Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Impacto da disfunção renal na evolução intra-hospitalar após cirurgia de revascularização miocárdica

FUNDAMENTO: A doença renal crônica (DRC) é um marcador de mortalidade na cirurgia de revascularização miocárdica (CRM). OBJETIVO: Avaliar em pacientes com DRC submetidos a CRM as características clínicas e os marcadores de morbimortalidade hospitalar; comparar a evolução intra-hospitalar entre os grupos com e sem DRC, e com e sem desenvolvimento de insuficiência renal aguda (IRA). MÉTODOS: Foram analisadas as CRM isoladas realizadas num hospital público cardiológico de 1999 a 2007. Considerado disfunção renal quando creatinina > 1,5 mg/dl. Avaliaram-se características clínicas, mortalidade e complicações pós-operatórias conforme a função renal. RESULTADOS: De 3.890 pacientes, 362 (9,3%) tinham DRC. Esse grupo apresentava idade mais avançada, maior prevalência de hipertensão, disfunção ventricular esquerda, acidente vascular encefálico (AVE) prévio, doença arterial periférica e triarteriais. No pós-operatório, apresentou maior incidência de AVE (5,5% vs 2,1%), fibrilação atrial (16 vs 8,3%), síndrome de baixo débito cardíaco (14,4% vs 8,5%), maior tempo de internação na unidade de terapia intensiva (4,04 vs 2,83 dias), e maior mortalidade intra-hospitalar (10,5% vs 3,8%). Sexo feminino, tabagismo, diabete e doença vascular periférica e/ou carotídea associaram-se com maior mortalidade no grupo DRC. Pacientes que não desenvolveram IRA pós-operatória apresentaram 3,5% de mortalidade; grupo IRA não dialítica: 35,4%; grupo IRA dialítica: 66,7%. Calculando-se a taxa de filtração glomerular, observou-se aumento da mortalidade conforme o aumento da classe da DRC. CONCLUSÃO: Pacientes com DRC submetidos a CRM constituem população de elevado risco, apresentando maior morbimortalidade. IRA pós-operatória é importante marcador de mortalidade. A taxa de filtração glomerular foi inversamente relacionada com mortalidade

Consequences of the Prolonged Waiting Time for Patients Candidates for Heart Surgery

OBJECTIVE - To assess mortality and the psychological repercussions of the prolonged waiting time for candidates for heart surgery. METHODS - From July 1999 to May 2000, using a standardized questionnaire, we carried out standardized interviews and semi-structured psychological interviews with 484 patients with coronary heart disease, 121 patients with valvular heart diseases, and 100 patients with congenital heart diseases. RESULTS - The coefficients of mortality (deaths per 100 patients/year) were as follows: patients with coronary heart disease, 5.6; patients with valvular heart diseases, 12.8; and patients with congenital heart diseases, 3.1 (p<0.0001). The survival curve was lower in patients with valvular heart diseases than in patients with coronary heart disease and congenital heart diseases (p<0.001). The accumulated probability of not undergoing surgery was higher in patients with valvular heart diseases than in the other patients (p<0.001), and, among the patients with valvular heart diseases, this probability was higher in females than in males (p<0.01). Several patients experienced intense anxiety and attributed their adaptive problems in the scope of love, professional, and social lives, to not undergoing surgery. CONCLUSION - Mortality was high, and even higher among the patients with valvular heart diseases, with negative psychological and social repercussions

Atividade microbiana em solo cultivado com cana-de-açúcar após aplicação de herbicidas Microbial activity in soil cultivated with sugarcane after herbicide application

