RESUMO
BACKGROUND: In patients with COVID-19-related acute respiratory failure (ARF), awake prone positioning (AW-PP) reduces the need for intubation in patients treated with high-flow nasal oxygen (HFNO). However, the effects of different exposure times on clinical outcomes remain unclear. We evaluated the effect of AW-PP on the risk of endotracheal intubation and in-hospital mortality in patients with COVID-19-related ARF treated with HFNO and analyzed the effects of different exposure times to AW-PP. METHODS: This multicenter prospective cohort study in six ICUs of 6 centers in Argentine consecutively included patients > 18 years of age with confirmed COVID-19-related ARF requiring HFNO from June 2020 to January 2021. In the primary analysis, the main exposure was awake prone positioning for at least 6 h/day, compared to non-prone positioning (NON-PP). In the sensitivity analysis, exposure was based on the number of hours receiving AW-PP. Inverse probability weighting-propensity score (IPW-PS) was used to adjust the conditional probability of treatment assignment. The primary outcome was endotracheal intubation (ETI); and the secondary outcome was hospital mortality. RESULTS: During the study period, 580 patients were screened and 335 were included; 187 (56%) tolerated AW-PP for [median (p25-75)] 12 (9-16) h/day and 148 (44%) served as controls. The IPW-propensity analysis showed standardized differences < 0.1 in all the variables assessed. After adjusting for other confounders, the OR (95% CI) for ETI in the AW-PP group was 0.36 (0.2-0.7), with a progressive reduction in OR as the exposure to AW-PP increased. The adjusted OR (95% CI) for hospital mortality in the AW-PP group ≥ 6 h/day was 0.47 (0.19-1.31). The exposure to prone positioning ≥ 8 h/d resulted in a further reduction in OR [0.37 (0.17-0.8)]. CONCLUSION: In the study population, AW-PP for ≥ 6 h/day reduced the risk of endotracheal intubation, and exposure ≥ 8 h/d reduced the risk of hospital mortality.
Assuntos
COVID-19 , Oxigenoterapia , Insuficiência Respiratória , Administração Intranasal , COVID-19/complicações , Humanos , Oxigênio/administração & dosagem , Oxigenoterapia/métodos , Decúbito Ventral , Estudos Prospectivos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Fatores de Tempo , Resultado do Tratamento , VigíliaAssuntos
COVID-19 , Cuidados Críticos/métodos , Hospitalização/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/mortalidade , COVID-19/terapia , Teste de Ácido Nucleico para COVID-19 , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND: Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. METHODS: In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. FINDINGS: Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. INTERPRETATION: In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. FUNDING: None. TRANSLATION: For the Spanish translation of the Summary see Supplementary Materials section.
Assuntos
COVID-19/terapia , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/terapia , Adulto , Idoso , Argentina/epidemiologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/mortalidade , Teste de Ácido Nucleico para COVID-19 , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial/métodos , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/virologia , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Volume de Ventilação Pulmonar , Resultado do Tratamento , Adulto JovemRESUMO
The COVID-19 pandemic significates an enormous number of patients with pneumonia that get complicated with severe acute respiratory distress syndrome (ARDS), some of them with refractory hypercapnia and hypoxemia that need mechanical ventilation (MV). Those patients who are not candidate to extracorporeal membrane oxygenation (ECMO), the extracorporeal removal of CO2 (ECCO2 R) can allow ultra protective MV to limit the transpulmonary pressures and avoid ventilatory induced lung injury (VILI). We report a first case of prolonged ECCO2 R support in 38 year male with severe COVID-19 pneumonia refractory to conventional support. He was admitted tachypneic and oxygen saturation 71% without supplementary oxygen. The patient's clinical condition worsens with severe respiratory failure, increasing the oxygen requirement and initiating MV in the prone position. After 21 days of protective MV, PaCO2 rise to 96.8 mmHg, making it necessary to connect to an ECCO2 R system coupled continuous veno-venous hemodialysis (CVVHD). However, due to the lack of availability of equipment in the context of the pandemic, a pediatric gas exchange membrane adapted to CVVHD allowed to maintain the removal of CO2 until completing 27 days, being finally disconnected from the system without complications and with a satisfactory evolution.
