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4.
Respir Res ; 23(1): 68, 2022 Mar 22.
Article in English | MEDLINE | ID: covidwho-1759751

ABSTRACT

BACKGROUND: Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. METHODS: Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. RESULTS: Among 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. CONCLUSION: Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.


Subject(s)
COVID-19/complications , Exercise Tolerance/physiology , Pneumonia/physiopathology , Aged , COVID-19/physiopathology , Cohort Studies , Echocardiography/methods , Echocardiography/statistics & numerical data , Exercise Test/methods , Exercise Test/statistics & numerical data , Exercise Tolerance/immunology , Female , Follow-Up Studies , France , Humans , Lung/physiopathology , Male , Middle Aged , Pneumonia/etiology , Prospective Studies , Respiratory Function Tests/methods , Respiratory Function Tests/statistics & numerical data , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology
5.
BMC Anesthesiol ; 22(1): 59, 2022 03 04.
Article in English | MEDLINE | ID: covidwho-1724413

ABSTRACT

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Lung/physiopathology , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/epidemiology , Aged , COVID-19/physiopathology , Critical Care/methods , Female , Humans , Male , Middle Aged , Noninvasive Ventilation/statistics & numerical data , Positive-Pressure Respiration , Prospective Studies , Respiratory Insufficiency/physiopathology , Respiratory Mechanics , Russia/epidemiology , SARS-CoV-2 , Survival Analysis , Tidal Volume , Treatment Failure
6.
Respir Med ; 191: 106709, 2022 01.
Article in English | MEDLINE | ID: covidwho-1556145

ABSTRACT

INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19. METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19. RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease. CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Lung/physiopathology , Quality of Life , Respiratory Insufficiency/physiopathology , Adult , Aged , COVID-19/diagnostic imaging , COVID-19/therapy , Extracorporeal Membrane Oxygenation , Female , Forced Expiratory Volume/physiology , Hospitalization , Humans , Longitudinal Studies , Lung/diagnostic imaging , Male , Middle Aged , Oxygen Inhalation Therapy , Pulmonary Diffusing Capacity/physiology , Recovery of Function , Respiration, Artificial , Respiratory Function Tests , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires , Tomography, X-Ray Computed , Total Lung Capacity/physiology , Vital Capacity/physiology
7.
Can J Anaesth ; 67(9): 1217-1248, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1536371

ABSTRACT

PURPOSE: We conducted two World Health Organization-commissioned reviews to inform use of high-flow nasal cannula (HFNC) in patients with coronavirus disease (COVID-19). We synthesized the evidence regarding efficacy and safety (review 1), as well as risks of droplet dispersion, aerosol generation, and associated transmission (review 2) of viral products. SOURCE: Literature searches were performed in Ovid MEDLINE, Embase, Web of Science, Chinese databases, and medRxiv. Review 1: we synthesized results from randomized-controlled trials (RCTs) comparing HFNC to conventional oxygen therapy (COT) in critically ill patients with acute hypoxemic respiratory failure. Review 2: we narratively summarized findings from studies evaluating droplet dispersion, aerosol generation, or infection transmission associated with HFNC. For both reviews, paired reviewers independently conducted screening, data extraction, and risk of bias assessment. We evaluated certainty of evidence using GRADE methodology. PRINCIPAL FINDINGS: No eligible studies included COVID-19 patients. Review 1: 12 RCTs (n = 1,989 patients) provided low-certainty evidence that HFNC may reduce invasive ventilation (relative risk [RR], 0.85; 95% confidence interval [CI], 0.74 to 0.99) and escalation of oxygen therapy (RR, 0.71; 95% CI, 0.51 to 0.98) in patients with respiratory failure. Results provided no support for differences in mortality (moderate certainty), or in-hospital or intensive care length of stay (moderate and low certainty, respectively). Review 2: four studies evaluating droplet dispersion and three evaluating aerosol generation and dispersion provided very low certainty evidence. Two simulation studies and a crossover study showed mixed findings regarding the effect of HFNC on droplet dispersion. Although two simulation studies reported no associated increase in aerosol dispersion, one reported that higher flow rates were associated with increased regions of aerosol density. CONCLUSIONS: High-flow nasal cannula may reduce the need for invasive ventilation and escalation of therapy compared with COT in COVID-19 patients with acute hypoxemic respiratory failure. This benefit must be balanced against the unknown risk of airborne transmission.


