DynaMed Plus - Subarachnoid Hemorrhage

11/10/2018 DynaMed Plus: Subarachnoid hemorrhage
Subarachnoid hemorrhage
Overview and Recommendations
Background
Subarachnoid hemorrhage is bleeding in the cerebrospinal fluid filled compartment surrounding the
central nervous system.
Nontraumatic subarachnoid hemorrhage is due to an aneurysmal rupture in about 80% of patients.
Complications of subarachnoid hemorrhage:
More than 50% of subarachnoid hemorrhage survivors report some cognitive impairment including
problems with memory, mood, or neuropsychologic function, and about 20% of patients have global
cognitive impairment.
Symptomatic cerebral vasospasm frequently develops and typically occurs between 4 and 12 days
after subarachnoid hemorrhage and often spontaneously resolves after 21 days.
Seizures or seizure-like episodes have been reported in up to 26% of patients and most commonly
occur within 24 hours of aneurysmal subarachnoid hemorrhage.
Aneurysm rebleeding is reported in 4%-14% of patients in the first 24 hours.
Patients may develop acute hydrocephalus and some will become chronically shunt dependent.
Evaluation
Maintain a high index of suspicion in patients with sudden onset of severe headache.
The "worst headache of my life" is reported by 80% of patients.
The headache may have an extremely sudden onset reaching maximum intensity immediately
(thunderclap headache).
Headache may be the only symptom in about 40% of patients with subarachnoid hemorrhage and
may resolve in minutes to hours.
Seizure occurs in about 20% of patients within the first 24 hours of hemorrhage.
Patients may have an altered level of consciousness and may have nuchal rigidity.
An acute diagnostic workup should include a noncontrast head computed tomography (CT), and a lumbar
puncture for patients with a nondiagnostic CT scan (Strong recommendation).
About 50% of patients presenting at the first visit may be misdiagnosed, with the failure to obtain a proper
imaging study being the most common reason for misdiagnosis.
When evaluating the aneurysm, a full assessment of all cerebral vessels is required, since about 15% of
patients will have multiple aneurysms.
Management
Urgent evaluation and treatment is recommended due to the risk of rebleeding in the first 24 hours (Strong
recommendation).
The goals of treatment are to prevent rebleeding, to prevent and manage vasospasm, and to treat other
medical and neurologic complications.
Oral nimodipine should be given to all patients with aneurysmal subarachnoid hemorrhage to reduce
mortality and dependence (Strong recommendation).
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Other medications to consider include:

endothelin receptor antagonists
methylprednisolone
antiplatelet agents
tirilazad
Perform surgical clipping or endovascular coiling of a ruptured aneurysm as early as feasible in the
majority of patients to reduce the rate of rebleeding after aneurysmal subarachnoid hemorrhage (Strong
recommendation).
Early goal-directed fluid therapy may reduce delayed cerebral ischemia and improve function in patients
with poor clinical grade subarachnoid hemorrhage (Strong recommendation).
After aneurysmal subarachnoid hemorrhage, transcranial Doppler ultrasound is reasonable to monitor for
the development of arterial vasospasm (Strong recommendation).
Screening for intracranial aneurysm:
is controversial in first-degree relatives of patients with sporadic subarachnoid hemorrhage; the
slight increase in life expectancy is offset by postoperative sequelae (Weak recommendation)
is not routinely recommended for patients with autosomal dominant polycystic kidney disease
(Strong recommendation), but may be appropriate in patients > 45 years old with autosomal
dominant polycystic kidney disease
Related Summaries
Stroke (list of topics)
Stroke (acute management)
Long-term management of stroke
General Information
Description
bleeding in the cerebrospinal fluid filled compartment surrounding central nervous system, often caused
by rupture of intracranial aneurysm(2)
Also called
SAH
Types
for nontraumatic subarachnoid hemorrhage(2)

aneurysmal rupture in 80% of patients
without aneurysm in 20% of patients
Epidemiology
Who is most affected
for aneurysmal hemorrhage

incidence increases with age, with mean age of onset ≥ 50 years(1, 2)
about 1.24 times more common in females than males(1)
about 2 times more common in low-to-middle income countries than high-income countries(1)
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Incidence/Prevalence
aneurysmal hemorrhage incidence rates vary widely with world region(1, 2)

