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1.
Front Med (Lausanne) ; 9: 883950, 2022.
Article in English | MEDLINE | ID: covidwho-1872087

ABSTRACT

Background: The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model. Methods: In 10 pigs (63-73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3-4 s, with I:E > 6:1. Results: Both lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p < 0.05). Conclusion: No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.

2.
Aging Dis ; 13(2): 614-623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1856376

ABSTRACT

The SARS-COV2 pandemic induces tensions on health systems and ethical dilemmas. Practitioners need help tools to define patients not candidate for ICU admission. A multicentre observational study was performed to evaluate the impact of age and geriatric parameters on 30-day mortality in patients aged ≥60 years of age. Patients or next of kin were asked to answer a phone questionnaire assessing geriatric covariates 1 month before ICU admission. Among 290 screened patients, 231 were included between March 7 and May 7, 2020. In univariate, factors associated with lower 30-day survival were: age (per 10 years increase; OR 3.43, [95%CI: 2.13-5.53]), ≥3 CIRS-G grade ≥2 comorbidities (OR 2.49 [95%CI: 1.36-4.56]), impaired ADL, (OR 4.86 [95%CI: 2.44-9.72]), impaired IADL8 (OR 6.33 [95%CI: 3.31-12.10], p<0.001), frailty according to the Fried score (OR 4.33 [95%CI: 2.03-9.24]) or the CFS ≥5 (OR 3.79 [95%CI: 1.76-8.15]), 6-month fall history (OR 3.46 [95%CI: 1.58-7.63]). The final multivariate model included age (per 10 years increase; 2.94 [95%CI:1.78-5.04], p<0.001) and impaired IADL8 (OR 5.69 [95%CI: 2.90-11.47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85]. Age and IADL8 provide independent prognostic factors for 30-day mortality in the considered population. Considering a risk of death exceeding 80% (82.6% [95%CI: 61.2% - 95.0%]), patients aged over 80 years with at least 1 IADL impairment appear as poor candidates for ICU admission.

3.
Annals of Intensive Care ; 12(1), 2022.
Article in English | ProQuest Central | ID: covidwho-1837129

ABSTRACT

BackgroundLymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7.ResultsPeripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients.ConclusionsSevere COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far.Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.

4.
Crit Care ; 26(1): 94, 2022 04 04.
Article in English | MEDLINE | ID: covidwho-1775327

ABSTRACT

OBJECTIVE: To compare old patients hospitalized in ICU for respiratory distress due to COVID-19 with old patients hospitalized in ICU for a non-COVID-19-related reason in terms of autonomy and quality of life. DESIGN: Comparison of two prospective multi-centric studies. SETTING: This study was based on two prospective multi-centric studies, the Senior-COVID-Rea cohort (COVID-19-diagnosed ICU-admitted patients aged over 60) and the FRAGIREA cohort (ICU-admitted patients aged over 70). PATIENTS: We included herein the patients from both cohorts who had been evaluated at day 180 after admission (ADL score and quality of life). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 93 COVID-19 patients and 185 control-ICU patients were included. Both groups were not balanced on age, body mass index, mechanical ventilation, length of ICU stay, and ADL and SAPS II scores. We modeled with ordered logistic regression the influence of COVID-19 on the quality of life and the ADL score. After adjustment on these factors, we observed COVID-19 patients were less likely to have a loss of usual activities (aOR [95% CI] 0.47 [0.23; 0.94]), a loss of mobility (aOR [95% CI] 0.30 [0.14; 0.63]), and a loss of ADL score (aOR [95% CI] 0.30 [0.14; 0.63]). On day 180, 52 (56%) COVID-19 patients presented signs of dyspnea, 37 (40%) still used analgesics, 17 (18%) used anxiolytics, and 14 (13%) used antidepressant. CONCLUSIONS: COVID-19-related ICU stay was not associated with a lower quality of life or lower autonomy compared to non-COVID-19-related ICU stay.


