ART - Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART)

Randomized Controlled Trial of Maximum Alveolar Recruitment Maneuver Plus Titrated PEEP Versus ARDSNet Strategy for ARDS

Acute respiratory distress syndrome (ARDS) is a common scenario in intensive care unit. Discussions about it is exponentially growing up due its high mortality rates all over the world and low quality of life among survivors. Mechanical ventilation is recognized to play an important role in treatment of patients with ARDS. However, mechanical ventilation itself has the potential to produce or worsen alveolar injury if inadequate strategies are chosen. Several studies compared different mechanical ventilation strategies in ARDS but the results remain uncertain regarding their influence on survival in patients with ARDS. Thus, this is a multicentric randomized controlled trial, with allocation concealment and intention to treat analysis to investigate if maximum alveolar recruitment maneuver in association to Positive end-expiratory pressure (PEEP) titrated by static compliance of respiratory system (ART strategy) is able to increase 28 days survival in patients with moderate to severe ARDS compared to conventional strategy proposed by the ARDS Clinical Network (ARDSNet strategy). Patients considered to this trial are those in mechanical ventilation with diagnosis of moderate to severe ARDS less than 72hours. Patients included will be randomized to receive ART strategy or ARDSNet strategy and will be followed until hospital discharge, 28 days and 6 months.

Maximum alveolar recruitment maneuver in association with PEEP titrated by the static compliance of respiratory system.

We consider as pneumothorax requiring chest tube within 7 days any case that is possibly due to barotrauma, that is, we do not consider cases judged to be clearly caused by invasive procedures such as central venous punction or thoracocentesis.

We consider as barotrauma within 7 days any pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele > 2cm detected on image exams between randomization and 7 days, except those judged to be clearly caused by invasive procedures.

Number of days alive and out of mechanical ventilation between randomization and 28 days after randomization.

Need of commencement/increase of vasopressors or hypotension (MAP < 65mmHg) in the first hour after randomization.

Cardiorespiratory arrest defined as unexpected cardiac arrest, not due to progressive refractory shock within 24 hours after randomization.

Death with refractory hypoxemia, defined as PaO2 < 55 mmHg in the last arterial blood gas analysis with FiO2 = 100%.

Death with refractory acidosis within 7 days, defined as pH ≤ 7.10 in the last arterial blood gas analysis

Death with barotrauma within 7 days after randomization. We consider as barotrauma any pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele > 2cm detected on image exams, except those judged to be clearly caused by invasive procedures.

Inclusion Criteria: intubated, mechanically ventilated patients with diagnosis of moderate to severe ARDS less than 72 hours Exclusion Criteria: age less than 18 years use of vasopressor drugs in increasing doses over the last 2 hours or mean arterial blood pressure less than 65mmHg presence of any contraindication to hypercapnia as intracranial hypertension or acute coronary syndrome pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele patient with no therapeutic perspective, candidates for palliative care exclusively patient previously randomized in the ART

Zampieri FG, Costa EL, Iwashyna TJ, Carvalho CRR, Damiani LP, Taniguchi LU, Amato MBP, Cavalcanti AB; Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial Investigators. Heterogeneous effects of alveolar recruitment in acute respiratory distress syndrome: a machine learning reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial. Br J Anaesth. 2019 Jul;123(1):88-95. doi: 10.1016/j.bja.2019.02.026. Epub 2019 Apr 5.

Damiani LP, Berwanger O, Paisani D, Laranjeira LN, Suzumura EA, Amato MBP, Carvalho CRR, Cavalcanti AB. Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial. Rev Bras Ter Intensiva. 2017 Apr-Jun;29(2):142-153. doi: 10.5935/0103-507X.20170024.

Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators; Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimaraes HP, Romano ER, Regenga MM, Taniguchi LNT, Teixeira C, Pinheiro de Oliveira R, Machado FR, Diaz-Quijano FA, Filho MSA, Maia IS, Caser EB, Filho WO, Borges MC, Martins PA, Matsui M, Ospina-Tascon GA, Giancursi TS, Giraldo-Ramirez ND, Vieira SRR, Assef MDGPL, Hasan MS, Szczeklik W, Rios F, Amato MBP, Berwanger O, Ribeiro de Carvalho CR. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1335-1345. doi: 10.1001/jama.2017.14171.

Morais CC, De Santis Santiago RR, Filho JR, Hirota AS, Pacce PH, Ferreira JC, Camargo ED, Amato MB, Costa EL. Monitoring of Pneumothorax Appearance with Electrical Impedance Tomography during Recruitment Maneuvers. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1070-1073. doi: 10.1164/rccm.201609-1780LE. No abstract available.

ART Investigators. Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial. Trials. 2012 Aug 28;13:153. doi: 10.1186/1745-6215-13-153.