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1.
JAMA Intern Med ; 181(1): 71-78, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910179

RESUMO

Importance: Lymphopenia is common and correlates with poor clinical outcomes in patients with coronavirus disease 2019 (COVID-19). Objective: To determine whether a therapy that increases peripheral blood leukocyte and lymphocyte cell counts leads to clinical improvement in patients with COVID-19. Design, Setting and Participants: Between February 18 and April 10, 2020, we conducted an open-label, multicenter, randomized clinical trial at 3 participating centers in China. The main eligibility criteria were pneumonia, a blood lymphocyte cell count of 800 per µL (to convert to ×109/L, multiply by 0.001) or lower, and no comorbidities. Severe acute respiratory syndrome coronavirus 2 infection was confirmed with reverse-transcription polymerase chain reaction testing. Exposures: Usual care alone, or usual care plus 3 doses of recombinant human granulocyte colony-stimulating factor (rhG-CSF, 5 µg/kg, subcutaneously at days 0-2). Main Outcomes and Measures: The primary end point was the time from randomization to improvement of at least 1 point on a 7-category disease severity score. Results: Of 200 participants, 112 (56%) were men and the median (interquartile range [IQR]) age was 45 (40-55) years. There was random assignment of 100 patients (50%) to the rhG-CSF group and 100 (50%) to the usual care group. Time to clinical improvement was similar between groups (rhG-CSF group median of 12 days (IQR, 10-16 days) vs usual care group median of 13 days (IQR, 11-17 days); hazard ratio, 1.28; 95% CI, 0.95-1.71; P = .06). For secondary end points, the proportion of patients progressing to acute respiratory distress syndrome, sepsis, or septic shock was lower in the rhG-CSF group (rhG-CSF group, 2% vs usual care group, 15%; difference, -13%; 95%CI, -21.4% to -5.4%). At 21 days, 2 patients (2%) had died in the rhG-CSF group compared with 10 patients (10%) in the usual care group (hazard ratio, 0.19; 95%CI, 0.04-0.88). At day 5, the lymphocyte cell count was higher in the rhG-CSF group (rhG-CSF group median of 1050/µL vs usual care group median of 620/µL; Hodges-Lehmann estimate of the difference in medians, 440; 95% CI, 380-490). Serious adverse events, such as sepsis or septic shock, respiratory failure, and acute respiratory distress syndrome, occurred in 29 patients (14.5%) in the rhG-CSF group and 42 patients (21%) in the usual care group. Conclusion and Relevance: In preliminary findings from a randomized clinical trial, rhG-CSF treatment for patients with COVID-19 with lymphopenia but no comorbidities did not accelerate clinical improvement, but the number of patients developing critical illness or dying may have been reduced. Larger studies that include a broader range of patients with COVID-19 should be conducted. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000030007.


Assuntos
/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Mortalidade Hospitalar , Linfopenia/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Linfócitos B , Contagem de Linfócito CD4 , /complicações , China , Progressão da Doença , Feminino , Humanos , Células Matadoras Naturais , Contagem de Leucócitos , Contagem de Linfócitos , Linfopenia/sangue , Linfopenia/complicações , Masculino , Pessoa de Meia-Idade , Mortalidade , Ventilação não Invasiva , Oxigenoterapia , Proteínas Recombinantes , Insuficiência Respiratória/fisiopatologia , Sepse/fisiopatologia , Choque Séptico/fisiopatologia , Fatores de Tempo
2.
JAMA Intern Med ; 181(1): 41-51, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080002

RESUMO

Importance: Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective: To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants: The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures: Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures: Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results: Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Mortalidade Hospitalar , Insuficiência Respiratória/terapia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Anticoagulantes/uso terapêutico , Estudos de Coortes , Estado Terminal , Intervenção Médica Precoce , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Mortalidade , Escores de Disfunção Orgânica , Posicionamento do Paciente , Decúbito Ventral , Modelos de Riscos Proporcionais , Receptores de Interleucina-6/antagonistas & inibidores , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Adulto Jovem
3.
JAMA Intern Med ; 181(1): 24-31, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080005

