Mechanisms of the Effects of Short-Term Inhalations of Xe and O2 Gas Mixture in the Rehabilitation of Post-COVID Ventilation Failure.

The article presents a theoretical rationale and a clinical case of relief of post-COVID ventilation failure by inhalation of Xe and O2 gas mixture. Pneumonitis of coronavirus etiology transforms saturated phospholipids of surfactant into a solid-ordered phase, which disrupts surface tension, alveolar pneumatization, and alveolar-capillary gas exchange. Using molecular modeling (B3LYP/lanl2dz; GAUSSIAN09), we demonstrated that Xe atom due to the van der Waals dispersion interaction increases the distance between the phospholipid acyl chains providing a phase transition from the solid-ordered to liquid phase and restored the surface-active monolayer surfactant film. A clinical case confirmed that short-term inhalations of the Xe and O2 gas mixture relieved manifestations of ventilation insufficiency and increased SpO2 and pneumatization of the terminal parts of the lungs.

Aerosol release, distribution, and prevention during aerosol therapy: a simulated model for infection control.

Aerosol therapy is used to deliver medical therapeutics directly to the airways to treat respiratory conditions. A potential consequence of this form of treatment is the release of fugitive aerosols, both patient derived and medical, into the environment and the subsequent exposure of caregivers and bystanders to potential viral infections. This study examined the release of these fugitive aerosols during a standard aerosol therapy to a simulated adult patient. An aerosol holding chamber and mouthpiece were connected to a representative head model and breathing simulator. A combination of laser and Schlieren imaging was used to non-invasively visualize the release and dispersion of fugitive aerosol particles. Time-varying aerosol particle number concentrations and size distributions were measured with optical particle sizers at clinically relevant positions to the simulated patient. The influence of breathing pattern, normal and distressed, supplemental air flow, at 0.2 and 6 LPM, and the addition of a bacterial filter to the exhalation port of the mouthpiece were assessed. Images showed large quantities of fugitive aerosols emitted from the unfiltered mouthpiece. The images and particle counter data show that the addition of a bacterial filter limited the release of these fugitive aerosols, with the peak fugitive aerosol concentrations decreasing by 47.3-83.3%, depending on distance from the simulated patient. The addition of a bacterial filter to the mouthpiece significantly reduces the levels of fugitive aerosols emitted during a simulated aerosol therapy, p≤ .05, and would greatly aid in reducing healthcare worker and bystander exposure to potentially harmful fugitive aerosols.

Effectiveness of Pulmonary Rehabilitation in Interstitial Lung Disease, Including Coronavirus Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: A meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of pulmonary rehabilitation on functional capacity and quality of life in interstitial lung diseases, including those caused by coronaviruses. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, Cochrane Library, Web of Science, and MedRxiv from inception to November 2020 were searched to identify documents. STUDY SELECTION: Publications investigating the effect of pulmonary rehabilitation on lung function (forced vital capacity [FVC]), exercise capacity (6-minute walk distance [6MWD]), health related quality of life (HRQOL), and dyspnea were searched. DATA EXTRACTION: The data were extracted into predesigned data extraction tables. Risk of bias was evaluated with the Cochrane Risk of Bias tool (RoB 2.0). DATA SYNTHESIS: A total of 11 RCTs with 637 interstitial lung disease patients were eligible for analyses. The pooled effect sizes of the association for pulmonary rehabilitation were 0.37 (95% confidence interval [CI], 0.02-0.71) for FVC, 44.55 (95% CI, 32.46-56.64) for 6MWD, 0.52 (95% CI, 0.22-0.82) for HRQOL, and 0.39 (95% CI, -0.08 to 0.87) for dyspnea. After translating these findings considering clinical improvements, pulmonary rehabilitation intervention increased predicted FVC by 5.5%, the 6MWD test improved by 44.55 m, and HRQOL improved by 3.9 points compared with baseline values. Results remained similar in sensitivity analyses. CONCLUSIONS: Although specific evidence for pulmonary rehabilitation of coronavirus disease 2019 patients has emerged, our data support that interstitial lung disease rehabilitation could be considered as an effective therapeutic strategy to improve the functional capacity and quality of life in this group of patients.

