Subarachnoid Haemorrhage (SAH)

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Obstructive Hydrocephalus
Foramina of Monro
Third Ventricle
Aqueduct of Sylvius
Fourth ventricle
Basilar
Communicating Hydrocephalus
  • Arachnoid granuloma dysfunction:
    • Post-infectious (meningitis / ventriculitis)
    • Post-haemorrhagic
  • Normal pressure hydrocephalus
  • Neoplasm
  • Haemorrhage
  • Neoplasm
  • Aneurysm
  • Arachnoid cyst
  • Infection
  • Haemorrhage
  • Aqueductal stenosis
  • Arnold-Chiari malformation
  • Neoplasm
  • Infection
  • Haemorrhage
  • Arnold-Chiari malformation
  • Neoplasm
  • Dandy-Walker cyst
  • Haemorrhage
  • Arnold-Chiari malformation

Introduction & Definition

What is a subarachnoid haemorrhage?

  • Subarachnoid haemorrhage (SAH) is the presence of blood in the subarachnoid space, between the pia and arachnoid dural membranes
  • Approximately 5% of all cerebrovascular events in the United Kingdom are the result of a SAH
  • Symptoms and signs include the classical ‘thunderclap’ headache, focal neurological signs, reduced GCS, and signs of meningism
  • It is associated with a high disability rate and mortality

Epidemiology, Clinical Course & Prognosis

How common is subarachnoid haemorrhage and who is affected?

  • Accounts for 5% of strokes in the UK
  • Incidence of 9 per 100,000 adults per year
  • More common in:
    • Women
    • Older age with a peak around 50 years
  • Aneurysms account for about 85% of spontaneous SAH

What is the prognosis for people with subarachnoid haemorrhage (SAH)?

  • Mortality rates currently 35-50% (incidence varies highly in studies)
  • Of those that die:
    • ~15% die prior to reaching hospital
    • 60% die within first 24 hours
    • 19% die within 1 week
    • 6% die within 3 weeks
    • 1% die later than 3 weeks
  • High long term morbidity for survivors:
    • ~ 20-30% will be dependent on carers
    • Up to half have cognitive impairment sufficient to affect quality-of-life
  • Prognosis worsens with increasing severity grade (Glasgow outcome scale 1-3 or modified Rankin scale 4-6):

WFNS (World Federation of Neurosurgical Societies) Grade

I
II
III
IV
V

Proportion with Bad Outcome

14.8%
29.4%
52.6%
58.3%
92.7%

Figures from AHA Guidance and ESO Guidance

Which factors predict a poor prognosis in subarachnoid haemorrhage (SAH)?

Patient Factors
  • Old age
  • Co-morbidities
  • Smoking
  • Past SAH
SAH Factors
  • High grade
  • Blood > 1mm thick on CT
  • Seizures
  • Cerebral oedema
  • Basilar artery aneurysm
  • Symptomatic vasospasm
  • Complications
Modifiable Illness Factors
  • Fever
  • Hyperglycaemia
  • Anaemia
  • Sepsis
  • Treatment at non-specialist centre

Pathophysiology

What are the underlying pathophysiological mechanisms in pancreatitis?

  • When an aneurysm ruptures:
    • Blood pushes into the subarachnoid space at arterial pressure
    • Intracranial pressure equalizes across the rupture site and stops the bleeding
    • Thrombus formation at the bleeding site.
  • Physical damage due to bleeding and mass effect
  • Early brain injury occurs due to:
    • Raised intracranial pressure
    • Decreased cerebral blood flow
  • Complex pathological process ensues characterised by:
    • Microthrombosis, oedema, blood-brain-barrier disruption and inflammation
    • Results in apoptosis, necrosis and cell death
  • Leads to global cerebral ischaemia and infarction
  • Sympathetic activation produces systemic manifestations
Pathophysiology leading to brain injury in subarachnoid haemorrhage (SAH)

Aetiology

  •  

What are the causes of subarachnoid haemorrhage (SAH)?

What are the risk factors for developing a subarachnoid haemorrhage (SAH)?

Individual Factors
  • Female gender
  • Age (peak incidence 40-60)
  • Previous aneurysm or SAH
  • Family history
  • Smoking
  • OCP
  • Alcohol abuse
Parenchymal
  • Hypertension:
    • Atherosclerotic disease
    • Cocaine or sympathomimetic use
  • Connective tissue disorders:
    • Marfan's syndrome
    • Ehlers-Danlos syndrome
    • Vasculitides
    • Alpha 1 anti-trypsin deficiency
  • Polycystic kidney disease
  • Coarctation of the aorta
  • Fibromuscular dysplasia
  • Neurofibromatosis

Cerebral Aneurysms

What are the different forms of cerebral aneurysms that occur?