worldwide incidence about 10.5 cases per 100,000 person-years(2)
21,000-33,000 new cases annually in United States(2)
estimated 14.5 discharges per 100,000 adults annually in United states(1)
prevalence of cerebral aneurysm 1.8% in analysis of brain magnetic resonance images of 2,000 persons
(mean age 63 years) in the Netherlands (N Engl J Med 2007 Nov 1;357(18):1821), commentary can be
found in N Engl J Med 2008 Feb 21;358(8):853
incidence of subarachnoid hemorrhage per region in systematic review of 51 prospective studies
22.7 per 100,000 person-years in Japan
19.7 per 100,000 person-years in Finland
4.2 per 100,000 person-years in South and Central America
Reference - J Neurol Neurosurg Psychiatry 2007 Dec;78(12):1365 full-text
incidence of nonaneurysmal perimesencephalic subarachnoid hemorrhage 0.5 per 100,000 person-years in
prospective cohort study of adults (J Stroke Cerebrovasc Dis 2005 Nov-Dec;14(6):267 full-text)
Likely risk factors
Genetic
family history of subarachnoid hemorrhage or intracranial aneurysms in first degree relative associated
with increased risk(1, 2)
4.7% lifetime risk of subarachnoid hemorrhage in first-degree relatives of patients with
subarachnoid hemorrhage
based on study of 5,478 relatives of patients from Scotland with subarachnoid hemorrhage in
same year
absolute lifetime risk (birth to age 70 years) of subarachnoid hemorrhage
4.7% in persons with first-degree relative with subarachnoid hemorrhage
1.9% in persons with second-degree relatives with subarachnoid hemorrhage
Reference - Brain 2005 Jul;128(7):1677
risk of subarachnoid hemorrhage about 2-3 times higher in patients with first-degree relative
with subarachnoid hemorrhage
based on 1 population-based cohort study and 1 case-control study
9,367 patients admitted to hospital with subarachnoid hemorrhage in Denmark between
1977 and 1995 and 14,781 of their first-degree relatives were analyzed
18 patients with subarachnoid hemorrhage had 19 first-degree relatives develop
subarachnoid hemorrhage during 108,933 persons years follow-up
standardized incidence ratio 2.9 (95% CI 1.9-4.6) among first-degree relatives of
patients with subarachnoid hemorrhage
Reference - BMJ 2000 Jan 15;320(7228):141 full-text, commentary can be found
in BMJ 2000 May 6;320(7244):1277
5,282 patients with subarachnoid hemorrhage, 26,402 controls without subarachnoid
hemorrhage, and 130,373 first-degree relatives of cases and controls were analyzed
incidence of subarachnoid hemorrhage in 3% of patients with subarachnoid
hemorrhage vs. 1.4% of controls (odds ratio 2.2, 95% CI 1.8-2.6)
Reference - Brain 2008 Oct;131(Pt 10):2662 full-text
patients with small unruptured intracranial aneurysms plus first degree relative with intracranial
aneurysm reported to have increased risk of rupture compared to patients with similar size sporadic
unruptured intracranial aneurysms (Stroke 2009 Jun;40(6):1952)
heritable connective-tissue disorders(1, 2)
polycystic kidney disease
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Ehlers-Danlos syndrome (EDS) (type IV)

