Intracerebral haemorrhage

Contents

Epidemiology and Classification

Spontaneous (non-traumatic) intracerebral haemorrhage (ICH) accounts for ~15% of all strokes but carries disproportionate mortality (~40% at 30 days) and high morbidity among survivors.

Primary ICH

  • Hypertension (most common): chronic hypertension causes lipohyalinosis of small penetrating arteries → microaneurysm formation (Charcot-Bouchard aneurysms) → rupture
  • Cerebral amyloid angiopathy (CAA): amyloid deposition in cortical vessel walls → cortical/lobar haemorrhage; typically in older patients; recurrence risk high; APOE-ε4 association
  • Location: hypertensive ICH — basal ganglia (putamen most common), thalamus, pons, cerebellum; CAA — lobar (cortical)

Secondary ICH

  • Anticoagulation (warfarin, DOAC): major risk factor for ICH with haematoma enlargement
  • Vascular malformations: arteriovenous malformation (AVM), cavernoma, dural AV fistula
  • Haematological: thrombocytopenia, haemophilia, DIC
  • Tumour: primary or metastatic (haemorrhagic metastases: melanoma, renal cell carcinoma, choriocarcinoma, thyroid)
  • Cerebral venous thrombosis (CVT): haemorrhagic infarction

Pathophysiology and Haematoma Expansion

Haematoma Expansion

The initial haematoma forms rapidly (minutes). In 30–40% of patients, the haematoma expands over the first 3–24 hours — the single most important determinant of early neurological deterioration and poor outcome. Expansion occurs from:

  • Ongoing bleeding from the ruptured vessel
  • Dissection into surrounding tissue by haematoma pressure
  • Secondary bleeding from surrounding vessels disrupted by haematoma expansion

Perihematomal Oedema

Develops over hours to days:

  • Phase 1 (hours): hydrostatic fluid flux from clot retraction; blood breakdown products (thrombin, haemoglobin) → inflammatory cascade → vasogenic oedema
  • Phase 2 (days 1–3): inflammatory cell infiltration; cytotoxic oedema → maximal oedema at day 3–5
  • Oedema is a secondary injury; contributes to mass effect and ICP elevation

ICP and Herniation

Large haematoma + oedema → mass effect → ↑ ICP → transtentorial herniation (if supratentorial) or tonsillar herniation (if posterior fossa). Cerebellar haemorrhage is particularly dangerous — the posterior fossa is rigid and small; obstructive hydrocephalus and tonsillar herniation can develop rapidly.

Clinical Assessment and Grading

Symptoms

  • Sudden onset headache (severe, often "worst ever" — less pronounced than in SAH)
  • Focal neurological deficits (contralateral weakness/sensory loss for basal ganglia; limb ataxia for cerebellar; diplopia, nausea, vomiting, ataxia for brainstem)
  • Deteriorating consciousness
  • Vomiting (from ↑ ICP)
  • Seizures (~10% at onset)

ICH Score (Hemphill, 2001)

Simple bedside prognostic tool:

Variable Score
GCS 3–4 +2; GCS 5–12
ICH volume ≥30 mL +1
Intraventricular extension +1
Infratentorial origin +1
Age ≥80 years +1

ICH score 0: 0% 30-day mortality; ICH score 5: ~100% 30-day mortality. Used to guide prognosis and treatment escalation discussions.

Investigations

Imaging

  • CT brain non-contrast (immediate): diagnosis of ICH, haematoma size and location, intraventricular extension, hydrocephalus, oedema, midline shift
  • CT angiography (CTA): recommended for all ICH patients aged <70 years without clear hypertensive aetiology, or any patient with lobar haemorrhage — identifies underlying AVM, aneurysm, or tumour; spot sign (contrast extravasation within haematoma) predicts haematoma expansion
  • MRI (delayed): identifies underlying cavernoma, tumour, CAA (gradient echo/SWI sequences show microbleeds)
  • CT venography: if CVT suspected (superior sagittal sinus territory haemorrhage)

Blood Tests

  • INR, APTT, DOAC level (anti-Xa for rivaroxaban/apixaban; diluted thrombin time for dabigatran)
  • FBC, platelets, U&E, glucose
  • Group and save

Blood Pressure Management

Rationale

Elevated BP in ICH causes haematoma expansion; very low BP risks ischaemia in the perihematomal penumbra. Both extremes are harmful.

