What is the impact of time to treatment and time to surgery on outcomes in patients with intracerebral hemorrhage (ICH)?

Impact of Time to Treatment and Time to Surgery on Intracerebral Hemorrhage Outcomes

For most patients with supratentorial ICH, the benefit of early surgery remains uncertain, with trials showing no clear advantage for surgery performed within 24-96 hours compared to medical management, except for specific subgroups including patients with superficial lobar hemorrhages within 1 cm of the cortical surface and those with Glasgow Coma Scale scores of 9-12. 1

Time to Medical Treatment

Blood Pressure Management

• Intensive blood pressure lowering to <140 mmHg systolic within 6 hours of ICH onset is recommended based on moderate-quality evidence, as this may reduce hematoma expansion and improve functional outcomes 1
• Careful, targeted, and sustained blood pressure reduction during the first 24 hours appears optimal, avoiding drops ≥60 mmHg within 1 hour to prevent secondary injury 2
• Recent evidence from 2024 confirms that intensive blood pressure lowering initiated within the first few hours substantially improves outcomes 3

Anticoagulation Reversal

• Rapid reversal of anticoagulation reduces hematoma expansion risk and may improve outcomes 2
• Vitamin K antagonists should be reversed with prothrombin complex concentrate 2
• Dabigatran requires idarucizumab, while anti-Xa agents are reversed with PCC or andexanet alfa (where available) 2
• The 2023 ANNEXa-I trial demonstrated treatment benefits for factor Xa-inhibitor reversal with andexanet alfa 3

Prehospital and Emergency Department Time Metrics

• EMS prenotification to the destination emergency department is associated with faster door-to-CT times (24 minutes versus 48 minutes) and faster time to hemostatic medication when used (63 minutes versus 99 minutes) 1
• Mobile stroke units reduce time from symptom onset to CT and laboratory results, with 41% of MSU patients receiving blood pressure management in the field after diagnosis compared to none in standard care 1

Time to Surgery: Supratentorial ICH

General Timing Evidence

• Clinical studies show wide variability in surgical timing (4 hours to 96 hours from onset), making direct comparison difficult 1
• A retrospective Japanese series of putaminal ICH evacuation within 7 hours (60 cases within 3 hours) reported better than expected outcomes 1
• However, randomized trials treating patients within 12 hours showed mixed results 1

Ultra-Early Surgery Concerns

• Ultra-early craniotomy within 4 hours of ictus is associated with increased risk of rebleeding 1, 4
• This finding has tempered enthusiasm for immediate surgical intervention in most cases 1

STICH Trial Findings (Largest Evidence Base)

• The International Surgical Trial in Intracerebral Haemorrhage randomized 1033 patients to surgery within 96 hours versus initial medical management 1
• Overall, surgery showed no statistically significant benefit (absolute benefit 2.3% in 6-month outcomes) 1
• Trials randomizing patients within 24,48,72, and 96 hours demonstrated no clear benefit for surgery compared to initial medical management 1

Specific Subgroups That May Benefit from Early Surgery

• Patients with superficial lobar hemorrhages within 1 cm of the cortical surface showed a trend toward better outcomes with surgery (OR 0.69,95% CI 0.47-1.01), though not statistically significant after multiple testing adjustment 1, 4
• Patients with Glasgow Coma Scale scores of 9-12 may benefit from early surgery 1, 4
• One study of supratentorial subcortical or putaminal ICH >30 cc randomized to craniotomy within 8 hours showed significantly better good outcomes (good recovery or moderate disability) at 1 year, though no difference in overall survival 1, 4
• Meta-analysis data suggests surgery within 8 hours may improve outcomes in selected patients 4

Patients Who Do Worse with Surgery

• Patients with ICH more than 1 cm from the cortical surface or with GCS score ≤8 tend to do worse with surgical removal compared to medical management 1
• Deep ICH (thalamic and pontine) has limited enthusiasm for surgical evacuation 1

Minimally Invasive Approaches

• Minimally invasive techniques (stereotactic or endoscopic aspiration with thrombolytic enhancement) show decreased mortality when performed within 12-72 hours in subcortical hemorrhages, but improved functional outcome has not been consistently demonstrated 1, 4
• The 2023 ENRICH trial showed treatment benefits for early minimally invasive hematoma evacuation 3

Time to Surgery: Cerebellar ICH

Immediate Surgical Indications

• Patients with cerebellar hemorrhage who are deteriorating neurologically, have brainstem compression, hydrocephalus from ventricular obstruction, or cerebellar ICH volume ≥15 mL should undergo immediate surgical removal 1, 4
• This represents the strongest and most consistent surgical recommendation across all guidelines 1
• Initial treatment with ventricular drainage alone rather than surgical evacuation is not recommended for cerebellar hemorrhage with mass effect due to risk of worsening outcomes 4

Evidence Base

• Large (>3 cm) cerebellar hemorrhages with brainstem compression managed medically often result in poor outcomes, while surgically treated patients show good outcomes in case series 1
• Smaller cerebellar hemorrhages without brainstem compression managed medically do reasonably well 1

Decompressive Craniectomy

• Decompressive craniectomy with or without hematoma evacuation might reduce mortality for patients with supratentorial ICH who are in coma, have large hematomas with significant midline shift, or have elevated intracranial pressure refractory to medical management 4
• The 2024 SWITCH trial confirmed that decompressive hemicraniectomy is a viable treatment strategy in patients with large deep ICH 3
• This approach may be particularly beneficial for patients with putaminal hemorrhage 4

Bundles of Care and Systems Approach

• The 2023 INTERACT3 trial demonstrated treatment benefits for a hyperacute care bundle approach, revolutionizing the perception that ICH outcomes cannot be improved 3
• Implementation of acute ICH care using a care bundle approach with regular monitoring ensures consistent and optimal care 2
• Expert supportive care on a stroke unit or critical care unit improves outcomes regardless of surgical intervention 2

Critical Pitfalls

Early Prognostication

• Early do-not-resuscitate orders or withdrawal of active care should be used judiciously in the first 24-48 hours, as early care limitations are independent outcome predictors and may create self-fulfilling prophecies of poor outcome 1, 2
• Most ICH deaths occur during initial hospitalization in the setting of withdrawal of support due to presumed poor prognosis 1
• Current outcome prediction models fail to account for these care limitations, potentially biasing prognostication 1

Surgical Decision-Making

• The usefulness of surgery for most patients with supratentorial ICH remains uncertain (Class IIb, Level of Evidence C) 1
• Neurosurgeons should avoid operating on patients in deep coma (GCS 5-8) with supratentorial ICH, as they tend to do better with medical management 1
• The lack of consensus on what constitutes "early surgery" has made comparison across studies difficult 1