pseudoxanthoma elasticum
fibromuscular dysplasia
Modifiable risk factors
modifiable risk factors include hypertension, smoking, alcohol abuse, and sympathomimetic drug use (for
example, cocaine)(1, 2)
hypertension, smoking, and excessive alcohol intake each associated with increased risk of
based on systematic review
systematic review of 14 cohort studies and 23 case-control studies including 3,936 patients with
in analysis of cohort studies, increased risk of subarachnoid hemorrhage associated with
hypertension compared to no hypertension (risk ratio 2.5, 95% CI 2-3.1)
ever smoking compared to never smoking (risk ratio 2.2, 95% CI 1.1-4.5)
excessive alcohol intake (≥ 150 g/week) compared to no alcohol intake (risk ratio 2.1, 95% CI
1.5-2.8)
consistent results in analysis of case-controls studies
Reference - Stroke 2005 Dec;36(12):2773 full-text
consistent association between risk of subarachnoid hemorrhage and each of hypertension and
smoking in analysis of 26 prospective cohort studies with 306,620 persons from Asian or
Australasian regions (Stroke 2005 Jul;36(7):1360 full-text)
elevated blood pressure and smoking each associated with increased risk of aneurysmal
based on prospective cohort study
74,977 persons ≥ 20 years old participating in Nord-Trondelag Health (HUNT) study from 1984 to
1986 were analyzed
compared with systolic blood pressure < 130 mm Hg, increased risk of aneurysmal subarachnoid
hemorrhage with
systolic blood pressure 130-139 mm Hg (adjusted hazard ratio [HR] 2.3, 95% CI 1.4-3.8)
systolic blood pressure > 170 mm Hg (adjusted HR 3.3, 95% CI 1.7-6.3)
consistent results in analysis of diastolic blood pressure
compared with never smokers, increased risk of aneurysmal subarachnoid hemorrhage in
former smokers (adjusted HR 2.7, 95% CI 1.4-5.1)
current smokers (adjusted HR 6.1, 95% CI 3.6-10.4)
Reference - Stroke 2009 Jun;40(6):1958 full-text
current smoking associated with increased risk for aneurysmal subarachnoid hemorrhage
based on case-control study
339 patients with aneurysmal subarachnoid hemorrhage and 1,016 controls without aneurysmal
subarachnoid hemorrhage were analyzed
family history defined as having first-degree relative with brain aneurysm or subarachnoid
hemorrhage
compared to current nonsmokers with no family history, increased risk of aneurysmal subarachnoid
hemorrhage in
current smokers with family history (odds ratio [OR] 6.4, 95% CI 3.1-13.2)
current smokers no family history (OR 3.1, 95% CI 2.2-4.4)
current nonsmokers with family history (OR 2.5, 95% CI 0.9-6.9)
Reference - Neurology 2009 Jan 6;72(1):69 full-text
Other risk factors
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larger size and location in posterior circulation each associated with increased risk of rupture in
patients with unruptured intracranial aneurysm
based on prospective study of 4,060 patients with unruptured intracranial aneurysms
1,692 did not have aneurysmal repair, 1,917 had open surgery, 451 had endovascular procedures
5-year cumulative rupture rates by aneurysm size
for aneurysms in internal carotid, anterior communication, anterior cerebral, or middle
cerebral arteries
size < 7 mm - 0%
7-12 mm - 2.6%
13-24 mm - 14.5%
≥ 25 mm - 40%
for aneurysms in posterior circulation
size < 7 mm - 2.5%
7-12 mm - 14.5%
13-24 mm - 18.4%
≥ 25 mm - 50%
spontaneous rupture rates frequently ≤ risks associated with infarctions caused by surgical or
endovascular repair
larger size and location in posterior circulation each associated with significantly increased risk of
rupture in adjusted analysis
Reference - Lancet 2003 Jul 12;362(9378):103, editorial can be found in Lancet 2003 Jul
12;362(9378):90, summary can be found in Am Fam Physician 2004 Feb 15;69(4):942
risk of rupture might be 1% or less for intracranial aneurysms ≤ 5 mm in diameter
based on systematic review of observational studies
systematic review of 26 observational studies evaluating rupture and growth of intracranial
aneurysms ≤ 7 mm in diameter
range of estimated annual rupture rates of aneurysms
≤ 3 mm diameter 0%-0.4% in 7 studies
Reference - Ann Intern Med 2017 Jul 4;167(1):26
Possible risk factors

current use of combined oral contraceptives and postmenopausal period each associated with
increased risk of subarachnoid hemorrhage in women
based on systematic review of 16 observational studies
risk of subarachnoid hemorrhage
increased with current use of combined oral contraceptives (adjusted odds ratio [OR] 1.31,
95% CI 1.05-1.64) in analysis of 5 studies
increased with postmenopausal period (adjusted OR 1.29, 95% CI 1.03-1.61) in analysis of 5
studies
decreased with pregnancy, labor, or puerperium in 1 study (p < 0.05)
no association between risk of subarachnoid hemorrhage and
ever combined oral contraceptive use in analysis of 7 studies
current use of hormone replacement therapy in analysis of 6 studies
ever use of hormone replacement therapy in analysis of 3 studies
Reference - Neurology 2012 Sep 18;79(12):1230
significant legal or financial problems in past month or physical assault in past year associated with
slightly increased risk of subarachnoid hemorrhage in population-based case-control setting with 388
cases and 473 matched controls (Stroke 2010 Jun;41(6):1304 full-text)
appetite suppressants containing phenylpropanolamine associated with increased risk of symptomatic
subarachnoid or intracerebral hemorrhage in case-control study with 702 cases and 1,376 matched
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controls (N Engl J Med 2000 Dec 21;343(25):1826), editorial can be found in N Engl J Med 2000 Dec
21;343(25):1886
insufficient evidence for association between apolipoprotein E genotype and risk of ischemic stroke,
intracerebral hemorrhage, or subarachnoid hemorrhage in systematic review of 31 studies with 5,961 cases
and 17,965 controls, including 3 studies of subarachnoid hemorrhage (Stroke 2006 Feb;37(2):364 full-
text)
Factors not associated with increased risk

recent use of nonaspirin nonsteroidal anti-inflammatory drugs do not appear to be associated with
risk of intracerebral or subarachnoid hemorrhage
based on case-control study
940 patients aged 30-84 years with first nontraumatic acute hemorrhagic stroke and 940 matched
controls were analyzed
exposure to nonaspirin nonsteroidal anti-inflammatory drug (NSAID) within 14 days prior to
hemorrhagic event in 2.9% of cases vs. 2% of controls (odds ratio 1.12, 95% CI 0.77-1.65)
Reference - Stroke 2008 Mar;39(3):845 full-text
no significant association between recurrent headache and subarachnoid hemorrhage in case-control study
of 432 patients with first-ever subarachnoid hemorrhage and 473 matched controls (J Clin Neurosci 2005
Jun;12(5):534)
pregnancy, labor, and puerperium not associated with increased risk of aneurysmal subarachnoid
hemorrhage in retrospective cohort study of 244 women aged 18-42 years (Stroke 2009
Apr;40(4):1148 full-text)
Associated conditions
multiple cerebral aneurysms in about 15% of patients with aneurysmal hemorrhage(2)
Etiology and Pathogenesis