Cardiopulmonary Telerehabilitation.

Cardiopulmonary telerehabilitation is a safe and effective alternative to traditional center-based rehabilitation. It offers a sustainable solution to more conveniently meet the needs of patients with acute or chronic, preexisting or newly acquired, cardiopulmonary diseases. To maximize success, programs should prioritize basic, safe, and timely care options over comprehensive or complex approaches. The future should incorporate new strategies learned during a global pandemic and harness the power of information and communication technology to provide evidence-based patient-centered care. This review highlights clinical considerations, current evidence, recommendations, and future directions of cardiopulmonary telerehabilitation.

The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.

BACKGROUND: The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. METHODS: In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. RESULTS: Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab. CONCLUSION: To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

[Consensus on treatment of multisystemic inflammatory syndrome associated with COVID-19]. / Consenso sobre el tratamiento del síndrome inflamatorio multisistémico asociado a COVID-19.

The pandemic caused by the SARS-CoV-2 virus declared by the WHO in March 11th 2020, affects a small number of pediatric patients, who mostly present mild respiratory compromise and favorable evolution. However began to be observed in previously healthy children, an increase in cases defined as "Multisystemic Inflammatory Syndrome" (MIS-C) or "Kawasaki-like" post-COVID 19 (KLC) that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit. MIS-C and KL-C are characterized by fever; signs of inflammation, gastrointestinal symptoms, and cardiovascular dysfunction, associated with sever forms of presentation with higher incidence of hypotension and/or shock. In the laboratory, markers of inflammation, hypercoagulability and myocardial damage are observed. Firstline drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid. A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment, in order to reduce morbidity and mortality.

La pandemia ocasionada por el nuevo coronavirus (SARS-CoV-2), declarada por la Organización Mundial de la Salud OMS) en marzo de 2020, afecta a un reducido número de pacientes pediátricos, quienes presentan, en su mayoría, compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos, comenzó a observarse un aumento de casos definidos como síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por el nuevo coronavirus (COVID-19) (KL-C) que evolucionan al shock y requieren internación en la unidad de cuidados intensivos. Los cuadros de SIM-C y los KL-C se caracterizan por fiebre, signos de inflamación, síntomas gastrointestinales y disfunción cardiovascular; las formas graves de presentación tienen mayor incidencia de hipotensión y/o shock. En el laboratorio se observan marcadores de inflamación, hipercoagulabilidad y daño miocárdico. El tratamiento farmacológico de primera línea consiste en la administración de inmunoglobulina por vía intravenosa más ácido acetilsalicílico por vía oral. Se recomienda un abordaje multidisciplinario para un diagnóstico certero y un tratamiento temprano y eficaz para disminuir la morbimortalidad.

An in vitro visual study of fugitive aerosols released during aerosol therapy to an invasively ventilated simulated patient.

COVID-19 can cause serious respiratory complications resulting in the need for invasive ventilatory support and concurrent aerosol therapy. Aerosol therapy is considered a high risk procedure for the transmission of patient derived infectious aerosol droplets. Critical-care workers are considered to be at a high risk of inhaling such infectious droplets. The objective of this work was to use noninvasive optical methods to visualize the potential release of aerosol droplets during aerosol therapy in a model of an invasively ventilated adult patient. The noninvasive Schlieren imaging technique was used to visualize the movement of air and aerosol. Three different aerosol delivery devices: (i) a pressurized metered dose inhaler (pMDI), (ii) a compressed air driven jet nebulizer (JN), and (iii) a vibrating mesh nebulizer (VMN), were used to deliver an aerosolized therapeutic at two different positions: (i) on the inspiratory limb at the wye and (ii) on the patient side of the wye, between the wye and endotracheal tube, to a simulated intubated adult patient. Irrespective of position, there was a significant release of air and aerosol from the ventilator circuit during aerosol delivery with the pMDI and the compressed air driven JN. There was no such release when aerosol therapy was delivered with a closed-circuit VMN. Selection of aerosol delivery device is a major determining factor in the release of infectious patient derived bioaerosol from an invasively mechanically ventilated patient receiving aerosol therapy.