RESUMO

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/terapia , Idoso , Gasometria , Proteína C-Reativa/metabolismo , /fisiopatologia , Progressão da Doença , Término Precoce de Ensaios Clínicos , Feminino , Febre , Hospitalização , Humanos , Itália , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Receptores de Interleucina-6/antagonistas & inibidores , Insuficiência Respiratória/fisiopatologia
4.
JAMA Intern Med ; 181(1): 32-40, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33080017

RESUMO

Importance: Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). Objective: To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. Design, Setting, and Particpants: This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. Interventions: Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. Main Outcomes and Measures: Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. Results: Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] -9.0%; 90% credible interval [CrI], -21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI -28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). Conclusions and Relevance: In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care unit, TCZ did not reduce WHO-CPS scores lower than 5 at day 4 but might have reduced the risk of NIV, MV, or death by day 14. No difference on day 28 mortality was found. Further studies are necessary for confirming these preliminary results. Trial Registration: ClinicalTrials.gov Identifier: NCT04331808.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Mortalidade Hospitalar , Intubação Intratraqueal/estatística & dados numéricos , Ventilação não Invasiva/estatística & dados numéricos , Insuficiência Respiratória/terapia , Corticosteroides/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Progressão da Doença , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Oxigenoterapia , Receptores de Interleucina-6/antagonistas & inibidores , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença , Vasoconstritores/uso terapêutico
5.
Eur Rev Med Pharmacol Sci ; 24(22): 11945-11952, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33275268

RESUMO

OBJECTIVE: COVID-19 can cause severe acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We performed a rapid systematic review focusing on the use of ECMO in patients with COVID-19. MATERIALS AND METHODS: PubMed/MEDLINE, Google Scholar, Embase, the Cochrane Library, EBSCO and Ovid (updated 30 April 2020) were systematically searched. Case reports/Case series from COVID-19 patients treated with ECMO were included in the study. Three reviewers assessed, selected, and abstracted data from studies. All disparate opinions were resolved through discussion. RESULTS: We included 13 articles for systematic evaluation, including 10 case reports and 3 case series studies, with a total of 72 patients. We search for the following information: First author of articles; Patient's location; age; gender; body mass index (BMI); Comorbidities; Time on ECMO; Mode of ECMO; treatments and clinical outcomes. As of all reporting times, our data show that 38 patients (52.8%) have died definitively, 13 patients (18.0%) were still receiving ECMO treatment, 12 patients (16.7%) were alive, 7 patients (9.7%) were recovery and 2 cases (2.8%) remained hospitalized. CONCLUSIONS: ECMO plays an important role in the stabilization and survival critically ill patients with COVID-19, but the usefulness of ECMO in reducing the mortality of severe ARDS caused by COVID-19 was limited. Therefore, a larger sample size study and a comprehensive analysis of evaluating the medical value of using ECMO on COVID-19 patients are urgently required.


Assuntos
/terapia , Oxigenação por Membrana Extracorpórea/métodos , /terapia , /fisiopatologia , Humanos , Prognóstico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia
6.
Trials ; 21(1): 1014, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302976

