Surgical outcomes from haematoma evacuation for intracerebral haemorrhage in the INTERACT3 study

Abstract

Background: There is ongoing controversy as to whether surgical intervention to haematoma evacuation benefits patients with acute intracerebral haemorrhage (ICH). This study aimed to evaluate the association of surgical intervention to evacuate the haematoma and 6-month functional outcome in participants of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3).

Methods: This was a secondary analysis of INTERACT3, which enrolled adults (age ≥18 years) spontaneous ICH patients within 6 h after onset. INTERACT3 was an international, multicentre, prospective, stepped-wedge, cluster randomised, blinded outcome assessed, clinical trial undertaken at 121 hospitals in 10 countries between December 12, 2017 and December 31, 2021. To limit heterogeneity in the results, we restricted analyses to participants in China. The primary outcome was poor functional outcome, defined by a score of 5-6 on the modified Rankin scale (mRS), at 6 months. Secondary outcomes include a mRS score of 4-6 and mortality at 6 months. Sensitivity analysis included propensity score matched analysis and the imputation of missing outcome variables. The effect of timing on surgical outcome was also evaluated. The INTERACT3 trial was registered at ClinicalTrials.gov (NCT03209258) and CHiCTR.org.cn (ChiCTR-IOC-17011787).

Findings: Of 5772 participants (mean age 62.0 ± 12.5 years) at 82 sites in China, 1411 (24.4%) received surgery in which craniotomy (72.6%) was the most common approach. After adjustment for confounding variables, surgery to evacuate the haematoma was associated with lower odds of a poor functional outcome (odds ratio 0.71, 95% CI 0.55-0.92; p = 0.010) and mortality (odds ratio 0.55, 95% CI 0.40-0.75; p = 0.0001) at 6 months. The association was consistent in propensity score matching analysis and sensitivity analysis by imputation. We did not detect significant differences in outcome between those who received surgery on the same day of hospital arrival compared to those who received surgery on the second or later days. In analysis limited to participants with supratentorial ICH and with a haematoma volume 30 mL or more, evacuation of the haematoma was associated with lower odds of poor functional outcome (n = 1234, odds ratio 0.68, 95% CI 0.46-0.99; p = 0.042) and mortality (n = 1291, OR 0.45, 95% CI 0.29-0.69; p = 0.0003).

Interpretation: This secondary analysis of the INTERACT3 indicates that evacuation of the haematoma is associated with better chances of surviving free of severe disability after acute ICH. With the evolution of instrument and techniques, further trial should address the role of haematoma evacuation in deep ICH patients, the time window and difference between mini-invasive techniques.

Funding: Joint Global Health Trials (JGHT) funding scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, the Medical Research Council and Wellcome Trust; the West China Hospital Outstanding Discipline Development 1-3-5 programme; National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutical; and Takeda (China).

Keywords: Haematoma evacuation; INTERACT3; Intracerebral haemorrhage; Secondary analysis.

Fig. 1

Patient flow.

Fig. 2

Subgroup analysis on primary outcome of mRS 5–6. Note: Multivariable logistic regression model with a random effect for cluster (hospital site), a fixed effect indicating the group assignment of each cluster at each step, and a fixed categorical effect of 6-month interval, adjusted baseline characteristics variables characteristics: mRS before stroke, age, sex, baseline NIHSS score, baseline haematoma volume, baseline systolic blood pressure, location of haematoma, intraventricular haemorrhage, previous history of stroke, current smoker and current alcohol user, and hospital management variables during including admission ward, BP lowering treatment (intravenous or oral), insulin treatment, antipyrexia treatment, anticoagulant reversal treatment (administrated PCC, FFP or VitK), Mechanical ventilation, and assist feeding.