Causes
trauma (Lancet Neurol 2006 Dec;5(12):1029, Neurosurgery 2002 Feb;50(2):261)
for nontraumatic subarachnoid hemorrhage(2)
aneurysmal rupture in 80% of patients
nonaneurysmal cause
isolated perimesencephalic subarachnoid hemorrhage in 20% of patients
pretruncal nonaneurysmal subarachnoid hemorrhage hypothesized secondary to intramural
hematoma of basilar artery (Mayo Clin Proc 2000 Nov;75(11):1169)
case reports of
ginkgo biloba associated with increased bleeding time in patient with subarachnoid hemorrhage
(Lancet 1998 Jul 4;352(9121):36), commentary can be found in Lancet 1998 Oct 3;352(9134):1145
subarachnoid hemorrhage and multiple cerebral contusions following roller coaster ride (JAMA
2000 Aug 16;284(7):832)
History and Physical

History
Chief concern (CC)

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acute onset of severe headache(1, 2)

"worst headache of my life" described by 80% of patients able to give history(1)
extremely sudden onset reaching maximum intensity immediately (thunderclap headache)(1, 2)
unable to be clinically distinguished from migraine or tension-type(2)
preceded by sentinel headache in 10%-43% of patients(2)
headache may be only symptom in about 40% of patients with subarachnoid hemorrhage (SAH) and may
resolve in minutes to hours(2)
seizure in 20% of patients within first 24 hours of hemorrhage(1, 2)
atypical presentations(2)
seizure
confusional state
associated head trauma
History of present illness (HPI)
most aneurysms asymptomatic until rupture, but 15%-37% patients may have sentinel headache from
minor hemorrhage (warning leak)(1)
usually occur 2-8 weeks before SAH
sentinel headache milder than that of rupture, but may last a few days
nausea and vomiting may occur
meningismus uncommon
headache reported in 74% of patients with proven subarachnoid hemorrhage
based on retrospective chart review
109 patients with proven subarachnoid hemorrhage presented with
neurologic findings in 64%
nausea or vomiting in 77%
headache in 74%
loss of consciousness in 53% (most often altered level of consciousness)
nuchal rigidity in 35%
Reference - Ann Emerg Med 1989 Nov;18(11):1199
additional symptoms include(1, 2)
nausea
vomiting
stiff neck
photophobia
loss of consciousness
focal neurological deficits
moderate-to-extreme physical exertion may precede subarachnoid hemorrhage
based on interviews of 432 patients with first subarachnoid hemorrhage
338 patients could establish level of physical activity during 26 hours prior to subarachnoid
hemorrhage and time of onset of SAH
moderate-to-extreme exertion reported in preceding 2 hours in 19% of 432 patients with first
compared to controls, moderate to extreme exertion had odds ratio 2.7 for subarachnoid hemorrhage
heavy smoking and binge drinking not associated with increased risk of subarachnoid hemorrhage
Reference - Stroke 2003 Jul;34(7):1771
aneurysmal subarachnoid hemorrhage occurred most frequently during daily activities without strenuous
physical activity in retrospective chart review of 513 patients (J Stroke Cerebrovasc Dis 2007 Jan-
Feb;16(1):25)
Past medical history (PMH)

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ask about history of high blood pressure or hypertension(1)
Family history (FH)
ask about family history of intracranial aneurysms or subarachnoid hemorrhage(1, 2)
Social history (SH)
ask about smoking, alcohol, and drug use(1)
Physical
General physical
may have altered level of consciousness(2)
HEENT
look for retinal hemorrhages(2)

rare, but if present, may be only sign of subarachnoid hemorrhage if patient is unconscious (Am
Fam Physician 2013 Oct 1;88(7):451)
differentiate retinal hemorrhage from preretinal or subhyaloid hemorrhages associated with Terson
syndrome (occurrence of a vitreous hemorrhage), indicating a more abrupt increase in intracranial
pressure and increased risk of mortality
abnormal fundus findings can include disc swelling, retinal hemorrhage, subhyaloid hemorrhage,
and vitreous hemorrhage
based on study of 202 eyes of 101 patients with subarachnoid hemorrhage
50 patients had normal funduscopic exam and 51 patients had abnormal funduscopic exam
among 202 eyes, abnormal fundus findings included
disc swelling in 85 eyes (42.1%)
retinal hemorrhage in 51 eyes (25.2%)
subhyaloid hemorrhage in 6 eyes (3%)
vitreous hemorrhage in 3 eyes (1.5%)
Reference - Eur J Ophthalmol 2009 May-Jun;19(3):460
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Subhyaloid hemorrhage: Characteristic boat-shaped subhyaloid hemorrhages on funduscopic exam