RESUMO

OBJECTIVES: SARS-Cov-2 virus preferentially binds to the Angiotensin Converting Enzyme 2 (ACE2) on alveolar epithelial type II cells, initiating an inflammatory response and tissue damage which may impair surfactant synthesis contributing to alveolar collapse, worsening hypoxia and leading to respiratory failure. The objective of this study is to evaluate the feasibility, safety and efficacy of nebulised surfactant in COVID-19 adult patients requiring mechanical ventilation for respiratory failure. TRIAL DESIGN: This study is a dose-escalating randomized open-label clinical trial of 20 COVID-19 patients. PARTICIPANTS: This study is conducted in two centres: University Hospital Southampton and University College London Hospitals. Eligible participants are aged ≥18, hospitalised with COVID-19 (confirmed by PCR), who require endotracheal intubation and are enrolled within 24 hours of mechanical ventilation. For patients unable to consent, assent is obtained from a personal legal representative (PerLR) or professional legal representative (ProfLR) prior to enrolment. The following are exclusion criteria: imminent expected death within 24 hours; specific contraindications to surfactant administration (e.g. known allergy, pneumothorax, pulmonary hemorrhage); known or suspected pregnancy; stage 4 chronic kidney disease or requiring dialysis (i.e., eGFR < 30); liver failure (Child-Pugh Class C); anticipated transfer to another hospital, which is not a study site, within 72 hours; current or recent (within 1 month) participation in another study that, in the opinion of the investigator, would prevent enrollment for safety reasons; and declined consent or assent. INTERVENTION AND COMPARATOR: Intervention: The study is based on an investigational drug/device combination product. The surfactant product is Bovactant (Alveofact®), a natural animal derived (bovine) lung surfactant formulated as a lyophilized powder in 108 mg vials and reconstituted to 45 mg/mL in buffer supplied in a prefilled syringe. It is isolated by lung lavage and, by weight, is a mixture of: phospholipid (75% phosphatidylcholine, 13% phosphatidylglycerol, 3% phosphatidylethanolamine, 1% phosphatidylinositol and 1% sphingomyelin), 5% cholesterol, 1% lipid-soluble surfactant-associated proteins (SP-B and SP-C), very low levels of free fatty acid, lyso-phosphatidylcholine, water and 0.3% calcium. The Drug Delivery Device is the AeroFact-COVID™ nebulizer, an investigational device based on the Aerogen® Solo vibrating mesh nebulizer. The timing and escalation dosing plans for the surfactant are as follows. Cohort 1: Three patients will receive 10 vials (1080 mg) each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 2: Three patients will receive 10 vials (1080 mg) of surfactant at dosing times of 0 hours and 8 hours, and 30 vials (3240 mg) at a dosing time of 24 hours. 2 controls with no placebo intervention. Cohort 3: Three patients will receive 10 vials (1080 mg) of surfactant at a dosing time of 0 hours, and 30 vials (3240 mg) at dosing times of 8 hours and 24 hours. 2 controls with no placebo intervention. Cohort 4: Three patients will receive 30 (3240 mg) vials each of surfactant at dosing times of 0 hours, 8 hours and 24 hours. 2 controls. 2 controls with no placebo intervention. The trial steering committee, advised by the data monitoring committee, will review trial progression and dose escalation/maintenance/reduction after each cohort is completed (48-hour primary outcome timepoint reached) based on available feasibility, adverse event, safety and efficacy data. The trial will not be discontinued on the basis of lack of efficacy. The trial may be stopped early on the basis of safety or feasibility concerns. Comparator: No placebo intervention. All participants will receive usual standard of care in accordance with the local policies for mechanically ventilated patients and all other treatments will be left to the discretion of the attending physician. MAIN OUTCOMES: The co-primary outcome is the improvement in oxygenation (PaO2/FiO2 ratio) and pulmonary ventilation (Ventilation Index (VI), where VI = [RR x (PIP - PEEP) × PaCO2]/1000) at 48 hours after study initiation. The secondary outcomes include frequency and severity of adverse events (AEs), Adverse Device Effects (ADEs), Serious Adverse Events (SAEs) and Serious Adverse Device Events (SADEs), change in pulmonary compliance, change in positive end-expiratory pressure (PEEP) requirement of ventilatory support at 24 and 48 hours after study initiation, clinical improvement defined by time to one improvement point on the ordinal scale described in the WHO master protocol (2020) recorded while hospitalised, days of mechanical ventilation, mechanical ventilator free days (VFD) at day 21, length of intensive care unit stay, number of days hospitalised and mortality at day 28. Exploratory end points will include quantification of SARS-CoV-2 viral load from tracheal aspirates using PCR, surfactant dynamics (synthesis and turnover) and function (surface tension reduction) from deep tracheal aspirate samples (DTAS), surfactant phospholipid concentrations in plasma and DTAS, inflammatory markers (cellular and cytokine) in plasma and DTAS, and blood oxidative stress markers. RANDOMISATION: After informed assent, patients fulfilling inclusion criteria will be randomised to 3:2 for the treatment and control arms using an internet-based block randomization service (ALEA tool for clinical trials, FormsVision BV) in combination with electronic data collection. Randomisation will be done by the recruiting centre with a unique subject identifier specific to that centre. BLINDING (MASKING): This is an open-labelled unblinded study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total sample size is 20 COVID-19 mechanically ventilated patients (12 intervention; 8 control). TRIAL STATUS: Current protocol version is V2 dated 5th of June 2020. The recruitment is currently ongoing and started on the 14th of October 2020. The anticipated study completion date is November 2021. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04362059 (Registered 24 April 2020), EUDAMED number: CIV-GB-20-06-033328, EudraCT number: 2020-001886-35 (Registered 11 May 2020) 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
/tratamento farmacológico , Nebulizadores e Vaporizadores/normas , Tensoativos/uso terapêutico , Adulto , /mortalidade , Estudos de Casos e Controles , Estudos de Viabilidade , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Londres/epidemiologia , Mortalidade/tendências , Nebulizadores e Vaporizadores/estatística & dados numéricos , Respiração Artificial/métodos , Insuficiência Respiratória/metabolismo , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Segurança , Tensoativos/administração & dosagem , Tensoativos/química , Resultado do Tratamento , Ventilação/estatística & dados numéricos
7.
Trials ; 21(1): 940, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225990

