Intracranial Haemorrhage

 

Intraparenchymal

•   10% of strokes

•   50% mortality

Aetiology

•   Structural factors (derangements of cerebral blood vessels)

o   Chronic Hypertensive changes

o   Amyloid angiopathy

o   Transformation of ischaemic CVA (occurs in 1-6%)

-   Including venous sinus thrombosis

o   Saccular aneurysm

o   AV-malformations/cavernous haemangioma

o   Septic embolism/mycotic aneurysm

o   Dissection

o   Moyamoya syndrome

•   Haemodynamic factors

o   Hypertension (acute)

o   Migraine

•   Haemostatic factors

o   Inherited Coagulopathy

o   Iatrogenic coagulopathy – warfarin

o   Antiplatelets

o   Thrombolysis

o   Thrombocytopaenia

•   Other

o   Tumour

o   CNS infection – HSV encephalitis

o   Vasculitis

o   Drugs

-   Cocaine, amphetamines, phenylpropanolamine (in appetite suppressants)

Main causes

•   Lobar haemorrhage (30-40%)

o   Amyloid 30% of lobar

•    

Causes of multiple haemorrhages

•   Amyloid angiopathy – multiple lobar haemorrhages specifically

•   Venous thrombosis

•   Thrombolysis

•   Metastases

•   Vasculitis

•   DIC

•   Haemostatic disorder

•   Leukaemia

•   Eclampsia

•   Trauma

Causes by age

•   <40years – More likely malformation

•   40-70yrs – Often hypertensive

•   >70yrs – Lobar haemorrhages, often amyloid angiopathy

 

Young ICH

•   Most common cause in most series – HTN or AVM

•   Other ‘common’ causes:

o   Cavernoma

o   Drug abuse

o   Coagulopathy

o   CVST

o   RCVS

o   PRES

 

Specific Aetiologies

Hypertensive

•   Spontaneous rupture of small penetrating deep artery

o   Frequently at junction of these arteries with large arteries – where higher pressure may be experienced. 

•   Most common sites

o   Basal ganglia (esp. putamen)

-   Results in disruption of internal capsule and contralateral hemiparesis is most common sign.

o   Thalamus

o   Cerebellum

o   Pons

-   Deep coma with quadraplegia

•   Develop rapidly over 30-90min

•   Usually occur when patient is awake

•   No clear association with exertion but ? with stress

Cerebral Microbleeds

•   Occur often in hypertensive patients due to pseudoaneurysms that occur in small penetrating arteries

o   Amyloid deposition and subacute IE must also be considered

•   RF

o   HTN (OR 3.9), DM (OR2.2)

•   Small-subclinical bleeds can occur frequently prior to a large haemorrhage

•   Multifocal haemosiderin deposition can be detected on Gradient echo imaging.

•   Represent risk factor for pathology, found in:

o   Normal population – 5%

o   Patients with ischaemic stroke – 34%

o   Patients with ICH – 60%

Amyloid Angiopathy

•   Arteriolar degeneration associated with amyloid deposition in the vessel walls

•   Association between ApoE2, ApoE3, haemorrhage and amyloid

•   Associated with lobar haemorrhages occurring at grey-white boundary  (no association with deep haemorrhages)

o   Often have irregular outer border.

•   Frequently multiple small haemorrhages over time – like small emboli

•   Larger lesion can then develop

•   Can make vessels fragile such that bleed is then triggered by a minor trauma

•   Recurrent haemorrhage more common (see below)

•   Association with other manifestations :

o   Intellectual deterioration (associated with diffuse demyelination of subcortical white matter)

o   Rare – cerebral vasculitis type syndrome

o   Rare – TIA type episodes from micro-bleeds

Saccular aneurysm

•   ICH in this setting usually associated with SAH – 25% of SAH will have associated ICH

 

Septic arteritis and mycotic aneurysms

•   ICH usually due to acute pyogenic necrosis of arterial wall rather than mycotic aneurysm haemorrhage which occurs later

•   Occurs in up to 5% of IE

Investigation

Acute:

•   Non-contrast CT-B

•   +/- MRI

•   CT with contrast

o   Looking for spot sign – strong indicator of haematoma enlargement but as yet no recommended alteration to treatment

Investigation for underlying cause:

•   Risk factors for an underlying vascular abnormality:

o   Age <65

o   Female

o   Non-smoker

o   Lobar ICH

o   Intraventricular extension

o   Absence of HTN or coagulopathy

•   Radiological evidence suggestive of a vascular abnormality as causative:

o   Presence of subarachnoid haemorrhage

o   Enlarged vessels or calcifications along the margin of the ICH

o   Hyperattenuation within the dural venous sinuses or cortical veins

o   Unusual haematoma shape

o   Presence of oedema out of proportion to the time of the presumed ICH

o   An unusual haematoma location

o   Presence of a mass

•   CTA

o   High accuracy for vascular malformations

•   CTV (/MRV)

o   Should be considered if any suggestion of venous sinus thrombosis

•   MRI

o   Can detect amyloid in addition to other aetiologies

•   DSA

o   Reserved for cases of high suspicion of vascular malformation or to define a lesion already seen

·         Timing of intervention - ??

·         Guidelines:

o    ASA – CT should be done for all patients, CTA/MRI may be useful in selected patients

o    ESO – not mentioned

Progression

o   Frequently progress rapidly initially

o   If imaged at 3hours after onset there is 25% chance of further enlargement in the next hour a further 15-20% chance if imaged later (>3hours)

o   Progression after 24hours is rare

Prognosis

•   Supratentorial

o   <30 ml – good

o   30-60 – intermediate

o   >60ml – poor

•   Ventricular extension worsens prognosis

•   Infratentorial/posterior fossa – poor prognosis

•   Haematoma growth worsens prognosis (?in addition to actual initial size)

•   Previous anti-coagulation therapy weakly associated with worse prognosis

 

Determination of the ICH score

GCS score

3-4

5-12

13-15

 

ICH volume (cm3)

≥30

<30

 

IVH

Yes

No

 

Infratentorial origin of ICH

Yes

No

 

Age (years)

≥80

<80

 

Total ICH score

 

2

1

0

 

 

1

0

 

 

1

0

 

 

1

0

 

 

1

0

 

0-6

(ICH volume should be calculated from CT. The largest extension of the haematoma in all three axis is multiplied together and the product divided by two)

 

Score   0 – Negligible mortality

            1 – 20%

            2 – 30%

            3 – 70%

            4 or more – over 90%

 

Recurrence

·         2.3% per annum chance of rebleed

o    2.1% for deep bleeds

o    4.4% for bleeds at grey-white border (amyloid)

 

Treatment

Acute

Reversal of anti-coagulation

Warfarin

•   Prothromin complex concentrates (PCC – “Pro-thrombinex”) – likely better than FFP

•   Guidelines:

o   ASA – Vit K/PCC/FFP indicated

o   ESO – Insufficient evidence to make strong recommendations

•   Australian Warfarin Reversal Guidelines (MJA 2004)

o   Give 5-10mg IV vitamin K

o   Give Prothrombinex-HT (25-50IU/kg)

o   Give FFP (150-300ml)

o   Further treatment may be necessary if INR remains >5.

NOACs

•   Consider activated charcoal if last dose <2hours before

•   Consider dialysis for dabigatran

•   Dabigitran/Rivaroxaban/apixiban

o   Consider the use of one of the following (Australian Haemostasis Guidelines 2014)

-   Prothrombinex-VF 25-50IU/kg

-   FEIBA (activated PCC) 25-100IU/kg

-   rVIIa 90ug/kg

-   Tranexamic acid 15-30mg/kg IV +/- infusion (mainly for mucosal bleeds)

Reversal of Anti-platelet agents

•   No evidence to date that any intervention is warranted

•   Guidelines – ASA/ESO – agree with above

Pro-coagulant therapy

•   Tranexamic acid

o   Currently being trialled in the STOP-AUST trial

•   Factor VIIa

o   Two trials in NEJM 2005, 2008

o   They both showed reduced haematoma size in the treatment group however the newer and larger trial did not demonstrate improvement in outcomes for patients (due to increased occurrence of thromboembolic events)

 

Surgery

ICP monitoring and treatment

•   Guidelines :

o   ASA –

-   Ventricular drainage as treatment for hydrocephalus is reasonable, especially in patients with decreased consciousness

-   ICP monitoring may be considered for patients with:

•   GCS </= 8, clinical evidence of transtentorial herniation, significant IVH or hydrocephalus

