Highlights
- The SELECT2 trial’s prespecified secondary analysis found no significant difference in 90-day functional outcomes between general anesthesia (GA) and non-GA during EVT for large core strokes.
- GA was associated with longer times to arterial puncture and greater intraprocedural systolic blood pressure variability but did not negatively impact reperfusion success or functional recovery.
- Current evidence from SELECT2 and the ANGEL-ASPECT trial suggests anesthesia modality does not substantially change neurological outcomes in patients with large ischemic cores undergoing EVT.
- Optimizing institutional anesthesia protocols tailored to patient and procedural factors may improve EVT procedural efficiency and safety without compromising efficacy.
Background
Large core ischemic strokes, characterized by extensive cerebral infarction often defined radiologically by ASPECTS scores of 3-5 or ischemic core volumes ≥50 mL, present significant therapeutic challenges. Endovascular thrombectomy (EVT) has demonstrated efficacy in improving functional outcomes in selected acute ischemic stroke patients, but large core infarcts traditionally posed concerns regarding benefit due to extensive irreversible injury. The anesthesia approach during EVT – general anesthesia (GA) versus non-GA (conscious sedation or local anesthesia) – has been debated, with observational studies and small trials yielding conflicting results largely in patients with smaller infarct cores. The impact of anesthesia modality on outcomes for patients with large core strokes undergoing EVT remains underexplored. Against this backdrop, the SELECT2 trial and its prespecified secondary analyses provide timely, high-quality data to guide anesthesia strategy decisions in this subgroup.
Key Content
The SELECT2 Trial and Anesthesia Approach
The SELECT2 trial (NCT03876457) was a multicenter, international, randomized, open-label trial investigating EVT versus medical management in patients with large core ischemic strokes. Within the EVT-treated cohort, a prespecified secondary analysis compared outcomes by anesthesia type (GA vs non-GA) in 178 patients. Eligibility included patients with large ischemic cores defined by NCCT ASPECTS 3-5 or perfusion/MRI core volumes ≥50 mL.
Key findings:
- Of the cohort, 58% received GA. Patients under GA had a longer median time from randomization to arterial puncture (40 vs 27 minutes), but procedural durations were comparable.
- Rates of successful reperfusion (mTICI 2b-3) were similar (GA 78% vs non-GA 84%; aRR 0.91 [95% CI 0.79-1.06]).
- No significant differences in 90-day functional outcome distribution (mRS), functional independence (mRS 0-2), or independent ambulation (mRS 0-3) were observed between anesthesia groups.
- Stroke severity, ASPECTS, ischemic core volume, and collateral status did not modify the association of anesthesia type and outcomes.
- GA was linked with higher intraprocedural systolic blood pressure variability and episodes of hypotension (SBP <100 mm Hg), but these hemodynamic factors did not mediate outcomes.
This study provides Class II evidence that anesthesia type does not substantially influence functional outcomes post-EVT in large core stroke patients.
Corroborative Evidence from ANGEL-ASPECT Trial Post Hoc Analysis
The ANGEL-ASPECT trial conducted in China further explored anesthesia modality effects in large infarct volume strokes undergoing EVT within a randomized controlled design with subsequent post hoc subgroup analyses. Among 230 patients treated with EVT, no significant difference existed between GA and non-GA groups for 90-day mRS 0-2 outcomes. GA was associated with a longer median procedural time and heightened risk of postoperative pneumonia but not increased mortality or hemorrhage risk. These findings align with SELECT2, suggesting anesthesia choice may not critically affect neurological outcomes in large core infarcts but requires attention toward procedural and complication profiles.
Mechanistic and Procedural Considerations
GA traditionally offers airway control, patient immobility, and optimized procedural conditions, which can facilitate technical aspects of EVT. However, concerns include time delays to treatment initiation, hypotension, and blood pressure variability that may exacerbate ischemic injury. The SELECT2 anesthesia subanalysis revealed time delays with GA but no resultant functional disadvantage. Intraprocedural hypotension and blood pressure fluctuations – known to influence penumbral tissue viability – were more frequent with GA yet did not alter clinical outcomes. This suggests that meticulous perioperative hemodynamic management, regardless of anesthesia technique, may preserve EVT effectiveness in large core strokes.