RESUMO

OBJECTIVES: To assess the effect of prone positioning therapy on intubation rate in awake patients with COVID-19 and acute respiratory failure. TRIAL DESIGN: This is a two-center parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hospital Civil de Guadalajara and Hospital General de Occidente in Mexico for COVID-19 associated acute respiratory failure and in need of supplementary oxygen through high-flow nasal cannula are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the COVID-19 unit who test positive for COVID-19 by PCR-test and in need for oxygen are eligible for inclusion. Randomization starts upon identification of requirement of a fraction of inspired oxygen ≥30% for an oxygen capillary saturation of ≥90% Exclusion criteria: less than 18 years-old, pregnancy, patients with immediate need of invasive mechanical ventilation (altered mental status, fatigue), vasopressor requirement to maintain median arterial pressure >65 mmHg, contraindications for prone positioning therapy (recent abdominal or thoracic surgery or trauma, facial, pelvic or spine fracture, untreated pneumothorax, do-not-resuscitate or do-not-intubate order, refusal or inability of the patient to enroll in the study. INTERVENTION AND COMPARATOR: Patients of the intervention group will be asked to remain in a prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of 92%-95%. For patients in the control group, prone positioning will be allowed as a rescue therapy. Staff intensivists will monitor the patient's status in both groups on a 24/7 basis. All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: Endotracheal intubation rate for mechanical ventilation at 28 days. RANDOMISATION: Patients will be randomly allocated to either prone positioning or control group at 1:1 ratio. Such randomization will be computer generated and stratified by center with permuted blocks and length of 4. BLINDING (MASKING): Due to logistical reasons, only principal investigators and the data analyst will be blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): With an intubation rate of 60% according to recent reports from some American centers, and assuming a decrease to 40% to be clinically relevant, we calculated a total of 96 patients per group, for a beta error of 0.2, and alpha of 0.5. Therefore, we plan to recruit 200 patients, accounting for minimal losses to follow up, with 100 non-intubated patients in the prone position group and a 100 in the control group. TRIAL STATUS: The local registration number is 048-20, with the protocol version number 2.0. The date of approval is 3rd May 2020. Recruitment started on 3rd May and is expected to end in December 2020. TRIAL REGISTRATION: The protocol was retrospectively registered under the title: "Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure. The PRO-CARF trial" in ClinicalTrials.gov with the registration number: NCT04477655. Registered on 20 July 2020. 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. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Assuntos
Infecções por Coronavirus/complicações , Intubação Intratraqueal/instrumentação , Oxigênio/uso terapêutico , Pneumonia Viral/complicações , Decúbito Ventral/fisiologia , Insuficiência Respiratória/etiologia , Doença Aguda , Adulto , Betacoronavirus/genética , Cânula/efeitos adversos , Cânula/provisão & distribução , Estudos de Casos e Controles , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , México/epidemiologia , Oxigênio/administração & dosagem , Oxigênio/sangue , Oxigênio/provisão & distribução , Pandemias , Posicionamento do Paciente/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia
8.
BMJ Open Respir Res ; 7(1)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33148777

