INTRACEREBRAL HEMORRHAGE

Management of intracerebral hemorrhage

Created 26/04/2021, last revision 20/11/2023

The INTERACT3 trial (2023) showed that timely administration of a care bundle that included early intensive lowering of systolic blood pressure, strict glucose control, treatment of fever, and rapid reversal of abnormal coagulation resulted in reduced disability, lower mortality rates, and better overall quality of life

General therapy

The tabs below discuss specific issues related to the conservative treatment of ICH. Otherwise, general principles of acute stroke management and intensive care, including management of intracranial hypertension, apply.

Prognosis

assess the extent and characteristics of ICH on baseline CT scan
- high ICH score is associated with poor prognosis
- spot sign predicts ICH progression
asses neurological deficits, age, comorbidities, and biological status
assess ICH etiology (SMASH-U)
start intensive therapy for the first 24-48hours, then consider whether to continue or switch to DNR (AHA/ASA 2015 IIa/B)
- involve family members in decision-making

Care setting

according to AHA/ASA guidelines 2022

start care in a specialized unit (e.g., stroke unit) with a multidisciplinary team providing the full range of high-acuity care and expertise
- patients with clinical signs of evolving hydrocephalus should be transferred to centers with neurosurgical capabilities for definitive management (e.g., EVD placement and monitoring)
- it is reasonable to provide care in a neuro-specific ICU rather than a general ICU for patients with moderate-to-severe spontaneous ICH, IVH, hydrocephalus, or infratentorial bleeding
- patients with IVH or infratentorial bleeding should be transferred to centers with neurosurgical capabilities
using standardized protocols and/or order sets is recommended to reduce disability/mortality
frequent neurological assessment is reasonable for up to 72 hours after admission to detect early neurological deterioration

VTE prevention

→ prevention of VTE in stroke patients

start intermittent pneumatic compression (IPC) on the admission day, if possible (AHA/ASA 2022 1/B-R)
after bleeding has ceased and coagulation is normal, consider starting enoxaparin 0.4 mL SC 1-0-0 (low-dose LMWH) 24-48 hours after the onset of ICH (AHA/ASA 2022 2b/C-LD)
a retrievable IVC filter should be considered for patients with pulmonary embolism (PE) or acute deep vein thrombosis (DVT) AHA/ASA 2022 2a/C-LD)
- a medical device that is temporarily implanted into the inferior vena cava (IVC) to prevent life-threatening pulmonary embolism in patients with contraindications to full anticoagulation
- delaying treatment with UFH or LMWH for 1-2 weeks after the onset of ICH might be considered (AHA/ASA 2022 2b/C-LD)
graduated compression knee-high or thigh-high length stockings alone are not beneficial for VTE prophylaxis

Statins

do not discontinue statin therapy
- continuation of prior statin treatment appears to be safe
- patients already using statins have a better outcome and lower mortality [Flint, 2014]
do not start statin therapy in the acute phase of ICH due to the increased risk of perihemorrhagic edema [Sprügel, 2021]
statins can be safely started later if necessary

Strict glucose and fever control

Strict glycemia and fever control according to INTERACT3 trial

no diabetes: target 6.1-7.8 mmol/L (109-140 mg/dL)
diabetes: target 7.8-10.0 mmol/L (140-180 mg/dL)

target body temperature ≤ 37.5° C

Intracranial hypertension

→ more about intracranial hypertension here

it is important to maintain intracranial pressure (ICP) and cerebral perfusion pressure (CPP) within normal ranges to reduce the risk of secondary brain injury
the head should be elevated to reduce ICP and maintain adequate CPP (15-45°)
sedation
indication for ICP monitoring in ICH is ambiguous
- consider in patients with GCS ≤ 8 with extensive hematoma, intraventricular bleeding, or hydrocephalus (AHA/ASA 2022 IIb/B-NR)
if ICP is monitored, start treatment at ICP 20-25 mmHg
- target ICP < 20mm Hg, target CPP 50-70mmHg
- bolus hyperosmolar therapy ( MANNITOL or hypertonic saline) → more here
the efficacy of early prophylactic hyperosmolar therapy to improve outcome is not well established (AHA/ASA 2022 2b/B-NR)
corticosteroids should not be used! (AHA/ASA 2022 III/B-R)