Evidence

INTERACT2 trial (Anderson, NEJM 2013):

  • 2839 patients with spontaneous ICH within 6 hours; SBP 150–220 mmHg
  • Intensive BP lowering (target SBP <140 mmHg) vs guideline-based (SBP <180 mmHg)
  • No significant mortality benefit at 90 days; significant improvement in functional outcome (modified Rankin Scale) in intensive group

ATACH-2 trial (Qureshi, NEJM 2016):

  • 1000 patients; intensive target SBP 110–139 vs standard 140–179 mmHg
  • No benefit from intensive lowering on 90-day disability; trend to harm; intensive group had more renal adverse events

Current Guidance (AHA/ASA 2022, NICE)

  • If SBP 150–220 mmHg: acute lowering to target SBP 130–150 mmHg is reasonable; maintain consistently for first 24 hours
  • If SBP >220 mmHg: consider IV antihypertensive with target SBP <180 mmHg initially; then 130–150 once stabilised
  • Agents: IV labetalol, IV nicardipine, IV clevidipine (most rapidly titratable), IV glyceryl trinitrate; avoid sodium nitroprusside (risk of ↑ ICP from cerebral vasodilation)

Anticoagulation Reversal

Anticoagulation-associated ICH has higher haematoma expansion rates and mortality. Reversal is urgent.

Warfarin

  • Target INR <1.5 immediately
  • 4-factor prothrombin complex concentrate (4F-PCC): Beriplex/Octaplex — immediate reversal; dose 25–50 IU/kg based on INR; give with vitamin K 10 mg IV (PCC effect wanes in hours without concurrent vitamin K)
  • FFP: large volumes, slow, associated with fluid overload — use only if PCC unavailable

DOACs

  • Dabigatran: idarucizumab (Praxbind) 5 g IV — complete, immediate reversal
  • Rivaroxaban, apixaban: andexanet alfa if available; 4F-PCC 50 IU/kg (off-label, partial reversal) if not
  • Check last dose and time; timing of reversal matters (DOACs are half-life-dependent)

Heparin

  • Protamine sulfate: 1 mg per 100 units UFH given in last 2 hours; APTT reassessment

Antiplatelet Agents

  • PATCH trial (Baharoglu, Lancet 2016): platelet transfusion in ICH patients on antiplatelet agents was harmful (worse outcomes) compared to standard care
  • Platelet transfusion is NOT recommended in ICH patients on antiplatelets unless surgical haemostasis is needed

Surgical Management

Cerebellar Haemorrhage

  • Surgical evacuation is indicated for: diameter >3 cm, neurological deterioration, compression of brainstem, or obstructive hydrocephalus
  • Posterior fossa is unforgiving — rapid deterioration; low threshold for surgical intervention
  • EVD for hydrocephalus

Supratentorial ICH

Evidence for surgical evacuation is weak:

  • STICH trial (Mendelow, Lancet 2005): no benefit from early surgery vs initial conservative management in supratentorial ICH
  • STICH II trial (Mendelow, Lancet 2013): early surgery in lobar ICH (1–3 cm from surface) also showed no clear benefit
  • Surgery may be considered for: deteriorating consciousness with surgically accessible haematoma; young patients with lobar haematoma; haematoma >60 mL with clinical deterioration
  • Minimally invasive surgery (MIS): catheter aspiration ± thrombolysis; several RCTs underway; MISTIE III showed no functional benefit despite haematoma reduction

Intraventricular Extension and Hydrocephalus

  • External ventricular drain (EVD): drains CSF, monitors ICP; indicated for hydrocephalus with altered consciousness
  • Intraventricular fibrinolysis (alteplase via EVD) clears intraventricular blood — CLEAR III trial showed no functional benefit but reduced CSF flow obstructions

ICU Management

Airway and Ventilation

  • GCS ≤8: intubate; use RSI to avoid ↑ ICP from laryngoscopy (fentanyl 3 mcg/kg + thiopental or propofol induction + suxamethonium); or ketamine + midazolam
  • Target SpO₂ >94%; avoid hypercapnia (vasodilation → ↑ ICP)

ICP Management

See traumatic brain injury page for stepwise ICP management — same principles apply:

  • Head elevated 30°; neck neutral
  • Normoglycaemia (6–10 mmol/L)
  • Normothermia (avoid fever)
  • Osmotherapy for raised ICP: mannitol 0.25–1 g/kg IV bolus; or hypertonic saline
  • Avoid hyperventilation except as temporising measure

Seizure Prevention

  • Clinical or EEG-confirmed seizures: treat with levetiracetam (or phenytoin)
  • Prophylactic anti-epileptics: not recommended in current guidelines (no mortality benefit; possible harm)
  • Continuous EEG if unexplained neurological deterioration or impaired consciousness without clear cause

Glucose and Temperature

  • Hyperglycaemia worsens outcome in ICH; target 6–10 mmol/L
  • Fever actively treated (paracetamol ± cooling blankets); pyrexia ↑ metabolic demand and worsens ICP

Viva Questions

1. What is haematoma expansion in ICH, how common is it, and how do you reduce it?

Haematoma expansion (HE) occurs in 30–40% of spontaneous ICH patients, typically within the first 3–6 hours, and is the primary driver of early neurological deterioration. It occurs from ongoing bleeding from the initial ruptured vessel and dissection of blood into surrounding tissue. The CT angiography "spot sign" — contrast extravasation within the haematoma on CTA — is the best imaging predictor of HE, with a positive predictive value of ~60%. The key modifiable interventions to reduce HE: (1) urgent BP lowering — targeting SBP <140–150 mmHg within the first hour; evidence from INTERACT2 shows improved functional outcomes with intensive BP lowering, though ATACH-2 suggested harm below 110 mmHg; (2) urgent reversal of anticoagulation — warfarin-associated ICH should be reversed with 4F-PCC immediately (target INR <1.5); DOAC-associated ICH with idarucizumab (dabigatran) or andexanet alfa/PCC (FXa inhibitors); (3) haemostatic agents (tranexamic acid, recombinant FVIIa) — trialled in randomised studies but have not shown clinical benefit despite reducing HE radiologically; not currently standard of care.

2. What is the evidence for blood pressure management in ICH?

The two major RCTs are INTERACT2 and ATACH-2. INTERACT2 (Anderson, NEJM 2013, n=2839) showed that targeting SBP <140 mmHg (vs <180 mmHg) did not reduce mortality but did improve functional outcomes (mRS shift, p=0.04). ATACH-2 (Qureshi, NEJM 2016, n=1000) compared SBP targets 110–139 vs 140–179 mmHg — the intensive group showed no benefit on disability at 90 days and a trend to harm (renal adverse events). The synthesis: there is a therapeutic window. Current guidance recommends targeting SBP 130–150 mmHg in the first 24 hours for patients presenting with SBP 150–220 mmHg — this balances the benefit of reducing haematoma expansion (which drives HE) against the risk of perihematomal ischaemia from excessive lowering. Consistent maintenance of BP within the target window matters as much as the initial target — labile BP is associated with worse outcomes. Agents: IV labetalol, nicardipine, or clevidipine; avoid sodium nitroprusside (cerebral vasodilation → ↑ ICP).

3. A 70-year-old on warfarin (INR 3.2) presents with a 25 mL putaminal haemorrhage and GCS 12. How do you manage the first 2 hours?

Simultaneously: (1) Airway assessment — GCS 12 with active deterioration risk; prepare for intubation; at this point GCS is borderline; if deteriorating rapidly, intubate early to protect airway and allow safe CTA/MRI; (2) Reverse anticoagulation urgently — give 4-factor PCC (Beriplex) based on weight and INR (INR 3.2 → typically 30–35 IU/kg) immediately; vitamin K 10 mg IV concurrently (sustains reversal as PCC effect wanes); recheck INR at 30 minutes — target <1.5; (3) BP management — start IV labetalol or nicardipine to target SBP 130–150 mmHg; avoid systemic hypotension; titrate carefully; (4) CT angiography — urgent CTA to assess for spot sign (predicts haematoma expansion), underlying AVM, and to exclude pseudoaneurysm; (5) Neurosurgical consultation — 25 mL putaminal haematoma with GCS 12; not typically a surgical case by current evidence, but neurosurgery must be involved; cerebellar or posterior fossa ICH would be different; (6) ICU admission, continuous monitoring, glucose and temperature control; (7) Consider repeat CT at 6 hours (if spot sign positive on initial CTA or clinical deterioration) to assess for expansion.