  • An aneurysm is an abnormal local dilatation in the wall of a blood vessel, usually an artery, due to a defect, disease or injury
  • Morphological forms include:
Saccular
(Berry)
Fusiform
Mycotic
Dissecting
  • The most common form
  • Mainly occurs at the bifurcation of intracranial arteries
  • Results from local medial degenerations following haemodynamic-induced stress on the wall between the two exiting branches
  • Size varies from a few millimetres to several centimetres - those >2.5 cm are termed ‘giant’ aneurysms
  • Most commonly seen in the carotid and basilar artery
  • Found in older patients
  • Caused by unusual and excessive atherosclerotic breakdown of the intima
  • Rarely lead to rupture
  • Weakening of the vessel wall due to infection
  • Occur secondary to haematogenous spread (e.g. bacterial endocarditis)
  • Accumulation of blood within the wall of the vessel between the intima and the elastic lamina
  • Can arise spontaneously or following trauma
  • Also found in underlying vasculopathy, usually within the vertebral artery

Where in the cerebral circulation do saccular aneurysms occur?

Common sites of saccular (berry) aneurysms in the cerebral circulation

Presentation

  •  

What are the symptoms & signs of subarachnoid haemorrhage (SAH)?

Symptoms
  • Sudden onset headache (70-80%):
    • 'Worst ever' or 'thunderclap' in nature
    • Occipital location is classic
    • Sentinel headache in 40%
  • Nausea and vomiting (77%)
Signs
  • Fluctuating / loss of consciousness (53%)
  • Signs of meningism (35%):
    • Neck stiffness
    • Photophobia
    • Kernig’s sign
  • Seizures (10-40%)
  • Focal neurological signs
  • Ophthalmic signs:
    • Sub-hyaloid retinal haemorrhage
    • Papilloedema
  • Pyrexia

Severity Grading

How can subarachnoid haemorrhage be graded?


Grade 1
Grade 2
Grade 3
Grade 4
Grade 5
Clinical
WFNS (World Federation of Neurosurgical Societies)
GCS score of 15 without focal deficit
GCS score of 13 or 14 without focal deficit
GCS score of 13 or 14 with focal deficit
GCS score of 7-12
GCS score of 3-6
Hunt & Hess
Asymptomatic or minimal headache and slight neck stiffness
Moderate to severe headache and neck stiffness
No neurologic deficit except cranial nerve palsy
Lethargy or confusion
Mild neurological deficit
Stuporous
More severe neurological defecit
Possibly early decerebrate rigidity and vegetative disturbances
Deep coma
Decerebrate rigidity and posturing
Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage (PAASH)
GCS 15
GCS 11–14
GCS 8–10
GCS 4–7
GCS 3
Radiological
Fisher
No SAH detected
Diffuse or vertical layer of subarachnoid blood <1mm thick
Localized clot and/or vertical layer within the subarachnoid space >1mm thick
Intracerebral hemorrhage (ICH) or intraventricular hemorrhage (IVH) with diffuse or no SAH

Why are severity grading scores used in subarachnoid haemorrhage?

  • The severity of initial clinical presentation is the strongest prognostic indicator in aSAH
  • Multiple clinical scales have been validated to predict the likelihood of a poor outcome (Glasgow outcome scale 1–3 or modified Rankin score 4–6) following subarachnoid haemorrhage:
Grade
I
II
III
IV
V
Proportion with Bad Outcome
WFNS (World Federation of Neurosurgical Societies)
14.8%
29.4%
52.6%
58.3%
92.7%
PAASH (Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage)
14.8%
41.3%
74.4%
84.7%
93.9%
  • The Fisher radiological scale has been used to predict the incidence of vasospasm following subarachnoid haemorrhage:
Grade
I
II
III
IV
Proportion with Vasospasm
Fisher
21%
25%
37%
31%

Work-Up Summary

How do you work up the patient with suspected subarachnoid haemorrhage (SAH)?