RESUMO

OBJECTIVE: To evaluate the role of continuous positive air pressure (CPAP) in the management of respiratory failure associated with COVID-19 infection. Early clinical management with limited use of CPAP (3% of patients) was compared with a later clinical management strategy which had a higher proportion of CPAP use (15%). DESIGN: Retrospective case-controlled service evaluation for a single UK National Health Service (NHS) Trust during March-June 2020 designed and conducted solely to estimate the effects of current care. SETTING: The acute inpatient unit in Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust, a medium-sized English NHS Trust. PARTICIPANTS: 206 patients with antigen confirmed COVID-19 disease and severe acute respiratory syndrome admitted between 17 March 2020 and 3 April 2020 for the early group (controls), and between 10 April 2020 and 11 May 2020 for the late group (cases). Follow-up for all cases was until 11 June by which time all patients had a final outcome of death or discharge. Both groups were composed of 103 patients. Cases and controls were matched by age and sex. OUTCOME MEASURE: The outcome measure was the proportion of patients surviving at time t (time from the positive result of COVID-19 test to discharge/death date). The predictors were CPAP intervention, intubation, residence in care homes and comorbidities (renal, pulmonary, cardiac, hypertension and diabetes). A stratified Cox proportional hazard for clustered data (via generalised estimating equations) and model selection algorithms were employed to identify the effect of CPAP on patients' survival and the effect on gas exchange as measured by alveolar arterial (A-a) gradient and timing of CPAP treatment on CPAP patients' survival. RESULTS: CPAP was found to be significantly (HR 0.38, 95% CI 0.36 to 0.40) associated with lower risk of death in patients with hospital stay equal to, or below 7 days. However, for longer hospitalisation CPAP was found to be associated with increased risk of death (HR 1.72, 95% CI 1.40 to 2.12). When CPAP was initiated within 4 days of hospital admission, the survival probability was above 73% (95% CI 53% to 99%). In addition, lower A-a gradient was associated with lower risk of death in CPAP patients (HR 1.011, 95% CI 1.010 to 1.013). The selected model (best fit) was stratified by sex and clustered by case/control groups. The predictors were age, intubation, hypertension and the residency from care homes, which were found to be statistically significantly associated with patient's death/discharge. CONCLUSIONS: CPAP is a simple and cost-effective intervention. It has been established for care of other respiratory disorders but not for COVID-19 respiratory failure. This evaluation establishes that CPAP as a potentially viable treatment option for this group of patients during the first days of hospital admission. As yet there is limited availability of quantitative research on CPAP use for COVID-19. Whist this work is hampered by both the relatively small sample size and retrospective design (which reduced the ability to control potential confounders), it represents evidence of the significant benefit of early CPAP intervention. This evaluation should stimulate further research questions and larger study designs on the potential benefit of CPAP for COVID-19 infections. Globally, this potentially beneficial low cost and low intensity therapy could have added significance economically for healthcare provision in less developed countries.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Insuficiência Respiratória/terapia , Fatores Etários , Idoso , Betacoronavirus , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Feminino , Humanos , Hipertensão/complicações , Pacientes Internados/estatística & dados numéricos , Intubação Intratraqueal , Tempo de Internação , Masculino , Casas de Saúde , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Modelos de Riscos Proporcionais , Troca Gasosa Pulmonar , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo
9.
Arterioscler Thromb Vasc Biol ; 40(11): 2586-2597, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32960072

RESUMO

The severe acute respiratory syndrome coronavirus-2 emerged as a serious human pathogen in late 2019, causing the disease coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is acute respiratory failure consistent with the acute respiratory distress syndrome. Airway, lung parenchymal, pulmonary vascular, and respiratory neuromuscular disorders all feature in COVID-19. This article reviews what is known about the effects of severe acute respiratory syndrome coronavirus-2 infection on different parts of the respiratory system, clues to understanding the underlying biology of respiratory disease, and highlights current and future translation and clinical research questions.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Pulmão/virologia , Pneumonia Viral/virologia , Respiração , Insuficiência Respiratória/virologia , Pesquisa Médica Translacional , Animais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/fisiopatologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Prognóstico , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Embolia Pulmonar/virologia , Respiração Artificial , /fisiopatologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Fatores de Risco , Tromboembolia Venosa/fisiopatologia , Tromboembolia Venosa/terapia , Tromboembolia Venosa/virologia
10.
Anesth Analg ; 131(4): 993-999, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32925314