Objetivou-se neste trabalho avaliar os efeitos dos herbicidas na atividade respiratória da microbiota, na biomassa microbiana e no quociente metabólico em solo cultivado com plantas de cana-de-açúcar. Utilizou-se o delineamento inteiramente casualizado, no esquema de parcelas subdivididas, com quatro repetições. Nas parcelas, avaliou-se o efeito dos herbicidas e, nas subparcelas, o efeito do tempo após a aplicação destes. Os herbicidas utilizados foram: 2,4-D (1,30 kg ha-1), ametryn (1,00 kg ha-1), trifloxysulfuron-sodium (0,0225 kg ha-1) e a mistura ametryn+trifloxysulfuron-sodium (1,463+0,0375 kg ha-1, respectivamente). Realizou-se a aspersão dos herbicidas aos 60 dias após a brotação das gemas do material propagativo. Aos 15, 30, 45 e 60 dias após a aplicação dos herbicidas, amostras de solos rizosférico e não-rizosférico foram coletadas e analisadas quanto às seguintes características: taxa respiratória (TR), carbono da biomassa microbiana (CBM), quociente metabólico (qCO2) e acúmulo total de C-CO2 evoluído do solo (ATC). O ametryn aplicado isolado ou em mistura com trifloxysulfuron-sodium propiciou maiores TRs, ao passo que o 2,4-D apresentou pouca influência nessa variável. Maiores acúmulos de C-CO2 aos 60 dias após a aplicação dos herbicidas foram verificados nos tratamentos com trifloxysulfuron-sodium, ametryn e na mistura de ambos os produtos. A BM do solo foi reduzida na presença do ametryn isolado ou em mistura. Esses tratamentos resultaram em maiores valores de qCO2 aos 45 e 60 dias da aplicação.<br>The objective of this work was to evaluate the impact of the herbicides ametryn and trifloxysulfuron-sodium, singly or combined, and 2,4-D, on respiratory rate, microbial biomass, and metabolic quotient on sugar cane-cultivated soil. A completely randomized design was adopted in a split-plot scheme with four replications. The effect of the herbicides was evaluated in the plots and the effect of time after herbicide application in the split-plots. The herbicide doses, in kg ha-1, were: 1.30 (2,4-D), 1.00 (ametryn), 0.0225 (trifloxysulfuron-sodium), and 1.463 + 0.0375 for the mixture ametryn + trifloxysulfuron-sodium,, respectively. At 60 days after shoot emergence, the herbicides were sprayed on the sugarcane plants. At 15, 30, 45, and 60 days after herbicide application, rhizospheric and non-rhizospheric soil samples were collected and analyzed for respiratory rate (RR) microbial biomass (MB), metabolic quotient (qCO2), and total C-CO2 evolved from the soil (TCE). Ametryn applied singly or combined with trifloxysulfuron-sodium led to higher RR, while 2,4-D alone had little influence on this variable. Higher TCEs were verified in the soils of the treatments with trifloxysulfuron-sodium, ametryn, and with the compounds combined. Soil MB was reduced in the presence of ametryn applied singly or combined. These treatments resulted in higher values of qCO2 at 45 and 60 days of application, respectively

Atividade microbiana do solo após aplicação de herbicidas em sistemas de plantio direto e convencional Microbial activity in soil after herbicide application under no-tillage and conventional planting systems

Avaliaram-se neste trabalho os efeitos de cinco concentrações (0,0; 1,05; 2,10; 4,20; e 8,40 µg g-1) dos herbicidas fluazifop-p-butil e fomesafen e da mistura comercial destes (Robust®) sobre a atividade microbiana de um solo submetido aos sistemas de plantio direto (SPD) e convencional (SPC). Amostras do solo coletadas em SPD e SPC foram colocadas em erlenmeyer de 250 mL, tratadas com as diferentes concentrações dos herbicidas e umedecidas próximo à capacidade de campo. A cada intervalo de quatro dias fez-se a quantificação da respiração microbiana, por meio da captura do CO2 liberado do solo. Aos 20 dias após o início da incubação determinou-se o carbono da biomassa microbiana (CBM) e o quociente metabólico (qCO2). No solo proveniente do SPD, a atividade microbiana aumentou com as concentrações do fluazifop-p-butil e reduziu para concentrações superiores a 4,20 µg g-1 de fomesafen. Os efeitos dos herbicidas sobre a respiração microbiana e o CBM do solo em SPC foram inferiores aos observados no solo do SPD. Entre os herbicidas, com o aumento das concentrações, verificou-se maior CBM para fluazifop-p-butil e menores valores de CBM para o fomesafen. A mistura comercial dos herbicidas (Robust®) não influenciou o CBM no SPD, mas sua redução foi maior no solo sob SPC quando aplicado nas maiores concentrações. No SPD, o qCO2 aumentou com as concentrações dos herbicidas sem, contudo, variar entre eles. No SPC, a mistura dos herbicidas proporcionou o maior qCO2. Em geral, os herbicidas promoveram efeito negativo sobre a biomassa microbiana. Esse efeito foi proporcional às concentrações aplicadas, sendo menor em solo cultivado no SPD, em comparação aquele cultivado no SPC.<br>This study evaluated the effect of the herbicides fluazifop-p-butyl and fomesafen in five concentrations (0.0; 1.05; 2.10; 4.20 and 8.40 µg g-1) and their mixture (Robust®) on microbial activity in soil submitted to no-tillage system (NTS) and conventional planting system (CPS). Samples in Erlenmeyer of 250 mL were treated with herbicide and wetted to field capacity. After every four days, microbial respiration was quantified through CO2 left by the soil. Metabolic quotient (qCO2) and carbon of microbial biomass (CMB) were determined 20 days after incubation. Under NTS, microbial activity increased with fluazifop-p-butyl and decreased with up to 4.20 µg g-1 of fomesafen. Herbicide effect on soil microbial respiration and CMB under CPS was below that observed under NTS.CMB increased with the increase of fluazifop-p-butyl concentration and decrease of fomesafen concentration. The mixture (Robust®) did not influence CMB under NTS, but it was reduced under CPS in higher concentrations. Under NTS, qCO2 increased with the herbicide concentrations, without, however, varying between them. Under CPS, herbicide mixture provided a higher qCO2. In general, the herbicides provided a negative effect on microbial biomass, proportional to the concentrations applied, being smaller in soil under NTS than in soil under CPS