OSCAR: High-Frequency Oscillation in ARDS (2013)

“In patients with ARDS, the use of high-frequency oscillatory ventilation, as compared with conventional mechanical ventilation, does not reduce, and may increase, mortality.”

  • The OSCAR Study Group

1. Publication Details

  • Trial Title: High-Frequency Oscillation for Acute Respiratory Distress Syndrome
  • Citation: Young D, Lamb SE, Shah S, et al. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013;368(9):806-813. DOI: 10.1056/NEJMoa1215716
  • Published: February 28, 2013, in The New England Journal of Medicine
  • Author: Duncan Young, F.F.A.R.C.S.I.
  • Funding: UK National Institute for Health Research Health Technology Assessment programme.

2. Keywords

  • ARDS, Acute Respiratory Distress Syndrome, High-Frequency Oscillatory Ventilation (HFOV), Mechanical Ventilation, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with moderate to severe ARDS (Population), does a strategy of high-frequency oscillatory ventilation (HFOV) (Intervention) compared to standard, conventional mechanical ventilation (Comparison) reduce 30-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: High-frequency oscillatory ventilation (HFOV) is a mode of ventilation that uses very small tidal volumes at very high frequencies. It was hypothesized to be a “super” lung-protective strategy that could maintain lung recruitment and prevent ventilator-induced lung injury even more effectively than standard low-tidal-volume ventilation.
  • Knowledge Gap: Despite its physiological appeal and use in some centers as a rescue therapy, there was no high-quality evidence from a large, pragmatic randomized trial to determine if HFOV was superior to modern, protocolized conventional ventilation for patients with ARDS.
  • Proposed Hypothesis: The authors hypothesized that a strategy of early HFOV would be superior to conventional ventilation in reducing 30-day mortality in patients with moderate to severe ARDS.

5. Study Design and Methods

  • Design: A large, multicenter, pragmatic, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 29 intensive care units (ICUs) in the United Kingdom.
  • Trial Period: Enrollment ran from December 2008 to July 2012.
  • Population:
    • Inclusion Criteria: Adult patients (≥16 years) with moderate to severe ARDS (PaO2:FiO2 ratio < 200 mm Hg [26.7 kPa]) who were receiving mechanical ventilation.
    • Exclusion Criteria: Included contraindications to HFOV (e.g., severe obstructive airway disease, high intracranial pressure) and patients for whom death was deemed imminent.
  • Intervention: Patients were randomized to receive high-frequency oscillatory ventilation (HFOV) as soon as possible.
  • Control: Patients were randomized to receive ongoing conventional mechanical ventilation according to a standardized, best-practice protocol.
  • Management Common to Both Groups: Both groups were managed with a lung-protective strategy. The control group protocol was detailed and represented a high standard of care.
  • Power and Sample Size: The authors calculated that a sample size of 1000 patients would provide 80% power to detect a 7.5% absolute risk reduction in 30-day mortality. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: All-cause mortality at 30 days.
    • Secondary Outcomes: Included duration of ventilation, length of ICU stay, and cause of death.

6. Key Results

  • Enrollment and Baseline: 795 patients were randomized (398 to HFOV and 397 to control). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in 30-day mortality. 167 of 398 patients (42%) in the HFOV group died, compared with 166 of 397 patients (42%) in the conventional-ventilation group (p=0.98).
  • Secondary Outcomes: There were no significant differences between the groups in any of the secondary outcomes, including duration of ventilation or length of ICU stay.
  • Adverse Events: The incidence of adverse events was similar in both groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of death between the two groups.
  • Key Statistic(s) Reported: Relative Risk (RR) for death at 30 days: 1.00 (95% CI, 0.84 to 1.19; P-value: 0.98).
  • Interpretation of Key Statistic(s):
    • Relative Risk (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: The paper reports the result as 1.00.
      • Clinical Meaning: An RR of 1.00 indicates absolutely no difference in the risk of death between the two groups.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.84 to 1.19.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. Clinically, this means the true effect could range from a 16% benefit to a 19% harm.
    • P-value: The p-value of 0.98 is much higher than the 0.05 threshold, indicating the result is not statistically significant and providing strong evidence of no effect (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The large, multicenter, randomized controlled design provided high-quality evidence on an important clinical question.
  • Generalizability: The pragmatic design and inclusion of a large number of diverse ICUs make the findings highly generalizable to real-world practice in similar healthcare systems.
  • Statistical Power: The study was large and adequately powered to confidently rule out a modest but clinically important mortality benefit.
  • Patient-Centered Outcomes: The primary outcome of 30-day mortality is a robust and patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded, which introduces a risk of performance bias.
  • External Validity (Generalizability): The study was conducted in a system where clinicians may have had variable experience with HFOV, which could have affected the results.
  • Other: The control group received a very high standard of protocolized conventional ventilation, which may have made it more difficult for HFOV to show a superior benefit.

10. Conclusion of the Authors

  • The authors concluded that in adults with moderate-to-severe ARDS, a strategy of early HFOV does not reduce 30-day mortality as compared with a strategy of conventional mechanical ventilation.

11. To Summarize

  • Impact on Current Practice: This was a major practice-changing trial. Its definitive neutral result, combined with the signal of harm seen in the concurrent OSCILLATE trial, effectively ended the routine use of HFOV as a primary ventilation strategy for ARDS.
  • Specific Recommendations:
    • Patient Selection: For the broad population of adult ICU patients with moderate to severe ARDS.
    • Actionable Intervention: Do not use HFOV as a routine, first-line ventilation strategy.
  • What This Trial Does NOT Mean: This trial does NOT mean that HFOV has absolutely no role in the ICU. It may still be considered as a rescue therapy in highly selected patients who are failing all other forms of conventional ventilation, but this is not supported by high-level evidence.
  • Implementation Caveats: The key takeaway is that a well-executed, protocol-based conventional lung-protective ventilation strategy is the standard of care, and HFOV does not offer an advantage over it.

12. Context and Related Studies

  • Building on Previous Evidence: The OSCAR trial (2013) was designed to provide a definitive answer to the question of HFOV’s efficacy, which had been debated for years based on smaller, conflicting studies and physiological theory.
  • Influence on Subsequent Research: The definitive neutral-to-harmful findings of this trial and the concurrent OSCILLATE trial (2013) were highly influential and led to a rapid de-adoption of HFOV in adults and a major shift in international ARDS guidelines.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial definitively answered its primary question with a clear neutral result.
  • Future Directions: The failure of HFOV to improve outcomes has reinforced the importance of optimizing conventional lung-protective ventilation and has shifted the focus of ARDS research towards other adjunctive therapies, such as prone positioning and neuromuscular blockade.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, testing a complex and expensive technology that was thought to be a promising new standard of care for ARDS.
  • Methods: The large, multicenter, pragmatic RCT design was appropriate and robust. A key strength is that the control arm represented a very high standard of modern, protocolized ARDS care, making the comparison a fair and relevant test. The main methodological weakness is the open-label design.
  • Results: The study reported a clear neutral finding for its primary outcome, with a narrow confidence interval centered on the null value. This provides strong evidence against a meaningful clinical benefit of routine HFOV in this population.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable. This is a classic example of a high-quality “negative” trial that was profoundly practice-changing by providing strong evidence that a more complex and expensive intervention is not superior to a well-executed standard of care.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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