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1.
Intensive Care Med ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825256

RESUMO

PURPOSE: Systematic review and network meta-analysis to investigate the efficacy of noninvasive respiratory strategies, including noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula (HFNC), in reducing extubation failure among critically ill adults. METHODS: We searched databases from inception through October 2021 for randomized controlled trials (RCTs) evaluating noninvasive respiratory support therapies (NIPPV, HFNC, conventional oxygen therapy, or a combination of these) following extubation in critically ill adults. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was reintubation. We used GRADE to rate the certainty of our findings. RESULTS: We included 36 RCTs (6806 patients). Compared to conventional oxygen therapy, NIPPV (OR 0.65 [95% CI 0.52-0.82]) and HFNC (OR 0.63 [95% CI 0.45-0.87]) reduced reintubation (both moderate certainty). Sensitivity analyses showed that the magnitude of the effect was highest in patients with increased baseline risk of reintubation. As compared to HFNC, no difference in incidence of reintubation was seen with NIPPV (OR 1.04 [95% CI 0.78-1.38], low certainty). Compared to conventional oxygen therapy, neither NIPPV (OR 0.8 [95% CI 0.61-1.04], moderate certainty) or HFNC (OR 0.9 [95% CI 0.66-1.24], low certainty) reduced short-term mortality. Consistent findings were demonstrated across multiple subgroups, including high- and low-risk patients. These results were replicated when evaluating noninvasive strategies for prevention (prophylaxis), but not in rescue (application only after evidence of deterioration) situations. CONCLUSIONS: Our findings suggest that both NIPPV and HFNC reduced reintubation in critically ill adults, compared to conventional oxygen therapy. NIPPV did not reduce incidence of reintubation when compared to HFNC. These findings support the preventative application of noninvasive respiratory support strategies to mitigate extubation failure in critically ill adults, but not in rescue conditions.

2.
Lancet ; 398(10307): 1230-1238, 2021 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599878

RESUMO

BACKGROUND: Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. METHODS: We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. FINDINGS: In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]). INTERPRETATION: Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. FUNDING: None.


Assuntos
COVID-19/terapia , Oxigenação por Membrana Extracorpórea/métodos , Mortalidade Hospitalar/tendências , Síndrome do Desconforto Respiratório/terapia , Adulto , COVID-19/mortalidade , Duração da Terapia , Oxigenação por Membrana Extracorpórea/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Sistema de Registros , Síndrome do Desconforto Respiratório/mortalidade , SARS-CoV-2
4.
J Clin Med ; 10(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34640318

RESUMO

STUDY DESIGN: This is a prospective, multicenter, and observational study with the aim of describing physiological characteristics, respiratory management, and outcomes of children with acute hypoxemic respiratory failure (AHRF) from different etiologies receiving invasive mechanical ventilation (IMV) compared with those affected by SARS-CoV-2. METHODS AND MAIN RESULTS: Twenty-eight patients met the inclusion criteria: 9 patients with coronavirus disease 2019 (COVID-19) and 19 patients without COVID-19. Non-COVID-19 patients had more pre-existing comorbidities (78.9% vs. 44.4%) than COVID-19 patients. At AHRF onset, non-COVID-19 patients had worse oxygenation (PaO2/FiO2 = 95 mmHg (65.5-133) vs. 150 mmHg (105-220), p = 0.04), oxygenation index = 15.9 (11-28.4) vs. 9.3 (6.7-10.6), p = 0.01), and higher PaCO2 (48 mmHg (46.5-63) vs. 41 mmHg (40-45), p = 0.07, that remained higher at 48 h: 54 mmHg (43-58.7) vs. 41 (38.5-45.5), p = 0.03). In 12 patients (5 COVID-19 and 7 non-COVID-19), AHRF evolved to pediatric acute respiratory distress syndrome (PARDS). All non-COVID-19 patients had severe PARDS, while 3 out of 5 patients in the COVID-19 group had mild or moderate PARDS. Overall Pediatric Intensive Care Medicine (PICU) mortality was 14.3%. CONCLUSIONS: Children with AHRF due to SARS-CoV2 infection had fewer comorbidities and better oxygenation than patients with non-COVID-19 AHRF. In this study, progression to severe PARDS was rarely observed in children with COVID-19.