To Determine Diagnosis
  • CT head:
    • Detects the presence of subarachnoid blood
    • Highly sensitive on day 1 (>95%) but reduced thereafter (50% on day 5)
  • MRI an alternative though not readily available at most centres
  • LP:
    • Detects presence of xanthochromia
    • Should be performed >12 hours after symptom onset if CT non-diagnostic
To Assess Severity / Prognosis
  • Graded using clinical severity scale:
    • World Federation of Neurosurgeons (WFNS)
    • Prognosis on Admission of Aneurysmal Subarachnoid Hemorrhage (PAASH)
    • Hunt & Hess
To Determine Aetiology
  • CTA: assesses vascular anatomy
  • Digital subtraction cerebral angiography (DSA):
    • Remains the gold standard
    • Allows intervention
  • MRI: mostly used for detection of AVM
  • Screen for vasculitis and amyloidosis
To Assess for Complications
  • To assess for cardiac dysfunction:
    • ECG - peaked T waves, ST depression, prolonged QT, arrhythmias
    • Echo - neurogenic cardiomyopathy, regional wall motion abnormalities
    • Troponin
    • Pro-BNP
  • To assess for metabolic dysfunction:
    • Plasma and urinary sodium / osmolality
    • Urine output monitoring
  • To assess for respiratory dysfunction:
    • CXR - pulmonary oedema
    • ABG

Imaging Investigations

What are the signs of subarachnoid haemorrhage (SAH) on CT head?

  •  
  • Diagnosis is made by the appearance of hyperdense blood in the subarachnoid space on non-contrast CT
  • This may be widely distributed or more localised, which helps aid the site of a ruptured aneurysm:
Widely Distributed
  • Within the basal cisterns, Sylvian and interhemispheric fissures
  • Result classical "star sign" distribution with blood distributed around 'circle of Willi's and along basal vessels.
  • Within the ventricular system
  • Over the cortical sulci
Locally Distributed
  • Sylvian fissure – suggests middle cerebral artery (MCA) aneurysm
  • Interhemispheric fissure – suggests anterior communicating artery (ACA)aneurysm
  • Perimesenchephalic - restricted to the interpeduncular region and not extending into the lateral Sylvian or interhemispheric fissures
  • Usually not associated with an aneurysm but basilar aneurysms must be excluded





How sensitive is CT in diagnosing subarachnoid haemorrhage?

  •  
  • Sensitivity depends upon:
    • The time between initial headache and scan
    • Extent of the bleeding
  • When performed during the first 24 -hours it has a sensitivity of 95%

Other than diagnosis what else may CT be useful for in subarachnoid haemorrhage?

  • Identification of aetiology:
    • Aneurysm (CT angiogram)
    • A-V malformation (CT angiogram)
    • Tumour
  • Identification of complications:
    • Hydrocephalus
    • Intracerebral haematoma
    • Vasospasm (CT angiogram)
    • Cerebral ischaemia

Other than CT which imaging modalities may be useful in subarachnoid haemorrhage?

MRI scan
CT/MR angiography
Digital subtraction angiography
Transcranial Doppler
  • May be more sensitive than CT for diagnosis when performed later after presentation
  • Useful in detecting spinal A-V malformations if suspected as cause of SAH (pain beginning in back or neck / features of cord compression)
  • Non-invasive techniques used to identify intracranial aneurysms
    • Can detect up to 95%
    • May miss those <3mm in diameter
  • Can be used to plan treatment appropriate treatment
  • Can be used to detect cerebral vasospasm
  • Invasive investigation with angiogram of four main cerebral vessels combined with computer cropping of unwanted data
  • Performed in patients with a negative CTA or MRA or where further clarification is needed of the vessels or aneurysm
  • Can be used to detect cerebral vasospasm
  • Useful in detection of cerebral vasospasm as a complication of subarachnoid haemorrhage
  • Identified by significant in increase in flow velocity within an intracranial vessel

Laboratory Investigations

What is the role of lumbar puncture is the diagnosis of subarachnoid haemorrhage (SAH)?

  • Lumbar puncture can be used to diagnose subarachnoid haemorrhage in the setting of a clinically suspected SAH but negative or indeterminant CT / MRI
  • It should be performed >6-12 hours after initial presentation:
    • Allows the presence of xanthochromia to develop
    • Prior to this may be difficult to differentiate SAH from a ‘traumatic tap’

What are the characteristic CSF findings of subarachnoid haemorrhage? How do they compare with that of a ‘traumatic tap’?