RéSUMé: OBJECTIF: Nous avons réalisé deux comptes rendus sur commande de l'Organisation mondiale de la santé pour guider l'utilisation de canules nasales à haut débit (CNHD) chez les patients ayant contracté le coronavirus (COVID-19). Nous avons synthétisé les données probantes concernant leur efficacité et leur innocuité (compte rendu 1), ainsi que les risques de dispersion des gouttelettes, de génération d'aérosols, et de transmission associée d'éléments viraux (compte rendu 2). SOURCE: Des recherches de littérature ont été réalisées dans les bases de données Ovid MEDLINE, Embase, Web of Science, ainsi que dans les bases de données chinoises et medRxiv. Compte rendu 1 : nous avons synthétisé les résultats d'études randomisées contrôlées (ERC) comparant les CNHD à une oxygénothérapie conventionnelle chez des patients en état critique atteints d'insuffisance respiratoire hypoxémique aiguë. Compte rendu 2 : nous avons résumé sous forme narrative les constatations d'études évaluant la dispersion de gouttelettes, la génération d'aérosols ou la transmission infectieuse associées aux CNHD. Pour les deux comptes rendus, des réviseurs appariés ont réalisé la sélection des études, l'extraction des données et l'évaluation du risque de biais de manière indépendante. Nous avons évalué la certitude des données probantes en nous fondant sur la méthodologie GRADE. CONSTATATIONS PRINCIPALES: Aucune étude éligible n'incluait de patients atteints de COVID-19. Compte rendu 1 : 12 ERC (n = 1989 patients) ont fourni des données probantes de certitude faible selon lesquelles les CNHD réduiraient la ventilation invasive (risque relatif [RR], 0,85; intervalle de confiance [IC] 95 %, 0,74 à 0,99) et l'intensification de l'oxygénothérapie (RR, 0,71; IC 95 %, 0,51 à 0,98) chez les patients atteints d'insuffisance respiratoire. Les résultats n'ont pas démontré de différences en matière de mortalité (certitude modérée), ni de durée du séjour hospitalier ou à l'unité des soins intensifs (certitude modérée et faible, respectivement). Compte rendu 2 : quatre études évaluant la dispersion de gouttelettes et trois évaluant la génération et la dispersion d'aérosols ont fourni des données probantes de très faible certitude. Deux études de simulation et une étude croisée ont donné des résultats mitigés quant à l'effet des CNHD sur la dispersion des gouttelettes. Bien que deux études de simulation n'aient rapporté aucune augmentation associée concernant la dispersion d'aérosols, l'une a rapporté que des taux de débit plus élevés étaient associés à des régions à densité d'aérosols élevée plus grandes. CONCLUSION: Les canules nasales à haut débit pourraient réduire la nécessité de recourir à la ventilation invasive et l'escalade des traitements par rapport à l'oxygénothérapie conventionnelle chez les patients atteints de COVID-19 souffrant d'insuffisance respiratoire hypoxémique aiguë. Cet avantage doit être soupesé contre le risque inconnu de transmission atmosphérique.


Subject(s)
Coronavirus Infections/therapy , Oxygen Inhalation Therapy/methods , Pneumonia, Viral/therapy , Respiratory Insufficiency/therapy , Aerosols , COVID-19 , Cannula , Coronavirus Infections/complications , Coronavirus Infections/mortality , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/mortality , Randomized Controlled Trials as Topic , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/virology
8.
BMC Cardiovasc Disord ; 21(1): 528, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1505900