5.
Eur Respir J ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625477

RESUMO

PURPOSE: To summarise the prognostic associations between various clinical risk factors and the development of the acute respiratory distress syndrome (ARDS) following traumatic injury. METHODS: We conducted this review in accordance with the PRISMA and CHARMS guidelines. We searched six databases from inception through December 2020. We included English language studies describing the clinical risk factors associated with the development of post-traumatic ARDS, as defined by either the American-European Consensus Conference or the Berlin definition. We pooled adjusted odds ratios for prognostic factors using the random effects method. We assessed risk of bias using the QUIPS tool and certainty of findings using GRADE methodology. RESULTS: We included 39 studies involving 5 350 927 patients. We identified the amount of crystalloid resuscitation as a potentially modifiable prognostic factor associated with the development of post-traumatic ARDS (adjusted odds ratio [aOR] 1.19 for each additional liter of crystalloid administered within first 6 h after injury, 95% CI 1.15 to 1.24, high certainty). Non-modifiable prognostic factors with a moderate or high certainty of association with post-traumatic ARDS included increasing age, non-Hispanic white race, blunt mechanism of injury, presence of head injury, pulmonary contusion, or rib fracture; and increasing chest injury severity. CONCLUSION: We identified one important modifiable factor, the amount of crystalloid resuscitation within the first 24 h of injury, and several non-modifiable factors associated with development of post-traumatic ARDS. This information should support the judicious use of crystalloid resuscitation in trauma patients and may inform the development of a risk-stratification tools.

6.
Biomedicines ; 9(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34572414

RESUMO

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

7.
Intensive Care Med ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505911

RESUMO

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

8.
N Engl J Med ; 385(9): 790-802, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34351721

RESUMO

BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.).


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Trombose/prevenção & controle , Adulto , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , COVID-19/mortalidade , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Heparina/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
9.
Ann Intensive Care ; 11(1): 132, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453620

RESUMO

BACKGROUND: Cardiogenic pulmonary oedema (CPE) may contribute to ventilator-associated lung injury (VALI) in patients with cardiogenic shock. The appropriate ventilatory strategy remains unclear. We aimed to evaluate the impact of ultra-low tidal volume ventilation with tidal volume of 3 ml/kg predicted body weight (PBW) in patients with CPE and veno-arterial extracorporeal membrane oxygenation (V-A ECMO) on lung inflammation compared to conventional ventilation. METHODS: A single-centre randomized crossover trial was performed in the Cardiac Intensive Care Unit (ICU) at a tertiary university hospital. Seventeen adults requiring V-A ECMO and mechanical ventilation due to cardiogenic shock were included from February 2017 to December 2018. Patients were ventilated for two consecutive periods of 24 h with tidal volumes of 6 and 3 ml/kg of PBW, respectively, applied in random order. Primary outcome was the change in proinflammatory mediators in bronchoalveolar lavage fluid (BALF) between both ventilatory strategies. RESULTS: Ventilation with 3 ml/kg PBW yielded lower driving pressures and end-expiratory lung volumes. Overall, there were no differences in BALF cytokines. Post hoc analyses revealed that patients with high baseline levels of IL-6 showed statistically significant lower levels of IL-6 and IL-8 during ultra-low tidal volume ventilation. This reduction was significantly proportional to the decrease in driving pressure. In contrast, those with lower IL-6 baseline levels showed a significant increase in these biomarkers. CONCLUSIONS: Ultra-low tidal volume ventilation in patients with CPE and V-A ECMO may attenuate inflammation in selected cases. VALI may be driven by an interaction between the individual proinflammatory profile and the mechanical load overimposed by the ventilator. Trial registration The trial was registered in ClinicalTrials.gov (identifier NCT03041428, Registration date: 2nd February 2017).