Assuntos
COVID-19/terapia , Dióxido de Carbono/metabolismo , Pneumonia Viral/terapia , Pneumonia Viral/virologia , Terapia de Substituição Renal , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Adulto , Humanos , Masculino , Pandemias , SARS-CoV-2RESUMO
We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient's deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies.
Assuntos
Brônquios/patologia , Tratamento Farmacológico da COVID-19 , Esteroides/uso terapêutico , Idoso , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/virologia , Biópsia/métodos , Brônquios/virologia , COVID-19/patologia , COVID-19/virologia , Humanos , Pulmão/patologia , Masculino , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/virologia , Insuficiência Respiratória/tratamento farmacológico , Insuficiência Respiratória/patologia , Insuficiência Respiratória/virologia , SARS-CoV-2/isolamento & purificaçãoRESUMO
BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.
Assuntos
Bradicinina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Proteína Inibidora do Complemento C1/administração & dosagem , Insuficiência Respiratória/tratamento farmacológico , Adulto , Enzima de Conversão de Angiotensina 2/metabolismo , Bradicinina/administração & dosagem , Bradicinina/efeitos adversos , Bradicinina/antagonistas & inibidores , Bradicinina/imunologia , Bradicinina/metabolismo , Antagonistas de Receptor B2 da Bradicinina/administração & dosagem , Antagonistas de Receptor B2 da Bradicinina/efeitos adversos , Brasil , COVID-19/complicações , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos Fase II como Assunto , Proteína Inibidora do Complemento C1/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Calicreínas/antagonistas & inibidores , Calicreínas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Respiratória/imunologia , Insuficiência Respiratória/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center. METHODS: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records. RESULTS: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02). CONCLUSION: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.
OBJETIVO: Descrever as características clínicas e os preditores de ventilação mecânica em pacientes adultos internados com COVID-19. MÉTODOS: Conduziu-se um estudo de coorte retrospectiva com inclusão de pacientes hospitalizados entre 17 de março e 3 de maio de 2020, que tiveram o diagnóstico de infecção pelo SARS-CoV-2. As características clínicas e demográficas foram extraídas de registros em prontuário eletrônico. RESULTADOS: Incluíram-se no estudo 88 pacientes consecutivos. A mediana da idade dos pacientes foi de 63 anos (IQR: 49 - 71); 59 (67%) pacientes eram do sexo masculino, 65 (86%) tinham educação universitária e 67 (76%) tinham, no mínimo, uma comorbidade. Dentre eles, 29 (33%) pacientes foram admitidos à unidade de terapia intensiva, 18 (20%) necessitaram de ventilação mecânica e nove (10,2%) morreram durante a hospitalização. O tempo mediano de permanência na unidade de terapia intensiva e o tempo mediano de ventilação mecânica foram, respectivamente, de 23 e 29,5 dias. Idade acima ou igual a 65 anos foi fator de risco independente para ventilação mecânica (RC: 8,4; IC95% de 1,3 - 55,6; valor de p = 0,02). CONCLUSÃO: Nossos achados descrevem a primeira onda de pacientes brasileiros hospitalizados por COVID-19. Em nossa população, idade foi o maior preditor de insuficiência respiratória e necessidade de ventilação mecânica.
