Acute Intracranial Hemorrhage (ICH)

Background: - Population-based studies show that most patients present with small ICHs that are readily survivable with good medical care. The most recent guidelines are the 2022 AHA/ASA ICH Guidelines, referenced below. - 10% of strokes in the USA/Canada are ICH. - ICH is arguably the deadliest form of acute stroke, with early-term mortality about 30% to 40% and no or minimal trend toward improvement over more recent time epochs.

General Concepts

• Small vessel disease accounts for the majority of primary ICH: arteriolosclerosis and cerebral amyloid angiopathy (CAA) which are common age-related pathologies (30-35%)
  • Arteriolosclerosis (also referred to as lipohyalinosis) is detected as concentric hyalinized vascular wall thickening favoring the penetrating arterioles of the basal ganglia, thalamus, brainstem, and deep cerebellar nuclei (collectively referred to as deep territories). Its major associated risk factors are hypertension, diabetes, and age.
  • CAA is defined by deposition of beta-amyloid peptide in arterioles and capillaries in the leptomeninges, cerebral cortex, and hemispheres. The major risk factors are age and apolipoprotein E genotypes e2/e4 alleles.
  • the small vessel pathologies that underlie ICH are also associated with increased risk of ischemic stroke
  • CAA is associated with higher rates of recurrent hemorrhage than arteriolosclerosis
• mechanisms of ICH induced injury
  • direct pressure effects - local compression, increased ICP, hydrocephalus, herniation
  • secondary physiologic and cellular pathway effects - cerebral edema, inflammation, biochemical inflammation

Diagnosis and Assessment

Acute ICH Assessment

• routine labwork: CBC, INR, PRR, Cr/eGFR, glucose, cTn, ECG, tox screen, inflammatory markers, beta-hCG
• history:
  • symptoms: headache (thunderclap, slower onset), focal neurologic deficits, seizures, dec LOC
  • risk factors: ischemic stroke, prior ICH, HTN, DLD, DM, metabolic syndrome, imaging biomarkers
  • medications: antithrombotics, anticoagulants, vasoconstrictive agents (triptans, SSRIs, decongestants, sympathomimetics), antihypertensives, estrogen-containing OCP
  • substances: smoking, etoh, marijuana (RCVS), sympathomimetics
• physical examination: ABCs, focused neurological examination (NIHSS), GCS

Initial Neuroimaging

1. Rapid CT or MRI in patients with stroke-like symptoms to confirm the diagnosis of spontaneous ICH
2. Consider CTA within the first few hours of ICH after the initial CT, to identify patients at risk of subsequent HE
3. Serial head CT within the first 24 hours to evaluation for hemorrhage expansion (HE).  HE tends to occur early after ICH (typically within 24 hours of ICH onset) and is associated with poor outcome and mortality
4. Consider serial head CT in patients with low GCS or neurologic death to evaluate for hemorrhage expansion (HE), hydrocephaly, brain swelling, herniation

Diagnostic Assessment for ICH Pathogenesis

Among individuals <70 years of age who did not have typical hypertension-related deep territory ICH, an underlying macrovascular cause (arteriovenous malformations, aneurysm, dural arteriovenous fistula, cavernoma and cerebral venous thrombosis) is present in 1 of 4 to 1 of 7 patients, depending on age category.

Catheter intra-arterial DSA remains the gold standard to search for macrovascular causes of ICH. Here are the recommendations from the 2022 ICH Guidelines for further imaging after initial CT/MR.