11.
Ann Rheum Dis ; 80(9): 1236-1240, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33903092

RESUMO

BACKGROUND: Reports of severe COVID-19 being associated with thrombosis, antiphospholipid antibodies (APLA), and antiphospholipid syndrome have yielded disparate conclusions. Studies comparing patients with COVID-19 with contemporaneous controls of similar severity are lacking. METHODS: 22 COVID-19+ and 20 COVID-19- patients with respiratory failure admitted to intensive care were studied longitudinally. Demographic and clinical data were obtained from the day of admission. APLA testing included anticardiolipin (aCL), anti-ß2glycoprotien 1 (ß2GP1), antidomain 1 ß2GP1 and antiphosphatidyl serine/prothrombin complex. Antinuclear antibodies (ANAs) were detected by immunofluorescence and antibodies to cytokines by a commercially available multiplexed array. Analysis of variance was used for continuous variables and Fisher's exact test was used for categorical variables with α=0.05 and the false discovery rate at q=0.05. RESULTS: APLAs were predominantly IgG aCL (48%), followed by IgM (21%) in all patients, with a tendency towards higher frequency among the COVID-19+. aCL was not associated with surrogate markers of thrombosis but IgG aCL was strongly associated with worse disease severity and higher ANA titres regardless of COVID-19 status. An association between aCL and anticytokine autoantibodies tended to be higher among the COVID-19+. CONCLUSIONS: Positive APLA serology was associated with more severe disease regardless of COVID-19 status. TRIAL REGISTRATION NUMBER: NCT04747782.


Assuntos
Anticorpos Anticardiolipina/imunologia , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , COVID-19/imunologia , Idoso , Anticorpos Anticardiolipina/sangue , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , COVID-19/sangue , COVID-19/complicações , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2
12.
JAMA ; 325(12): 1173-1184, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755077

RESUMO

Importance: Although most critically ill patients receive invasive mechanical ventilation (IMV), few studies have characterized how IMV is discontinued in practice. Objective: To describe practice variation in IMV discontinuation internationally, associations between initial discontinuation events and outcomes, and factors associated with the use of select discontinuation strategies and failed initial spontaneous breathing trials (SBTs). Design, Setting, and Participants: Prospective, multinational, observational study of critically ill adults who received IMV for at least 24 hours from 142 intensive care units (ICUs) in 19 countries within 6 regions (27 in Canada, 23 in India, 22 in the UK, 26 in Europe, 21 in Australia/New Zealand, and 23 in the US). Exposures: Receiving IMV. Main Outcomes and Measures: Primary analyses characterized types of initial IMV discontinuation events (extubation, SBT, or tracheostomy) and associations with clinical outcomes (including duration of ventilation, ICU and hospital mortality, and ICU and hospital length of stay). Secondary analyses examined the associations between SBT outcome and SBT timing and clinical outcomes. Results: Among 1868 patients (median [interquartile range] age, 61.8 [48.9-73.1] years; 1173 [62.8%] men) 424 (22.7%) underwent direct extubation, 930 (49.8%) had an initial SBT (761 [81.8%] successful), 150 (8.0%) underwent direct tracheostomy, and 364 (19.5%) died before a weaning attempt. Across regions, there was variation in the use of written directives to guide care, daily screening, SBT techniques, ventilator modes, and the roles played by clinicians involved in weaning. Compared with initial direct extubation, patients who had an initial SBT had higher ICU mortality (20 [4.7%] vs 96 [10.3%]; absolute difference, 5.6% [95% CI, 2.6%-8.6%]), longer duration of ventilation (median of 2.9 vs 4.1 days; absolute difference, 1.2 days [95% CI, 0.7-1.6]), and longer ICU stay (median of 6.7 vs 8.1 days; absolute difference, 1.4 days [95% CI, 0.8-2.4]). Patients whose initial SBT failed (vs passed) had higher ICU mortality (29 [17.2%] vs 67 [8.8%]; absolute difference, 8.4% [95% CI, 2.0%-14.7%]), longer duration of ventilation (median of 6.1 vs 3.5 days; absolute difference, 2.6 days [95% CI, 1.6-3.6]), and longer ICU stay (median of 10.6 vs 7.7 days; absolute difference, 2.8 days [95% CI, 1.1-5.2]). Compared with patients who underwent early initial SBTs, patients who underwent late initial SBTs (>2.3 days after intubation) had longer duration of ventilation (median of 2.1 vs 6.1 days; absolute difference, 4.0 days [95% CI, 3.7-4.5]), longer ICU stay (median of 5.9 vs 10.8 days; absolute difference, 4.9 days [95% CI, 4.0-6.3]), and longer hospital stay (median of 14.3 vs 22.8 days; absolute difference, 8.5 days [95% CI, 6.0-11.0]). Conclusions and Relevance: In this observational study of invasive mechanical ventilation discontinuation in 142 ICUs in Canada, India, the UK, Europe, Australia/New Zealand, and the US from 2013 to 2016, weaning practices varied internationally. Trial Registration: ClinicalTrials.gov Identifier: NCT03955874.