Opening Pressure (cm/H2O)
Appearance
RBC (per mm3)
WCC (per mm3)
Protein (g/L)
Glucose-Serum Ratio
Xanthochromia
Normal
5-20
Clear
<5
<3
0.2-0.4
0.5-0.66
(2.5-3.5 mmol/L)
-
Subarachnoid Haemorrhage
May be Elevated (60% of cases)
Grossly bloody to clear
Elevated
(usually uniform in all tubes)
Elevated
(can corrected eby subtracting 1 per 1000 RBCs)
Elevated
(can corrected by subtracting 10mg/L for every 1000 RBCs/mm3)
Normal
Typically present if duration over 2-12 hours
Traumatic Tap
Normal
Grossly bloody or clear
Elevated
(typically varies from tube to tube, being greatest in Tube #1)
Elevated
(can corrected by subtracting 1 per 1000 RBCs)
Elevated
(can corrected by subtracting 10mg/L for every 1000 RBCs/mm3)
Normal
Absent
(unless CSF protein >150 mg/dl or severe jaundice)

Clinical Investigations

What are the ECG changes are seen in subarachnoid haemorrhage (SAH)?

Morphological Changes
  • High R waves (19%)
  • ST depression (15%)
  • T-wave abnormalities (32%)
  • Large U waves (47%)
  • Prolonged QTc (23%)
Arrhythmias
  • Sinus tachycardia
  • Sinus bradycardia
  • Supraventricular arrhythmias
  • Sinoatrial blocks
  • Ventricular arrhythmias

Management Summary

How do you manage a patient with subarachnoid haemorrhage (SAH)?

Key Principles

  • Secure the airway if obtunded
  • Instigate neuroprotective measures
  • Manage hypertension to prevent rebleeding whilst maintaining CPP
  • Secure the aneurysm early
  • Monitor for and manage complications
Resuscitation & Supportive Care
  • Consider need for intubation:
    • Intubation if not maintaining airway
    • May require semi-elective intubation if not protecting adequately or for neuroprotective measures
    • Tape tube in position
  • Manage hypertension / hypotension
    • Until aneurysm secured target systolic blood pressure <180mmHg-160mmHg (ESO/AHA)
    • If required use a titratable IV antihypertensive and invasive arterial monitoring
    • Maintain MAP >90mmHg (ESO)
  • Manage arrhythmias
  • Manage seizures with benzodiazepines, phenytoin and levetiracetam
  • Instigate appropriate neuroprotective measures:
    • Maintain CO2 4.5-6.0 kPa, pO2 >10
    • Sit up, avoid neck lines
    • Analgesics, laxatives, antiemetics to reduce ICP
  • Maintain glucose 6-10mmol and temperature <37.5
  • Careful management of fluids:
    • Urinary catheter and fluid balance monitoring for all patients
    • Aim for euvolaemia
  • Reverse any coagulopathy
  • DVT prophylaxis:
    • Mechanical methods until aneurysm secured
    • LMWH >12 after surgical clipping
Specific Management

Secure the aneurysm:

  • Should be secured within 72 hours
  • Multi-disciplinary decision based on patient and aneurysm characteristics
    • Coiling: first line as better functional outcomes at one year
    • Clipping: for those not amenable to coiling (anatomically and location)
  • Consider tranexamic acid if likely to be a delay in securing aneurysm

Manage complications:

  • Prevention and management of vasospasm:
    • Physical: Targeted hypertensive therapy, maintain euvolaemia
    • Pharmacological: nimodipine prevent hypomagnesemia:
      • Start immediate nimodipine 60mg 4 hourly NG/PO
    • Interventional: Intra-arterial stenting, intra-arterial nimodipine
  • Treat hydrocephalus
    • Emergency EVD placement if obtunded
    • Consider osmotic therapy as temporising measure
Referral & Deposition
  • Needs urgent discussion with neurosurgical teamBest managed at high volume centres with neurosurgical and IR services
  • Operating theatre if urgent EVD placement required
  • ICU if intubated or Neuro HDU prior to securing aneurysm
  • Consider need for cerebral oxygen / pressure monitoring

Medical & Supportive Management

What are the indications for intubation in SAH?

  • GCS <8
  • Drop in GCS >2 points
  • Optimization of ventilation
  • Seizures
  • To facilitate transfer to neurosurgical centre
  • Uncontrolled hypertension in the presence of an unsecured aneurysm

How should blood pressure be managed following subarachnoid haemorrhage?