Population	Imaging Recommendation	COR
Lobar spontaneous ICH and age <70; deep/posterior fossa ICH and age <45; deep/posterior fossa and age 45-70 without hypertension	CTA +/- venography to exclude macrovascular causes or cerebral venous sinus thrombosis	1
Spontaneous IVH and no detectable parenchymal hemorrhage	catheter intra-arterial DSA	1
Spontaneous ICH and CTA/MRA suggestive of macrovascular cause	Catheter intra-arterial DSA	1
Lobar spontaneous ICH and age <70; deep/posterior fossa ICH and age <45; deep/posterior fossa and age 45-70 without hypertension; and NEGATIVE CTA/V	Catheter intra-arterial DSA	2a
Spontaneous ICH and negative CTA/V	MRI + MRA	2a
Spontaneous ICH who have CT/MR at admission	CTA+/-V or MRA+/-V acutely to exclude macrovascular causes	2a
Spontaneous ICH and negative catheter intra-arterial DSA and no clear microvascular diagnosis or defined strutural lesions	Repeat catheter intra-arterial DSA in 3-6 months	2b

Consider the following pathway:

Medical and Neurointensive Treatment for ICH

Acute BP Lowering

Most patients with acute ICH have hypertension which is associated with HE, ND, death, and dependency. RCT evidence is equivocal. Mostly informed on the results of the two largest RCTS (INTERACT2, ATACH-2).

1. BP lowering needs to be careful and smooth, sustained, and avoid peaks and variability which tend to be correlated with HE.
2. BP lowering seems to have better outcomes when started earlier (<2 hours) as opposed to later, but results from the RIGHT-2 trial suggest that ultra-early (74 minutes) lowering is associated with poor outcomes.
3. In spontaneous ICH of mild to moderate severity with presenting SBP 150-220 mmHg, acute lowering of SBP to target 140 mmHg (range 130-150 mmHg) is safe and may improve functional outcomes. SBP <130 is potentially harmful.
4. Acute BP lowering targets are not well defined in patients who have large or severe ICH or ICH requiring surgical decompression.
5. There is limited evidence for patients presenting with hypotension or normotension.
6. Methods of BP measurement for early BP lowering after ICH have not been studied, including noninvasive versus invasive devices and frequency of measurements, which may be defined by studies evaluating targets for minimizing BP variability.

Hemostasis and Coagulopathy

Anticoagulant-Related Hemorrhage

Anticoagulation is unsurprisingly associated with HE and worse outcomes. Stop anticoagulation and rapidly reverse it. In general, treatment should be administered when clinically significant anticoagulant levels are suspected on the basis of type and timing of anticoagulant dosing rather than waiting for results of blood tests.

1. Warfarin/VKA
   1. INR ≥2.0: 4-factor PCC is recommended over FFP (Grade 1)
   2. INR 1.3 to 1.9: reasonable to use PCC (Grade 2b)
   3. Provide IV vitamin K directly after coagulation factor replacement to prevent late increases in INR and late HE (Grade 1)
2. DOACs
   1. Anti-Xa agent
      1. Andexanet alfa is reasonable (Grade 2a)
      2. Consider four-factor PFF or activated PCC (Grade 2b)
   2. Anti-IIa agent
      1. Idarucizumab is reasonable (Grade 2a)
      2. If idarucizumab is not available, consider aPCC or PCCs (Grade 2b)
      3. Consider dialysis to reduce dabigatran concentration (Grade 2b)
   3. Consider activate charcoal to prevent absorption if the last dose was taken within the previous few hours (Grade 2b)
3. Heparins
   1. UFH
      1. IV protamine is reasonable (Grade 2a)
   2. LMWH
      1. IV protamine may be considered to partially reverse to effect. (Grade 2b)

Antiplatelet-Related Hemorrhage

The effect of antiplatelet agents on the outcome of ICH is uncertain. A systematic review of 25 observational studies found that antiplatelet therapy at the time of the hemorrhage was associated with a 27% increase in mortality but not with functional outcome. The studies generally do not provide separate results for different antiplatelet agents, which vary in terms of degree of platelet inhibition, half-life, and reversibility. Platelet transfusions, desmopressin, and TXA have proven effective in reducing bleeding in other clinical indications, whereas for spontaneous ICH in patients being treated with antiplatelet agents, no convincing benefit has been demonstrated.