Assuntos
Estado Terminal/terapia , Desmame do Respirador/métodos , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração Artificial , Resultado do Tratamento
13.
Am J Respir Crit Care Med ; 204(3): 303-311, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784486

RESUMO

Rationale: Mortality in acute respiratory distress syndrome (ARDS) has decreased after the adoption of lung-protective strategies. Lower Vt, lower driving pressure (ΔP), lower respiratory rates (RR), and higher end-expiratory pressure have all been suggested as key components of lung protection strategies. A unifying theoretical explanation has been proposed that attributes lung injury to the energy transfer rate (mechanical power) from the ventilator to the patient, calculated from a combination of several ventilator variables.Objectives: To assess the impact of mechanical power on mortality in patients with ARDS as compared with that of primary ventilator variables such as the ΔP, Vt, and RR.Methods: We obtained data on ventilatory variables and mechanical power from a pooled database of patients with ARDS who had participated in six randomized clinical trials of protective mechanical ventilation and one large observational cohort of patients with ARDS. The primary outcome was mortality at 28 days or 60 days.Measurements and Main Results: We included 4,549 patients (38% women; mean age, 55 ± 23 yr). The average mechanical power was 0.32 ± 0.14 J · min-1 · kg-1 of predicted body weight, the ΔP was 15.0 ± 5.8 cm H2O, and the RR was 25.7 ± 7.4 breaths/min. The driving pressure, RR, and mechanical power were significant predictors of mortality in adjusted analyses. The impact of the ΔP on mortality was four times as large as that of the RR.Conclusions: Mechanical power was associated with mortality during controlled mechanical ventilation in ARDS, but a simpler model using only the ΔP and RR was equivalent.


Assuntos
Mortalidade , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , Transferência de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Taxa Respiratória , Lesão Pulmonar Induzida por Ventilação Mecânica
15.
Lancet Digit Health ; 3(3): e166-e174, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33573999