RESUMO

BACKGROUND: The cellular immune system is of pivotal importance with regard to the response to severe infections. Monocytes/macrophages are considered key immune cells in infections and downregulation of the surface expression of monocytic human leukocyte antigen-DR (mHLA-DR) within the major histocompatibility complex class II reflects a state of immunosuppression, also referred to as injury-associated immunosuppression. As the role of immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS: In a preliminary prospective monocentric observational study, 16 COVID-19-positive patients (75% male, median age: 68 [interquartile range 59-75]) requiring hospitalization were included. The median Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with acute respiratory failure was 30 (interquartile range 25-32). Standardized quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ cells) was performed using calibrated flow cytometry at baseline (ICU/hospital admission) and at days 3 and 5 after ICU admission. Baseline data were compared to hospitalized noncritically ill COVID-19 patients. RESULTS: While normal mHLA-DR expression was observed in all hospitalized noncritically ill patients (n = 7), 89% (8 of 9) critically ill patients with COVID-19-induced acute respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. mHLA-DR expression at admission was significantly lower in critically ill patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 14,118-42,971), P = .002. Reduced mHLA-DR expression was observed to persist until day 5 after ICU admission. CONCLUSIONS: When compared to noncritically ill hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, indicating a dysfunctional immune response. This immunosuppressive (monocytic) phenotype remained unchanged over the ensuing days after ICU admission. Strategies aiming for immunomodulation in this population of critically ill patients should be guided by an immune-monitoring program in an effort to determine who might benefit best from a given immunological intervention.


Assuntos
Infecções por Coronavirus/imunologia , Estado Terminal , Antígenos HLA-DR/biossíntese , Antígenos HLA-DR/imunologia , Tolerância Imunológica/imunologia , Pneumonia Viral/imunologia , APACHE , Idoso , Anticorpos/análise , Anticorpos/imunologia , Infecções por Coronavirus/terapia , Cuidados Críticos , Regulação para Baixo/imunologia , Feminino , Humanos , Imunoterapia , Receptores de Lipopolissacarídeos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Pandemias , Pneumonia Viral/terapia , Estudos Prospectivos , Insuficiência Respiratória/imunologia , Insuficiência Respiratória/fisiopatologia
12.
In Vivo ; 34(5): 3029-3032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871848

RESUMO

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.


Assuntos
Infecções por Coronavirus/terapia , Diabetes Mellitus/terapia , Hiperglicemia/terapia , Insulina/metabolismo , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Glicemia/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Diabetes Mellitus/genética , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia
13.
PLoS One ; 15(9): e0238619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32956395

RESUMO

PURPOSE: Long-term non-invasive ventilation (NIV) is recommended for patients with stable chronic obstructive lung disease (COPD) and chronic hypercapnia. High inspiratory pressure NIV (hiNIV) and a significant reduction of arterial pCO2 have been shown to prolong survival. Often, patients on hiNIV describe severe respiratory distress, known as "deventilation syndrome", after removal of the NIV mask in the morning. Mechanical pursed lips breathing ventilation (PLBV) is a new non-invasive ventilation mode that mimics the pressure-curve of pursed lips breathing during expiration. The clinical impact of switching patients from standard NIV to PLBV has not been studied so far. PATIENTS AND METHODS: In this hypothesis generating study, we retrospectively analysed the effects of switching COPD patients (stage GOLD III-IV) from conventional NIV to PLBV. Medical records of all patients who had an established NIV and were switched to PLBV between March 2016 and October 2017 were screened. Patients were included if they complained of shortness of breath on mask removal, used their conventional NIV regularly, and had a documented complete diagnostic workup including lung function testing, blood gas analysis and 6-minute walk test (6MWT) before and after 3-7 days of PLBV. RESULTS: Six male and 10 female patients (median age 65.4 years; IQR 64.0-71.3) with a previous NIV treatment duration of 38 months (median; IQR 20-42) were analysed. After PLVB initiation, the median inspiratory ventilation pressure needed to maintain the capillary pre-switch pCO2 level was reduced from 19.5 mbar (IQR 16.0-26.0) to 13.8 mbar (IQR 12.5-14.9; p<0.001). The median 6MWT distance increased from 200m (IQR 153.8-266.3) to 270m (IQR 211.3-323.8; p<0.001). Median forced vital capacity (FVC) increased from 49.5% to 53.0% of the predicted value (p = 0.04), while changes in FEV1 and residual volume (RV) were non-significant. CONCLUSION: Based on this small retrospective analysis, we hypothesise that switching patients with COPD GOLD III-IV and chronic hypercapnia from conventional NIV to PLBV may increase exercise tolerance and FVC in the short term.


