TELSTAR: Transpulmonary Pressure-Guided PEEP in ARDS (2023)

“Among patients with moderate to severe ARDS, a strategy of setting PEEP levels based on transpulmonary pressure compared with a high PEEP-FiO2 table did not significantly improve 28-day mortality.”

— The TELSTAR Study Group

1. Publication Details

  • Trial Title: Transpulmonary Pressure-Guided PEEP in Moderate to Severe Acute Respiratory Distress Syndrome: The TELSTAR Randomized Clinical Trial.
  • Citation: Beun R, Kusadasi N, Kucukakcali N, et al; for the TELSTAR study group. Transpulmonary Pressure-Guided PEEP in Moderate to Severe Acute Respiratory Distress Syndrome: The TELSTAR Randomized Clinical Trial. JAMA. 2023;329(10):823-833. doi:10.1001/jama.2023.1953.
  • Published: March 14, 2023, in The Journal of the American Medical Association (JAMA).
  • Author: Rob Beun, M.D., Ph.D.
  • Funding: The Netherlands Organisation for Health Research and Development.

2. Keywords

Acute Respiratory Distress Syndrome (ARDS), Mechanical Ventilation, Positive End-Expiratory Pressure (PEEP), Transpulmonary Pressure, Esophageal Manometry, Lung Injury.

3. The Clinical Question

In adult patients with moderate to severe ARDS (Population), does a PEEP titration strategy guided by transpulmonary pressure (Intervention) compared to a high PEEP-FiO2 table strategy (Comparison) reduce all-cause mortality at 28 days (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Setting positive end-expiratory pressure (PEEP) in ARDS is a balance between recruiting collapsed lung tissue and avoiding overdistension of healthy lung. Standard practice often involves using a PEEP-FiO2 table. Esophageal manometry allows for the estimation of transpulmonary pressure, which theoretically enables clinicians to set a PEEP level that keeps the lung open at end-expiration without causing injury.
  • Knowledge Gap: While physiologically appealing, it was unknown if this more complex, individualized approach of using esophageal manometry to guide PEEP actually improved patient-centered outcomes compared to a standardized high-PEEP strategy.
  • Proposed Hypothesis: The authors hypothesized that a PEEP titration strategy guided by transpulmonary pressure would reduce 28-day mortality in patients with moderate to severe ARDS.

5. Study Design and Methods

  • Design: A prospective, multicenter, randomized, open-label, controlled trial. The trial was stopped early for futility.
  • Setting: 11 intensive care units (ICUs) in the Netherlands.
  • Trial Period: Enrollment from November 2016 to May 2022.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with moderate to severe ARDS (PaO2:FiO2 ratio <150 mmHg) within 36 hours of diagnosis.
    • Exclusion Criteria: Contraindications to esophageal catheter placement, severe hemodynamic instability, or a decision to withhold life-sustaining treatment.
  • Intervention: PEEP was titrated to achieve a positive end-expiratory transpulmonary pressure (Ptp,ee) between 0 and 6 cm H2O, as measured by an esophageal balloon catheter.
  • Control: PEEP was set according to the high PEEP-FiO2 table from the ARDS Network ARMA trial.
  • Management Common to Both Groups: All patients were managed with low tidal volume ventilation (6 mL/kg predicted body weight) and other standard ARDS care.
  • Power and Sample Size: The trial was powered to detect a 15% absolute risk reduction in 28-day mortality, requiring 434 patients.
  • Outcomes:
    • Primary Outcome: All-cause mortality at 28 days.
    • Secondary Outcomes: Included 90-day mortality, ventilator-free days, ICU length of stay, and incidence of barotrauma.

6. Key Results

  • Enrollment and Baseline: 200 patients were randomized (100 to the transpulmonary pressure group, 100 to the control group). The groups were well-matched at baseline.
  • Trial Status: The trial was stopped early by the data and safety monitoring board for futility after a planned interim analysis.
  • Primary Outcome: There was no significant difference in 28-day mortality between the transpulmonary pressure group and the control group (41% vs 42%; P=0.89).
  • Secondary Outcomes: There were no significant differences in 90-day mortality, ventilator-free days, ICU length of stay, or the incidence of barotrauma.
  • Adverse Events: The rates of adverse events were similar between the two groups.