suggesting an aneurysmal subarachnoid hemorrhage.
Neck
check for meningismus, nuchal rigidity(2)
Neuro
use validated scale to determine severity (CSBPR Evidence Level B), such as(3)
World Federation of Neurological Surgeons (WFNS)
Glasgow Coma Scale (GCS)
Hunt and Hess scale (H&H)
National Institutes of Health Stroke Scale (NIHSS)
Fisher Scale
conduct regular neurological assessments using standardized tools as part of regular vital sign assessment
to monitor changes, ideally every 1-4 hours until patient is stable (CSBPR Evidence Level C)(3)
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adjust frequency of assessments according to clinical condition

for example, increase frequency during vasospasm
World Federation of Neurological Surgeons clinical grade assessed based on Glasgow Coma Scale and
clinical appearance(2)
World Federation of Neurological Surgeons Clinical Grading Scale:
Grade Glasgow Coma Scale score Clinical Appearance
1 15 No motor deficit
2 13-14 No motor deficit
3 13-14 With motor deficit
4 7-12 With or without motor deficit
5 3-6 With or without motor deficit
Glasgow Coma Scale (GCS) in adults
best possible score 15 points
eye opening
spontaneously - 4 points
to verbal commands - 3 points
to pain - 2 points
none - 1 point
best motor response
follows verbal command - 6 points
localizes painful stimuli - 5 points
normal flexion to painful stimuli - 4 points
abnormal flexion to painful stimuli - 3 points
decerebrate posturing to painful stimuli - 2 points
none - 1 point
best verbal response
oriented conversation - 5 points
disoriented conversation - 4 points
inappropriate words - 3 points
incomprehensible words - 3 points
incomprehensible sounds - 2 points
none - 1 point
Reference - Scottish Intercollegiate Guidelines Network (SIGN) guideline on early management of
patients with head injury (SIGN 2009 May PDF)
Hunt and Hess clinical grade assessed based on intensity of meningeal inflammation, severity of
neurologic deficit, and level of arousal
Grade 1 - asymptomatic or minimal headache and slight nuchal rigidity
Grade 2 - moderate-to-severe headache, nuchal rigidity, no neurologic deficit other than cranial
nerve palsy
Grade 3 - drowsiness, confusion, or mild focal deficit
Grade 4 - stupor, moderate-to-severe hemiparesis, possible early decerebrate rigidity, and vegetative
disturbances
Grade 5 - deep coma, decerebrate rigidity, moribund appearance
Reference - Neurocrit Care 2005;2(2):110
National Institutes of Health Stroke Scale (NIHSS)

stroke scale ranges from 0 to 42 points, with higher score indicating more severe stroke
level of consciousness
alert (0 points)
not alert, but arousable by minor stimulation to obey, answer, or respond (1 point)
not alert, requires repeated stimulation to attend, or is obtunded and requires strong or painful
stimulation to make movements (not stereotyped) (2 points)
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responds only with reflex motor or autonomic effects or totally unresponsive, flaccid, and
areflexic (3 points)
patient knows month and own age
answers both questions correctly (0 points)
answers 1 question correctly (1 point)
answers neither question correctly (2 points)
patient opens and closes eyes on command
performs both tasks correctly (0 points)
performs 1 task correctly (1 point)
performs neither task correctly (2 points)
best gaze (only horizontal eye movement)
normal (0 points)
partial gaze palsy (1 point)
forced deviation (2 points)
visual field testing
no visual loss (0 points)
partial hemianopia (1 point)
complete hemianopia (2 points)
bilateral hemianopia (blind including cortical blindness) (3 points)
facial palsy (ask patient to show teeth or raise eyebrows and close eye)
normal symmetrical movement (0 points)
minor paralysis (flattened nasolabial fold, asymmetry on smiling) (1 point)
partial paralysis (total or near total paralysis of lower face) (2 points)
complete paralysis of 1 or both sides (absence of facial movement in the upper and lower
face) (3 points)
motor function of right arm
no drift (0 points)
drift (1 point)
some effort against gravity (2 points)
no effort against gravity (3 points)
no movement (4 points)
UN (untestable) = amputation or joint fusion
motor function of left arm
no drift (0 points)
drift (1 point)
UN = amputation or joint fusion
motor function of right leg
no drift (0 points)
drift (1 point)
motor function of left leg
no drift (0 points)
drift (1 point)
limb ataxia
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absent (0 points)
present in 1 limb (1 point)
present in 2 limbs (2 points)
sensory by pinprick
normal (0 points)
mild-to-moderate sensory loss (1 point)
severe or total sensory loss (2 points)
language
no aphasia (0 points)
mild-to-moderate aphasia (1 point)
severe aphasia (2 points)
mute, global aphasia (3 points)
dysarthria
normal (0 points)
mild-to-moderate dysarthria (1 point)
severe dysarthria (2 points)
UN = intubated or other physical barrier
extinction and inattention
no abnormality (0 points)
visual, tactile, auditory, spatial, or personal inattention or extinction to bilateral simultaneous
stimulation in one of the sensory modalities (1 point)
profound hemi-inattention or extinction to more than 1 modality (2 points)
Reference - NIH Stroke Scale PDF or booklet
focal neurological signs most commonly include(2)