Unsecured Aneurysm
(Before clipping /coiling)
Secured Aneurysm
(After clipping /coiling)
  • Systolic pressure should be maintained <180-160 mmHg (ESO / AHA guidance) to reduce risk of rebleeding
  • May be achieved with nimodipine and analgesia
  • If required a titratable agent should be used (e.g. labetalol, nitrates, hydralazine)
  • Labetalol 5-10mg bolus and infusion may be first line
  • MAP >90 mmHg should be targeted to maintain cerebral perfusion
  • Targets are individualised to the patient depending upon the clinical picture
  • Hypertension does generally not require treatment unless concomitant cardiac myocardial ischaemia / dysfunction
  • MAP >90 mmHg should be targeted to maintain cerebral perfusion
  • Higher MAP targets (induced hypertension) may be required in the setting of cerebral ischaemia

What is the role of nimodipine in prevention and management of vasospasm and DCI?

  • The calcium-channel blocker nimodipine, the only drug known to improve outcomes following subarachnoid haemorrhage:
  • Acts as a calcium channel antagonist:
    • Blocks the slow calcium channel of vascular smooth muscle and cardiac muscle
    • High lipid solubility of nimodipine allows it to cross the BBB offering a more cerebral selective effect over other calcium channel blockers
  • Recommended to be administered orally to all patients from the time of presentation:
    • Should be continued for 21 days
    • Administered at a dose of 60mg PO every 4 hours
    • May be reduced to 30mg every 2 hours in the event of hypotension
    • In case oral administration is not possible nimodipine can be administered IV

Should tranexamic acid be given in patients with subarachnoid haemorrhage (SAH) to prevent re-bleeding?

  • No evidence that tranexamic acid can improve outcomes
  • Some studies have shown reduced rates of rebleeding (2% vs 11%) though this was associated with increased risks of deep vein thrombosis
  • May be reasonable to give short-term therapy if a delay in securing the aneurysm is expected and there are no compelling medical contraindications

How should VTE prophylaxis be managed in patients with subarachnoid haemorrhage?

  • Prior to occlusion of the aneurysm thromboprophylaxis should be with mechanical means only (pneumatic devices and/or compression stockings)
  • After occlusion of the aneurysm LMWH may be started:
    • Immediately after endovascular coiling
    • Not earlier than 12 hours after surgical clipping (decision should be made in conjunction with neurosurgical team)

Aneurysm Management

How can a ruptured aneurysm be secured following subarachnoid haemorrhage (SAH)?

Coiling
Clipping
Stenting
Trapping
  • Endovascular treatment which involves navigating a catheter to the aneurysm site under fluoroscopic guidance
  • A microcatheter is then advanced into the aneurysm sac and metal coils are deposited
  • Coils arrest blood flow and induces thrombus formation which occludes aneurysm
  • The coils are kept within the aneurysm sac an out of the vessel lumen by either a stent (stent-assisted coiling) or a balloon (balloon-assisted coiling)
  • Requires a craniotomy and exploration of the subarachnoid spaces around the cerebral arteries
  • Once the aneurysm is exposed, a single or multiple titanium clips are placed across the neck of the aneurysm
  • Results in mechanical occlusion the sac at its neck while preserving blood flow through the vessel lumen
  • Endovascular insertion of stents may be utilised in certain situations
  • Flow-diverting stents are a new generation of stents designed to occlude the aneurysm by isolating the sac from the circulation - useful in fusiform and wide neck aneurysms
  • Simple stenting is often used to treat dissecting aneurysms of the cerebral vessels
  • Used for giant aneurysms (>25mm diameter) where other methods have failed
  • The aneurysm is trapped by two clips applied to the vessel either side
  • A bypass graft is then used to provide blood flow to the distal vessels

When should an aneurysm be secured following subarachnoid haemorrhage (SAH)?

  • Securing of the aneurysm should be performed as early as is feasible in the majority of patients to reduce rebleeding
  • The aim should be to intervene within 72 hours of first symptoms

How is it decided whether an aneurysm should be managed by coiling or cilpping?

