SUBARACHNOID HEMORRHAGE

Definition
The presence of blood within the subarachnoid space.
Can occur spontaneously or after head injury. The most common sites are: Anterior
communicating artery (30%)
Posterior communicating (25%),
Middle cerebral artery (20%)
Rarer sites include internal carotid,, tip of basilar artery,, pericallosal and posterior
inferior cerebellar artery, and peri-mesencephalic.

Risk Factors:
Acquired: Smoking, alcohol, hypertension,.
Inherited: Platelet glycoprotein polymorphism, Elastin deficiency (chromosome 7q
deficiency), chromosomal deletions 1p, 2p, 11q, 14q, 22xp.

Epidemiology
Major cause is due to rupture of saccular aneurysms
Other causes are, traumatic, AVM, dissections, vasculitides, amyloid angiopathy,
illicit drugs.
According to several series, 5% of general population has saccular aneurysms at
autopsy, 30% are multiple.

Presentation
30 to 50% of presentations have a warning leak preceding 6 to 20 days of bleed
Presents as the worse headache of my life
30% of the times as a headache ipsilateral to the bleed.
Rapid release of blood with arterial pressure into ventricles may raise ICP
Meningeal symptoms if presence of blood within CSF.

Classification
There are four different classifications for subarachnoid haemorhage: Hunt-Hess
(clinical but subjective); Claassen (radiological but complex); World Federation
Neurosurgery (WFNS) and Fisher scale; among these classifications, only Fisher
and WFNS are currently in use.
The Fisher scale is a radiological classification and has been correlated to the risk of
developing cerebral vasospasm Of those patients presenting with a Fisher 3 or
higher 70 % will develop radiological vasospasm, and 30% will develop clinical
vasospasm (1)

Fisher Group
1
2
3
4

Blood on CT Scan
No subarachnoid blood seen
Localised and unilateral with clot
thickness of <1mm
Bilateral clot with clot thickness of
> 1mm
Fisher
2
or
3
with
intraparenchimal
or
intraventricular blood.

The World Federation of Neuro-Surgeons classification is a clinical classification

according to the GCS on presentation. This classification has prognostic value in
terms of neurological outcome.

WFNS
Grade 1
2
3
4
5

Clinical presentation
GCS 15 with NO motor deficit
GCS 13-14 with no motor deficit
GCS 13-14 WITH motor deficit
GCS 7-12 with or without motor deficit
GCS < 7 with or without motor deficit.

COMPLICATIONS

(a) Neurological
Early
Rebleed. Highest risk in the first 24h. Peak incidence first 6 hours.
Risk related to the amount of blood and the poor clinical presentation.
Increased ICP (secondary to hydrocephalus, cerebral swelling,
re-bleed)
Hydrocephalus (secondary to blood in CSF)
Seizures (seizures are an independent risk factor for late seizures and
a predictor of poor outcome)
Hypothalamic ischemia
Delayed
Vasospasm (symptomatic vasospasm has a 30% incidence. It is the leading
cause of disability and mortality. Presents from the 4th day to the 15th day
with a peak presentation between D7-D10). Risk factors for vasospasm
include the amount of blood on presentation (Fisher grade 3) + age < 50 years
+ hyperglycaemia.

Ischaemic stroke secondary to established cerebral vasospasm.

(b) Cardiovascular (mediated by a sympathetic storm)

Acute LV dysfunction / Cardiogenic shock / Cardiac stunning
Subendocardial ischemia with normal angiography
Takotsubo cardiomyopathy
Arrhythmias, conduction abnormalities.
(c) Respiratory
Neurogenic or cardiogenic pulmonary oedema
VAP/HAP secondary to long ICU stay
(d) Metabolic
Hyponatremia (Cerebral salt wasting or SIADH)
(e) Renal
Renal medullary washout
(f) Ophtalmological
Terson syndrome: Vitreous / aqueous haemorrhage.
Visual field defect that may be irreversible.
DIAGNOSIS

