Low-Frequency Ventilation May Facilitate Weaning in Acute Respiratory Distress Syndrome Treated with Extracorporeal Membrane Oxygenation: A Randomized Controlled Trial

Although extracorporeal membrane ventilation offers the possibility for low-frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low-frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low-frequency ventilation on ventilator-free days (VFDs) in patients suffering from ARDS who were treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to the control group (conventional ventilation) or the treatment group (low-frequency ventilation during first 72 h on ECMO: respiratory rate 4-5/min; PEEP 14-16 cm H₂O; plateau pressure 23-25 cm H₂O, tidal volume: <4 mL/kg). The primary endpoint was VFDs at day 28 after starting ECMO treatment. The major secondary endpoint was ICU mortality, 28-day mortality and 90-day mortality. Results: Twenty-three (52%) patients were successfully weaned from ECMO and were discharged from the intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 of ECMO treatment. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (p = 0.117). Until day 28 of ECMO initiation, patients in the treatment group could be successfully weaned off of the ventilator more often (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036-0.758; p = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; p = 0.227). Conclusions: Low-frequency ventilation is comparable to conventional protective ventilation in patients with ARDS who have been treated with ECMO. However, low-frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS and treated with ECMO therapy.