  • Should be an MDT decision made by experienced surgeons and radiologists
  • Decision based on:
    • Characteristics of the patient:
      • Surgical approach favoured in younger age and in presence of space occupying ICH
      • Radiological approach favoured in older age, poor grade SAH and in presence of significant co-morbidities
    • Characteristics of the aneurysm:
      • Surgical approach favoured with:
        • Middle cerebral artery aneurysm
        • Wide aneurysm neck
        • Arterial branches exiting directly out of the aneurysmal sac
      • Radiological approach favoured with:
        • Posterior location
        • Small aneurysm neck
      • Technical skills and availability
  • Coiling is the preferred treatment where it is judged that the aneurysm is amenable to either coiling or clipping

What are the advantages and disadvantages of using clipping or coiling in the management of a ruptured aneurysm following subarachnoid haemorrhage (SAH)?


Coiling
Clipping
Advantages
  • Increased survival, decreased disability and decreased morbidity (ISAT trial)
  • Lower vasospasm risk
  • Less invasive
  • Lower cost
  • Can co-administer therapies to treat vasospasm
  • Better for posterior fossa aneurysms
  • Has greater experience base (original technique)
  • More aneurysms are amenable to clipping
  • Best for wide-necked aneurysms (low neck to fundus ratio), giant aneurysms and distal segment lesions
  • Able to suction blood and manage procedural complications
  • Best for young patients to ensure non-recurrence
Disadvantages
  • Requires specialist interventional radiologist
  • Not able to manage complications
  • Requires anticoagulation
  • Expensive equipment
  • Risk of rupture
  • Not all aneurysms can be coiled
  • Requires GA and craniotomy
  • Higher cost

What is the evidence to support the use of clipping or coiling in the management of a ruptured aneurysm following subarachnoid haemorrhage (SAH)?

  • The largest trial comparing surgical and endovascular management of ruptured aneurysms is the ISAT trial:

RCT: ISAT

Molyneux et al
Lancet (2002)

View Paper

Intervention

  • Endovascular coiling vs. surgical clipping for acute ruptured intracranial aneurysm

Population

  • 2143 with ruptured intracranial aneurysms

Conclusion

  • Risk of death or dependence at 1 year (primary outcome) was significantly less common in those that received endovascular coiling (23.5% vs 30.9%, ARR 6-9%, 95%CI 3.6 - 11.2%)
  • Longer term follow-up from this trial has raised concerns about delayed re-bleeding and higher need for retreatment

Complications Overview

What are the complications after subarachnoid haemorrhage?

Neurological
  • Vasospasm and cerebral ischaemia
  • Hydrocephalus
  • Re-bleeding
  • Seizures
  • Cerebral oedema and raised ICP
  • Focal neurology due to haemorrhage
Systemic
Metabolic
  • Fever
  • Hyperglycemia
  • Disorders of sodium balance (50-60%):
    • Syndrome of inappropriate antidiuretic hormone secretion
    • Cerebral salt wasting syndrome
    • Diabetes insipidus
  • Hypokalaemia
  • Hypomagnesaemia
Respiratory
  • Neurogenic / cardiogenic pulmonary oedema
  • Pneumonia
  • ARDS
  • Atelectasis
Cardiovascular
  • Neurogenic stunned myocardium syndrome (15%) - catecholamine induced, similar to Takutosubo's:
    • LV dysfunction (systolic and diastolic)
    • Regional wall motion abnormalities
    • Cardiogenic shock
    • ECG changes and troponin rise
  • Arrhythmias
  • Venous thromboembolism

What are the causes of neurological deterioration (neurological complications) in subarachnoid haemorrhage?

Seizures

6-18%

Re-bleeding

<72 hours
5-10%

Hydrocephalus

Day 1-3
20-30%

Vasospasm & Delayed Cerebral Ischaemia

Day 4-14
70%

Systemic Conditions
  • May indicate a re-bleed and should be treated aggressively
  • Perform an EEG in patients with neurological deterioration or those who fail to recover to exclude non-convulsive status epilepticus (NCSE)
  • Routine seizure prophylaxis is not recommended
  • Highest risk immediately following primary bleed, and in patients with high clinical grade or larger aneurysms
  • May occur following rapid reduction in ICP, e.g. following EVD insertion in a patient with an unsecured aneurysm
  • Unlikely to occur following securing of the aneurysm
  • More common in those with high clinical grade or large amounts of sub-arachnoid and/or intraventricular blood
  • Should be suspected in patients with a neurological deterioration within the first three days (although 25% will present later)
  • CT is diagnostic and treatment is with placement of an EVD
  • Delayed cerebral ischaemia is a neurological deficit that lasts > 1 hour that is due to ischaemia and has no other cause
  • Vasospasm is thought to be the cause of most cases and occurs between day 4 and 14 (although maximally between day 7 and 10) and lasts for several days.
  • Only about half of all episodes are associated with neurological deficit.
  • Transcranial Doppler ultrasonography can be used to detect vasospasm by measuring flow velocities in the cerebral arteries
  • Neurological decline can also occur secondary to systemic complications:
    • Hypoxia
    • Hypotension
    • Pyrexia and infection
    • Electrolyte disturbance

Vasospasm & Delayed Cerebral Ischaemia

What is vasospasm?