ASM

anti-seizure medications (ASMs) are not recommended for prophylaxis (even in lobar hematomas, which are associated with a higher risk of seizures) (AHA/ASA 2022 3/B-NR)
patients with seizures should be treated with ASM to reduce their morbidity → follow protocol for the treatment of symptomatic seizures (AHA/ASA 2022 1/C-LD)
in patients with unexplained abnormal or fluctuating mental status or suspected seizures, continuous EEG monitoring (≥24 hours) is reasonable to diagnose electrographic seizures and epileptiform discharges (AHA/ASA 2022 2a/C-LD)

Physiotherapy

start early (around day 2) in hemodynamically stable patients
focus on support of circulatory and respiratory functions and prevention of DVT and pressure ulcers (bed sores)

Blood pressure management in the acute stage

2021 ESO guidelines on blood pressure management in acute ischemic stroke and intracerebral hemorrhage

on admission, check BP every 5-10 minutes or start invasive BP monitoring
aggressive and rapid treatment of hypertension is an essential therapeutic approach (along with correction of coagulopathy)
- high BP is associated with an increased risk of hematoma progression with worse clinical outcome
- initiating treatment within 2 hours of ICH onset and achieving the target within 1 hour may be useful to reduce the risk of hematoma expansion and improve functional outcome (AHA/ASA 2022, 2a/C-LD)
- ischemia around the hematoma plays a minor role (except perhaps in large hematomas), and BP reduction seems safe
continue with chronic PO medications if possible; if dysphagia or decreased LOC is present, use parenteral therapy or place a nasogastric (NG) tube
in patients with known hypertension, the target BP may be higher due to altered autoregulation with the risk of CBF decrease
nitroprusside is not recommended (the potential to increase ICP)
smooth and sustained control of BP is required; avoid sudden drops or peaks in BP and maintain MAP >85 mmHg
if the intracranial pressure (ICP) is monitored, then correct BP to maintain CPP 60-80 mmHg

Initial systolic blood pressure (SBP) 150-220 mm Hg in patients with ICH of mild-to-moderate severity

target SBP ≤ 140 mmHg (ESO guidelines 2021) (AHA/ASA 2022 2b/B-R)
- lowering SBP to 140mmHg is safe and may reduce hematoma expansion and lead to improved outcomes
- maintain in the range of 130-150 mm Hg
- target <140 mm Hg was used in the INTERACT3 trial
no significant clinical benefit of lowering < 140 mmHg has been demonstrated
- In the INTERACT2 trial, there were fewer patients with mRS 3-6 in the intensive treatment group (SBP<140 mmHg) compared to the standard treatment group (SBP <180 mmHg); the difference was not statistically significant
- the benefit of lowering SBP <140 mmHg was not demonstrated in the ATACH-2 trial – lowering SBP <120 mm Hg may even be harmful
acute lowering of SBP to <130 mm Hg is potentially harmful (AHA/ASA 2022 3/B-R)
start antihypertensive treatment ASAP (ideally within 2h of symptom onset)
the decrease of SBP should not exceed 90 mmHg from baseline values (ESO guidelines 2021)
- greater BP reduction was significantly associated with acute kidney injury regardless of preexisting CKD (Burgess, 2018)

Initial SBP > 220 mmHg or large hematoma

limited data on the safety and efficacy of a target SBP ≤ 140 mmHg
SBP reduction should not exceed 90 mmHg from the baseline
cautious BP lowering is required in such patients ⇒ maintain CPP > 60–70 mmHg

the 1st line of IV drugs:
- urapidil (EBRANTIL)
- enalapril (ENAP)
- labetalol (TRANDATE)
if they fail, try nitrates – isosorbide dinitrate (ISOKET)
start peroral medication ASAP (e.g., via NG tube if necessary) and gradually reduce/withdraw parenteral medication