RESUMO

BACKGROUND: Non-invasive respiratory strategies (NIRS) including high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV) have become widely used in patients with COVID-19 who develop acute respiratory failure. However, use of these therapies, if ineffective, might delay initiation of invasive mechanical ventilation (IMV) in some patients. We aimed to determine early predictors of NIRS failure and develop a simple nomogram and online calculator that can identify patients at risk of NIRS failure. METHODS: We did a retrospective, multicentre observational study in 23 hospitals designated for patients with COVID-19 in China. Adult patients (≥18 years) with severe acute respiratory syndrome coronavirus 2 infection and acute respiratory failure receiving NIRS were enrolled. A training cohort of 652 patients (21 hospitals) was used to identify early predictors of NIRS failure, defined as subsequent need for IMV or death within 28 days after intensive care unit admission. A nomogram was developed by multivariable logistic regression and concordance statistics (C-statistics) computed. C-statistics were validated internally by cross-validation in the training cohort, and externally in a validation cohort of 107 patients (two hospitals). FINDINGS: Patients were enrolled between Jan 1 and Feb 29, 2020. NIV failed in 211 (74%) of 286 patients and HFNC in 204 (56%) of 366 patients in the training cohort. NIV failed in 48 (81%) of 59 patients and HFNC in 26 (54%) of 48 patients in the external validation cohort. Age, number of comorbidities, respiratory rate-oxygenation index (ratio of pulse oximetry oxygen saturation/fraction of inspired oxygen to respiratory rate), Glasgow coma scale score, and use of vasopressors on the first day of NIRS in the training cohort were independent risk factors for NIRS failure. Based on the training dataset, the nomogram had a C-statistic of 0·80 (95% CI 0·74-0·85) for predicting NIV failure, and a C-statistic of 0·85 (0·82-0·89) for predicting HFNC failure. C-statistic values were stable in both internal validation (NIV group mean 0·79 [SD 0·10], HFNC group mean 0·85 [0·07]) and external validation (NIV group value 0·88 [95% CI 0·72-0·96], HFNC group value 0·86 [0·72-0·93]). INTERPRETATION: We have developed a nomogram and online calculator that can be used to identify patients with COVID-19 who are at risk of NIRS failure. These patients might benefit from early triage and more intensive monitoring. FUNDING: Ministry of Science and Technology of the People's Republic of China, Key Research and Development Plan of Jiangsu Province, Chinese Academy of Medical Sciences.


Assuntos
COVID-19/terapia , Nomogramas , Ventilação não Invasiva , Falha de Tratamento , Adulto , Idoso , China , Comorbidade , Feminino , Previsões , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Adulto Jovem
16.
Am J Respir Crit Care Med ; 203(11): 1378-1385, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33439781

RESUMO

Rationale: If the risk of ventilator-induced lung injury in acute respiratory distress syndrome (ARDS) is causally determined by driving pressure rather than by Vt, then the effect of ventilation with lower Vt on mortality would be predicted to vary according to respiratory system elastance (Ers). Objectives: To determine whether the mortality benefit of ventilation with lower Vt varies according to Ers. Methods: In a secondary analysis of patients from five randomized trials of lower- versus higher-Vt ventilation strategies in ARDS and acute hypoxemic respiratory failure, the posterior probability of an interaction between the randomized Vt strategy and Ers on 60-day mortality was computed using Bayesian multivariable logistic regression. Measurements and Main Results: Of 1,096 patients available for analysis, 416 (38%) died by Day 60. The posterior probability that the mortality benefit from lower-Vt ventilation strategies varied with Ers was 93% (posterior median interaction odds ratio, 0.80 per cm H2O/[ml/kg]; 90% credible interval, 0.63-1.02). Ers was classified as low (<2 cm H2O/[ml/kg], n = 321, 32%), intermediate (2-3 cm H2O/[ml/kg], n = 475, 46%), and high (>3 cm H2O/[ml/kg], n = 224, 22%). In these groups, the posterior probabilities of an absolute risk reduction in mortality ≥ 1% were 55%, 82%, and 92%, respectively. The posterior probabilities of an absolute risk reduction ≥ 5% were 29%, 58%, and 82%, respectively. Conclusions: The mortality benefit of ventilation with lower Vt in ARDS varies according to elastance, suggesting that lung-protective ventilation strategies should primarily target driving pressure rather than Vt.