partial or complete third-nerve palsy (posterior communicating artery aneurysm)
sixth-nerve palsy (due to increased intracranial pressure)
bilateral leg weakness (anterior communicating aneurysm)
abulia (anterior communicating aneurysm)
hemiparesis with aphasia or visuospatial neglect (middle cerebral artery aneurysm)
Diagnosis
Making the diagnosis
high index of suspicion for aneurysmal subarachnoid hemorrhage should exist in patients with sudden
onset of severe headache since it is a frequently misdiagnosed medical emergency (AHA Class I, Level of
Evidence B)(1)
acute diagnostic workup should include immediate noncontrast head computed tomography (CT) (CSBPR
Evidence Level B), then lumbar puncture for patients with nondiagnostic CT scan (AHA Class I, Level of
Evidence B, CSBPR Evidence Level C )(1, 3)
noncontrast head CT is primary diagnostic tool for detection of aneurysmal subarachnoid
hemorrhage(1)
lumbar puncture may be required if high index of suspicion and neuroimaging negative or
equivocal, especially in cases of delayed neuroimaging as a small percentage of patients with a
negative CT will have positive findings on cerebrospinal fluid (CSF) analysis(1, 2, 3)
magnetic resonance imaging (MRI) may also be useful in diagnosis if head CT negative and clinical
suspicion of subarachnoid hemorrhage is high, but negative result does not eliminate need for CSF
analysis(1)
if results of lumbar puncture are equivocal or diagnostic, further diagnostic procedures may include
CT angiography or digital-subtraction cerebral angiography(2)
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neuroimaging of "first" or "worst" headache reduces risk of misdiagnosing subarachnoid hemorrhage(1, 2)

noncontrast head CT has very high sensitivity (close to 100%) if performed in first 3 days after
after 5-7 days, sensitivity of noncontrast head CT declines significantly and lumbar puncture is
often required to show xanthochromia
use Hunt and Hess and World Federation of Neurological Surgeons grading scales to assess initial severity
of hemorrhage(1, 2)
misdiagnosis common(2)
about 50% of patients presenting at first visit may be misdiagnosed
failure to obtain proper imaging study most common reason for misdiagnosis
failure to correctly perform or interpret lumbar puncture second most common reason for
misdiagnosis
misdiagnosed patients usually less ill and may have normal neurologic examination
50% of misdiagnosed patients may go on to have neurologic complications
missed diagnosis in 12% of patients with subarachnoid hemorrhage admitted to tertiary care
hospital
based on cohort study
482 patients admitted to tertiary care hospital with subarachnoid hemorrhage
56 patients (12%) initially misdiagnosed (42 of 221 [19%] of patients presenting with normal
mental status)
missed diagnosis associated with increased mortality and morbidity at 12 months
Reference - JAMA 2004 Feb 18;291(7):866 full-text
Differential diagnosis
other types of intracranial hemorrhage
intracerebral hemorrhage
epidural hematoma
subdural hematoma
headache disorders
migraine(2)
tension-type headache(2)
clinical presentation unable to differentiate between subarachnoid hemorrhage and benign
thunderclap headache
based on prospective study of 102 patients referred to emergency room for sudden onset of
severe headache with normal level of consciousness and no focal neurologic deficits
computed tomography (CT) and lumbar puncture (LP) established diagnosis of aneurysmal
subarachnoid hemorrhage (SAH) in 41%, nonaneurysmal SAH in 23%, and benign
thunderclap headache in 36%
unable to clearly differentiate among these 3 groups based upon clinical presentation
seizures in 3 patients and diplopia in 2 patients were symptoms that occurred solely in
aneurysmal SAH group
Reference - J Neurol Neurosurg Psychiatry 1998 Nov;65(5):791
Testing overview
detecting subarachnoid hemorrhage

noncontrast computed tomography (CT) scan is primary diagnostic tool
lumbar puncture and cerebrospinal fluid (CSF) analysis performed in patients with suspected
hemorrhage and equivocal or negative results on head CT
magnetic resonance imaging (MRI) may be used in patients with high clinical suspicion but
negative head CT scan
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cerebral angiography or CT angiography may be used to detect aneurysm in patients with negative
results on head CT and equivocal lumbar puncture
evaluating aneurysms in patients with subarachnoid hemorrhage(2)
full evaluation of all cerebral vessels required, since about 15% of patients have multiple aneurysms
if no aneurysm on initial imaging, repeat imaging 7-14 days after initial presentation
if no aneurysm on repeat imaging, perform MRI to assess for vascular malformation of brain,
brainstem, or spinal cord
MRI may determine size of aneurysm, especially if partial thrombosis of aneurysm
3-dimensional digital subtraction cerebral angiography helps delineate morphology of aneurysm
Clinical prediction rules