ABSTRACT

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Heart-Assist Devices , Influenza A virus/isolation & purification , Influenza, Human , Respiration, Artificial/methods , Respiratory Insufficiency , Ventricular Dysfunction, Left , Adult , COVID-19/diagnosis , Clinical Deterioration , Critical Care/methods , Echocardiography/methods , Female , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Influenza, Human/complications , Influenza, Human/diagnosis , Influenza, Human/physiopathology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Serologic Tests/methods , Severity of Illness Index , Shock, Cardiogenic/etiology , Shock, Cardiogenic/physiopathology , Shock, Cardiogenic/therapy , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy
9.
Crit Care Med ; 49(10): e1001-e1014, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1475867

ABSTRACT

OBJECTIVES: Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019-related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes. DESIGN AND SETTING: We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020. SUBJECTS AND INTERVENTION: Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included. MEASUREMENTS AND MAIN RESULTS: Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25-54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14-25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3-6%). Respiratory rate decreased post prone positioning (mean difference, -3.2 breaths/min; 95% CI, -4.6 to -1.9). Intubation and mortality rates were 24% (95% CI, 17-32%) and 13% (95% CI, 6-19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them. CONCLUSIONS: Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Prone Position/physiology , COVID-19/mortality , Humans , Patient Positioning , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology
10.
Sci Rep ; 11(1): 14407, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1309466

ABSTRACT

Prone position (PP) is known to improve oxygenation and reduce mortality in COVID-19 patients. This systematic review and meta-analysis aimed to determine the effects of PP on respiratory parameters and outcomes. PubMed, EMBASE, ProQuest, SCOPUS, Web of Sciences, Cochrane library, and Google Scholar were searched up to 1st January 2021. Twenty-eight studies were included. The Cochran's Q-test and I2 statistic were assessed heterogeneity, the random-effects model was estimated the pooled mean difference (PMD), and a meta-regression method has utilized the factors affecting heterogeneity between studies. PMD with 95% confidence interval (CI) of PaO2/FIO2 Ratio in before-after design, quasi-experimental design and in overall was 55.74, 56.38, and 56.20 mmHg. These values for Spo2 (Sao2) were 3.38, 17.03, and 7.58. PP in COVID-19 patients lead to significantly decrease of the Paco2 (PMD: - 8.69; 95% CI - 14.69 to - 2.69 mmHg) but significantly increase the PaO2 (PMD: 37.74; 95% CI 7.16-68.33 mmHg). PP has no significant effect on the respiratory rate. Based on meta-regression, the study design has a significant effect on the heterogeneity of Spo2 (Sao2) (Coefficient: 12.80; p < 0.001). No significant associations were observed for other respiratory parameters with sample size and study design. The pooled estimate for death rate and intubation rates were 19.03 (8.19-32.61) and 30.68 (21.39-40.75). The prone positioning was associated with improved oxygenation parameters and reduced mortality and intubation rate in COVID-19 related respiratory failure.


Subject(s)
COVID-19/mortality , COVID-19/physiopathology , Prone Position/physiology , COVID-19/therapy , Humans , Intubation, Intratracheal/statistics & numerical data , Models, Theoretical , Respiratory Insufficiency/mortality , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy
12.
BMC Pulm Med ; 21(1): 202, 2021 Jun 17.
Article in English | MEDLINE | ID: covidwho-1274550

ABSTRACT

BACKGROUND: Mechanical power (MP) of artificial ventilation, the energy transferred to the respiratory system, is a chief determinant of adequate oxygenation and decarboxylation. Calculated MP, the product of applied airway pressure and minute ventilation, may serve as an estimate of respiratory muscle workload when switching to spontaneous breathing. The aim of the study was to assess MP's discriminatory performance in predicting successful weaning from prolonged tracheostomy ventilation. METHODS: Prospective, observational study in 130 prolonged mechanically ventilated, tracheotomized patients in a specialized weaning center. Predictive weaning outcome ability of arterial blood gas analyses and indices derived from calculated MP at beginning and end of weaning was determined in terms of area under receiver operating characteristic curve (AUROC) and measures derived from k-fold cross-validation (likelihood ratios, diagnostic odds ratio, F1 score, and Matthews correlation coefficient [MCC]). RESULTS: Forty-four (33.8%) patients experienced weaning failure. Absolute MP showed poor discrimination in predicting outcome; whereas specific MP (MP normalized to dynamic lung-thorax compliance, LTCdyn-MP) had moderate diagnostic accuracy (MCC 0.38; AUROC 0.79, 95%CI [0.71‒0.86], p < 0.001), further improved by correction for corresponding mechanical ventilation PaCO2 (termed the power index of the respiratory system [PIrs]: MCC 0.52; AUROC 0.86 [0.79‒0.92], p < 0.001). Diagnostic performance of MP indices increased over the course of weaning, with maximum accuracy immediately before completion (LTCdyn-MP: MCC 0.49; AUROC 0.86 [0.78‒0.91], p < 0.001; PIrs: MCC 0.68; AUROC 0.92 [0.86‒0.96], p < 0.001). CONCLUSIONS: MP normalized to dynamic lung-thorax compliance, a surrogate for applied power per unit of ventilated lung volume, accurately discriminated between low and high risk for weaning failure following prolonged mechanical ventilation.