Correction of hemostasis disorders

early detection and urgent correction of coagulopathy is a key procedure in ICH therapy
antifibrinolytic agents are not recommended except for thrombolysis-related bleeding

Patients with normal coagulation parameters

the FAST trial with recombinant f.VII (NOVOSEVEN) failed to show a reduction in mortality and disability. Mayer, 2008]
- reduced hematoma growth was offset by an increased risk of thromboembolic complications (especially in the 80 μg dose cohort) (AHA/ASA 2010 class III, LoE A)
similarly, the effect of etamsylate (DICYNONE) and tranexamic acid (EXACYL) has not been demonstrated
- negative TICH-2 and STOP-AUST trials
- negative meta-analysis of 4 RCTs – hemostatic therapy showed a marginally significant benefit in reducing hematoma expansion in high-risk patients (predicted by CT scan markers). However, no significant improvement in functional outcome or reduction of mortality was observed [Nie, 2021]
- the TICH-2 trial showed no benefit in the subgroup of patients with positive spot sign [Ovesen, 2021]

Intracerebral hemorrhage in thrombocytopenia and thrombocytopathy

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Hemorrhagic infarction, thrombolysis-related bleeding

→ bleeding complications during thrombolysis

usually a consequence of late reperfusion with extravasation of blood into infarcted tissue (0.6-5%)
risk factors:
- early anticoagulation (therefore not recommended)
- thrombolysis (symptomatic IC bleeding ~ 6%)
- extensive infarction
- large artery occlusion with late recanalization
- poorly controlled hypertension and hyperglycemia
clinical presentation depends on the extent of bleeding (ECASS classification)

Hemorrhage classification after stroke/reperfusion (ECASS II)

Intracerebral hemorrhage during anticoagulation therapy

prolonged bleeding on anticoagulant therapy is present in ~ 36-54% of patients (warfarin > DOAC) ⇒ neutralization of the anticoagulant effect is therefore essential [Steiner, 2017]

→ neutralization of the anticoagulant therapy

Surgical treatment

the goals of surgery are to:
- decrease ICP
- reduce the secondary damage from edema
- reduce the risk of herniation
- eliminate potential sources of bleeding

Monitoring of intracranial pressure (ICP)

ICP sensor can be implanted after correction of coagulation parameters
indications are equivocal
- patients with GCS ≤ 8 with extensive parenchymal hematoma, intraventricular hemorrhage with obstructive hydrocephalus (AHA/ASA 2015 IIb/C)
intraparenchymal or intraventricular sensor
- the intraventricular catheter is inserted through the brain into the lateral ventricle; it allows concurrent CSF drainage
major risks:
- bleeding – the type of the hemorrhage depends on the site of insertion (intraparenchymal, intraventricular, or subdural)
- infection (up to 12%, the risk is higher with intraventricular catheters) – CSF should be sent for cytology and culture analysis if infection is suspected
leave the sensor for a maximum of 5-7 days; beyond this time, the risk of infection increases, and the accuracy of the measurement decreases
manage ICP according to head trauma protocols
- target CPP 50-70 mmHg
- target ICP < 20 mmHg

External ventricular drainage (EVD)

typically used for massive intraventricular hemorrhage or expanding cerebellar hematoma with acute obstructive hydrocephalus (AHA/ASA 2022 I/B-NR)
- modern catheters allow concurrent ICP monitoring
- careful monitoring of consciousness and repeated CT scans are required

Hematoma evacuation

relieving the pressure of the hematoma on the surrounding tissue may reduce secondary damage
craniotomy is associated with complications, including continued bleeding
- the benefit of surgery is unknown (AHA-ASA 2015 IIb/A)
- the STICH and STICH III trials showed no benefit of standard surgery over conservative management (< 48h, lobar hematomas 10-100mL, no IVH)
minimally invasive surgery seems to be beneficial
- positive results of ENRICH trial with minimally invasive parafascicular surgery (MIPS) may change current practice
  - age 18-80 years, ICH volume 30 – 80 mL, GCS 5-14, premorbid mRS 0-1, intervention initiated within 24 hours after the onset of stroke symptoms
urgent evacuation of ICH (< 4h) does not improve outcome or mortality and may increase the risk of bleeding (AHA/ASA 2015 IIb/A)

