Effect of Onset-to-Admission Time and Care Bundle Achievement on Functional Outcomes in Patients With ICH: A Population-Based Study

BACKGROUND AND OBJECTIVES: Intracerebral hemorrhage (ICH) remains a leading cause of morbidity and mortality, with limited effective treatments. Early implementation of a care bundle protocol (CBP) within 6 hours of symptom onset has been shown to improve functional outcomes, although its effect beyond this time frame remains unclear. We assessed the impact of onset-to-admission (OTA) time and CBP achievement on functional outcome and mortality in patients with acute spontaneous ICH. METHODS: We conducted a population-based study of a prospective cohort of consecutive patients diagnosed with acute spontaneous ICH between 2020 and 2022 in Catalonia, Spain. Inclusion criteria were patients aged 18 years or older, OTA time <24 hours, and a baseline modified Rankin Scale (mRS) score ≤3. CBP achievement was defined as attaining control in the first 24 hours of blood pressure (<140/90 mm Hg), glycemia (<150 mg/dL), body temperature (<37.5°C), and blood oxygen saturation (>92%) and, if required, anticoagulation reversal. The primary outcome was the proportion of patients with a favorable functional outcome, defined as mRS score ≤3 at 3-month follow-up. The effects of OTA time and CBP achievement on outcomes were evaluated using multivariable logistic regression. Potential interaction between OTA time and CBP achievement was assessed using the likelihood ratio test. RESULTS: A total of 1,821 patients were included (mean age 70.3 ± 14.1 years, 37.7% women). CBP was achieved in 27.7% of patients. Shorter OTA time was independently associated with poorer functional outcome (adjusted odds ratio [aOR]x1h 1.04, 95% CI 1.02-1.06). CBP achievement was associated with a higher probability of favorable outcome at 3 months (aOR 1.66, 95% CI 1.29-2.15). An interaction between OTA time and CBP achievement was observed (p = 0.016), indicating greater CBP benefits for earlier admission. This interaction was evident up to 13.8 hours after symptom onset, with the CBP benefit concentrated in the first 8 hours. DISCUSSION: Our findings highlight the importance of timely CBP application to improve functional outcome in patients with ICH, even beyond the first 6 hours after symptom onset. While earlier intervention remains ideal, our results support expanding CBP implementation and promoting "Code ICH" initiatives to enhance patient outcomes in stroke care systems. TRIAL REGISTRATION INFORMATION: Multicentre Registry of Patients With Spontaneous Acute Intracerebral Hemorrhage in Catalonia (HIC-CAT). ClinicalTrials.gov ID: NCT03956485. Registration submission: May 2019. First patient enrolled March 2020. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in patients with acute ICH, achievement of a standardized CBP is associated with better functional outcomes at 3 months.