Subject(s)
COVID-19 , Quality of Life , Aftercare , Aged , Critical Care , Humans , Intensive Care Units , Outcome Assessment, Health Care , Patient Discharge , Prospective Studies
5.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-310191

ABSTRACT

Background: Current SARS-COV2 pandemic induces tensions on the health systems and ethical dilemmas. A triage tool is needed to define older patients with individual advantage to be considered for intensive care unit (ICU) transfer.Methods: This multicentre observational cohort study included patients over 60 admitted into 7 ICUs between 7th March and 7th May 2020. The primary objective was to evaluate age impact on 30-day mortality, to construct a multivariate prognostic model. This analysis explores the prediction value of geriatric parameters 1 month before ICU admission. This trial is registered with ClinicalTrials.gov, number NCT04422340.Findings: Among 290 screened patients, 231 were included in the cohort. In univariate analysis, factors associated with decreased day-30 survival were: age>75 (OR 4·82 [95%CI: 2·56-9·06]), three or more CIRS-G grade ≥2 comorbidities (OR 2·49 [95%CI: 1·36-4·56]), impaired ADL (Activities of Daily Living), (OR 4·86 [95%CI: 2·44-9·72]), impaired IADL8 (Instrumental ADL, 8 variables, OR 6·33 [95%CI: 3·31-12·10], p<0·001), frailty according Fried score (OR 4·33 [95%CI: 2·03-9·24] or the Clinical Frailty Score≥5 (OR 3·79 [95%CI: 1·76-8·15), six months fall history (OR 3·46 [95%CI: 1·58-7·63]). The final multivariate model included age>75 (OR 4·64 [95%CI: 2·36-9·39], p<0.001) and impaired IADL8 (OR 5·69 [95%CI: 2·90-11·47], p<0.001)). Considered as continuous variables, the model led to an AUC of 0.78 [95% CI: 0.72, 0.85].Interpretation: Age and IADL8 provide independent prognostic factors for day-30 mortality in patients over 60 admitted in ICU for severe COVID-19 infection. Our triage model proposes 3 classes of day-30 mortality risks: 8-14% for patients younger than 80 with no impairment in IADL, 30-40% for patients either younger than 70 with at least one impairment in IADL8 or older than 80 with no impairment in IADL and 67-88% for patients over 80 with at least one impairment in IADL.Trial Registration: ClinicalTrials platform on June 9, 2020 (NCT04422340).Funding Statement: Hospices Civils de LyonDeclaration of Interests: All the authors declare grants from Hospices Civils de Lyon, during the conduct of the study, no other competing interests with the considered topic. CF reports outside of the present work consulting/advisory roles for GSK, Leo Pharma, Pfizer, MSD Oncology, Teva, AstraZeneca, Baxter, Eisai, Janssen, and Novartis;research funding from Chugai Pharma, Pfizer, Pierre Fabre, and Astellas Pharma;and travel/accommodation/expenses from Janssen Oncology, Pierre Fabre, and Leo Pharma.Ethics Approval Statement: The study protocol (V1.0 of April 7, 2020) was approved by a COVID-19-dedicated Ethics Committee of the Hospices Civils de Lyon on May 12, 2020.

6.
Trials ; 22(1): 692, 2021 Oct 11.
Article in English | MEDLINE | ID: covidwho-1463262

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19 pneumonia, with a mortality rate amounting to 34-50% in moderate and severe ARDS, and is associated with prolonged duration of invasive mechanical ventilation. Such as in non-COVID ARDS, harmful mechanical ventilation settings might be associated with worse outcomes. Reducing the tidal volume down to 4 mL kg-1 of predicted body weight (PBW) to provide ultra-low tidal volume ventilation (ULTV) is an appealing technique to minimize ventilator-inducted lung injury. Furthermore, in the context of a worldwide pandemic, it does not require any additional material and consumables and may be applied in low- to middle-income countries. We hypothesized that ULTV without extracorporeal circulation is a credible option to reduce COVID-19-related ARDS mortality and duration of mechanical ventilation. METHODS: The VT4COVID study is a randomized, multi-centric prospective open-labeled, controlled superiority trial. Adult patients admitted in the intensive care unit with COVID-19-related mild to severe ARDS defined by a PaO2/FiO2 ratio ≤ 150 mmHg under invasive mechanical ventilation for less than 48 h, and consent to participate to the study will be eligible. Patients will be randomized into two balanced parallels groups, at a 1:1 ratio. The control group will be ventilated with protective ventilation settings (tidal volume 6 mL kg-1 PBW), and the intervention group will be ventilated with ULTV (tidal volume 4 mL kg-1 PBW). The primary outcome is a composite score based on 90-day all-cause mortality as a prioritized criterion and the number of ventilator-free days at day 60 after inclusion. The randomization list will be stratified by site of recruitment and generated using random blocks of sizes 4 and 6. Data will be analyzed using intention-to-treat principles. DISCUSSION: The purpose of this manuscript is to provide primary publication of study protocol to prevent selective reporting of outcomes, data-driven analysis, and to increase transparency. Enrollment of patients in the study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT04349618 . Registered on April 16, 2020.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Extracorporeal Circulation , Humans , Prospective Studies , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , SARS-CoV-2
7.
BMJ Open ; 11(7): e044449, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1299231