Assuntos
Resistência das Vias Respiratórias/fisiologia , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Teorema de Bayes , Elasticidade , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome do Desconforto Respiratório/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida , Volume de Ventilação Pulmonar , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle
18.
Respir Care ; 66(4): 559-565, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33082218

RESUMO

BACKGROUND: The ratio of dead space to tidal volume (VD/VT) is a clinically relevant parameter in ARDS; it has been shown to predict mortality, and it determines the extent to which extracorporeal CO2 removal reduces tidal volume (VT) and driving pressure (ΔP). VD/VT can be estimated with volumetric capnography, but empirical formulas using demographic and physiological information have been proposed to estimate VD/VT without the need of additional equipment. It is unknown whether estimated and measured VD/VT produce similar estimates of the predicted effect of extracorporeal CO2 removal on ΔP. METHODS: We performed a secondary analysis of data from a previous clinical trial including subjects with ARDS in whom VD/VT and CO2 production ([Formula: see text]) were measured with volumetric capnography. The estimated ratio of dead space to tidal volume (VD,est/VT) was calculated using standard empiric formulas. Agreement between measured and estimated values was evaluated with Bland-Altman analysis. Agreement between the predicted change in ΔP with extracorporeal CO2 removal as computed using the measured ratio of alveolar dead space to tidal volume (VDalv/VT) or estimated VDalv/VT (VDalv,est/VT) was also evaluated. RESULTS: VD,est/VT was higher than measured VD/VT, and agreement between them was low (bias 0.05, limits of agreement -0.21 to 0.31). Differences between measured and estimated [Formula: see text] accounted for 57% of the error in VD,est/VT. The predicted reduction in ΔP with extracorporeal CO2 removal computed using VDalv,est/VT was in reasonable agreement with the expected reduction using VDalv/VT (bias -0.7 cm H2O, limits of agreement -1.87 to 0.47 cm H2O). In multivariable regression, measured VD/VT was associated with mortality (odds ratio 1.9, 95% CI 1.2-3.1, P = .01), but VD,est/VT was not (odds ratio 1.2, 95% CI 0.8-1.8, P = .3). CONCLUSIONS: VD/VT and VD,est/VT showed low levels of agreement and cannot be used interchangeably in clinical practice. Nevertheless, the predicted decrease in ΔP due to extracorporeal CO2 removal was similar when computed from either estimated or measured VDalv/VT.


Assuntos
Síndrome do Desconforto Respiratório , Capnografia , Dióxido de Carbono , Humanos , Pulmão , Espaço Morto Respiratório , Síndrome do Desconforto Respiratório/terapia , Volume de Ventilação Pulmonar
19.
EMBO Mol Med ; 13(1): e13426, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33179852

RESUMO

There is a critical need for safe and effective drugs for COVID-19. Only remdesivir has received authorization for COVID-19 and has been shown to improve outcomes but not decrease mortality. However, the dose of remdesivir is limited by hepatic and kidney toxicity. ACE2 is the critical cell surface receptor for SARS-CoV-2. Here, we investigated additive effect of combination therapy using remdesivir with recombinant soluble ACE2 (high/low dose) on Vero E6 and kidney organoids, targeting two different modalities of SARS-CoV-2 life cycle: cell entry via its receptor ACE2 and intracellular viral RNA replication. This combination treatment markedly improved their therapeutic windows against SARS-CoV-2 in both models. By using single amino-acid resolution screening in haploid ES cells, we report a singular critical pathway required for remdesivir toxicity, namely, Adenylate Kinase 2. The data provided here demonstrate that combining two therapeutic modalities with different targets, common strategy in HIV treatment, exhibit strong additive effects at sub-toxic concentrations. Our data lay the groundwork for the study of combinatorial regimens in future COVID-19 clinical trials.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Enzima de Conversão de Angiotensina 2/farmacologia , Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Animais , Células Cultivadas , Chlorocebus aethiops , Sinergismo Farmacológico , Humanos , Modelos Moleculares , Proteínas Recombinantes/farmacologia , SARS-CoV-2/fisiologia , Células Vero , Internalização do Vírus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos
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