SETPOINT2

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

Bösel J. JAMA 2022; doi:10.1001/jama.2022.4798

Clinical Question

  • In patients with severe stroke does early (≤5 days of intubation) tracheostomy when compared to standard timing (from day 10) of tracheostomy improve functional outcome at 6 months?

Background

  • TRACMAN was one of the largest multi-centre RCTs looking at timing of tracheostomy in ICU
    • The results did not provide any evidence supporting early tracheostomy
    • The number of patients with a primary neurological reason for ICU admission were low (~5%) within this trial
  • Rates of tracheostomy have been shown to be higher in those with acute brain injury compared to the general ICU population
  • Concerns around weak cough, impaired swallow or an inability to maintain a patent upper airway often delay extubation in this population
  • The SETPOINT trial looked at the timing of tracheostomy in stroke patients
    • This small pilot RCT of 60 patients found no difference in ICU LOS (the primary outcome) but did show a lower ICU mortality (a secondary outcome)

Design

  • Investigator initiated, multi-centre, randomised trial
  • Blinding of outcome assessors (long term functional and cause of mortality)
  • Outcomes assessed using pre-structured telephone interview
  • Informed consent by patient or their legally authorised representative prior to day 4 of intubation
  • Randomised in 1:1 ratio
    • Central web-based tool
    • Blocks stratified in groups of 4 to achieve equal group size per centre
  • Only centres with routine use of percutaneous dilatational tracheostomy (PDT) were recruited
  • Sample sized based on pilot trial
    • 15% increase from 30% to 45% in intervention group
    • With 80% power and alpha of 0.05 and 15% drop out rate a sample size of 380 (190 per group was required)
  • Pre-specified subgroups
  • Confidence intervals for secondary end-points and subgroups not adjusted for multiplicity
    • Thus, these can only be interpreted as exploratory
  • Missing values for mRS at 6 months handled by a multiple imputation approach
  • Appropriate ethical approval
  • Registered with Clinical Trials

Setting

  • 26 neurocritical care units in Germany and USA
  • July 2015 – August 2020

Population

  • Inclusion:
    • 18 years or older
    • Invasive mechanical ventilation (IMV)
    • Acute ischemic stroke (AIS), intracerebral haemorrhage (ICH) or sub arachnoid haemorrhage (SAH) (all non traumatic)
    • SETscore > 10
      • Predicts the need for IMV for at least 2 weeks
      • Calculated on day of enrolment
    • Clinical judgement of treating neuro-intensivist that tracheostomy likely to be needed
    • Principle indication for tracheostomy had to be at least one of:
      • Ongoing demand for suctioning secretions
      • CNS related respiratory insufficiency
      • aspiration or danger of aspiration due to dysphagia
  • Exclusion:
    • mRS > 1 (pre-morbid)
    • IMV > 4 days
    • Clinical conditions prohibiting early tracheostomy or mandating surgical tracheostomy
    • Pregnancy
    • Life expectancy < 3 weeks
    • Anticipated withdrawal of life sustaining therapies
    • Inability to obtain informed consent
    • Participation in other interventional trial
  • 4562 assessed for eligibility –> 4180 excluded for not meeting eligibility criteria
    • 188 randomised to early tracheostomy –> 177 had tracheostomy (95.2%)
      • 177 in primary analysis as 9 lost to follow up and 2 withdrew consent
    • 194 randomised to late tracheostomy –> 130 had tracheostomy (67%)
      • 189 in primary analysis as 4 lost to follow up and 1 withdrew consent
  • Comparing baseline characteristics (early vs. standard tracheostomy groups):
    • Age: 59.2 vs 57.6
    • Male: 48.4% vs 52.1%
    • Pre-hospital mRS of 0: 86.0% vs 87.1 %
    • Admission:
      • Median NIHSS: 21 vs 21
      • Median GCS: 7 vs 6
      • Median SETscore: 14 vs 14
    • Diagnosis:
      • AIS: 26.3% vs 30.4%
        • Decompressive Craniectomy: 49.0% vs 50.8%
      • ICH: 41.9% vs 40.2%
        • Volume > 30cc: 60.5% vs 71.8%
        • Supratentorial: 71.8% vs 75.6%
      • SAH: 31.7% vs 29.4%
        • WFNS Score: 5 vs 5
        • Fisher Scale of 4: 67.2% vs 73.7%
    • Baseline Lung Injury Score: 1.0 vs 1.0
    • PDT (if tracheostomy performed): 89.3% vs 83.1%
    • Time from intubation: 4 days vs 11 days