Compatible history
Compatible examination
Investigations:
- CT head non-contrast: Diagnostic sensitivities decrease with time after onset,
being at the first 12h: 95-98%; between first 12-24h: 92-95%; within first 48h: 8086%; within first 5 days: 60-75%; after first 7 days: 40-50% (2,3)
- Lumbar Puncture: Indicated in all patients with compatible symptomatology and
history with a normal CT scan; however this should NOT be performed within 9h
of the possible bleed. This interval is necessary as it allows time for bilirubin to be
formed from metabolised hemoglobin. If performed earlier it will be impossible to
distinguish true subarachnoid blood from a traumatic tap.

Xantochromic index of CSF using spectrophotometry detects

oxyhemoglobin (present in 100% of all patients with SAH, after 9h post-bleed
and remains positive for 14 days, although initial sensitivity of 95% decreases
to 70% after 4 weeks). A Net Bilirrubin Absorbance (NBA) > 0.007 with a Net
Oxyhemoglobin Absorbance (NOA) > 0.02 or alternatively, a NBA < 0.007
with adjusted NBA (for plasma bilirubin) >0.007 and low CSF proteins (<
1g/L), are currently diagnostic for SAH under national guidelines (4, 5).
Digital Subtraction Angiography may localise the aneurysm
1. If DSA negative repeat after Day 4 (especially if
perimesencephalic SAH as 10% of all SAH are non-aneurismal
due to rupture of small pial fistula or prepontine veins).
2. CT Angiogram - less sensible than DSA; However CT Perfusion
is highly sensitive and digitally subtracts interstitial blood,
improving image quality.

MRI-MRA - need an aneurysm of a diameter > 3mm

MRI more sensitive to detect subacute bleed than CT
MRI FLAIR indicated for early bleed detection. AS sensitive as
CT in early stages. More sensitive than CT for sub-acute
phases.

TREATMENT
RESUCITATION

According to usual principles; ABC.

ICU admission
Central venous and arterial monitoring mandatory.
Basic principles of management are initially aimed at blood pressure control to
prevent rebleeding until the aneurysm is secured. Management then moves to
detection and prevention of complications, particularly vasospasm.

DECREASE RISK OF REBLEEDING: it is the most common complication during

first 3 days and leads to worsen neurological outcome.
AVOID hypertension whilst the aneurisms are not secured; use beta-blockers,blockers, hydralazine.
Definitive management: Early aneurism clipping or Early aneurysm coiling (ISAT
trial Lancet 2002). Although the ISAT trial showed that coiling was safer than
clipping in chosen patients, many controversies have raise after this trial, therefore
the final therapeutic modality needs to be based in patients co-morbidities,
neurological state and aneurysmal anatomy and resources.
PREVENTION OF VASOSPASM
NIMODIPINE (Level I evidence). Nimodipine 2mg/h infusion/iv or 60mg/po/Q4h
reduces the severity of vasospasm; improves microcirculatory rheology and
improves collateral blood flow.
Other calcium antagonists have been tried however nimodipine preserves
cerebral autoregulation which is an added advantage.
Magnesium : A phase II trial in 283 patients using 64 mmol/day of magnesium
sulphate showed a risk reduction of delayed cerebral injury by 34% and reduced

poor outcome of 23%. A phase III trial aiming to recruit 1200 patients over 5
years is currently in progress.
Statins: 2 meta-analysis (JAMA 2005 and Stroke 2008) showed contradictory
results. Currently recruiting STASH trial (phase III with simvastatin) aims to
finalise end 2011 and a posterior Cochrane analysis may result in a definitive
answer (6, 7,8).
Endothelin antagonists: Clazosenthan. Preliminary results from a phase II study
(9) supported the design of a current phase III study, Conscious 2 Trial -clipped
patients (10) and Conscious 3 Trial -coiled patients (11) studies are in progress.
The aim of these phase II trials is study is to demonstrate if the use of continuous
infusion of Endothelin 1A receptor antagonists, reduce the incidence and severity
of cerebral vasospasm.