Pulmonary Rehabilitation.

Commenting on this book is a great privilege and an opportunity to share some emerging aspects regarding the development of pulmonary rehabilitation. Indeed, appreciating the therapeutic value of this modality is possible because of continuous research and tireless commitment of all professionals involved in the care of patients with respiratory diseases and pulmonary-related impairments....

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

BACKGROUND: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. METHODS: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. RESULTS: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). CONCLUSION: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk.

Therapeutic respiratory and functional rehabilitation protocol for intensive care unit patients affected by COVID-19: a structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objective of the presented study is to analyze the respiratory and functional effects of a rehabilitation program in patients affected by hospitalization in Intensive Care Unit (ICU) due to COVID-19, in comparison with the group treated with standard of care, at discharge endpoint. The secondary objectives of the presented study are to evaluate different outcomes of the rehabilitation program in comparison to standard of care regarding: functional performance at 4-week and 12-week post- discharge mark; health-related quality of life, the impact on the health services (namely days of hospitalization), the cost-effectiveness of the intervention proposed. TRIAL DESIGN: This is a randomized, controlled, double-blind, double-arm clinical trial of treatment, with an allocation ratio 1:1 and framework of superiority. PARTICIPANTS: The study will be conducted at Centro Hospitalar Entre Douro e Vouga, Santa Maria da Feira, Portugal. Potential participants will be adult patients (≥18 years old) hospitalized in ICU with respiratory insufficiency due to COVID-19, who are referred to respiratory and functional rehabilitation. Only patients approved by physical rehabilitation doctors to perform respiratory and functional rehabilitation will be considered potential participants. To be eligible for inclusion participants must have been independent in their activities of daily living before the onset of critical illness (verbal statement by their proxy) and have to meet the safety criteria defined by the Portuguese Society of Physical Rehabilitation Medicine. INTERVENTION AND COMPARATOR: Both groups will receive usual medical and nursing care in the ICU, which involves assessment and treatment of the respiratory system and may include positioning, hyperinflation techniques and suctioning. The physical function of the patient is assessed, and active bed exercises and mobility are encouraged as soon as possible and may include sitting out of bed. The intervention group will receive a functional and respiratory multidisciplinary rehabilitation protocol (that includes medical, nursing, physiotherapy and occupational therapy interventions) during their entire hospital stay. After reassurance that the patients fulfil the safety criteria, they will initiate the rehabilitation protocol, individualized to each patient based on the clinical status. The rehabilitation interventions and exercises implemented will be consistent with recommendations from the Portuguese Society of Physical Rehabilitation Medicine. The intervention will occur 6 days per week (Monday to Saturday), fifteen minutes, twice per day for each participant. Throughout all activities, progression will be increased successively, depending on the individual's tolerance and stability. After discharge, the intervention group will continue with rehabilitation exercises, prescribed by physical rehabilitation doctors. These exercises are designed for the patient to do at home, and then report their execution to rehabilitation nurses through teleconsultation, until 12 weeks after ICU discharge. MAIN OUTCOMES: Baseline descriptive data collection will include age, sex, comorbidities and date of admission to ICU. The need of mechanical ventilation and length of use, as well as the need for oxygen therapy, length of ICU stay (days/hours), incidence of ICU readmission, discharge destination and survival will also be recorded. Prior to intervention, every two days and at discharge, participants will be evaluated using the following scales: Glasgow Coma Scale, Richmond Agitation Sedation Scale, Chelsea Critical Care Physical Assessment, 5 standardized questions for cooperation, Medical Research Council Sum-Score, Handgrip strength test and Medical Research Council dyspnea scale. At discharge, Borg Rating of Perceived Exertion will be evaluated. The primary outcome measure will be functional capacity using the 6-Minute Walk Test, and it will be measured at discharge and at the 4-week and 12-week mark. Medical Research Council Sum-Score, Handgrip strength test, Medical Research Council dyspnea scale and Borg Rating of Perceived Exertion will also be re-evaluated at the 4-week and 12-week mark. The health related quality of life will also be used as an outcome measure, using the 12-Item Short Form Survey, at 12 weeks of follow-up. RANDOMISATION: Participants will be divided into two groups, standard care and intervention, by means of balanced randomization at a 1:1 ratio using blocks of 10 participants. The randomization sequence is going to be created using a free software ( http://www.randomized.org/ ). In order to ensure the confidentiality of the randomisation sequence, this process will be conducted by an assessor external to the study. BLINDING (MASKING): The evaluators in the study will be blinded during the entire process. The evaluators will be unaware of the study objectives and the randomized distribution of patients to study groups and will not have access to the randomization sequence. Although blinding for patients will not be possible to achieve completely, subjects will be unaware of other treatment modalities, and they will not know if they belong to the intervention or standard group. As for the treating physiotherapists and ICU staff, blinding will not be possible to achieve, but they will not be responsible for assessing outcomes. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We plan to randomise 40 participants to each group. 80 participants in total. TRIAL STATUS: This is the second and definitive protocol version, dated from 26th February 2021. Recruitment started on 8th March 2021. Participants will be recruited between March 8, 2021, and June 8, 2021. Study completion is expected to be October 2021. TRIAL REGISTRATION: ReBEC RBR-7rvhpq9 . Registry name: The effect of rehabilitation in hospitalized COVID-19 patients. Registered on 17 March 2021.Retrospectively registered. FULL PROTOCOL: "The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol".