Intervention

  • PDT within 5 days of IMV

Control

  • PDT after 10 days of IMV

Management common to both groups

  • Conversion to surgical tracheostomy allowed if clinically warranted
  • All other management (including ventilator settings, weaning, analgesia and sedation) centre specific but followed guidelines from American Heart and Stoke Associations and Neurocritical Care Society

Outcome

  • Primary outcome:
    • mRS of 0 – 4 or less at 6 months
    • 43.5% in early group vs 47.1% in standard group
      • Absolute difference -3.6% (95% CI -14.3 to 7.2%)
      • aOR 0.93 (95% CI 0.60 to 1.42)

  • Secondary outcomes:
  • Comparing early vs. standard group
    • No secondary outcome showed a significant difference
      • mRS 0 – 3 at 6 months
        • 24.3% vs 19.6%
          • aOR 1.48 (95% CI 0.89 – 2.48)
      • Death at 6 months
        • 35.0% vs 29.6%
          • aOR 1.06 (95% CI 0.74 – 1.53)
      • Median time to ICU discharge
        • 17 days vs 19 days
          • HR 1.12 (95% CI 0.90 – 1.39)
      • Median time to end mechanical ventilation
        • 14 days vs 11 days
          • HR 0.97 (0.73 to 1.31)
      • No difference in ICU stay without sedatives, opioids or vasopressors
  • Subgroups:
    • No subgroup had 95% CI that fully favoured one approach or other
    • These included Age (< 55, 55 – 65, > 65), Sex, Location (USA or Germany), Recruitment Numbers (<30 or > 30), Primary diagnosis (AIS, SAH or ICH), and GCS (<6, ≥6)
  • Safety Outcomes
    • (potentially) PDT related adverse event rate 17.3% (eTable 5)
      • 16.9% vs 17.7%
    • Periprocedural adverse events (up to 2 hours post tracheostomy): 15.8%
    • Any serious adverse event:
      • 47.3% vs 43.8%

Authors’ Conclusions

  • In patients with severe stroke receiving IMV, early tracheostomy did not improve rate of survival without significant disability at 6 months compared to standard timing
  • Clinically relevant benefit or harm can not be excluded due to wide confidence intervals

Strengths

  • Multi centre RCT across 2 countries increase external validity
  • Although 4130 were excluded, an accurate screening log minimises selection bias and shows that a majority were excluded for valid reasons (not meeting inclusion criteria or meeting exclusion criteria)
    • Only 1.3% (n=55) were excluded for “other” reasons
  • Analysed on intention to treat basis
  • Balanced baseline characteristics
  • Achieved a meaningful separation in timing of tracheostomy
  • Good adherence to protocol – no violations reported
  • Minimal loss to follow up (3.4%)

Weaknesses

  • The primary outcome of an mRS of 0-4 ranges from no disability to moderate severe disability that requires the assistance of others for mobility and daily needs
    • This is a very wide range of functional outcomes. One wonders if a patient who has an mRS of 4 would view this as a “better” functional outcome?
  • Secondary end-points regarding ICU medications were defined post-hoc
  • Understandably unable to blind clinicians and patients
  • No standardised weaning protocol used
  • 48.7% of all randomisations came from 4 centres (2 in USA, 2 in Germany)
  • 33% of standard tracheostomy group did not receive a tracheostomy
    • 22% were extubated and 11% died prior
    • This confirms prior studies about the utility of the SETscore and its ability to predict those that will be extubated successfully in the short term
    • However, over 1 in 5 patients did not have a procedure that had a near 20% complication rate
  • AIS, ICH and SAH may have different clinical courses
  • This appeared to be a cohort that had a poor prognosis (evidenced by high decompressive craniectomy rates, and high WFNS scores)
    • This is also evident in the fact that only ~10% in each group had a mRS of 0-2
    • Would a difference be shown if the cohort was less likely to have an unfavourable outcome?

The Bottom Line

  • This trial provides no evidence that in patients with severe stroke an early tracheostomy is better than standard time for tracheostomy, and that an early tracheostomy may mean a patient has to undergo a procedure that they did not need

External Links

Metadata

Summary author: George Walker @hgmwalker89
Summary date: 13th May 2022
Peer-review editor: @davidslessor

Picture by: iStock

 

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