Evidence Synthesis and Guidelines Context
Guidelines from stroke societies have historically been equivocal on anesthesia choice for EVT, often recommending institution-specific approaches adjusted to patient condition and expertise availability. Earlier randomized trials on anesthesia in mainly smaller core strokes showed variable results, with some favoring conscious sedation to avoid hypotension and delay, while others showed no significant outcome differences. Limited data existed for large core infarcts until SELECT2 and ANGEL-ASPECT results emerged. These contemporary large trials indicate comparable efficacy and safety profiles between GA and non-GA in this high-risk population, supporting flexibility in anesthesia protocols.
Expert Commentary
The rigorous design and broad international enrollment in SELECT2 strengthen the applicability of its anesthesia findings. While the study is limited by nonrandomized anesthesia allocation, sophisticated adjustment for confounders and interaction testing enhance confidence in the results. The absence of outcome differences despite hemodynamic variability implicates a threshold effect or successful management mitigating risks. Importantly, anesthetic strategy selection should consider operator experience, patient airway safety, and institutional workflow efficiencies.
The ANGEL-ASPECT findings caution about prolongation of procedure and increased pneumonia risk with GA, which merit clinical vigilance but do not negate GA’s use. Overall, these data counter past concerns that GA inherently worsens outcomes and advocate for optimization of anesthesia services and protocols tailored to patient and center characteristics rather than a blanket preference.
Future research might explore prospective randomized trials of anesthesia modalities specifically in large core stroke EVT populations, integrating hemodynamic monitoring technologies and biomarkers to delineate mechanistic links. Meanwhile, developing guidelines that emphasize individualized, protocol-driven anesthesia care pathways can improve outcomes and procedural quality.
Conclusion
The prespecified secondary analysis of the SELECT2 trial provides robust evidence that, in patients with large core ischemic strokes undergoing EVT, functional outcomes at 90 days are comparable whether managed under general anesthesia or non-general anesthesia. Although GA is associated with longer treatment initiation times and increased blood pressure variability, these factors do not adversely affect reperfusion success or neurological recovery. Combined with corroborative data from ANGEL-ASPECT and other studies, these findings suggest that institutional anesthesia protocols optimized for efficiency and patient safety, rather than anesthesia modality per se, are critical to enhancing EVT outcomes. Further prospective research may refine anesthesia management nuances, but current data support flexible, individualized anesthesia strategies in EVT for large core strokes.
References
- Sarraj A, Blackburn S, Abraham MG, et al. General vs Nongeneral Anesthesia for Endovascular Thrombectomy in Patients With Large Core Strokes: A Prespecified Secondary Analysis of SELECT2 Trial. Neurology. 2025;105(2):e213819. doi:10.1212/WNL.0000000000213819. PMID: 40570276.
- Gao F, Dong Q, Zhao Z, et al. Anaesthesia modality on endovascular therapy outcomes in patients with large infarcts: a post hoc analysis of the ANGEL-ASPECT trial. Stroke Vasc Neurol. 2025;10(2):e003320. doi:10.1136/svn-2024-003320. PMID: 39160092.
- Lansberg MG, Campbell BCV, Sarraj A, et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. N Engl J Med. 2023;388(14):1259-1271. doi:10.1056/NEJMoa2214403. PMID: 36762865.
- Sarraj A, Blackburn S, Abraham MG, et al. Endovascular Thrombectomy for Extracranial Internal Carotid Artery Occlusions With Large Ischemic Strokes: Insights From the SELECT2 Trial. Neurology. 2025;104(4):e210269. doi:10.1212/WNL.0000000000210269. PMID: 39869840.
- Sarraj A, Blackburn S, Abraham MG, et al. Clinical relevance of intracranial hemorrhage after thrombectomy versus medical management for large core infarct: a secondary analysis of the SELECT2 randomized trial. J Neurointerv Surg. 2025;17(2):120-127. doi:10.1136/jnis-2023-021219. PMID: 38471760.