  • Vasospasm is narrowing of cerebral vessels following subarachnoid haemorrhage (SAH), visible angiographically or via transcranial doppler
  • It occurs in 60-70% of patients with SAH
  • Typically starts at day 3 to 4 days after aneurysm rupture, peaking at day 7 to 10 days, and resolves by 14 to 21 days
  • It is more common in smokers and patients with high-grade SAH

What is delayed cerebral ischaemia (DCI)?

  • Defined as neurological deterioration related to ischaemia (unrelated to treatment of the aneurysm) that persists for one hour and has no other cause
  • The clinical syndrome is of focal neurologic deficits
  • Approximately 25% of patients develop clinical evidence of delayed ischaemia/infarction; of these 25% die as a result. About 10% of the survivors remain permanently disabled

What is the relationship between vasospasm and delayed cerebral ischaemia (DCI)?

  • Despite a general belief that vasospasm causes delayed cerebral ischemia, there is significant evidence to suggest other factors contributes to pathogenesis:
    • Less than half of patients with proven vasospasm develop DCI
    • DCI does not consistently occur in the territory supplied by vessels undergoing vasospasm and has been reported in its absence
  • Despite this many strategies aimed at treating DCI are developed with the view that vasospasm is the main cause

What is the role of nimodipine in prevention and management of vasospasm and DCI?

  • The calcium-channel blocker nimodipine, the only drug known to improve outcomes following subarachnoid haemorrhage:
  • Acts as a calcium channel antagonist:
    • Blocks the slow calcium channel of vascular smooth muscle and cardiac muscle
    • High lipid solubility of nimodipine allows it to cross the BBB offering a more cerebral selective effect over other calcium channel blockers
  • Recommended to be administered orally to all patients from the time of presentation:
    • Should be continued for 21 days
    • Administered at a dose of 60mg PO every 4 hours
    • May be reduced to 30mg every 2 hours in the event of hypotension
    • In case oral administration is not possible nimodipine can be administered IV

What is the evidence for the use of other medical therapies in the prevention and management of vasospasm?

Magnesium
Statins

How do you diagnose vasospasm and DCI?

Transcranial Doppler
Digital subtraction Angiography
CT Angiography
CT Perfusion
  • A non-invasive imaging technique that measures flow velocity in the basal cerebral arteries
  • Offers moderate sensitivity but is highly specific
  • Vasospasm is identified by increased flow velocity within a vessel:
    • Flow velocity >120 cm/s
    • Flow velocities increase >50 cm/s/day from baseline in 2 vessels
    • Lindegaard ratio >3 (ratio of flow velocity in ipsilateral MCA and internal carotid artery)
  • Invasive investigation requiring specialist neuroradiology staff
  • The gold standard but is rarely used with increasing availability of CT
  • Non-invasive investigation widely used to diagnose vasospasm
  • Highly specific but may overestimate the degree of spasm
  • Can be used to identify regions of possible brain ischemia in patients who have a new neurologic deficit

How do you manage vasospasm and delayed cerebral ischaemia?

Physical

Induced Hypertension

  • Improves CBF (possibly more in areas of vasospasm) with associated clinical improvement
  • Noradrenaline safe and usually first line - no risk of increased vasospasm
  • No evidence of new rupture risk
  • No clear BP target or duration:
    • Evidence limited
    • Used on clinical grounds assessing response to therapy or reductions
  • Limited value when infarct established

Euvolaemia

  • Optimises cerebral blood flow
  • Cardiac output monitoring may be useful to guide fluid therapy
  • Hypervolaemia associated with increased complications
Pharmacological

Nimodipine

  • Standard dose is 60mg 4 hourly
  • May cause hypotension - if so reduce dose to 30mg 2 hourly
  • Given for 21 days
  • Not used for traumatic SAH

Magnesium

  • No proven benefit
  • Maintenance within normal levels usually advocated
Endovascular

Angiography & stents / intraarterial vasodilators

  • Lower risk of DCI
  • Higher risk of vessel rupture
  • No change in all cause mortality - role unclear
  • Consider in those refractory to medical therapy

How should patient haemodynamics be managed in the setting of delayed cerebral ischaemia (DCI)?