ABSTRACT

INTRODUCTION: With the spread of COVID-19 epidemic, health plans must be adapted continuously. There is an urgent need to define the best care courses of patients with COVID-19, especially in intensive care units (ICUs), according to their individualised benefit/risk ratio. Since older age is associated with poorer short-term and long-term outcomes, prediction models are needed, that may assist clinicians in their ICU admission decision. Senior-COVID-Rea was designed to evaluate, in patients over 60 years old admitted in ICU for severe COVID-19 disease, the impact of age and geriatric and paraclinical parameters on their mortality 30 days after ICU admission. METHODS AND ANALYSIS: This is a multicentre survey protocol to be conducted in seven hospitals of the Auvergne-Rhône-Alpes region, France. All patients over 60 years old admitted in ICU for severe COVID-19 infection (or their legally acceptable representative) will be proposed to enter the study and to fill in a questionnaire regarding their functional and nutritional parameters 1 month before COVID-19 infection. Paraclinical parameters at ICU admission will be collected: lymphocytes and neutrophils counts, high-fluorescent lymphoid cells and immature granulocytes percentages (Sysmex data), D-dimers, C-reactive protein, lactate dehydrogenase (LDH), creatinine, CT scan for lung extension rate as well as clinical resuscitation scores, and the delay between the first signs of infection and ICU admission. The primary outcome will be the overall survival at day 30 post-ICU admission. The analysis of factors predicting mortality at day 30 will be carried out using univariate and multivariate logistic regressions. Multivariate logistic regression will consider up to 15 factors.The ambition of this trial, which takes into account the different approaches of geriatric vulnerability, is to define the respective abilities of different operational criteria of frailty to predict patients' outcomes. ETHICS AND DISSEMINATION: The study protocol was ethically approved. The results of the primary and secondary objectives will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04422340.


Subject(s)
COVID-19 , Aged , France/epidemiology , Humans , Intensive Care Units , Middle Aged , Multicenter Studies as Topic , Risk Factors , SARS-CoV-2 , Surveys and Questionnaires
8.
Ann Intensive Care ; 10(1): 129, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-810354

ABSTRACT

BACKGROUND: Data on respiratory mechanics of COVID-19 ARDS patients are scarce. Respiratory mechanics and response to positive expiratory pressure (PEEP) may be different in obese and non-obese patients. METHODS: We investigated esophageal pressure allowing determination of transpulmonary pressures (PL ) and elastances (EL) during a decremental PEEP trial from 20 to 6 cm H2O in a cohort of COVID-19 ARDS patients. RESULTS: Fifteen patients were investigated, 8 obese and 7 non-obese patients. PEEP ≥ 16 cm H2O for obese patients and PEEP ≥10 cm H2O for non-obese patients were necessary to obtain positive expiratory PL. Change of PEEP did not alter significantly ΔPL or elastances in obese patients. However, in non-obese patients lung EL  and ΔPL increased significantly with PEEP increase. Chest wall EL was not affected by PEEP variations in both groups.

9.
J Crit Care ; 60: 169-176, 2020 12.
Article in English | MEDLINE | ID: covidwho-710098

ABSTRACT

PURPOSE: The aim of this study was to assess whether the computed tomography (CT) features of COVID-19 (COVID+) ARDS differ from those of non-COVID-19 (COVID-) ARDS patients. MATERIALS AND METHODS: The study is a single-center prospective observational study performed on adults with ARDS onset ≤72 h and a PaO2/FiO2 ≤ 200 mmHg. CT scans were acquired at PEEP set using a PEEP-FiO2 table with VT adjusted to 6 ml/kg predicted body weight. RESULTS: 22 patients were included, of whom 13 presented with COVID-19 ARDS. Lung weight was significantly higher in COVID- patients, but all COVID+ patients presented supranormal lung weight values. Noninflated lung tissue was significantly higher in COVID- patients (36 ± 14% vs. 26 ± 15% of total lung weight at end-expiration, p < 0.01). Tidal recruitment was significantly higher in COVID- patients (20 ± 12 vs. 9 ± 11% of VT, p < 0.05). Lung density histograms of 5 COVID+ patients with high elastance (type H) were similar to those of COVID- patients, while those of the 8 COVID+ patients with normal elastance (type L) displayed higher aerated lung fraction.


Subject(s)
COVID-19/diagnostic imaging , Image Processing, Computer-Assisted/methods , Respiratory Distress Syndrome/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Case-Control Studies , Female , Humans , Lung , Lung Compliance , Male , Middle Aged , Positive-Pressure Respiration , Prospective Studies
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