General therapy

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

Prognosis
  • assess the extent and characteristics of ICH on the baseline CT scan (ICH score, spot sign…)
    • high ICH score is associated with a poor prognosis
    • the spot sign predicts bleeding progression
  • asses neurological deficits, age, comorbidities, and biological condition
  • estimate ICH etiology (SMASH-U)
  • start intensive therapy for the first 24-48h, then consider whether to continue with full therapy or switch to DNR (AHA/ASA 2015 IIa/B)
    • engage relatives in decision-making
Care setting

according to AHA/ASA guidelines 2022

  • provision of care in a specialized unit (e.g., stroke) with a multidisciplinary team providing the full range of high-acuity care and expertise is recommended
    • for patients with clinical signs indicating evolving hydrocephalus, transfer to centers with neurosurgical capabilities for definitive hydrocephalus management (e.g., EVD placement and monitoring) is recommended
    • 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
    • for patients with IVH or infratentorial bleeding, transfer to centers with neurosurgical capabilities might be reasonable
  • using standardized protocols and/or order sets is recommended to reduce disability/mortality
  • frequent neurological assessments are reasonable for up to 72h of 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, enoxaparin 0.4 mL SC 1-0-0 (low-dose LMWH) can be started 24-48 h from ICH onset (AHA/ASA 2022  2b/C-LD)
  • in patients with PE or acute deep vein thrombosis (DVT), consider retrievable IVC filter 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 stockings of knee-high or thigh-high length 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 – there is an increased risk of perihemorrhagic edema [Sprügel, 2021]
  • statins can be started later if needed
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 sufficient CPP (15-45°) – reverse Trendelenburg position
  • 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 for improving outcomes is not well established (AHA/ASA 2022 2b/B-NR)
  • corticosteroids should not be administered!  (AHA/ASA 2022 III/B-R)
AED
  • it is not recommended to administer AEDs prophylactically (even with lobar hematomas, which are associated with a greater risk of seizures). (AHA/ASA 2022 3/B-NR)
  • patients with seizures should be treated with antiepileptic drugs 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 suspicion of seizures, continuous EEG monitoring (24 hours) is reasonable to diagnose electrographic seizures and epileptiform discharges  (AHA/ASA 2022 2a/C-LD)
Physiotherapy
  • start early (approx. from the 2nd day) in a hemodynamically stable patient
  • focus on support of circulatory and respiratory functions and prevention of deep vein thrombosis and pressure ulcers (bed sores)

Blood pressure management in the acute stage

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

Correction of hemostasis disorders

  • early detection and urgent correction of coagulation disorders is a key procedure in ICH therapy
  • antifibrinolytic drugs 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 growth of the hematoma was counteracted by an increased risk of thromboembolic complications (especially in cohort with 80 μg dose) (AHA/ASA 2010 class III, LoE A)
  • similarly, the effect of etamsylate (DICYNONE) and tranexamic acid (EXACYL) was not proven
    • 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]
    • in the TICH-2  trial, no benefit was present in the subgroup of patients with positive spot sign   [Ovesen, 2021]

Intracerebral hemorrhage in thrombocytopenia and thrombocytopathy

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→ bleeding complications during thrombolysis

  • usually a consequence of late reperfusion with blood extravasation into the 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
    • not well-controlled hypertension and hyperglycemia
  • clinical manifestation depends on the extent of bleeding (ECASS classification)
Bleeding classification after Stroke and Reperfusion Therapy (ECASS II)

Intracerebral hemorrhage during anticoagulation therapy

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

Surgical treatment

  • the aim of surgery is:
    • to decrease ICP
    • to reduce the secondary damage from edema
    • to reduce the risk of herniation
    • to eliminate a potential source of bleeding

Monitoring of intracranial pressure (ICP)

  • ICP sensor can be implanted after correction of coagulation parameters
  • indications are ambiguous
    • 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 CSF drainage
  • main 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 the infection is suspected
  • leave sensor for a maximum of 5-7 days; later, the risk of infection increases, and the accuracy of the measurement decreases
  • ICP treatment according to cranial trauma protocols
    • ⇒ target CPP 50-70 mmHg
    • ⇒ target ICP < 20mmHg

External ventricular drainage (EVD)

  • used typically in massive intraventricular hemorrhage or expanding cerebellar hematomas 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 burdened with complications, including continued bleeding
  • the usefulness of surgery is unknown in most patients, and the indication for ICH evacuation remains controversial (AHA-ASA 2015 IIb/A)
    • the STICH and STICH III trials did not show a benefit of surgery over conservative management (< 48h, lobar hematomas 10-100ml, no IVH)
  • urgent evacuation of ICH (< 4h) does not improve outcome and mortality and may additionally increase the risk of bleeding (AHA/ASA 2015 IIb/A)
Indications
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Surgical procedures
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Treatment of the source of bleeding

  • the source of bleeding is mostly found in atypically localized hematomas and younger patients without hypertension
  • acute management is indicated in aneurysms with a high risk of early rebleeding
  • acute management of other sources of bleeding follows the general indications for surgery:
    • mostly expansive behavior of the 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 radiation therapy)

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 be useful to 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 is 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 and accelerate the evacuation of thrombus from the ventricles; it appears to be safe, but the clinical effect is unclear
      • CLEAR-IVH study – systemic bleeding 4%, ventriculitis 2%
      • CLEAR III trial – no substantial improvement in functional outcome at the mRS 3 cutoff compared to saline irrigation; mortality reduced by 10%
    • alternative procedures include the endoscopic evacuation of the hematoma with ventriculostomy, VP shunt, or lumbar drainage – benefit is unclear (AHA/ASA 2022 2b/C-LD)

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