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Acute respiratory distress syndrome: Implications of recent studies

Cleveland Clinic Journal of Medicine. 2014 November;81(11):683-690 | 10.3949/ccjm.81a.14018
November 1, 2014|Cleveland Clinic Journal of Medicine
Abhijit Duggal, MD, MPH;Eduardo Mireles-Cabodevila, MD;Sudhir Krishnan, MD;Alejandro C. Arroliga, MD
Author and Disclosure Information

Abhijit Duggal, MD, MPH
Medical Intensive Care Unit, Department of Pulmonary, Allergy, and Critical Care, Respiratory Institute, Cleveland Clinic; Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Eduardo Mireles-Cabodevila, MD
Program Director, Critical Care Medicine, Department of Pulmonary, Allergy, and Critical Care, Respiratory Institute, Cleveland Clinic; Assistant Professor of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Sudhir Krishnan, MD
Medical Intensive Care Unit, Department of Pulmonary, Allergy, and Critical Care, Respiratory Institute, Cleveland Clinic

Alejandro C. Arroliga, MD
Professor and Chair of Medicine, Dr. A. Ford Wolf & Brooksie Nell Boyd Wolf Centennial Chair of Medicine, Scott & White/Texas A&M HSC College of Medicine, Temple, TX

Address: Abhijit Duggal, MD, MPH, FACP, Medical Intensive Care Unit, Respiratory Institute, G62, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: Duggala2@ccf.org

ABSTRACTAcute respiratory distress syndrome (ARDS) remains challenging to diagnose and manage. This article reviews the new definition of ARDS and the key findings of landmark studies over the last 5 years of prone-position ventilation, high-frequency oscillatory ventilation (HFOV), extracorporeal membrane oxygenation (ECMO), and neuromuscular blockade in patients with ARDS.

KEY POINTS

  • The new definition of ARDS categorizes it as mild, moderate, or severe on the basis of oxygenation, specifically, the PaO2/FiO2 ratio.
  • Neuromuscular blockade and prone positioning, used early in moderate or severe cases of ARDS, have shown some promise in trials, but questions remain about their application in critically ill patients.
  • Based on two large trials, HFOV is no longer recommended as a primary therapy for ARDS, but it may still be considered as a rescue therapy in patients with refractory hypoxemia.
  • In light of observational studies and randomized trials, ECMO should be considered an option in cases of refractory hypoxemia.

Extracorporeal membrane oxygenation: Is it a viable option in severe ARDS?

Extracorporeal membrane oxygenation (ECMO) uses cardiopulmonary bypass technology to provide gas exchange. In patients with severe hypoxemia, ECMO can ensure adequate oxygenation and ventilation while ensuring the optimization of lung-protective ventilation. But ECMO was never as successful in adults with ARDS as it was in children and neonates.24

The first two trials of ECMO in ARDS24,25 reported equal or worse survival rates compared with conventional ventilation, and the overall mortality rate in these studies was staggeringly high. However, these studies were carried out before the era of lung-protective ventilation and at a time when ECMO technology was relatively primitive.

With new technology such as venovenous circuits and smaller cannulas, ECMO has gained more acceptance. It was used in patients with severe or refractory hypoxemia associated with ARDS during the H1N1 pandemic.26,27

The CESAR trial

The Conventional Ventilatory Support Versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) trial28 assessed the safety, clinical efficacy, and cost-effectiveness of ECMO in managing severe ARDS. It compared best standard practice vs a protocol that included ECMO. The trial was conducted from 2001 to 2006.

Patients with severe ARDS, as defined by a Murray score29 greater than 3 or uncompensated hypercapnea, were prospectively randomized and recruited from an ECMO center and 148 tertiary intensive care units and referral hospitals in England. This was a pragmatic trial, with minimal exclusion criteria (essentially, mechanical ventilation with high pressures and high FiO2 for more than 7 days, intracranial bleeding, or contraindication to heparinization).

A total of 180 patients were randomized in a one-to-one ratio to receive ECMO or conventional management. The ventilator management in the conventional treatment group was not done according to a protocol but in general was low-volume and low-pressure. All patients randomized to ECMO were transferred to the ECMO center and treated according to a standardized ventilation protocol. After 12 hours, if predefined goals were not reached, venovenous ECMO was started. Patients assigned to conventional management could not cross over to ECMO.

The primary outcomes were death or severe disability at 6 months after randomization, and cost-effectiveness. The secondary outcomes were hospital resource use (eg, rescue techniques, length of stay, duration of ECMO) and health status after 6 months.

Findings. The groups were similar at baseline. Sixty-eight (75%) of the 90 patients randomized to receive ECMO actually received it. Of the 22 patients who did not receive ECMO, 16 (18% of the 90) improved on conventional therapy, 5 (6%) died during or before transfer, and 1 could not receive heparin.

Two patients had severe complications in the ECMO group: one had an arterial puncture, and one had an oxygen delivery failure during transport. In each case, these events contributed to the death of the patient.

More patients in the ECMO group received lung-protective ventilation, 84 (93%) vs 63 (70%).

The primary outcome, ie, death or severe disability at 6 months, occurred in 33 (37%) of the 90 patients in the ECMO group and in 46 (53%) of the patients in the conventional management group (relative risk 0.69, 95% CI 0.05–0.97, P = .03). More patients in the ECMO group survived, but the difference was not statistically significant (relative risk of death 0.73, 95% CI 0.52–1.03, P = .07). The most common cause of death in the ECMO group was multiorgan failure (42%), whereas in the conventional management group, the most common cause of death was respiratory failure (60%).

Length of stay in the hospital and in the critical care unit and health care costs were double for patients in the ECMO group. There was no difference in quality-of-life markers at 6 months in the survivors.

Conclusions. This pragmatic trial demonstrated that a protocol that includes ECMO could improve survival rates in ARDS.

Of note, the ECMO group got care in regional centers that used protocols. Therefore, in interpreting the results of this trial, we have to consider that being in a center with protocol-specified care for ARDS could drive some of the difference in mortality rates.

Regardless, this trial demonstrated that ECMO is feasible and led to better outcomes than expected. The findings were encouraging, and spurred the use of ECMO in severe ARDS during the 2009 H1N1 pandemic. Two propensity-matched studies and a number of case series reported a survival benefit associated with the use of ECMO in patients with severe ARDS.27,30

A recent meta-analysis also reported that ECMO might lower the mortality rate in ARDS; however, the patients in the H1N1 pandemic were younger and usually had isolated respiratory failure.31

The success of ECMO has opened new possibilities in the management of ARDS. As the technology improves and our experience increases, ECMO will likely gain more acceptance as a treatment for severe ARDS.

Airway pressure release ventilation

The use of airway pressure release ventilation and other ventilator modalities in ARDS is not supported by current evidence, though results of clinical trials may influence our practice in the future.

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