expiratory pressure of ⩾5 cm H2O (comparator). In patients transitioned from HFNO/NIV to invasive mechanical ventilation (IMV), we compared ARDS severity during HFNO/NIV and soon after IMV. We compared 28-day mortality in patients treated exclusively with HFNO/NIV versus patients transitioned to IMV. Measurements and Main Results: We analyzed 184 and 131 patients receiving HFNO or NIV, respectively. A total of 112 HFNO and 69 NIV patients transitioned to IMV. Of those, 104 (92.9%) patients on HFNO and 66 (95.7%) on NIV continued to have PaO2/FiO2 ⩽300 under IMV. Twenty-eight-day mortality in patients who remained on HFNO was 4.2% (3/72), whereas in patients transitioned from HFNO to IMV, it was 28.6% (32/112) (P < 0.001). Twenty-eight-day mortality in patients who remained on NIV was 1.6% (1/62), whereas in patients who transitioned from NIV to IMV, it was 44.9% (31/69) (P < 0.001). Overall mortality was 19.0% (35/184) and 24.4% (32/131) for HFNO and NIV, respectively (P = 0.2479). Conclusions: Broadening the ARDS definition to include patients on HFNO with PaO2/FiO2 ⩽300 may identify patients at earlier stages of disease but with lower mortality.

Extracorporeal carbon dioxide removal for treatment of exacerbated chronic obstructive pulmonary disease (ORION): study protocol for a randomised controlled trial.

BACKGROUND: Hypercapnic exacerbations are severe complications of chronic obstructive pulmonary disease (COPD), characterized by negative impact on prognosis, quality of life and healthcare costs. The present standard of care for acute exacerbations of COPD is non-invasive ventilation; when it fails, the use of invasive mechanical ventilation is inevitable, but is associated with extremely poor prognosis. Extracorporeal circuits designed to remove CO2 (ECCO2R) may enhance the efficacy of NIV to remove CO2 and avoid the worsening of respiratory acidosis, which inevitably leads to failure of non-invasive ventilation. Although the use of ECCO2R for acute exacerbations of COPD is steadily increasing, solid evidence on its efficacy and safety is scarce, thus the need for a randomized controlled trial. METHODS: multicenter randomized controlled unblinded clinical trial including 284 (142 per arm) patients with acute hypercapnic respiratory failure caused by exacerbation of COPD, requiring respiratory support with NIV. The primary outcome is event free survival at 28 days, a composite outcome defined by survival in absence of prolonged mechanical ventilation, severe hypoxemia, septic shock and second episode of COPD exacerbation. Secondary outcomes are incidence of endotracheal intubation and tracheostomy, intensive care and hospital length-of-stay and 90-day mortality. DISCUSSION: Acute exacerbations of COPD represent a significant burden in terms of prognosis, quality of life and healthcare costs. Lack definite evidence despite increasing use of ECCO2R justifies a randomized trial to evaluate whether patients with acute hypercapnic acidosis not responsive to NIV should undergo invasive mechanical ventilation (with all serious related risks) or be treated with ECCO2R to avoid invasive ventilation but be exposed to possible adverse events of ECCO2R. Owing to its pragmatic nature, sample size and composite primary outcome, this trial aims at providing valuable answers to relevant questions for clinical treatment of acute exacerbations of COPD. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04582799 . Registered 12 October 2020, .