Venovenous Extra-Corporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome: A Matched Cohort Study
Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by diffuse endothelial and epithelial injury, inflammatory pulmonary edema, and severe hypoxemia. Despite advancements in understanding its pathology, physiology, and mechanisms, as well as progress in mechanical ventilation techniques, the morbidity and mortality rates of ARDS remain unacceptably high. Extra-corporeal membrane oxygenation (ECMO) has emerged as an alternative cardiopulmonary support device, offering potential benefits for patients with severe ARDS. However, the efficacy of ECMO in improving survival for these patients remains a subject of debate. This study aims to investigate the impact of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS through a multi-center, retrospective, cohort study.
The study was conducted in the intensive care units (ICUs) of six teaching hospitals in China between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included, and their outcomes were compared with a matched cohort of ARDS patients who did not receive ECMO. The primary endpoint was the 28-day mortality rate, with secondary endpoints including 90-day mortality, duration of mechanical ventilation, ICU stay, and hospital stay.
A total of 99 patients with severe ARDS supported by VV-ECMO and 72 matched control patients without ECMO were included in the study. The baseline characteristics of the patients, including age, gender, height, ideal body weight, actual body weight, and disease severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, and Murray score, were comparable between the two groups. The mean APACHE II score was 23.1 in the ECMO group and 24.8 in the control group, while the mean SOFA score was 12.8 in the ECMO group and 13.7 in the control group. These differences were not statistically significant, indicating that the groups were well-matched in terms of disease severity.
The study found that the 28-day mortality rate in the ECMO group was 39.4%, significantly lower than the 55.6% mortality rate in the control group. Similarly, the 90-day mortality rate was 44.4% in the ECMO group compared to 62.5% in the control group. The survival analysis curve demonstrated a significant reduction in 28-day mortality for patients supported by ECMO. These findings suggest that VV-ECMO can improve survival in patients with severe ARDS.
The study also examined the effects of VV-ECMO on respiratory mechanics and hemodynamics. After ECMO initiation, significant improvements were observed in respiratory parameters. The tidal volume (VT) and plateau airway pressure (Pplat) were significantly reduced, indicating a protective effect on lung function. The PaO2/FiO2 ratio, a measure of oxygenation, improved dramatically after two days of ECMO support. The mean blood flow during the first day of ECMO was 4.7 L/min, with a gas flow of 4.0 L/min. By the second day, the blood flow was 4.5 L/min, and the gas flow was 3.8 L/min. These improvements in respiratory mechanics and oxygenation were statistically significant, further supporting the beneficial effects of ECMO.
Despite the positive outcomes, the study also highlighted the high rate of complications associated with ECMO. Bleeding complications occurred in 20% of the ECMO patients, with cannulation site bleeding being the most common. Intracranial hemorrhage occurred in one patient, resulting in death. Infection complications, including bloodstream infections, ventilator-associated pneumonia, and cannula site infections, were also observed in 6%, 4%, and 8% of the ECMO patients, respectively. These complications underscore the need for careful management and monitoring of patients on ECMO.
The study identified several risk factors associated with increased mortality in ECMO patients. Multivariate Cox regression analysis revealed that the duration of mechanical ventilation before ECMO and the requirement of vasopressors before ECMO were independent predictors of 28-day mortality. Patients who required vasopressors before ECMO had a higher risk of death, with a hazard ratio of 3.299. Similarly, longer durations of mechanical ventilation before ECMO were associated with increased mortality, with a hazard ratio of 1.006. These findings suggest that early initiation of ECMO, before the need for prolonged mechanical ventilation or vasopressors, may improve outcomes.
The study’s findings are consistent with previous research that has shown the potential benefits of ECMO in severe ARDS. The Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) study and other observational studies have demonstrated improved survival with ECMO support. However, the recent ECMO to Rescue Lung Injury in Severe ARDS (EOLIA) trial did not show a significant reduction in mortality compared to conventional therapy. This discrepancy highlights the need for further research to clarify the role of ECMO in ARDS management.
The study also emphasizes the importance of protective mechanical ventilation strategies in patients with ARDS. High tidal volumes and high transpulmonary pressures can exacerbate lung injury, leading to worse outcomes. With ECMO support, it is possible to achieve ultra-protective lung ventilation by reducing tidal volumes and transpulmonary pressures, thereby minimizing further lung injury. This approach was evident in the study, where significant reductions in VT and Pplat were observed after ECMO initiation.
The management of ECMO support requires a multidisciplinary approach, with careful attention to coagulation and anticoagulation to prevent bleeding and clotting complications. The study reported a high incidence of bleeding complications, with 20% of ECMO patients experiencing some form of bleeding. Cannulation site bleeding was the most common, affecting 11 patients. Mechanical complications, such as tube kinking and centrifugal pump dysfunction, were also noted, highlighting the technical challenges associated with ECMO.
In conclusion, this multi-center, retrospective cohort study demonstrates that VV-ECMO can improve survival in patients with severe ARDS. The significant reduction in 28-day and 90-day mortality rates, along with improvements in respiratory mechanics and oxygenation, supports the use of ECMO as a therapeutic option for severe ARDS. However, the high rate of complications, particularly bleeding and infections, underscores the need for careful patient selection and management. Early initiation of ECMO, before the need for prolonged mechanical ventilation or vasopressors, may further enhance outcomes. These findings contribute to the growing body of evidence on the role of ECMO in ARDS and highlight the importance of protective ventilation strategies and multidisciplinary care in managing these critically ill patients.
doi.org/10.1097/CM9.0000000000000424
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