Other experimental interventions such as Intracisternal fibrinolysis, Tirilizad

administration and Intracisternal nitroprusiate are small studies that although show a
trend towards lesser vasospasm, their safety profile does not support their use.
TRIPLE H THERAPY :
An obsolete approach with demonstrated systemic complications. This strategy was
based in establishing hypervolaemia (CVP ) 6-8 off PEEP or with PEEP+5) and
hemodilution (hematocrit 0.30-0.35) in order to improve microcirculation by
decreasing viscosity and improving rheological conditions. However, many studies
have demonstrated that by submitting patients to very high fluid intake, cardiac,
renal and pulmonary iatrogenic complications lead to worse outcomes and increased
morbidity.
There is data that supports those patients who are intravascularly under filled do
worse. The goal is to maintain a euvolaemic state.
CLINICAL MONITORING
HDU /ICU admission for neurological monitoring
Transcranial Doppler monitoring daily and when there is a new neurological
defect. Sensibility 85 90% / Specificity 95-99%)
There are two different TCD criteria for vasospasm are:
An increase of daily >50cm/sec in the MCA peak velocities (this is an
advantage as it identifies those patients hat are developing vasospasm,
allowing definitive treatment.
A positive Lindergaard ratio -MCA mean velocity / ICA extracranial mean
velocity > 3 for mild to moderate spasm and >6 for severe spasm- (12).

Transcranial Color-coded or powered Doppler (TCCD) is an imaging

Modality that directly visualises the Circle of Willis allowing direct
visualisation of the vessel diameter and correction of the angle of
insonation, increasing the diagnostic sensitivity and accuracy.

Color powered Doppler

Color Coded Doppler

TREATMENT OF ASSOCIATED COMPLICATIONS:

Treatment of high intracranial pressure
Medical management as indicated (see section on TBI)
Surgical evacuation of hematoma if needed
EVD insertion for CSF drainage of hydrocephalus if present.
Treatment of hydrocephalus
EVD placement for CSF drainage
Follow up of CSF cells and gram stain Q2d to identify early infection.
Treatment of seizures
Dilantin load and maintenance dose.
There is no Level I evidence for prophylaxis in SAH however high quantity of
blood clot on presentation increases the likelihood of seizures and the presence of
seizures has been correlated to worse neurological outcome.

TREATMENT OF CEREBRAL VASOSPASM

Induced Hypertension

In the setting of a secured aneurysm only; MAP target of 90-100mmHg in

discussion with neurosurgical team

Endovascular Arterial Vasodilation

Intra-arterial vasodilatory drugs such as nimodipine, nicardipine, papaverine or
verapamil. Multiple RCT comparing these drugs with no clear benefit of one over
another.

Arterial Balloon Angioplasty: multiple studies showing extremely high

angiographic efficacy to 98-100%, however requires highly skilled staff and there
are significant risks (5-7% incidence of vessel rupture).

Likely better option is a combined approach of balloon angioplasty (dilation of

proximal segments of the vessel) with injection of papaverine (good for distal
vasodilation of territories where balloon can not reach).

KEY POINTS
1) Subarachnoid haemorrhage is a leading cause of mortality and neurological
disability, requiring early definitive management.
2) Neurological observation and daily Transcranial Doppler have shown to
achieve early detection of cerebral vasospasm, facilitating early rescue
management.
3) Preventive treatment with Statins, Clazosenthan and Magnesium are
currently subjected to multicenter RCT, results of which may offer new
evidence based therapeutic options.

