PROTRATA: Prone Positioning in Trauma Patients with ARDS (2021)

“In patients with moderate-to-severe ARDS due to trauma, prone positioning did not significantly decrease 28-day mortality.”

  • The PROTRATA Study Group

1. Publication Details

  • Trial Title: Prone Positioning in Patients with Moderate to Severe Acute Respiratory Distress Syndrome due to Trauma: A Multicenter, Randomized, Controlled, Open-Label Trial (PROTRATA)
  • Citation: Guérin C, Cour M, Tuffet S, et al. Prone Positioning in Patients with Moderate to Severe Acute Respiratory Distress Syndrome due to Trauma: A Multicenter, Randomized, Controlled, Open-Label Trial (PROTRATA). Anesthesiology. 2021;135(6):1047-1059. DOI: 10.1097/ALN.0000000000003967
  • Published: December 1, 2021, in Anesthesiology
  • Author: Claude Guérin, M.D., Ph.D.
  • Funding: French Ministry of Health

2. Keywords

  • ARDS, Trauma, Prone Positioning, Mechanical Ventilation, Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In adult trauma patients with moderate to severe ARDS (Population), does a strategy of prone positioning (Intervention) compared to a strategy of remaining supine (Comparison) reduce 28-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: The PROSEVA trial (2013) had definitively shown that early and prolonged prone positioning reduces mortality in patients with moderate to severe ARDS from medical causes.
  • Knowledge Gap: Trauma patients were largely excluded from the PROSEVA trial due to concerns that the proning procedure could worsen associated injuries (e.g., unstable spine, pelvic fractures, or intracranial hypertension). It was a critical and unanswered question whether the benefits of proning seen in medical ARDS would translate to this high-risk trauma population, or if the risks would outweigh any potential benefit.
  • Proposed Hypothesis: The authors hypothesized that a strategy of prone positioning would be superior to remaining supine in reducing 28-day mortality in trauma patients with moderate to severe ARDS.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial (used to test the effectiveness of interventions).
  • Setting: 21 intensive care units (ICUs) in France.
  • Trial Period: Enrollment ran from March 2017 to January 2020.
  • Population:
    • Inclusion Criteria: Adult trauma patients (≥18 years) with moderate to severe ARDS (PaO2:FiO2 ratio < 150) who had been intubated for less than 48 hours.
    • Exclusion Criteria: Included contraindications to prone positioning (e.g., unstable spine, open abdominal wound, severe facial trauma) and severe traumatic brain injury with uncontrolled intracranial pressure.
  • Intervention: Patients were placed in the prone position for sessions of at least 16 consecutive hours.
  • Control: Patients were maintained in the semi-recumbent (supine) position.
  • Management Common to Both Groups: All patients were managed with a standardized lung-protective ventilation strategy and other supportive care according to best practices.
  • Power and Sample Size: The authors calculated that a sample size of 346 patients would be required to have 80% power to detect a 15% absolute risk reduction in 28-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 28 days.
    • Secondary Outcomes: Included 90-day mortality, ventilator-free days, and the incidence of complications.

6. Key Results

  • Enrollment and Baseline: 144 patients were randomized (74 to prone and 70 to supine). The groups were well-matched at baseline.
  • Trial Status: The trial was stopped early by the data and safety monitoring board for futility due to slow recruitment and a low probability of finding a significant benefit.
  • Primary Outcome: There was no significant difference in 28-day mortality. 15 of 74 patients (20.3%) in the prone group died, compared with 13 of 70 patients (18.6%) in the supine group (p=0.81).
  • Secondary Outcomes: There were no significant differences between the groups in 90-day mortality or in the number of ventilator-free days.
  • Adverse Events: The incidence of complications, including pressure sores and endotracheal tube obstruction, 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: The key statistics were the absolute mortality rates and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.81 for the primary outcome is much higher than the 0.05 threshold, indicating that the result was not statistically significant and very likely due to chance (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: Due to the small sample size, no meaningful subgroup analyses could be performed.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provided the first high-quality evidence on this important clinical question.
  • Generalizability: The inclusion of 21 diverse ICUs increases the applicability of the findings.
  • Patient-Centered Outcomes: The primary outcome of 28-day mortality is a robust and patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The study population was a highly selected group of trauma patients who were deemed safe for proning, which may limit generalizability to all trauma patients with ARDS.
  • Other: The trial was severely underpowered. It was stopped after enrolling only 144 of the planned 346 patients, which makes it impossible to draw any definitive conclusions from the neutral result. A true, modest benefit or harm could easily have been missed.

10. Conclusion of the Authors

  • The authors concluded that in patients with moderate-to-severe ARDS due to trauma, prone positioning did not significantly decrease 28-day mortality.

11. To Summarize

  • Impact on Current Practice: This trial, while underpowered, provides the best available evidence on this topic and suggests that the dramatic mortality benefit of prone positioning seen in medical ARDS may not translate to the trauma population.
  • Specific Recommendations:
    • Patient Selection: For adult trauma patients with moderate to severe ARDS.
    • Actionable Intervention: The results do not support the routine use of prone positioning in this population.
  • What This Trial Does NOT Mean: This trial does NOT definitively prove that prone positioning is not beneficial in trauma ARDS. Due to its early termination and small sample size, it can only conclude that a large benefit is unlikely.
  • Implementation Caveats: The decision to prone a trauma patient with ARDS remains a complex one that requires a careful, individualized assessment of the potential benefits (improved oxygenation) versus the potential risks (e.g., worsening of associated injuries).

12. Context and Related Studies

  • Building on Previous Evidence: The PROTRATA trial (2021) was a direct attempt to determine if the practice-changing findings of the PROSEVA trial (2013) could be extrapolated to the trauma population.
  • Influence on Subsequent Research: The inconclusive result of this underpowered trial highlights the ongoing clinical uncertainty and the need for a larger, definitive international trial to provide a clear answer.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is whether there is a true, albeit smaller, benefit of prone positioning in trauma ARDS that this underpowered trial was unable to detect.
  • Future Directions: A large, international, multicenter randomized controlled trial is needed to definitively determine the role of prone positioning in the management of trauma-associated ARDS.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a major area of clinical uncertainty in the management of a high-risk patient population.
  • Methods: The multicenter RCT design was appropriate. The main methodological limitation is the severe underpowering due to early termination for futility, which makes the results inconclusive and at high risk of a Type II error (i.e., missing a true difference between the groups).
  • Results: The study reported a clear neutral finding for its primary outcome. However, given the very small sample size, no definitive conclusions can be drawn from this. The confidence interval around the effect estimate would be very wide.
  • Conclusions and Applicability: The authors’ cautious conclusion is appropriate. The trial’s main contribution is to highlight the ongoing clinical equipoise and the need for a larger, definitive study. At present, the findings do not support the routine adoption of prone positioning for all trauma patients with ARDS.

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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