Subject(s)
Lung Compliance , Lung Volume Measurements , Respiration, Artificial , Ventilator Weaning , Aged , Area Under Curve , Blood Gas Analysis , Female , Humans , Male , Middle Aged , Prognosis , Prospective Studies , ROC Curve , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy
13.
Int Immunopharmacol ; 98: 107874, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1267706

ABSTRACT

BACKGROUND: Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. METHODS: The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). RESULTS: A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0-1] in the SoC arm vs. 2 [1-3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. CONCLUSION: In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results.


Subject(s)
COVID-19/therapy , Lung/physiopathology , Ozone/administration & dosage , Respiratory Insufficiency/therapy , Aged , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Female , Hospital Mortality , Humans , Italy , Length of Stay , Lung/virology , Male , Middle Aged , Ozone/adverse effects , Ozone/blood , Prospective Studies , Respiration, Artificial , Respiratory Insufficiency/blood , Respiratory Insufficiency/mortality , Respiratory Insufficiency/physiopathology , Severity of Illness Index , Time Factors , Treatment Outcome
14.
Am J Physiol Lung Cell Mol Physiol ; 321(1): L213-L218, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1234311

ABSTRACT

The renin-angiotensin system (RAS) is fundamental to COVID-19 pathobiology, due to the interaction between the SARS-CoV-2 virus and the angiotensin-converting enzyme 2 (ACE2) coreceptor for cellular entry. The prevailing hypothesis is that SARS-CoV-2-ACE2 interactions lead to an imbalance of the RAS, favoring proinflammatory angiotensin II (ANG II)-related signaling at the expense of the anti-inflammatory ANG-(1-7)-mediated alternative pathway. Indeed, multiple clinical trials targeting this pathway in COVID-19 are underway. Therefore, precise measurement of circulating RAS components is critical to understand the interplay of the RAS on COVID-19 outcomes. Multiple challenges exist in measuring the RAS in COVID-19, including improper patient controls, ex vivo degradation and low concentrations of angiotensins, and unvalidated laboratory assays. Here, we conducted a prospective pilot study to enroll 33 patients with moderate and severe COVID-19 and physiologically matched COVID-19-negative controls to quantify the circulating RAS. Our enrollment strategy led to physiological matching of COVID-19-negative and COVID-19-positive moderate hypoxic respiratory failure cohorts, in contrast to the severe COVID-19 cohort, which had increased severity of illness, prolonged intensive care unit (ICU) stay, and increased mortality. Circulating ANG II and ANG-(1-7) levels were measured in the low picomolar (pM) range. We found no significant differences in circulating RAS peptides or peptidases between these three cohorts. The combined moderate and severe COVID-19-positive cohorts demonstrated a mild reduction in ACE activity compared with COVID-19-negative controls (2.2 ± 0.9 × 105 vs. 2.9 ± 0.8 × 105 RFU/mL, P = 0.03). These methods may be useful in designing larger studies to physiologically match patients and quantify the RAS in COVID-19 RAS augmenting clinical trials.