Indications

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Surgical procedures

MIS (minimally invasive surgery) – stereotactic hematoma evacuation (with/without tPA application) (AHA/ASA 2022 2a/B-R)
- 12-72 h from the onset, GCS 5-12
- hematoma volume > 20-30mL
- puncture and aspiration of hematoma to reduce the volume to < 10-15 mL, possible tPA application of 1mg every 8h or 2mg every 12h
- favorable results in phase 2 trial (mortality 7% vs. 14%) – MISTIE (Minimally Invasive Stereotactic Surgery – rt-PA for ICH Evacuation)
- preliminary results of the phase 3 MISTIE III trial are negative (primary outcome mRS 0-3/year 45% vs. 41%); however, there appears to be a clinical effect with residual hematoma volume < 15 ml
- positive results of the ENRICH trial
- prefer MIS over craniotomy evacuation (AHA/ASA 2022)
osteoplastic craniotomy with hematoma evacuation or with decompressive craniectomy
- in most patients, the usefulness of craniotomy for hemorrhage evacuation to improve functional outcomes or mortality is uncertain (AHA/ASA 2022 class 2b/A)
- in patients with supratentorial ICH who are deteriorating, craniotomy for hematoma evacuation might be considered a lifesaving procedure (AHA/ASA 2022 class 2b/C-LD)
decompressive craniectomy (with or without hematoma evacuation) can be a lifesaving procedure in comatose patients with prominent mass effect (with midline shift) and drug-refractory IC hypertension (AHA/ASA 2022 2b/C-LD)
- the effectiveness of decompressive craniectomy with or without hematoma evacuation to improve functional outcomes is uncertain

Treatment of the source of bleeding

the source of bleeding is most common in atypically localized hematomas and younger patients without hypertension
acute intervention is indicated for aneurysms with an extremely high risk of early rebleeding
acute management of other bleeding sources follows the general indications for surgery:
- mostly expansive hematoma, 30-60 mL, GCS > 8
- cerebellar hematoma compressing the brainstem (usually > 3 cm)
malformations are often complicated and require a multidisciplinary approach (a combination of endovascular, surgical, and radiotherapy)

Surgery in intraventricular hemorrhage (IVH)

treat the underlying cause of bleeding
detect and treat possible obstructive hydrocephalus (serial neurological status examinations and repeated CT scans are required for the diagnosis)
- external ventricular drainage (EVD) may reduce mortality, especially in patients with large ICH/IVH and impaired level of consciousness (LOC) (AHA/ASA 2022 1/B-NR)
  - for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, minimally invasive IVH evacuation with EVD plus thrombolytics is safe and reasonable compared with EVD alone to reduce mortality (AHA/ASA 2022 2a/B-NR)
  - for patients with a GCS score >3 and primary IVH or secondary IVH (with supratentorial ICH of <30-mL volume) requiring EVD, the effectiveness of minimally invasive IVH evacuation with EVD plus the use of thrombolytics to improve functional outcomes is uncertain
  - for patients with large ICH/IVH and impaired LOC, the efficacy of EVD to improve functional outcome is not well-established
- intraventricular application of tPA may facilitate the thrombus evacuation from the ventricles; it appears safe, but clinical efficacy is unclear
  - CLEAR-IVH study – systemic bleeding 4%, ventriculitis 2%
  - CLEAR III trial – no substantial improvement in functional outcome at mRS 3 cutoff compared to saline irrigation; mortality reduced by 10%
    - intraventricular tPA protocol – 1 mg of alteplase, 8h apart; up to 12 doses
- alternative procedures: endoscopic evacuation of the hematoma with ventriculostomy, VP shunt, or lumbar drainage – benefit is unclear (AHA/ASA 2022 2b/C-LD)