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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.

High-frequency oscillatory ventilation: No benefit in two trials

Observational data and experimental studies suggested that high-frequency oscillatory ventilation (HFOV) is superior to conventional mechanical ventilation in ARDS patients.17,18 However, outdated and cumbersome equipment, lack of protocols, and a lack of high-quality evidence led to limited and inconsistent use of HFOV, mainly as a rescue therapy in ARDS.19

Over the last few years, HFOV has been gaining acceptance, especially earlier in the course of ARDS.20 After preliminary clinical trials reported promising results, two trials conducted in Canada and the United Kingdom compared HFOV vs conventional mechanical ventilation in patients with ARDS.

The OSCAR study

The Oscillation in ARDS (OSCAR) study21 was a “pragmatic” trial22 (ie, it had minimal exclusion criteria) of the safety and effectiveness of HFOV as a primary ventilatory strategy for ARDS. It included 795 patients randomized to receive conventional ventilation (n = 397) or HFOV (n = 398). Research centers followed detailed algorithms for HFOV management and adopted their usual practice for conventional ventilation. Medical care was given according to the clinician’s judgment.

The primary outcome studied was survival at 30 days. The secondary outcomes were all-cause mortality in the intensive care unit and the hospital, duration of mechanical ventilation, and use of antimicrobial, sedative, vasoactive, and neuromuscular-blocking drugs.

Findings. The patient baseline characteristics were similar in both groups.

There was no significant difference in intensive care unit mortality rates, hospital mortality rates, or mortality rates at 30 days (41.7% in the HFOV group vs 41.1% in the conventional ventilation group; P = .85, 95% CI 6.1–7.5) even after adjustments for center or severity of illness.

The duration of mechanical ventilation was similar in both groups (14.9 ± 13.3 days in the HFOV group vs 14.1 ± 13.4 days in the conventional ventilation group, P = .41). However, sedatives and neuromuscular-blocking drugs were used more often and longer in the HFOV group than in the conventional ventilation group. There was no difference in the use of vasoactive or antimicrobial medications.

Conclusions. This multicenter randomized control trial did not demonstrate any benefit from using HFOV for routine management of ARDS. Its pragmatic design made it less likely to reach a firm conclusion,22 but it at least made a case against routinely using HFOV in patients with ARDS.

The OSCILLATE study

The Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) study23 assessed the safety and efficacy of HFOV as a treatment for early-onset moderate-to-severe ARDS.

The inclusion criteria were similar to those in the OSCAR trial except that pulmonary symptoms had to be present less than 2 weeks and ARDS assessment was done under standard ventilator settings. As this was an efficacy trial, it had more exclusion criteria than the OSCAR trial. A total of 548 patients were randomized to receive conventional ventilation (n = 273) or HFOV (n = 275). The baseline characteristics were similar between groups.

Conventional ventilation was given according to a protocol used in an earlier trial2 and included recruitment maneuvers. HFOV was given in centers that had experience in this treatment, and there were protocols for ventilation management, hemodynamic optimization, and weaning. All other care was left to the clinician’s choice.

The primary outcome studied was in-hospital mortality. The investigators also evaluated whether there were interactions between the treatment and baseline severity of lung injury and center experience with HFOV.

Findings. The trial was stopped after an interim analysis found that HFOV might be harmful, although the statistical threshold for stopping was not reached. The in-hospital mortality rate was 47% in the HFOV group and 35% in the control group (relative risk of death with HFOV 1.33, 95% CI 1.09–1.64, P = .005). HFOV was worse than conventional ventilation regardless of the severity of disease or center experience. The HFOV group had higher mean airway pressures but similar FiO2 compared with the conventional ventilation group.

The HFOV group received significantly more vasopressors, sedatives, and neuromuscular blockers. This group’s fluid balance was higher as well, but not significantly so. Refractory hypoxemia (defined as PaO2 < 60 mm Hg for 1 hour with an FiO2 of 1.0 and neuromuscular blockade) was more frequent in the conventional ventilation group, but the number of deaths in the subgroup with refractory hypoxemia was similar with either treatment.

Conclusions. This multicenter randomized controlled trial demonstrated that HFOV was harmful when used routinely to manage ARDS. The trial’s protocol was based on the results of a pilot study carried out by the same investigators, which provided the best evidence available regarding the safety of HFOV at that time.

The results of the OSCAR and OSCILLATE trials have quelled enthusiasm for early, routine use of HFOV in ARDS. Although there are concerns that the protocol (ie, the way HFOV was implemented) rather than HFOV itself may have led to worse outcomes, there is no signal to support its routine use. We need further studies to define if it remains a viable rescue therapy.

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