A Review of the Current Status of Clinical Management of COVID-19 in the Elderly.

The high infectivity and severity of SARS-CoV-2 infection (COVID-19), and our limited understanding of the biology of the novel coronavirus, as well as the lack of an effective treatment for COVID-19, have created a global pandemic. Those most likely to become seriously ill with COVID-19 are adults, especially the elderly and those who are already weak or sick. At present, a specific drug for treatment of COVID-19 has not been developed. This, combined with the typical coexistence of a variety of chronic diseases in elderly patients, makes treatment challenging at present. In addition, for elderly patients, COVID-19 isolation measures during the epidemic can easily lead to psychological problems. Thus, how to manage elderly patients has become a focus of social attention in the current circumstances. This article reviews the effects of COVID-19 and makes management suggestions for elderly patients during this epidemic period. In addition to the elderly, critically ill people are also highly susceptible to this novel coronavirus. For elderly COVID-19 patients, antiviral therapy, immune regulation, and even auxiliary respiratory therapy can be given after a comprehensive evaluation of the disease. With the approval and use of COVID-19 vaccines, it is reasonable to expect that we can conquer SARS-CoV-2.

Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review. Update as of July 31st, 2020.

INTRODUCTION: This paper is the first update of the second edition of the rapid living systematic review on the latest scientific literature informing rehabilitation of patients with COVID-19 and/or describing consequences of the disease and its treatment, as they relate to limitations in functioning of rehabilitation interest. The aim of this study was to report data of a systematic search performed on papers published in July 2020. EVIDENCE ACQUISITION: The methodology described in the second edition of the rapid living systematic review was applied to search eligible papers included in the databases between July 1, 2020 and July 31, 2020. EVIDENCE SYNTHESIS: Eight-hundred-ninety-two papers were identified through database searching (after removal of duplicates); of these, only 23 studies were included. According to OCEBM 2011 Levels of Evidence Table, they were level 3 in 30.5% cases and level 4 in 69.5%. No RCT was found. Nineteen papers studied COVID-19 patients, assessed in the acute (10 studies), post-acute (8 studies) and chronic phase (one study). Four studies reported data on the impact of COVID-19 on subjects with pre-existing health conditions. CONCLUSIONS: The current literature production still focuses more on describing all the possible aspects and complications of the pathology than on interventions or new organization models to deal with it. Albeit evidence on handling COVID-19 from a rehabilitative point of view is improving each month, further studies are still mandatory to report the role of rehabilitation in this scenario.

