ADVERTISEMENT

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.

Continued progress in understanding the pathophysiology of acute respiratory distress syndrome (ARDS) is translating into changes in the way we diagnose and manage it. Over the past 20 years, low tidal volume,1 positive end-expiratory pressure (PEEP),2 and fluid restriction3 have become the standard of care. A multidisciplinary approach, including targeted use of sedatives, early mobilization, and protocols for weaning from the ventilator, has also brought about substantial changes in ARDS management and its outcomes.4–6

In this article, we review the most relevant articles about ARDS in the last 5 years. We include the new definition of ARDS and studies of ventilatory and nonventilatory therapies that have implications in managing patients with ARDS.

A STANDARDIZED APPROACH

ARDS is characterized by damage to the alveolar architecture, severe hypoxemia, and bilateral parenchymal opacities.

The working definition of ARDS developed in 1994 by the American-European Consensus Conference (AECC) was the basis for enrollment in most of the landmark trials and observational studies over the past 20 years.7,8 However, it was limited in its reliability and validity.

An updated definition

In 2011, the ARDS Definition Task Force, using a novel consensus process, updated the ARDS definition,9 focusing on its feasibility, reliability, and validity in predicting response to therapies and outcomes in ARDS. This new “Berlin” definition is not substantially different from the old, but defines the criteria more specifically:

  • Bilateral opacities, unexplained by nodules, atelectasis, or effusion, on chest radiography or computed tomography
  • New or worsening respiratory symptoms, or a clinical insult associated with ARDS within 7 days of diagnosis
  • Objective assessment of cardiac function (eg, with echocardiography) to exclude cardiogenic pulmonary edema
  • Hypoxemia, with a partial pressure of arterial oxygen divided by the percentage of inspired oxygen (PaO2/FiO2 ratio) of 300 mm Hg or less despite noninvasive or invasive mechanical ventilation with PEEP or continuous positive airway pressure (CPAP) of at least 5 cm H2O.

In addition, the new definition classifies the severity of disease on the basis of the degree of hypoxemia, ie, the PaO2/FiO2 ratio:

  • Mild: PaO2/FiO2 ratio > 200 and ≤ 300 mm Hg
  • Moderate: PaO2/FiO2 ratio > 100 and ≤ 200 mm Hg
  • Severe: PaO2/FiO2 ratio ≤ 100 mm Hg.

The term “acute lung injury” has been eliminated, as has the previous criterion of a pulmonary artery wedge pressure of 18 mm Hg or less.

The panel also evaluated four ancillary variables for predicting outcomes in severe ARDS:

  • Compliance of the respiratory system less than or equal to 40 mL/cm H2O
  • Radiographic severity (involvement of three or four quadrants on chest radiography)
  • PEEP of 10 cm H2O or greater
  • Corrected expired volume 10 L/min or greater.

The task force evaluated the reliability and validity of this definition in a meta-analysis of 4,400 patients previously enrolled in randomized controlled trials or observational studies.

Findings. The Berlin definition predicted the risk of death better than the AECC definition. The mortality rate increased with the severity of ARDS, from 27% with mild disease to 32% with moderate disease to 45% with severe disease. The four ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition.

Thille et al10 retrospectively reviewed autopsy findings from 712 patients and found that the new definition identified a homogeneous group who had severe ARDS.10

Conclusions. The new definition may overcome some of the limitations of the old one, but it needs to be validated in clinical practice, especially its ability to predict death.

VENTILATORY SUPPORT

Prompt recognition, lung-protective ventilation, and a conservative fluid strategy remain the cornerstones of ARDS management. However, other strategies are being tested.

Prone-position ventilation in severe ARDS: The right therapy in a specific population

Prone-position ventilation was first described almost 30 years ago, but it has been used inconsistently in clinical practice.

Physiologic and observational studies indicated that prone positioning might improve survival in patients with ARDS, but several randomized trials failed to demonstrate any positive effect on outcomes.11,12 Some trials also reported a higher rate of complications with this intervention.13 However, meta-analyses suggested that prone-position ventilation might have a beneficial effect in patients with severe ARDS (defined as a PaO2/FiO2 ratio ≤ 100 mm Hg).14

In view of these findings, investigators conducted a trial of prone-position ventilation exclusively in patients with severe ARDS.

The PROSEVA study

The Proning Severe ARDS Patients (PROSEVA) study was a randomized controlled trial designed to determine whether prone-position ventilation, applied early, would improve outcomes in patients with severe ARDS.15

In PROSEVA, 466 patients with severe ARDS (defined as a PaO2/FiO2 ratio < 150 mm Hg, FiO2 ≥ 60%, and PEEP ≥ 5 cm H2O) underwent either at least 16 hours of prone positioning or were left in the supine position after 12 to 24 hours of initial conventional mechanical ventilation. The patients were recruited from centers in France and Spain where prone-position ventilation had been used in daily practice for more than 5 years.

The primary outcome studied was the rate of death at 28 days. The secondary end points were the death rate at day 90, rates of successful extubation, the length of stay in the intensive care unit, and complications.

Findings. At study entry, the patients in the supine group were sicker, more of them required a vasopressor, and fewer of them were receiving neuromuscular blocking agents than those in the prone group. These baseline differences may have influenced the outcomes; the unadjusted 28-day mortality rate was 16.0% in the prone group compared with 32.8% in the supine group (P < .001). However, the hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI] 0.25–0.63) even after adjusting for severity and the use of vasopressors and neuromuscular blocking agents. Prone-position ventilation was not associated with a higher incidence of complications, and the rate of successful extubation was higher.

Conclusions. In patients with severe ARDS, early use of prolonged prone positioning significantly decreased the 28-day and 90-day mortality rates. This trial has made prone positioning one of the strategies in managing patients with early severe ARDS. To minimize complications such as pressure ulcers and line or tube dislodgement, personnel caring for these patients must follow a protocol and undergo specific training.

These results were corroborated by a meta-analysis by Beitler et al16 that found a significant decrease in mortality rate with prone-position ventilation even in older studies when lung-protective ventilation strategies were separated from high-tidal-volume ventilation.

ADVERTISEMENT
ADVERTISEMENT
ADVERTISEMENT