Ottawa subarachnoid hemorrhage rule can rule out subarachnoid hemorrhage in patients
presenting to emergency department with acute nontraumatic headache and normal neurologic
exam (level 1 [likely reliable] evidence)
based on independent derivation and validation cohort studies
derivation study included 2,131 patients (mean age 44 years) who presented to emergency
department with acute nontraumatic headache with maximal intensity within 1 hour and had normal
neurologic examination findings
patients excluded for history of ≥ 3 recurrent headaches of similar nature over at least 6 months, or
previous diagnosis of cerebral aneurysm, subarachnoid hemorrhage, brain neoplasm, or
hydrocephalus
6.2% had diagnosis of subarachnoid hemorrhage defined as any of
subarachnoid blood on unenhanced computed tomography
xanthochromia in cerebrospinal fluid
red blood cells > 1 × 106/L in final tube of cerebrospinal fluid plus aneurysm or arteriovenous
malformation on cerebral angiography
Ottawa subarachnoid hemorrhage rule requires investigation for possible hemorrhage if ≥ 1 of
following factors is present
≥ 40 years old
complaint of neck stiffness or pain
witnessed loss of consciousness
onset of pain during exertion
thunderclap headache (instantly peaking pain)
limited neck flexion on examination
validation study included 1,153 similar patients (mean age 44 years), with diagnosis of
subararchnoid hemorrhage in 5.8%
performance of Ottawa subarachnoid hemorrhage rule for prediction of subarachnoid hemorrhage
Derivation Cohort Validation Cohort
Sensitivity 100% 100%
Specificity 15.3% 13.6%
Positive Predictive Value 7.2% 6.7%
Negative Predictive Value 100% 100%
References
derivation study JAMA 2013 Sep 25;310(12):1248, editorial can be found at JAMA 2013 Sep
25;310(12):1237
validation study CMAJ 2017 Nov 13;189(45):E1379 full-text
original derivation study with 3 early prediction models can be found in BMJ 2010 Oct
28;341:c5204 full-text
Imaging studies
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Computed tomography (CT) imaging
Unenhanced CT
perform noncontrast CT immediately on arrival to hospital to confirm diagnosis (CSBPR Evidence Level
B)(3)
unenhanced computed tomography (CT) is main diagnostic tool for subarachnoid hemorrhage (SAH)(1)
very high sensitivity if performed in first 3 days after subarachnoid hemorrhage
after 5-7 days sensitivity significantly declines
extravasated blood has hyperdense appearance(2)
all scans should be performed with thin cuts through base of brain to pick up small amounts of blood(2)
CT may also show(2)
intraparenchymal hematoma
hydrocephalus
cerebral edema
CT may predict site of aneurysm rupture, especially in patients with aneurysms in anterior cerebral or
anterior communicating arteries(2)
head CT used for grading according to characteristics of subarachnoid hemorrhage and intraventricular
hemorrhage(2)
Head CT Grading Scale:
Grade Subarachnoid Hemorrhage Intraventricular Hemorrhage
0 Absent Absent
1 Minimal Absent in both lateral ventricles
2 Minimal Present in both lateral ventricles
Thick (filling ≥ 1 cisterns or
3 Absent in both lateral ventricles
fissures)
Thick (filling ≥ 1 cisterns or
4 Present in both lateral ventricles
fissures)
Abbreviation: CT, computed tomography.
multislice CT within 6 hours of nontraumatic headache onset appears to have high sensitivity and
specificity for diagnosing subarachnoid hemorrhage in neurologically intact patients in emergency
room (level 2 [mid-level] evidence)
based on systematic review of diagnostic studies with methodologic limitations
systematic review of 5 diagnostic studies (4 cohort studies and 1 case-control study) evaluating ≥
16-slice brain computed tomography (CT) within 6 hours of nontraumatic headache onset for
diagnosis of spontaneous subarachnoid hemorrhage in 8,907 neurologically intact patients in
emergency department
reference standard was CT or lumbar puncture and clinical follow-up
all studies had ≥ 1 limitation including
reference standard not applied to all patients
reference standard included test under investigation
patient selection bias
case-control design
2 studies only included patients with negative CT scans and/or did not report subarachnoid
hemorrhage incidence and were excluded from analyses
pooled incidence of subarachnoid hemorrhage was 19.1% by reference standard in analysis of 3
studies with 3,630 patients
pooled performance of multislice CT for diagnosis of subarachnoid hemorrhage in analysis of 3
studies with 3,630 patients
15/56
sensitivity 98.6% (95% CI 95.1%-99.6%)

