Extracorporeal membrane oxygenation in acute respiratory distress syndrome = Extracorporeal membrane oxygenation in acute respiratory distress syndrome
저자
발행기관
대한결핵 및 호흡기학회(The Korean Academy of Tuberculosis and Respiratory Diseases)
학술지명
권호사항
발행연도
2019
작성언어
-자료형태
학술저널
수록면
261-263(3쪽)
제공처
Acute respiratory distress syndrome (ARDS) is the most severe form of acute respiratory failure characterized by diffuse alveolar damage, and is associated with poor clinical outcomes, with a pooled mortality rate of approximately 40% despite best standards of care. Current therapeutic strategies are based on improving oxygenation and pulmonary compliance while minimizing ventilator-induced lung injury. Even in recent years, however, severe ARDS still has a high-mortality rate. Extracorporeal membrane oxygenation (ECMO) can be used in patients with severe ARDS to facilitate gas exchange in the setting of refractory hypoxemia or hypercapnic respiratory acidosis. It can also facilitate a reduction in the intensity of mechanical ventilation. In this brief review, the current state of ECMO for ARDS will be discussed.
ECMO had been used successfully in adults with ARDS since the early 1970s but, until recently, was limited to small numbers of patients at selected centers. In the last decade, use of venovenous ECMO has increased after publication of the Conventional Ventilatory Support vs. Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial and reports of successful use in several countries during the 2009 H1N1 influenza pandemic. Despite increasing use of venovenous ECMO, rigorous evidence is required to establish the appropriate role for this modality in the management of severe ARDS. Therefore, the ATS/ESICM/SCCM practice guideline published in 2017 concluded that evidence was insufficient to make a clinical recommendation for or against the use of venovenous ECMO in patients with severe ARDS.
The Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA) trial addressed the limitations of CESAR and randomized adult patients with early, severe ARDS to conventional, standard of care management that included a protocolized lung protective strategy in the control group vs immediate initiation of ECMO combined with an ultra-lung protective strategy in the intervention group. Although it was terminated early for futility (i.e., failure to demonstrate a difference in 60-day mortality of 20%), there was a nonsignificant, but clinically important, reduction in 60-day mortality (35% vs 46%, RR 0.76, 95% CI 0.55-1.04). The key secondary outcome of risk of treatment failure (defined as death in the ECMO group and death or crossover to ECMO in the control group) favored the ECMO group with a RR of 0.62 (95% CI, 0.47-0.82), as did other secondary endpoints such as free days of other organ failure. A major limitation of the trial was that 28% of control group patients ultimately crossed over to ECMO, which diluted the effect of ECMO observed in the intention- to-treat analysis. Mortality of these crossed over patients was 57 vs. 41% among the other patients in the control group (RR 1.39, 95% CI 0.95-2.03). In order to estimate the effect of ECMO on survival times if crossover had not occurred, the authors performed a post-hoc, rank-preserving structural failure time analysis. Although this relies on some assessment regarding the effect of the treatment itself, it showed a hazard ratio for mortality in the ECMO group of 0.51 (95% CI 0.24-1.02). Although the EOLIA trial was not positive by traditional interpretation, all three major analyses and all secondary endpoints suggest some degree of benefit in patients with severe ARDS managed with ECMO. More recently, a post-hoc Bayesian analysis of EOLIA trial demonstrated a high likelihood of mortality benefit, even assuming a strongly skeptical prior distribution.
In the early of this year, a systematic review and meta-analysis of the available data from the two largest randomized controlled trials (CESAR and EOLIA) of venovenous ECMO for severe ARDS and from three observational studies with matching revealed that venovenous ECMO was associated with a significant reduction in 60-day mortality compared with conventional mechanical ventilation in patients with severe ARDS. However, a moderate risk of major bleeding was also reported in relation to venovenous ECMO use. Nonetheless, as the EOLIA trial showed that early initiation of ECMO can lead to more favorable outcomes than late rescue, implementation of ECMO should be considered early if adequate oxygenation and ventilation cannot be maintained despite optimal conventional treatment in patients without any contraindication to ECMO.
If rescue was successful after initiation of ECMO support, the next step is to wait for the lungs to recover. As time to recover lung function depends on patient, and technology has enabled prolonged use of extracorporeal support, some patients rely on ECMO for a period of two weeks or more, which is usually considered the average duration of ECMO support in patients with severe respiratory failure. Sometimes, the potential regenerative capabilities of the lungs make it possible to be weaned from ECMO with improved lung function even months after initiation. While the longer is the duration of ECMO, the greater is the chance of exposure to complications, several studies have shown that long-term ECMO itself is not a predictor of poor prognosis if adequate management is pursued during ECMO support. I suggest regularly evaluating the reversibility of lung function if using ECMO support for more than four weeks. I recommend maintaining ECMO treatment until the lung recovers if reversibility remains, but a decision about transplantation or futility should be made according to the presence of significant extrapulmonary organ failure if pulmonary failure is irreversible. Patient management should be aimed at preventing further lung injury and maintaining the function of the extrapulmonary organs when ECMO support is to be maintained. For this purpose, awake, spontaneous breathing, and early mobilization are beneficial and can be safely performed in patients on ECMO. In particular, secondary right ventricle (RV) failure may occur if lung condition is not recovered or worsens; thereby, cardiac function monitoring and RV protective management should be performed. Optimal care of patients on ECMO, especially those who require prolonged ECMO, cannot be achieved by the treating physician alone. The ELSO guidelines recommend a multidisciplinary ECMO team approach as one of the key factors in ensuring effective use of ECMO. Therefore, all ECMO centers should have suitable physical facilities and equipment and provide physician and staff training and education for high-quality treatment and optimal outcomes.
Ultimately, the results of recent publications remind us of the role of ECMO in patients with severe ARDS. Beyond rescuing a patient dying of refractory hypoxemia, therefore, ECMO should now be considered early to minimize ventilator-induced lung injury (VILI) by reducing the intensity of mechanical ventilation, especially in high-volume ECMO centers with a multidisciplinary team. However, additional research focusing on selection of patients who are more likely to benefit from ECMO support, optimization of daily management of patients under ECMO to reduce extrapulmonary complications, and optimal ventilator management to reduce further VILI during ECMO should be conducted.
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