1. Patients on ASA and who require emergency neurosurgery - consider platelet transfusion to reduce postoperative bleeding and mortality (Grade 2b)
2. Patients on antiplatelet agents - unclear effect of DDAVP +/- platelet transfusions on HE
3. Patients on ASA and NOT scheduled for emergency surgery: platelet transfusions are potentially harmful and SHOULD NOT be administered.

Note: Ticagrelor is not reversed by platelet transfusions. Clopidogrel and ASA are permanent inhibitors and therefore are reversed.

General Hemostatic Treatments

A few RCTs have looked at rFVIIa and TXA in this setting for the prevention of HE. The modest effects of these agents on limiting HE have not translated into improvement in functional outcome.

General Inpatient Care

1. Care for these patients in a specialized inpatient setting (stroke unit) when stable enough.
2. Neurosurgical involvement for patients with clinical hydrocephalus, IVH, or intratentorial ICH. Also consider neuroICU admission if available.
3. Consider appropriate life-sustaining therapies prior to medical transport to prevent acute medical decompensation en route.
4. Use standardized protocols and order sets.
5. Dysphagia screening is recommended prior to oral intake initiation to reduce disability and pneumonia risk.
6. Consider cardiac monitoring for 24-72 hours to monitor for new cardiac ischemia and cardiac arrhythmias.
7. Continue to screen for infections after admission.

Thromboprophylaxis

Graduated compression stockings of any length are not effective against symptomatic DVT.

Glucose Management

Target normoglycemia using insulin.

Temperature Management

Essentially, prevent hyperthermia. TTM is again not shown to improve outcomes, just as in OHCA.

Seizure Management

Summary: only treat seizures if confirmed with clinical assessment or electrographically (EEG). Do not treat patients without evidence of seizures prophylactically.

Neuroinvasive Monitoring, ICP, and Edema Treatment

Because of a paucity of disease-specific data, indications for ICP monitoring in patients with ICH are often derived from the TBI literature. Guidelines suggest ICP monitoring in patients with a GCS score of 3 to 8 and maintenance of an ICP <22 mm Hg and a CPP of 50 to 70 mm Hg, depending on capacity for cerebral autoregulation.

Surgical Interventions for ICH

Minimally Invasive Surgery for ICH

Minimally Invasive EVD for IVH

Craniotomy for Supratentorial Hemorrhage

Craniotomy for Posterior Fossa Hemorrhage

Craniectomy for ICH

Predicting Outcomes, Goals of Care

Outcome Prediction

How do we grade severity of ICH? Consider use of the ICH score for initial baseline measurement of ICH severity, but the Max-ICH has been validated to be superior in patients who do not undergo WLST

Goals of Care and WLST

Most patients with ICH who die in the hospital do so after decisions are made by physicians and surrogate decision makers to limit the use of life-sustaining therapies such as artificial nutrition or hydration, intubation and mechanical ventilation, antibiotics, or vasopressors. These decisions are presumably made because of a low likelihood of favorable outcome and alignment with wishes of patients and their legally authorized surrogates (most often their family).

However, substantial uncertainty remains concerning the accuracy of prognostication, especially early after ICH onset. When a patient who was destined to recover from their ICH has limitations of life-sustaining therapies or withdrawal of life support, this results in a self-fulfilling prophecy of poor outcome.

Numerous studies have found that care limitations in the form of withdrawal of medical support or institution of DNAR orders are independently associated with increased risk of mortality and may lower the likelihood of favorable functional outcome when they are instituted early (usually within the first day) after ICH onset.

1. Provide initial aggressive care for ALL patients with ICH unless the patient has previously documented a desire for treatment limitations.
2. Implement a shared-decision making model.
3. Medical orders for DNR (cardiac/pulmonary) should be made INDEPENDENTLY of other decisions for medical care (surgical consideration, VTE prophylaxis, fluids, TTM, glucose management, feeding, infections, stroke unit admission, etcetera).

ICH Rehab

ICH Prevention of Recurrence

BP target <130/80 Patients with indications for antithrombotic agents:

References

1. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association | Stroke
2. Management of Spontaneous Intracerebral Hemorrhage | Canadian Stroke Best Practices