SETPOINT2: Early vs Standard Tracheostomy in Severe Stroke (2022)

“Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months.”

— The SETPOINT2 Investigators

1. Publication Details

  • Trial Title: Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial.
  • Citation: Bösel J, Niesen WD, Salih F, et al. Effect of Early vs Standard Approach to Tracheostomy on Functional Outcome at 6 Months Among Patients With Severe Stroke Receiving Mechanical Ventilation: The SETPOINT2 Randomized Clinical Trial. JAMA. 2022;327(18):1780-1791. doi:10.1001/jama.2022.4798.
  • Published: May 10, 2022, in The Journal of the American Medical Association (JAMA).
  • Author: Julian Bösel, MD.
  • Funding: German Research Foundation.

2. Keywords

Stroke, Neurocritical Care, Mechanical Ventilation, Tracheostomy, Functional Outcome, Modified Rankin Scale (mRS).

3. The Clinical Question

In adult patients with severe acute stroke requiring mechanical ventilation (Population), does a strategy of early tracheostomy (≤5 days of intubation) (Intervention) compared to a standard approach (tracheostomy if needed from day 10) (Comparison) improve functional outcome at 6 months (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Many patients with severe stroke require prolonged mechanical ventilation due to impaired consciousness and airway protective reflexes. The optimal timing for tracheostomy in this specific neurocritical care population was unknown. While some believed early tracheostomy could facilitate weaning and reduce sedation, leading to better neurological recovery, this was unproven.
  • Knowledge Gap: Previous trials on early tracheostomy (e.g., TRACMAN) included very few neurologic patients. There was no high-quality evidence to guide the timing of tracheostomy specifically for patients with severe stroke, a population with unique challenges and recovery trajectories.
  • Proposed Hypothesis: The authors hypothesized that a strategy of early tracheostomy would improve the rate of survival without severe disability at 6 months compared to a standard approach.

5. Study Design and Methods

  • Design: An investigator-initiated, multicenter, randomized, outcome assessor-blinded clinical trial (PROBE design).
  • Setting: 26 neurocritical care units in Germany and the United States.
  • Trial Period: Enrollment from July 2015 to August 2020.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) with severe acute ischemic or hemorrhagic stroke receiving invasive mechanical ventilation, with a high likelihood of needing prolonged ventilation (predicted by the SETscore >10).
    • Exclusion Criteria: Premorbid severe disability (mRS > 1), mechanical ventilation >4 days prior to screening, conditions mandating surgical tracheostomy, or life expectancy <3 weeks.
  • Intervention: A strategy of early tracheostomy, performed within 5 days of intubation.
  • Control: A standard approach involving ongoing ventilator weaning and consideration for tracheostomy only from day 10 onward if weaning failed.
  • Management Common to Both Groups: All other aspects of neurocritical care, including ventilator settings, weaning, sedation, and analgesia, were managed according to local center protocols and international guidelines.
  • Power and Sample Size: The trial was powered to detect a 15% absolute difference in the primary outcome, requiring a sample size of 380 patients.
  • Outcomes:
    • Primary Outcome: Favorable functional outcome at 6 months, defined as a modified Rankin Scale (mRS) score of 0-4 (survival without severe disability).
    • Secondary Outcomes: Included 6-month mortality, ICU and hospital length of stay, duration of mechanical ventilation, and ventilator-free days.

6. Key Results

  • Enrollment and Baseline: 382 patients were randomized (188 to the early group, 194 to the standard group). Baseline characteristics were well-balanced.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the rate of favorable functional outcome at 6 months between the early and standard tracheostomy groups (43.5% vs 47.1%; P=.73).
  • Secondary Outcomes: There were no significant differences between the groups in 6-month mortality, ICU length of stay, or hospital length of stay. Patients in the early group had a significantly shorter duration of mechanical ventilation (median 14 vs 19 days).
  • Adverse Events: The rate of serious adverse events related to tracheostomy was low and similar between the two groups (5.0% vs 3.4%).