Rehabilitation and COVID-19: the Cochrane Rehabilitation 2020 rapid living systematic review.

INTRODUCTION: This paper improves the methodology of the first edition of the rapid living systematic review started in April 2020, with the aim to gather and present the current evidence informing rehabilitation of patients with COVID-19 and/or describing the consequences due to the disease and its treatment. EVIDENCE ACQUISITION: The Cochrane methodology for a rapid living systematic review was applied. Primary research papers, published from 1 January to 30 June 2020, reporting patients' data, with no limits of study design were included. Studies were categorized for study design, research question, COVID-19 phase, limitations of functioning (disability) of rehabilitation interest and type of rehabilitation service involved. Methodological quality assessment was based on the Cochrane Risk of Bias tools, and the level of evidence table (OCEBM 2011) for all the other studies. EVIDENCE SYNTHESIS: Thirty-six, out of 3703 papers, were included. One paper was of level 2 (RCT), 7 were of level 3 (2 cohort studies, 2 cross-sectional studies and 3 case-control studies), and 28 papers of level 4 (descriptive studies); 61% of papers reported epidemiological data on clinical presentations, 5 investigated natural history/determining factors, 1 searched prevalence, 2 studies reported on intervention efficacy (though not on harms), and 5 studies looked at health service organization. CONCLUSIONS: Main issues emerging from the review: it is advised to test for COVID-19 people with neurological disorders presenting with symptom changes; dysphagia is a frequent complication after oro-tracheal intubation in COVID-19 patients admitted to the ICU; after discharge, COVID-19 survivors may report persistent restrictive ventilatory deficits regardless of disease severity; there is only sparse and low quality evidence concerning the efficacy of any rehabilitation intervention to promote functional recovery; a substantial increase in resource (staff and equipment) is needed for rehabilitation.

Early rehabilitation in post-acute COVID-19 patients: data from an Italian COVID-19 Rehabilitation Unit and proposal of a treatment protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading, putting under heavy stress health systems worldwide and especially Intensive Care Units (ICU). Rehabilitation Units have a crucial role in reducing disability in order to reintroduce patients in the community. AIM: The aim of this study is to characterize pulmonary function and disability status and to propose an early rehabilitation protocol in a cohort of post-acute COVID-19 patients admitted to an Italian Rehabilitation Unit. DESIGN: Cross-sectional observational study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Post-acute COVID-19 patients. METHODS: Demographic, anamnestic and clinical characteristics, laboratory exams and medical imaging findings were collected for the entire cohort. Outcome measures evaluated at the admission in Rehabilitation Unit were: type of respiratory supports needed, fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), FiO2/PaO2, Barthel Index (BI), modified Medical Research Council (mMRC) Dyspnoea Scale, and 6-Minute Walking Test (6-MWT). Furthermore, we proposed an early rehabilitation protocol for COVID-19 patients based on baseline FiO2. RESULTS: We included 32 post-acute COVID-19 patients (22 male and 10 female), mean aged 72.6±10.9 years. BI was 45.2±27.6, with patients in need of higher FiO2 (≥40%) showing lower values: 39.6±25.7 vs. 53.3±29.3. All patients had grade 4 or 5 on the mMRC Dyspnea Scale. Only 14 COVID-19 patients were able to walk (43.7%). 6-MWT was feasible in 6 (18.8%) patients with a mean distance of 45.0±100.6 meters. CONCLUSIONS: Taken together, our findings suggest that post-acute COVID-19 patients suffered from dyspnea and shortness of breath even for minimal activities, with a resulting severe disability, and only a few of them were able to perform 6-MWT with poor results. An early rehabilitation protocol was proposed according to the baseline conditions of the patients. CLINICAL REHABILITATION IMPACT: This study could provide an accurate description of COVID-19 sub-acute patients admitted to a Rehabilitation Unit along with a proposal of treatment to help physicians to tailor the best possible rehabilitative treatment.