-   Aim for Cerebral perfusion pressure (CPP) of 50-70mmHg

o   ESO – insufficient evidence to make recommendations

Cerebellar/Infratentorial

•   Suggested for cerebellar (if age <75ys)

o   <1cm – usually no surgery

o   1-3cm – observe

o   >3cm – usually need surgery

o   (>75yrs age – case by case basis)

•   In contrast to cerebellar haemorrhage, evacuation of brainstem haemorrhages may be harmful in many cases

•   Guidelines

o   ASA - Patients with cerebellar haemorrhage who are deteriorating neurologically or who have brainstem compression and/or hydrocephalus from ventricular obstruction should undergo surgical removal of the haemorrhage as soon as possible -  Initial treatment of these patients with ventricular drainage rather than surgical evacuation is not recommended

o   ESO – insufficient evidence to make recommendations

 

Supratentorial

•   STICH trial

o   showed routine evacuation not beneficial, however all patients had surgery if there was significant deterioration

•   STICH II (Lancet 2013)

o   STICH I suggested there may be benefit in subgroup with lobar haemorrhages, <1cm from cortical surface, without intraventricular haemorrhage – so this was tested

o   Suggestion of a very small mortality benefit (18% vs 24% - NS), otherwise no difference.

o   21% of patients in the conservative group crossed over to have surgery

o   Meta-analysis of previous trials included in this paper suggests a small benefit in favour of surgery.

•   Guidelines:

o   AHA/ASA

-   – For most patients with supraventricular ICH the usefulness of surgery is not established

-   Haematoma evacuation in deteriorating patients might be considered as a life-saving measure

-   A policy of early hematoma evacuation is not clearly beneficial compared with hematoma evacuation when patients deteriorate

-   Decompressive craniectomy with or without hematoma evacuation might reduce mortality for patients with supratentorial ICH who are in a coma, have large hematomas with significant midline shift, or have elevated ICP refractory to medical management

o   ESO – “No evidence to support routine intervention, but early surgery may be of benefit for patients with GCS 9-12)

Intraventricular rtPA/Endoscopic treatment

•   Efficacy and safety uncertain

Blood pressure

•   Reduction in BP recommended (ASA and ESO guidelines):

o   In patients presenting with SBP 150-220mmHg

o   Safe to treat to <140systolic within <1hour (INTERACT2)

o   Suggestion of slight benefit in disability

o   In patients with BP >220mmHg it may be reasonable to consider aggressive reduction of BP.

•   Should avoid vasodilating agents

•   Recommend – nicardipine, labetalol, esmolol

•   INTERACT Study Lancet Neurology 2008

o   Intensive vs standard BP lowering (140 vs 180 systolic)

o   No statistically significant difference in survival but suggestion of smaller haemorrhage size.

•    INTERACT2 (NEJM 2013)

o   Patients with BP between 150-220mmHg, recruited within 6 hours of onset of ICH.

o   Treated to a target of <140mmHg within one hour and kept below 140 for 7 days, treatment stopped if BP <130.

o   Outcomes:

-   Death or major disability 52 vs 55% (NS) – i.e. primary endpoint not significant

-   Improvement in mRS – HR 0.87 (P=0.04)

-   Death – no difference

-   No major increase in adverse events

o   Subgroup analysis showed that for the treatment arm:

-   Baseline BP did not affect outcome

-   Target BP achieved did affect outcome – improved outcome as systolic achieved approached 130, apparent worsening of outcome with BP below 130.

Seizures

•   Up to 16% of patients have early seizure (within 1 week)

o   Most occur at or near onset

•   Risk factors

o   Cortical involvement

•   Seizure occurrence does not affect prognosis

•   Continuous EEG

o   Shows electrographic seizures in ~30% of patients

•   Prophylactic anti-convulsants

o   Studies suggest they DO NOT reduce mortality

o   Do not reduce the incidence of long term seizures

•   Epilepsy develops in ~10% of pateints

o   Risk factors include:

-   Cortical location, delayed initial seizures, stroke severity

•   Guidelines:

o   ASA

-   Continuous EEG monitoring is probably indicated in ICH patients with depressed mental status that is out of proportion to the degree of brain injury

-   Prophylactic antiseizure medication is not recommended

o   ESO – Insufficient evidence to guide decision

Stroke unit management

·         Reduced death and dependency (RR0.79) – similar to ischaemic stroke

·         Guidelines – ASA and ESO – recommended

DVT prophylaxis

•   Graduated compression stockings not useful (CLOTS)