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using a Cox proportional-hazards model.
  • Primary Outcome Analysis: Time to death from any cause up to 28 days was compared between the two groups.
  • Key Statistic(s) Reported: Hazard Ratio (HR) for 28-day mortality: 1.03 (95% CI, 0.66 to 1.61; P=0.89).
  • Interpretation of Key Statistic(s):
    • Hazard Ratio (HR):
      • Formula: Conceptually, HR represents the instantaneous risk of death in the intervention group relative to the control group.
      • Calculation: The paper reports the result as 1.03.
      • Clinical Meaning: An HR of 1.03 means there was a 3% higher hazard of death at any given time in the transpulmonary pressure group compared to the control group, a difference that is not statistically significant.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The reported 95% CI was 0.66 to 1.61.
      • Clinical Meaning: This is a very wide confidence interval that comfortably crosses the line of no effect (1.0). It indicates that the true effect could be anywhere from a 34% benefit to a 61% harm, confirming a high degree of uncertainty and no significant difference.
    • P-value:
      • Calculation: The reported p-value was 0.89.
      • Clinical Meaning: The p-value of 0.89 is far above the 0.05 threshold, indicating that the observed result is very likely due to chance. A result is conventionally considered statistically significant if the p-value is less than 0.05.
  • Clinical Impact Measures:
    • Absolute Risk Reduction (ARR):
      • Formula: ARR = (Risk in Control Group) – (Risk in Intervention Group).
      • Calculation: ARR = 42% – 41% = 1%.
      • Clinical Meaning: The intervention was associated with a non-significant 1% absolute reduction in the risk of death at 28 days.
    • Number Needed to Treat (NNT): Not applicable, as the intervention showed no benefit.
  • Subgroup Analyses: No significant benefit was found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: This was a multicenter, randomized trial that addressed a highly relevant and debated physiological question in mechanical ventilation.
  • Standardized Protocols: Both arms of the trial used clearly defined and standardized protocols for PEEP management.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The trial was open-label (unblinded), which could introduce performance bias.
  • External Validity (Generalizability): The study was conducted exclusively in the Netherlands, which may limit generalizability.
  • Other: The trial was stopped early for futility after enrolling less than half of its target sample size. While this was based on a pre-planned analysis, it can sometimes lead to less precise estimates.

10. Conclusion of the Authors

“Among patients with moderate to severe ARDS, a strategy of setting PEEP levels based on transpulmonary pressure compared with a high PEEP-FiO2 table did not significantly improve 28-day mortality.”

11. To Summarize

  • Impact on Current Practice: This trial provides strong evidence against the routine use of esophageal manometry to guide PEEP titration in the general population of patients with moderate to severe ARDS. It suggests that a well-implemented, standardized high PEEP strategy is a reasonable and effective approach.
  • Specific Recommendations:
    • Patient Selection: For adult patients with moderate to severe ARDS.
    • Actionable Intervention: Do not routinely use esophageal manometry to guide PEEP titration. A high PEEP-FiO2 table strategy is an appropriate standard of care.
    • Expected Benefit: No benefit in mortality or other clinical outcomes was demonstrated with the transpulmonary pressure-guided strategy.
  • What This Trial Does NOT Mean: This trial does not mean that the concept of transpulmonary pressure is invalid or that esophageal manometry has no role in the ICU. It may still be a useful tool for physiological assessment in select, complex patients (e.g., morbid obesity, severe chest wall stiffness).
  • Implementation Caveats: The findings discourage the investment in and routine application of esophageal manometry for the purpose of improving survival in ARDS.

12. Context and Related Studies

  • Building on Previous Evidence: This trial adds to a growing body of evidence from studies like the EPVent-2 trial (2019), which also failed to show a benefit for esophageal manometry-guided PEEP titration in ARDS.
  • Influence on Subsequent Research: The consistent negative findings of these large RCTs have largely dampened enthusiasm for the routine use of this technology and have shifted the focus of PEEP research toward other methods of personalization, such as electrical impedance tomography (EIT) or lung imaging.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: Are there specific phenotypes of ARDS (e.g., patients with morbid obesity or high chest wall elastance) who might still benefit from a transpulmonary pressure-guided approach?
  • Future Directions: Future research will likely focus on other methods to personalize mechanical ventilation or on identifying specific patient subgroups who may respond differently to PEEP strategies.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was highly relevant, testing a complex, physiologically-guided intervention against a simpler, standardized approach.
  • Methods: The multicenter RCT design was appropriate. Stopping early for futility was based on pre-specified rules and adds confidence to the negative conclusion.
  • Results: The trial had a clear and robustly neutral result for its primary outcome and all secondary outcomes.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The results are highly applicable to the management of ARDS and provide a strong evidence-based recommendation against the routine use of esophageal manometry for PEEP titration in this population.

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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