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

Differential average daily gain of pregnant Holstein × Gyr dairy heifers causes placental adaptations to support fetal growth and development

ABSTRACT: This study aimed to evaluate the effects of differential average daily gain targets of dairy heifers throughout gestation on placental hemodynamics, uterine involution, colostrum production of the heifers, and effects on newborn calf weight and immunity transfer. Fourteen Holstein × Gyr heifers with an average body weight of 446 ± 46.7 kg and age of 25 ± 3.9 mo were randomly assigned to the following treatments: moderate body weight gain (MOD, n = 7), where heifers were fed to achieve 0.50 kg/d; and high body weight gain (HIG, n = 7), where heifers were fed to achieve 0.75 kg/d. Target average daily gains were established based on common tropical dairy production systems. The heifers received a total mixed ration feed twice daily starting at 70 d of gestation. Placentome vascularization was assessed using a color Doppler ultrasound at 180, 210, and 240 d of gestation. After calving, cotyledons were counted and sampled to analyze the mRNA expression of placental angiogenesis markers. After birth, calves were weighed and fed colostrum, and transfer of passive immunity efficiency was assessed. A significant increase in cotyledons was detected for MOD placenta soon after expulsion (81.5 ± 12.91 vs. 63.6 ± 10.52). Placentome vascularization at the final third of gestation increased for MOD heifers compared with HIG. Greater mRNA expression after membrane expulsion of VEGFB and IGFR1 in cotyledons and a greater estradiol concentration in circulation 1 d before calving was found for MOD heifers compared with HIG heifers; however, uterine involution postpartum was not different between treatment groups. Greater colostrum production was observed in HIG heifers (3.9 ± 1.05 vs. 2.2 ± 1.57 L) but with lower quality (25.2 ± 0.51 vs. 29.5 ± 0.65 Brix). No differences were observed in birth weight or transfer of passive immunity efficiency between treatments; however, HIG calves had significantly greater vitality scores than MOD calves. The results of this study indicate that a moderate feeding regimen enhances placental blood flow by increasing angiogenesis, which suggests improved nutrient transfer to the fetus without major effects on its development during the neonatal stage, colostrum production, or uterine involution in the heifers

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.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt