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 cmH2O 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 6430 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 metho

Addressing the role of triphenylphosphine in copper catalyzed ATRP

A new Atom Transfer Radical Polymerization (ATRP) process with triphenylphosphine (PPh3) and [CuIIMe6TREN]2+ as the catalyst system is reported. It is shown that PPh3 can act not only as an efficient reducing agent (RA) but also as a supplemental activator (SA). The kinetics and mechanism of SARA ATRP of methyl acrylate (MA) in DMSO and DMSO/H2O (90/10 v/v) were investigated in detail. The polymers presented controlled molecular weight, very low dispersity (\u110 48 1.03), and well-defined chain-end functionality. UV-Vis and electrochemical studies were performed to understand the role of PPh3 and the CuIIBr2/Me6TREN complex in MA polymerization. It is demonstrated that the presence of PPh3 does not affect the stability of the [BrCuIIMe6TREN]+ deactivator. The reported results reveal the high versatility of PPh3 in ATRP, which, besides being commonly used in iron-mediated polymerizations, can also be employed as a SARA agent in copper-based ATRP systems