Assuntos
Hipercapnia/fisiopatologia , Lábio/fisiopatologia , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Respiração , Insuficiência Respiratória/fisiopatologia , Idoso , Dióxido de Carbono/metabolismo , Exercício Físico , Feminino , Seguimentos , Humanos , Hipercapnia/complicações , Masculino , Pessoa de Meia-Idade , Pressão , Doença Pulmonar Obstrutiva Crônica/complicações , Insuficiência Respiratória/complicações , Estudos Retrospectivos , Teste de Caminhada
14.
Clin Immunol ; 220: 108591, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32920210

RESUMO

Most severe cases with COVID-19, especially those with pulmonary failure, are not a consequence of viral burden and/or failure of the 'adaptive' immune response to subdue the pathogen by utilizing an adequate 'adaptive' immune defense. Rather it is a consequence of immunopathology, resulting from imbalanced innate immune response, which may not be linked to pathogen burden at all. In fact, it might be described as an autoinflammatory disease. The Kawasaki-like disease seen in children with SARS-CoV-2 exposure might be another example of similar mechanism.


Assuntos
Autoimunidade/genética , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Insuficiência Respiratória/imunologia , Doença Aguda , Imunidade Adaptativa , Betacoronavirus/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Linfócitos T CD8-Positivos/virologia , Infecções por Coronavirus/genética , Infecções por Coronavirus/fisiopatologia , Síndrome da Liberação de Citocina/genética , Síndrome da Liberação de Citocina/fisiopatologia , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata , Ativação Linfocitária , Síndrome de Linfonodos Mucocutâneos/genética , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Pandemias , Pneumonia Viral/genética , Pneumonia Viral/fisiopatologia , Insuficiência Respiratória/genética , Insuficiência Respiratória/fisiopatologia , Índice de Gravidade de Doença
15.
Mol Neurobiol ; 57(12): 5263-5275, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32869183

RESUMO

Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/etiologia , Pandemias , Pneumonia Viral/complicações , Animais , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Tronco Encefálico/fisiopatologia , Tronco Encefálico/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Efeito Citopatogênico Viral , Surtos de Doenças , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/imunologia , Humanos , Camundongos , Esclerose Múltipla/etiologia , Esclerose Múltipla/imunologia , Proteínas do Tecido Nervoso/fisiologia , Doenças do Sistema Nervoso/imunologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/imunologia , Neuroglia/patologia , Neuroglia/virologia , Neurônios/patologia , Neurônios/virologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/imunologia , Receptores Virais/fisiologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Convulsões/etiologia , Convulsões/imunologia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/imunologia
16.
Crit Care ; 24(1): 479, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746877

RESUMO

BACKGROUND: Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. To date, little is known about the clearance effects of oscillating devices on patients with acute respiratory failure undergoing iMV. This study aimed to assess (1) the effects of high-frequency chest wall oscillation (HFCWO) on lung aeration and ventilation distribution, as assessed by electrical impedance tomography (EIT), and (2) the effect of the association of HFCWO with recruitment manoeuvres (RM). METHODS: Sixty critically ill patients, 30 classified as normosecretive and 30 as hypersecretive, who received ≥ 48 h of iMV, underwent HFCWO; patients from both subgroups were randomized to receive RM or not, according to two separated randomization sequences. We therefore obtained four arms of 15 patients each. After baseline record (T0), HFCWO was applied for 10 min. At the end of the treatment (T1) or after 1 (T2) and 3 h (T3), EIT data were recorded. At the beginning of each step, closed tracheobronchial suctioning was performed. In the RM subgroup, tracheobronchial suctioning was followed by application of 30 cmH2O to the patient's airway for 30 s. At each step, we assessed the change in end-expiratory lung impedance (ΔEELI) and in tidal impedance variation (ΔTIV), and the center of gravity (COG) through EIT. We also analysed arterial blood gases (ABGs). RESULTS: ΔTIV and COG did not differ between normosecretive and hypersecretive patients. Compared to T0, ΔEELI significantly increased in hypersecretive patients at T2 and T3, irrespective of the RM; on the contrary, no differences were observed in normosecretive patients. No differences of ABGs were recorded. CONCLUSIONS: In hypersecretive patients, HFCWO significantly improved aeration of the dorsal lung region, without affecting ABGs. The application of RM did not provide any further improvements. TRIAL REGISTRATION: Prospectively registered at the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ; number of registration: ACTRN12615001257550; date of registration: 17th November 2015).