  • Classic management is of Triple H therapy (hypertension / hypervoaemia / haemodilution:
    • No longer advocated given lack of evidence and potential for harm
    • Hypervolaemia: Advocated to improve cerebral blood flow. Not shown to improve outcomes but associated with increased rate of complications
    • Haemodilution: Theoretically improves rheology but decreases oxygen delivery
  • Induced hypertension recommended in the setting of DCI:
    • Can maintain flow in the setting of disrupted autoregulation
    • Up to 70% of ischaemic deficits may be reversed preventing infarction
    • Requires careful, invasive monitoring
    • Specific targets not clearly defined and may be individualised to the patient
    • Complications include haemorrhagic transformation, worsening oedema and myocardial infarction / dysfunction
  • Optimal haemoglobin targets not clearly defined

What is the role of endovascular therapies in treating vasospasm and DCI following subarchnoid hemorrhage?

  • May be useful in improving neurological outcome though strong evidence is lacking at present
  • Indications for use are:
    • New neurological deficit
    • Absence of cerebral infarction
    • Failure of medical therapy
    • Vasospasm on angiography
  • Options include:
    • Cerebral angioplasty: balloon dilatation of the vasospastic segment of the vessel
    • Intraarterial vasodilator therapy: infusion of an antispasmodic agent (nimodipine or papaverine)

Re-Bleeding

What is re-bleeding in subarachnoid haemorrhage (SAH)?

  • Rebleeding refers to re-rupture of a cerebral aneurysm with associated bleeding
  • The effects are often more severe than the initial bleed
  • It is associated with much higher mortality and morbidity than patients with a single aneurysm rupture
  • The risk of re-bleeding is 4-14% in the first 24 hours but remains high for up to 30 days unless the aneurysm is secured

Should tranexamic acid be given in patients with subarachnoid haemorrhage (SAH) to prevent re-bleeding?

  • No evidence that tranexamic acid can improve outcomes
  • Some studies have shown reduced rates of rebleeding (2% vs 11%) though this was associated with increased risks of deep vein thrombosis
  • May be reasonable to give short-term therapy if a delay in securing the aneurysm is expected and there are no compelling medical contraindications

Hydrocephalus

How common is hydrocephalus following subarachnoid haemorrhage?

  • Incidence of acute hydrocephalus varies widely in studies from 15 to 85%:
  • Many cases are not clinically significant
  • Chronic shunt dependent hydrocephalus occurs in 8-48% of cases

Why does hydrocephalus occur in subarachnoid haemorrhage (SAH)?

  • Hydrocephalus can be:
Obstructive
Non-obstructive
(Communicating)
Blood blocking normal CSF circulation through the subarachnoid cisterns
Blood blocking CSF reuptake by the arachnoid villi

How is hydrocephalus managed following subarachnoid haemorrhage?

  • Typically involves the placement of an EVD
  • Lumbar drainage may be used as an alternative:
    • Associated with a reduced risk of vasospasm
    • Ineffective in cases of obstructive hydrocephalus
    • Contraindicated in intraparenchymal hematoma or raised ICP due to risk of tissue shifts

Seizures

How common are seizure in subarachnoid haemorrhage?

  • Seizures occur in 6-18% of patients with subarachnoid haemorrhage
  • The majority occur before medical evaluation

Should prophylaxis be given against seizures following subarachnoid haemorrhage?

  • Lack of strong evidence to suggest use of anticonvulsants improve outcomes
  • Prophylaxis generally considered not warranted following subarachnoid
  • Some centers still consider prophylactic anticonvulsants useful in patients with risk factors for developing seizures

How should seizures be managed following subarachnoid haemorrhage?

  • Lack of strong evidence to suggest a specific anticonvulsant is optimal
  • Most commonly used drugs are phenytoin, levetiracetam, and valproic acid:
    • Choice of agent is often centre specific
    • Risks and benefits of specific agents must be carefully considered for each patient
  • Optimum duration not yet determined but long term therapy not recommended unless specific risk factors

Author

The Guidewire
Trainee in ICM & Anaesthesia

Reviewer

The Guidewire
Trainee in ICM & Anaesthesia