QUESTIONS
Q1---A Fisher 3 SAH implies hat:
a) Blood is present unilaterally with a clot of > 1mm thickness
b) Blood is present bilaterally
c) The clot size is > 1mm thickness
d) B and c are correct
e) None of the above is correct
Q2---Among the several classifications of SAH
a) The Hunt Hess classification is currently useful and has prognostic
value
b) Hunt Hess classification is useful but Claarsen classification is obsolete
c) The WFNS has radiological prognostication value

d)
e)

The Fisher classification has clinical prognostication value

None of the above

Q3---The most common position for aneurysmal SAH is:

a) The Internal carotid artery
b) The Anterior Communicating artery
c) The Middle Cerebral Artery
d) The Posterior Communicating artery
e) The Tip of the Basilar artery
Q4---In the Initial management of SAH
a) Inducing prophylactic hypertension reduces severity of vasospasm
b) The Triple H strategy is no longer recommended
c) Hypovolemia worsens vasospasm
d) Nimodipine is the only level I evidence based strategy in the
management of SAH
e) Options b, c and d, are correct
Q5---With respect to Transcranial Doppler (TCD):
a) Despite new modalities TCD shows a very low diagnostic sensitivity.
b) TCD only shows vasospasm once this is established, being of no use
as preventive technique
c) The subjectivity of TCD cannot be minimised regardless of technical
improvements
d) An increase of daily > 50cm/sec in mean velocities is a criteria for
cerebral vasospasm
e) None of he above is correct.

Answers:
1-d
2-e
3-b
4-e
5-e

References
(1)- Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl
J Med 2006; 354(4):387-396.

(2)- Anderson Glenn B, Ashforth R, et al. CT Angiography for the detection of

cerebral vasospasm in Patients with acute subarachnoid hemorrhage. AJNR Am. J.
Neuroradiol 2000 june, 21: 1011-1015.
(3)- Rordorf G, Koroshetz WJ, Copen WA et al. Diffusion- and perfusion-weighted
imaging in vasospasm after subarachnoid hemorrhage. Stroke 1999; 30(3):599-605.

(4)- Beetham R, Fahie-Wilson MN, Holbrook I et al. CSF spectrophotometry in the

diagnosis of subarachnoid haemorrhage. J Clin Pathol 2002; 55(6):479-480.
(5)- Watson ID, Beetham R, Keir G et al. Cerebrospinal fluid spectrophotometry of
bilirubin, not the Xanthochromic Index, for the detection of CT-negative subarachnoid haemorrhage. J Clin Neurosci 2007; 14(6):608-609.
(6)- Sillberg VAH, Wells GA, Perry JJ. Do statins improve outcomes and reduce the
incidence of vasospasm after aneurysmal subarachnoid hemorrhage: a metaanalysis. Stroke. 2008; 39: 26222626.
(7)- Vergouwen MDI, de Haan RJ, Vermeulen M, Roos Y. Effect of statin treatment
on vasospasm, delayed cerebral ischemia, and functional outcome in patients with
aneurysmal subarachnoid hemorrhagea systematic review and meta-analysis
update. Stroke. e47e52.
(8)- STASH Trial Group. Simvastatin in Aneurysmal Subarachnoid Haemorrhage
(STASH) trial. Available at: www.strokecenter.org/trials/TrialDetail.aspx?tid=930.
Accessed September 18, 2009.
(9)- Vajkoczy P, Meyer B, Weidauer S et al. Clazosentan (AXV-034343), a selective
endothelin A receptor antagonist, in the prevention of cerebral vasospasm following
severe aneurysmal subarachnoid hemorrhage: results of a randomized, doubleblind, placebo-controlled, multicenter phase IIa study. J Neurosurg 2005; 103(1):917.
(10)-ClinicalTrials.gov

Study Id : AC-054-301

(11)- ClinicalTrials.gov

identifier: NCT00940095

(12)- Lindegaard KF, Nornes H, Bakke SJ, Sorteberg W, Nakstad P. Cerebral

Vasospasm after subarachnoid hemorrhage investigated by means of transcranial
Doppler ultrasound. Acta Neurochir Suppl (Wien). 1988;42:81-4