Background

Mechanical ventilation is routinely used during veno-arterial extracorporeal membrane oxygenation (V-A ECMO), but its role in influencing hemodynamics and supporting cardiac recovery remains poorly understood. This systematic review aims to summarize and describe studies that investigated the effects of mechanical ventilation settings and adjunctive respiratory interventions on cardiac function, recovery, and clinical outcomes in V-A ECMO patients.

Methods

A systematic search in literature up to June 6th 2025 was conducted to identify studies assessing the effects of ventilation strategies or hypoxemia-rescue therapies on physiological and clinical outcomes in adults supported by V-A ECMO or in animal V-A ECMO models. Because of anticipated heterogeneity across studies, we refrained from pooling of results.

Results

Out of 5,750 records screened, 12 studies met the inclusion criteria (10 clinical, 1 experimental, 1 computational). Four studies in humans observed that lower driving and peak inspiratory pressures, along with reduced respiratory rates, were associated with improved survival in V-A ECMO patients. One study found that moderate positive end-expiratory pressure (PEEP) conveyed protective effects on the lungs without compromising cardiac function, whereas excessive PEEP impaired systolic function without causing systemic hypotension. A computational study suggested that higher intrathoracic pressures may have cardioprotective effects by unloading the left ventricle and reducing myocardial oxygen demand. Very limited studies have explored adjunctive ventilation strategies, including inhaled nitric oxide and defined oxygenation targets during V-A ECMO, exhibiting at least a moderate risk of bias.

Conclusions

Evidence on the effects of mechanical ventilation during V-A ECMO on cardiac function, recovery and clinical outcomes is limited, heterogeneous, and at considerable risk of bias. Well-designed mechanistic and interventional studies are needed to determine whether ventilation strategies can support myocardial recovery and facilitate successful V-A ECMO weaning.