7. Medical Statistics

  • Analysis Principle: An intention-to-treat analysis was performed.
  • Statistical Tests Used: The primary outcome was analyzed using a logistic regression model, adjusted for stroke type.
  • Primary Outcome Analysis: The proportion of patients with a favorable mRS score (0-4) at 6 months was compared between groups.
  • Key Statistic(s) Reported: Adjusted Odds Ratio (aOR) for favorable outcome: 0.93 (95% CI, 0.60 to 1.42; P=.73).
  • Interpretation of Key Statistic(s):
    • Odds Ratio (OR): An aOR of 0.93 suggests a slightly lower odds of a favorable outcome in the early tracheostomy group, but this was not statistically significant.
    • Confidence Interval (CI): The 95% CI is wide and crosses 1.0 (from a 40% reduction in odds to a 42% increase), indicating a high degree of uncertainty and no statistically significant difference.
    • P-value: The p-value of 0.73 is far from the 0.05 threshold, confirming the lack of a statistically significant difference.
  • Clinical Impact Measures: Not applicable as no benefit was shown for the primary outcome.
  • Subgroup Analyses: No significant treatment effects were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: This was a methodologically rigorous, multicenter, randomized trial that addressed a critical and specific question in neurocritical care.
  • Generalizability: The inclusion of 26 centers across two countries increases the external validity of the findings to similar neuro-ICU settings.
  • Patient-Centered Outcomes: The primary outcome of 6-month functional status (mRS) is the gold standard, patient-centered endpoint for stroke trials.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was unblinded to clinicians, which could introduce performance bias, though the primary outcome was assessed by blinded raters.
  • External Validity (Generalizability): The results are specific to patients with severe stroke and cannot be generalized to the broader ICU population.
  • Other: The confidence intervals for the primary outcome were wide, meaning that a clinically relevant benefit or harm could not be definitively excluded. About one-third of patients in the standard care group did not ultimately require a tracheostomy.

10. Conclusion of the Authors

“Among patients with severe stroke receiving mechanical ventilation, a strategy of early tracheostomy, compared with a standard approach to tracheostomy, did not significantly improve the rate of survival without severe disability at 6 months.”

11. To Summarize

  • Impact on Current Practice: This trial provides strong evidence that a routine policy of early tracheostomy for all severe stroke patients does not improve long-term functional outcomes. It supports a more patient-centered, individualized approach, allowing for a period of observation and weaning attempts before committing to a tracheostomy.
  • Specific Recommendations:
    • Patient Selection: For adult patients with severe stroke requiring mechanical ventilation.
    • Actionable Intervention: It is reasonable to pursue a standard approach of continued weaning efforts, reserving tracheostomy for patients who fail to liberate from the ventilator after about 10 days.
    • Expected Benefit: No improvement in 6-month functional outcome with early tracheostomy. A standard approach avoids an unnecessary procedure in about one-third of patients.
  • What This Trial Does NOT Mean: This trial does not mean that early tracheostomy is harmful or should never be performed. The decision can still be individualized based on specific patient factors, such as anticipated prolonged need for ventilation or difficulty managing secretions.
  • Implementation Caveats: The key takeaway is to avoid a one-size-fits-all “early tracheostomy” policy for this population.

12. Context and Related Studies

  • Building on Previous Evidence: This trial directly addressed the gap left by general ICU tracheostomy trials like TRACMAN (2013), which included too few stroke patients to draw meaningful conclusions for this specific population. It followed a smaller pilot trial, SETPOINT (2015).
  • Influence on Subsequent Research: SETPOINT2 is the largest and most definitive trial on this topic to date and is likely to heavily influence clinical practice guidelines for the management of mechanically ventilated stroke patients.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: Are there specific subgroups of stroke patients (e.g., those with severe brainstem strokes) who might still benefit from an early tracheostomy?
  • Future Directions: Future research may focus on developing better prediction tools to identify which stroke patients will ultimately require a tracheostomy, thereby avoiding both unnecessary delays and unnecessary procedures.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The question was highly relevant and specific to the neurocritical care population, addressing a common clinical dilemma with significant implications for patient care and resource use.
  • Methods: The multicenter, randomized, PROBE-design trial was methodologically sound. The use of a validated prediction score for enrollment and a blinded assessment of the primary outcome were major strengths.
  • Results: The trial showed a clear neutral result for its important, patient-centered primary outcome. The finding that a significant portion of the control group could be managed without a tracheostomy is also clinically important.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The results are highly applicable to neuro-ICUs and provide a clear answer to a long-standing clinical question, supporting a more conservative, watchful approach to tracheostomy timing in severe stroke.

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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