Assuntos
COVID-19/terapia , Hospitalização , Unidades de Terapia Intensiva/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Brasil , COVID-19/complicações , COVID-19/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
RESUMO Objetivo: Descrever as características clínicas e os preditores de ventilação mecânica em pacientes adultos internados com COVID-19. Métodos: Conduziu-se um estudo de coorte retrospectiva com inclusão de pacientes hospitalizados entre 17 de março e 3 de maio de 2020, que tiveram o diagnóstico de infecção pelo SARS-CoV-2. As características clínicas e demográficas foram extraídas de registros em prontuário eletrônico. Resultados: Incluíram-se no estudo 88 pacientes consecutivos. A mediana da idade dos pacientes foi de 63 anos (IQR: 49 - 71); 59 (67%) pacientes eram do sexo masculino, 65 (86%) tinham educação universitária e 67 (76%) tinham, no mínimo, uma comorbidade. Dentre eles, 29 (33%) pacientes foram admitidos à unidade de terapia intensiva, 18 (20%) necessitaram de ventilação mecânica e nove (10,2%) morreram durante a hospitalização. O tempo mediano de permanência na unidade de terapia intensiva e o tempo mediano de ventilação mecânica foram, respectivamente, de 23 e 29,5 dias. Idade acima ou igual a 65 anos foi fator de risco independente para ventilação mecânica (RC: 8,4; IC95% de 1,3 - 55,6; valor de p = 0,02). Conclusão: Nossos achados descrevem a primeira onda de pacientes brasileiros hospitalizados por COVID-19. Em nossa população, idade foi o maior preditor de insuficiência respiratória e necessidade de ventilação mecânica.
Abstract Objective: This study aims to describe the clinical characteristics and predictors of mechanical ventilation of adult inpatients with COVID-19 in a single center. Methods: A retrospective cohort study was performed and included adult inpatients hospitalized from March 17th to May 3rd, 2020, who were diagnosed with SARS-CoV-2 infection. Clinical and demographic characteristics were extracted from electronic medical records. Results: Overall, 88 consecutive patients were included in this study. The median age of the patients was 63 years (IQR 49 - 71); 59 (67%) were male, 65 (86%) had a college degree and 67 (76%) had at least one comorbidity. Twenty-nine (33%) patients were admitted to the intensive care unit, 18 (20%) patients needed mechanical ventilation, and 9 (10.2%) died during hospitalization. The median length of stay in the intensive care unit and the median duration of mechanical ventilation was 23 and 29.5 days, respectively. An age ≥ 65 years was an independent risk factor for mechanical ventilation (OR 8.4 95%CI 1.3 - 55.6 p = 0.02). Conclusion: Our findings describe the first wave of Brazilian patients hospitalized for COVID-19. Age was the strongest predictor of respiratory insufficiency and the need for mechanical ventilation in our population.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Respiração Artificial/estatística & dados numéricos , Insuficiência Respiratória/epidemiologia , COVID-19/terapia , Hospitalização , Unidades de Terapia Intensiva/estatística & dados numéricos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/virologia , Brasil , Estudos Retrospectivos , Fatores de Risco , Estudos de Coortes , Fatores Etários , COVID-19/complicações , COVID-19/fisiopatologia , Tempo de InternaçãoRESUMO
Brazil has 896,917 Indigenous individuals distributed among 505 Indigenous lands. There are 274 different Indigenous languages within 305 Indigenous ethnic groups. The Indigenous population is susceptible to pandemics, especially to the current pandemic of COVID-19, which has spread rapidly. In Brazil, after the first COVID-19-confirmed Indigenous case on 05th June 2020, more 420 suspected cases, 1727 confirmed cases being 934 active cases, 715 cases with clinical cure, and 70 cases of death were accounted through the first week of June. The number of cases is underestimated, according to the Special Secretariat for Indigenous Health (SESAI) database, since the deaths are due to respiratory failure, possibly caused by COVID-19, but not confirmed. The first COVID-19-caused death was a 15-year-old Indigenous Yanomami teenage from Roraima State without known previous diseases history and/or comorbidities. In the present study, the importance of social isolation, especially for Indigenous people who are more vulnerable to the COVID-19, was highlighted by the identification of the infection community. An Indigenous of the Kokama ethnicity was infected after coming in contact with a Medical Doctor who was infected with the disease. Later, it was noticed that both, Indigenous and doctor, were responsible for COVID-19's transmission to 43 other Indigenous individuals (30 in Alto Rio Solimões and 13 in Parintis), causing possibly other confirmed deaths. The impact of COVID-19 for Indigenous population might be an unprecedented tragedy, and the government in Brazil must take emergency measures as the social isolation.