Randomized controlled trial of ultra-protective vs. protective ventilation strategy in veno-arterial extracorporeal membrane oxygenation patients with refractory cardiogenic shock: a study protocol for the ultra-ECMO trial.

Background: A protective or ultra-protective tidal volume strategy is widely applied to patients with acute respiratory distress syndrome (ARDS). The use of very low tidal volume has the potential to further redece ventilation-induced lung injury (VILI) comparde with a "normal" lung protective management. Plus, cardiogenic pulmonary edema (CPE) caused by hydrostatic mechanisms in patients with cardiogenic shock has similar respiratory mechanics to those found in patients with ARDS. And no consensus exists on mechanical ventilation parameter settings in patients with VA-ECMO. The study aimed to investigate the impact of an ultra-protective tidal volume strategy on the 28-day ventilator-free day (VFD) number in VA-ECMO-supported patients with refractory cardiogenic shock, including cardiac arrest.
Methods: The Ultra-ECMO trial is a randomized controlled, open-label, single-center prospective superiority trial. At the onset of ECMO initiation, we will divide patients randomly into an intervention group and a control group in a 1:1 ratio. The control group will adopt protective ventilation settings [initial tidal volume: 6 ml/kg of predicted body weight (PBW)] for ventilation, and the intervention group will adopt ultra-protective ventilation settings (initial tidal volume: 4 ml/kg of PBW) for ventilation. The procedure is expected to last 72 h, after which the ventilator settings will be at the intensivists' discretion. The primary outcome is the VFD number at 28 days after inclusion. The secondary outcomes will include respiratory mechanics; analgesic/sedation dosage; lung ultrasound score; interleukin-6, interleukin-8, and monocyte chemotactic protein-1 levels in broncho-alveolar lavage fluid at the moment of enrollment (T0), 24, 48, and 72 h (T1, T2, and T3, respectively) after ECMO initiation; total time (in days) required for ECMO weaning; length of stay in the intensive care unit; total cost of hospitalization; amounts of resuscitative fluids; and in-hospital mortality.
Discussion: VA-ECMO-treated patients without ARDS possess abnormal lung function. CPE, thoracic compliance reduction, and poor pulmonary blood perfusion are frequently present, and these patients can more easily progress to ARDS. It seems that targeting the protective tidal volume can lower adverse outcome incidence rates, even in patients without ARDS. This trial seeks to answer the question of whether adopting an ultra-protective tidal volume strategy can lead to superior primary and secondary outcomes compared to adopting a protective tidal volume strategy in patients treated by VA-ECMO. The Ultra-ECMO trial will provide an innovative mechanical ventilation strategy for VA-ECMO-supported patients for improving treatment outcomes at biological and potentially clinical levels.
Clinical Trial Registration: ChiCTR2200067118.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2023 Li, Chen, Hu, Sun, Zhang, Zhang, Dong, Lv, Mei and Chen.)