•   Intermittent pneumatic compression effective

•   LMWH

o   Meta-analysis of 1000pts – decreased PE, no change in DVT, non-significant reduction in mortality, non-significant increase in haematoma enlargement

•   Guidelines:

o   ASA - compression stockings (short of long) not recommended, IPC recommended, LMWH may be considered in patients with lack of mobility 1-4days form onset, after documentation of cessation of bleeding.

o   ESO – compression stockings (short of long) not recommended, IPC recommended, insufficient evidence regarding anticoagulation

Steroids/Dexamethasone

•   NEJM 1987 – RCT of dexamethasone

o   No difference in mortality but significantly increased complications (Infection and glucose control)

•   Guidelines:

o   ASA – Not recommended

o   ESO – Not recommended

Treatment of fever

•   Guidelines:

o   ESO – insufficient evidence to make recommendation 

Glucose management

•   Guidelines:

o   ASA – Glucose should be monitored – both hyperglycaemia and hypoglycaemia should be avoided.

Dysphagia screening

•   Guidelines:

o   ASA – a formal dysphagia screening procedure should be performed in all patients before initiation of oral intake to reduce risk of pneumonia

Do not resuscitate orders

•   Prognostic scales are biased by the fact that many patients have been assumed to have a poor prognosis and thus the mortality, particularly for large haemorrhages, is probably overestimated. 

•   Guidelines:

o   ASA - Aggressive care early after ICH onset and postponement of new DNAR orders until at least the second full day of hospitalization is probably recommended

o   ESO – insufficient evidence to make strong recommendations

Long term management/secondary prevention

Blood Pressure:

•   Long term

-   Aim for <130/80

-   Benefit of perindopril/indapamide (regardless of initial BP)

•   Guidelines:

o   ASA – Long term BP aim <130/80mmHg

Other risk factor management

•   Alcohol consumption moderation

•   Smoking cessation

•   Illicit drug use cessation

•   Treatment of sleep apnoea

Cholesterol

•   Statin use and low cholesterol levels have been associated with increased risk of haemorrhage

•   Guidelines:

o   ASA - There are insufficient data to recommend restrictions on the use of statins in ICH patients

Restarting Anticoagulation

•   CHIRONE study (Neurology 2014) – looking at safety of restarting anticoagulants after a bleed

•   Guidelines:

o   ESO – insufficient evidence to guide decision

Rehabilitation

•   Guidelines:

o   ASA

-   it is recommended that all patients with ICH have access to multidisciplinary rehabilitation

-   Where possible, rehabilitation can be beneficial when begun as early as possible and continued in the community as part of a well-coordinated (“seamless”) program of accelerated hospital discharge and home-based resettlement to promote ongoing recovery

 

AUSTIN Guidelines

Upper limit of BP

·         Systolic < 180mmHg and Diastolic < 90mmHg

OR

·         Mean Arterial Pressure < 120mmHg

 

Lower Limit of BP

·         Systolic > 120mmHg and Diastolic > 60mmHg

OR

·         Mean Arterial Pressure > 80mmHg

Management steps

·         Usual antihypertensive medication orally

·         Early placement of NGT to deliver oral anti-hypertensive medications if patient has not been cleared to swallow

·         GTN patch

o   5mg initially

o   If not responding in an hour a further 5mg should be applied

·         IV Metoprolol

o   Use unless contraindicated by asthma, bradycardia (<55) or decompensated cardiac failure

o   2.5mg IV bolus over 3-5 mins initially; gives further 5mg bolus after 5 minutes if required.

o   Up to a total of 15mg may be used (do not give if HR<55)

·         Hydralazine (IV; 5mg bolus over 1 min, repeat in 5 mins) if no tachycardia. Bolus doses may be escalated to 10mg or even 20mg if required; interval between doses 5mins; maximal dose = 240mg

·         If these measures have not been successful transfer to ICU may be appropriate for IV sodium nitroprusside (although this is known to elevate intracranial pressure in some circumstances).

·         In patients not for Intensive Care Unit admission or while waiting for transfer:

o   Consider GTN infusion (1-100 micrograms/kg/hr)

o   Clonidine, initial dose 75 micrograms

o   Fast acting oral agents e.g. amlodipine 10mg or prazosin (0.5 mg as a test dose, then 2.5-5mg if this is required) may also be useful

·         After acute management it is appropriate to commence oral antihypertensives, usually ACE inhibitors or other agents as appropriate

 

 

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