Subject(s)
Angiotensin II/blood , Angiotensin I/blood , Angiotensin-Converting Enzyme 2/blood , COVID-19/blood , Peptide Fragments/blood , Renin-Angiotensin System , Respiratory Insufficiency/blood , SARS-CoV-2/metabolism , Adult , Aged , COVID-19/pathology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Pilot Projects , Respiratory Insufficiency/pathology , Respiratory Insufficiency/physiopathology
15.
Eur Respir Rev ; 30(160)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1218291

ABSTRACT

Prone positioning reduces mortality in the management of intubated patients with moderate-to-severe acute respiratory distress syndrome. It allows improvement in oxygenation by improving ventilation/perfusion ratio mismatching.Because of its positive physiological effects, prone positioning has also been tested in non-intubated, spontaneously breathing patients, or "awake" prone positioning. This review provides an update on awake prone positioning for hypoxaemic respiratory failure, in both coronavirus disease 2019 (COVID-19) and non-COVID-19 patients. In non-COVID-19 acute respiratory failure, studies are limited to a few small nonrandomised studies and involved patients with different diseases. However, results have been appealing with regard to oxygenation improvement, especially when combined with noninvasive ventilation or high-flow nasal cannula.The recent COVID-19 pandemic has led to a major increase in hospitalisations for acute respiratory failure. Awake prone positioning has been used with the aim to prevent intensive care unit admission and mechanical ventilation. Prone positioning in conscious, non-intubated COVID-19 patients is used in emergency departments, medical wards and intensive care units.Several trials reported an improvement in oxygenation and respiratory rate during prone positioning, but impacts on clinical outcomes, particularly on intubation rates and survival, remain unclear. Tolerance of prolonged prone positioning is an issue. Larger controlled, randomised studies are underway to provide results concerning clinical benefit and define optimised prone positioning regimens.


Subject(s)
COVID-19/therapy , Lung/physiopathology , Patient Positioning , Prone Position , Respiratory Insufficiency/therapy , Wakefulness , COVID-19/physiopathology , COVID-19/virology , Humans , Lung/virology , Recovery of Function , Respiration , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/virology , Treatment Outcome
16.
Turk J Med Sci ; 51(2): 440-447, 2021 04 30.
Article in English | MEDLINE | ID: covidwho-1211943

ABSTRACT

Background/aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Turkey on March 10, 2020 and the number of the patients are increasing day by day. Coronavirus disease 2019 (Covid-19) has high mortality rates in intensive care units (ICUs). We aimed to describe the demographic characteristics, comorbidities, treatment protocols, and clinical outcomes among the critically ill patients admitted to the ICU of our hospital. Materials and methods: This cohort study included 103 consecutive patients who had laboratory confirmed Covid-19 and admitted to ICU of Sakarya University Training and Research Hospital between March 19 and April 13, 2020. The final date of the follow-up was April 18. Results: The mean age of the patients was 69.6 ± 14.1 years. Most of the patients had increased CRP (99%), serum ferritin (73.8%), d-dimer (82.5%), and hs-troponin levels (38.8%). 34 patients (33%) had lymphocytopenia, 24 patients (23.3%) had thrombocytopenia. 63 patients (61.2%) developed acute respiratory distress syndrome (ARDS), 31 patients (30.1%) had acute kidney injury, and 52 patients (50.5%) had multiple organ dysfunction syndrome (MODS) during follow-up. Sixty-two patients (60.2%) received mechanical ventilation. As of April 18, of the 103 patients, 52 (50.5%) had died, 30 (29.1%) had been discharged from the ICU, 21 (20.4%) were still in the ICU. Conclusions: Covid-19 has high mortality rates in ICU. Patients with elevated procalcitonin, hs-troponin, d-dimer, and CRP levels and lower platelet count at admission have higher mortality.


Subject(s)
Acute Kidney Injury/physiopathology , COVID-19/physiopathology , Multiple Organ Failure/physiopathology , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , Age Factors , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/metabolism , COVID-19/mortality , COVID-19/therapy , Cohort Studies , Continuous Renal Replacement Therapy , Critical Illness , Female , Ferritins/metabolism , Fibrin Fibrinogen Degradation Products/metabolism , Glucocorticoids/therapeutic use , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Lymphopenia/blood , Male , Middle Aged , Oxygen Inhalation Therapy , Platelet Count , Procalcitonin/metabolism , Prognosis , Respiration, Artificial , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Thrombocytopenia/blood , Troponin/metabolism , Turkey
17.
Respiration ; 100(7): 594-599, 2021.
Article in English | MEDLINE | ID: covidwho-1194385

ABSTRACT

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.


