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

Abstract

Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation.

Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation.

Design, setting, and participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10. Patients were randomized between July 28, 2015, and January 24, 2020, at 26 US and German neurocritical care centers. The final date of follow-up was August 9, 2020.

Interventions: Patients were assigned to an early tracheostomy strategy (n = 188) or to a standard tracheostomy (control group) strategy (n = 194).

Main outcomes and measures: The primary outcome was functional outcome at 6 months, based on the modified Rankin Scale score (range, 0 [best] to 6 [worst]) dichotomized to a score of 0 (no disability) to 4 (moderately severe disability) vs 5 (severe disability) or 6 (death).

Results: Among 382 patients randomized (median age, 59 years; 49.8% women), 366 (95.8%) completed the trial with available follow-up data on the primary outcome (177 patients [94.1%] in the early group; 189 patients [97.4%] in the standard group). A tracheostomy (predominantly percutaneously) was performed in 95.2% of the early tracheostomy group in a median of 4 days after intubation (IQR, 3-4 days) and in 67% of the control group in a median of 11 days after intubation (IQR, 10-12 days). The proportion without severe disability (modified Rankin Scale score, 0-4) at 6 months was not significantly different in the early tracheostomy vs the control group (43.5% vs 47.1%; difference, -3.6% [95% CI, -14.3% to 7.2%]; adjusted odds ratio, 0.93 [95% CI, 0.60-1.42]; P = .73). Of the serious adverse events, 5.0% (6 of 121 reported events) in the early tracheostomy group vs 3.4% (4 of 118 reported events) were related to tracheostomy.

Conclusions and relevance: 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. However, the wide confidence intervals around the effect estimate may include a clinically important difference, so a clinically relevant benefit or harm from a strategy of early tracheostomy cannot be excluded.

Trial registration: ClinicalTrials.gov Identifier: NCT02377167.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Bösel reported receiving grants from the German Society of Neurological Intensive and Emergency Medicine during the conduct of the study and personal fees from Sedana Medical, BARD, Medtronic, Boehringer Ingelheim, and Pfizer outside the submitted work. Dr Niesen reported receiving personal fees from Fresenius Medical and Alexion Pharma outside the submitted work. Dr Hwang reported receiving philanthropic funds from the Apple Pickers Foundation, grants from the Neurocritical Care Society, honoraria from the Society of Critical Care Medicine, and royalties from Oxford University Press, all outside the submitted work. Dr Rao reported receiving grants from the National Aeronautics and Space Administration and fees for serving as a medicolegal consult outside the submitted work. Dr Suarez reported receiving personal fees from BARD and Idorsia and for serving on the editorial board of Stroke, all outside the submitted work. Dr Seder reported receiving grants from the National Institute of General Medical Sciences and the Maine Medical Center during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Randomization and Follow-up of Patients in the SETPOINT2 Trial

aTwo hundred ninety-four were not considered appropriate study candidates, 257 did not consent or had no legal proxy, 156 were participating in another trial, 96 had critical illness such that early tracheostomy could have compromised well-being, 64 were expected to need a permanent surgical tracheostomy, 14 had language barriers, 13 did not pursue maximal intensive care therapy, 9 required ventilation unrelated to stroke, 4 were admitted when tracheostomy interventionalists were unavailable, and 55 patients had other reasons. bDied before planned tracheostomy or deterioration of clinical condition prevented tracheostomy at the planned time and ultimately died. cCould not be reached or found for the telephone follow-up. SET indicates stroke-related early tracheostomy (range, 0-37; ≥10 estimates ≥2 weeks of ventilatory support).

Figure 2.. Functional Outcome Without Severe Disability 6 Months After Admission in Predesignated Subgroups According to Early or Standard Tracheostomy Timing

Odds ratios in prespecified subgroups for reaching an acceptable modified Rankin Scale score of 0 to 4 at 6 months in the early vs standard tracheostomy groups (see Table 1 footnotes for score definitions). The dashed vertical line indicates the point of no difference between the groups. The overall P value is the result of testing the treatment group effect in the primary analysis model. Other P values were obtained by testing an interaction between treatment group and the respective variables of interest in slightly modified versions of the primary analysis model. Scores on the Glasgow Coma Scale range between 3 and 15 points, with lower scores indicating reduced levels of consciousness. It is composed of best eye response, best verbal response, and best motor response.

Figure 3.. Functional Outcome 6 Months After Admission and Kaplan-Meier Estimates of Survival According to the Timing of Tracheostomy

A, The primary outcome was survival without severe disability, defined as a score of 0 to 4 in the modified Rankin Scale (mRS) score at 6 months after admission in both treatment groups. For definition of the scores, see the Table 1 footnotes. B, Product-limit survival estimates after admission to intensive care unit (ICU) during follow-up for both groups in the full analysis set. For early tracheostomy, the median observation time was 181 days (IQR, 61-194 days) and standard tracheostomy, 183.5 days (IQR, 93-194 days). Censored patients are indicated on the Kaplan-Meier curve by a vertical line.