Assuntos
Oscilação da Parede Torácica , Modalidades de Fisioterapia , Insuficiência Respiratória/terapia , Idoso , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Resultado do Tratamento
17.
Emerg Med J ; 37(9): 565-566, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32748797

RESUMO

We report the experience of prone ventilation in selected patients treated with helmet non-invasive ventilation (NIV) continuous positive airway pressure (CPAP) for acute respiratory failure in COVID-19 pneumonia. Preliminary results showed an improvement in the PaO2 value and PaO2/FiO2 ratio after 1 hour of prone ventilation. No variation of the lung ultrasound pattern before and after prone ventilation has been detected. At the time of writing, we attempted proning with helmet NIV CPAP in 10 patients. In 4 out of 10 patients, the attempt failed due to lack of compliance of the patient, scarce pain control even with ongoing treatment and refusal by the patient to prone positioning.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Infecções por Coronavirus , Ventilação não Invasiva/métodos , Pandemias , Pneumonia Viral , Decúbito Ventral , Insuficiência Respiratória , Idoso , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Itália/epidemiologia , Masculino , Consumo de Oxigênio , Oxigenoterapia/métodos , Posicionamento do Paciente , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Resultado do Tratamento
18.
Anatol J Cardiol ; 24(2): 76-80, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32749247

RESUMO

The pathological consequences of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) are multiple, with interstitial pneumonia and consecutive respiratory failure being the most dangerous clinical manifestations. Timely diagnosis and follow-up of pulmonary involvement need a comprehensive imaging strategy, which includes standard chest X-ray, chest computed tomography and lung ultrasound (LUS). In the last 10 years, LUS has become a useful, bedside and easily reproducible tool for lung examination. In the first part of this review, we present the pathophysiological background, technical principles and practical aspects of LUS in patients with SARS-CoV-2 infection. In the second part, the main echographic findings, their interpretation, and the clinical applications of LUS are overviewed. The review ends with the presentation of our work methodology, illustrated with images recorded from COVID-19 patients in our department.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/diagnóstico por imagem , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , Padrões de Prática Médica , Insuficiência Respiratória/complicações , Insuficiência Respiratória/fisiopatologia , Ultrassonografia
19.
Comput Biol Med ; 124: 103949, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798922

RESUMO

BACKGROUND: Currently, physicians are limited in their ability to provide an accurate prognosis for COVID-19 positive patients. Existing scoring systems have been ineffective for identifying patient decompensation. Machine learning (ML) may offer an alternative strategy. A prospectively validated method to predict the need for ventilation in COVID-19 patients is essential to help triage patients, allocate resources, and prevent emergency intubations and their associated risks. METHODS: In a multicenter clinical trial, we evaluated the performance of a machine learning algorithm for prediction of invasive mechanical ventilation of COVID-19 patients within 24 h of an initial encounter. We enrolled patients with a COVID-19 diagnosis who were admitted to five United States health systems between March 24 and May 4, 2020. RESULTS: 197 patients were enrolled in the REspirAtory Decompensation and model for the triage of covid-19 patients: a prospective studY (READY) clinical trial. The algorithm had a higher diagnostic odds ratio (DOR, 12.58) for predicting ventilation than a comparator early warning system, the Modified Early Warning Score (MEWS). The algorithm also achieved significantly higher sensitivity (0.90) than MEWS, which achieved a sensitivity of 0.78, while maintaining a higher specificity (p < 0.05). CONCLUSIONS: In the first clinical trial of a machine learning algorithm for ventilation needs among COVID-19 patients, the algorithm demonstrated accurate prediction of the need for mechanical ventilation within 24 h. This algorithm may help care teams effectively triage patients and allocate resources. Further, the algorithm is capable of accurately identifying 16% more patients than a widely used scoring system while minimizing false positive results.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Aprendizado de Máquina , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Técnicas de Laboratório Clínico/estatística & dados numéricos , Biologia Computacional , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Prognóstico , Estudos Prospectivos , Respiração Artificial , Insuficiência Respiratória/terapia , Sensibilidade e Especificidade , Triagem/métodos , Triagem/estatística & dados numéricos , Estados Unidos/epidemiologia
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