Cerebral Edema in Patients With Large Ischemic Core After Thrombectomy: A Secondary Analysis of SELECT2 Randomized Trial

BACKGROUND: Cerebral edema is a life-threatening complication of ischemic stroke that disproportionally affects patients with large established infarction. We assessed whether endovascular thrombectomy (EVT) reduces or exacerbates edema development, and the association between edema with short-term and long-term outcomes in this high-risk population. METHODS: In this prespecified secondary analysis of the SELECT2 randomized clinical trial (Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke), which tested the efficacy and safety of EVT versus medical management in adult patients with acute anterior circulation large vessel occlusion presenting with large ischemic core (defined as Alberta Stroke Program Early Computed Tomography Score of 3–5 or core volume ≥50 mL on computed tomography perfusion or diffusion magnetic resonance imaging), we assessed maximum midline shift (MLS) within 7 days of randomization between treatment groups using a probabilistic index model. RESULTS: After exclusion of 10 patients who underwent hemicraniectomy before follow-up imaging, 342 patients were analyzed. The median MLS on follow-up magnetic resonance imaging or computed tomography was 6.39 mm (interquartile range, 0–12.0) in the EVT and 4.18 mm (interquartile range, 0–9.66) in medical management patients ( P =0.021). EVT was independently associated with greater MLS (adjusted odds ratio, 1.63 [95% CI, 1.25–2.12]; P =0.0027) after adjusting for age and core volume. There was no interaction between EVT and core volume at presentation on the association with MLS ( P >0.79). MLS was associated with the development of early neurological worsening (adjusted odds ratio, 1.15 [95% CI, 1.07–1.23]; P <0.001), and a lower likelihood of long-term functional improvement assessed on modified Rankin Scale score at 90 days (adjusted odds ratio, 0.96 [95% CI, 0.93–0.98]; P =0.0029). On mediation analysis, cerebral edema reduced the effect of EVT on functional outcome by 10.6%. CONCLUSIONS: Despite overall clinical benefit, EVT in patients presenting with a large ischemic core was associated with increased cerebral edema, which, in turn, was associated with early neurological worsening and worse functional outcome at 90 days. Early recognition and individualized treatment to prevent secondary injury from cerebral edema in this population are warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03876457.