Subject(s)
COVID-19/prevention & control , Lung Diseases, Interstitial/physiopathology , Masks , Pulmonary Disease, Chronic Obstructive/physiopathology , Respiratory Insufficiency/physiopathology , Walk Test/methods , Blood Gas Analysis , Chronic Disease , Exercise Tolerance , Female , Forced Expiratory Volume , Humans , Lung Diseases/physiopathology , Lung Diseases/surgery , Lung Diseases, Interstitial/surgery , Lung Transplantation , Male , Middle Aged , Minimal Clinically Important Difference , Plethysmography, Whole Body , Pulmonary Disease, Chronic Obstructive/surgery , Reproducibility of Results , Respiratory Insufficiency/surgery , Retrospective Studies , SARS-CoV-2 , Vital Capacity
18.
Chest ; 159(4): 1426-1436, 2021 04.
Article in English | MEDLINE | ID: covidwho-921554

ABSTRACT

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.


Subject(s)
Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Aged , Female , Humans , Intubation, Intratracheal , Male , Middle Aged , Pilot Projects , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Mechanics
19.
Respir Med ; 181: 106379, 2021 05.
Article in English | MEDLINE | ID: covidwho-1164392

ABSTRACT

BACKGROUND: Awake prone positioning has been recommended as an adjunctive measure in spontaneously breathing patients with hypoxemic respiratory failure during the COVID-19 pandemic. It remains uncertain as to how long this should be implemented, what variables to follow and who would be the ideal candidates for this adjunctive therapy. METHODS: A retrospective chart review of patients admitted from April to August 2020 within our institution with multifocal pneumonia and hypoxemic respiratory failure secondary to COVID-19 who underwent awake-proning for at least 3 hours was conducted. RESULTS: Improvement in respiratory parameters including ROX (SpO2/Fio2/ Respiratory Rate) indices and inflammatory markers within 4 days of institution of awake proning predicted a higher chance for success of this strategy in preventing need for mechanical ventilation. Moreover, benefits of awake proning were limited to patients with mild to moderate ARDS. CONCLUSIONS: Awake prone positioning can be safely performed with improvement in oxygenation. However, its institution may be beneficial only in patients with mild to moderate ARDS and requires careful evaluation of respiratory parameters and serum inflammatory markers to avoid a delay in endotracheal intubation and consequent increase in mortality rates.


Subject(s)
COVID-19/complications , Patient Positioning/methods , Prone Position/physiology , Respiratory Insufficiency/therapy , Adult , Aged , Biomarkers/blood , Female , Humans , Inflammation Mediators/blood , Intubation, Intratracheal , Male , Middle Aged , Respiration, Artificial , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/physiopathology , Respiratory Rate , Retrospective Studies , Severity of Illness Index , Treatment Outcome
20.
Saudi Med J ; 42(4): 391-398, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1168263

ABSTRACT

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.


Subject(s)
COVID-19/physiopathology , Abdominal Pain/physiopathology , Adolescent , Asthma/epidemiology , Atrophy , Brain/pathology , Bronchiolitis Obliterans/epidemiology , COVID-19/blood , COVID-19/epidemiology , COVID-19/therapy , Child , Child, Preschool , Comorbidity , Cough/physiopathology , Diarrhea/physiopathology , Dyspnea/physiopathology , Female , Fever/physiopathology , Heart Defects, Congenital/epidemiology , Hospital Mortality , Hospitalization , Humans , Hydrocephalus/epidemiology , Infant , Intensive Care Units, Pediatric , Male , Pharyngitis/physiopathology , Respiration, Artificial , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/therapy , Retrospective Studies , Rhinorrhea/physiopathology , SARS-CoV-2 , Saudi Arabia/epidemiology , Severity of Illness Index , Vomiting/physiopathology
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