specificity 99.6% (95% CI 97.4%-99.9%)
Reference - Stroke 2016 Mar;47(3):750
multislice computed tomography within 6 hours of acute headache onset may have 100%
sensitivity for subarachnoid hemorrhage in adults (level 2 [mid-level] evidence)
based on diagnostic cohort study with reference standard using test under investigation
3,132 neurologically intact adults (mean age 45 years) in emergency department with new
acute headache (peaking in intensity within 1 hour of onset) had third generation multislice
CT
240 patients (7.7%) had subarachnoid hemorrhage defined as presence of any
subarachnoid blood on unenhanced CT
xanthochromia in cerebrospinal fluid (CSF)
> 5×106 red blood cells/L in final tube of CSF collected plus aneurysm on cerebral
angiography
patients without definitive cause of headache had telephone and medical record follow-up at 1
and 6 months to determine if subarachnoid hemorrhage was missed
for diagnosis of subarachnoid hemorrhage, CT had
sensitivity 92.9% (95% CI 89%-95.5%)
negative predictive value 99.4% (95% CI 99.1%-99.6%)
comparing 953 patients who had CT within 6 hours of headache onset vs. 2,179 patients who
had CT > 6 hours after headache onset
sensitivity of CT 100% vs. 85.7%
negative predictive value for CT 100% vs. 99.2%
Reference - BMJ 2011 Jul 18;343:d4277 full-text
negative CT result reported within 6 hours after headache onset in 11 patients later diagnosed
with subarachnoid hemorrhage by lumbar puncture (Ann Emerg Med 2013 Jul;62(1):1)
CT may rule out nontraumatic subarachnoid hemorrhage in patients with normal level of
consciousness if performed within 6 hours of symptom onset, but may have lower sensitivity
after 6 hours (level 2 [mid-level] evidence)
based on retrospective diagnostic cohort study without independent reference standard
250 patients with suspected nontraumatic subarachnoid hemorrhage but normal level of
consciousness had head CT followed by CSF spectrophotometry if CT was negative or
inconclusive
subarachnoid hemorrhage defined as positive result on either CT scan or on CSF
spectrophotometry
final diagnosis of subarachnoid hemorrhage in
68 of 137 patients (49.6%) who had CT scan ≤ 6 hours after symptom onset
40 of 113 patients (35.4%) who had CT scan > 6 hours after symptom onset
sensitivity of CT scan alone for diagnosis of subarachnoid hemorrhage
98.5% (95% CI 92.1%-100%) in patients with CT scan ≤ 6 hours after symptom onset
90% (95% CI 76.3%-97.2%) in patients with CT scan > 6 hours after symptom onset
Reference - Stroke 2012 Aug;43(8):2115 full-text, editorial can be found in Stroke 2012
Aug;43(8):2031, commentary can be found in Stroke 2012 Nov;43(11):e163
CT appears to have high detection rate in patients referred to neurosurgical unit (level 2 [mid-level]
evidence)
based on diagnostic cohort study without independent reference standard
499 patients referred to neurosurgical unit on suspicion of subarachnoid hemorrhage were evaluated
with head CT scans and lumbar puncture if CT was negative
reference standard was CT scan if positive, or lumbar puncture if CT was negative
subarachnoid hemorrhage detected by CT in 295 patients (99.7%) and by lumbar puncture at day 6
of admission in 1 patient
Reference - Neurosurgery 2010 May;66(5):900, commentary can be found in Am Fam Physician
2011 Sep 15;84(6):632
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Intracranial hemorrhage: CT brain showing subarachnoid hemorrhage
CT perfusion
CT perfusion or magnetic resonance imaging (MRI) may be useful for identifying regions of potential
brain ischemia (AHA Class IIa, Level of Evidence B)(1)
CT perfusion may be more accurate than noncontrast CT and CT angiography for diagnosing
delayed cerebral ischemia in patients with subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on small diagnostic cohort study
42 patients with suspected delayed cerebral ischemia within 21 days after subarachnoid hemorrhage
had CT perfusion, noncontrast CT and CT angiography on admission and directly after clinical
deterioration
25 had patients had delayed cerebral ischemia, 14 did not and 3 had failed imaging
for diagnosis of delayed cerebral ischemia
CT perfusion had 84% sensitivity, 79% specificity, 88% positive predictive value, 73%
negative predictive values
noncontrast CT had 56% sensitivity, 71% specificity, 78% positive predictive value, 48%
negative predictive value
CT angiography 64% sensitivity, 50% specificity, 70% positive predictive value, 44%
negative predictive value
Reference - Stroke 2009 Nov;40(11):3493
Magnetic resonance imaging (MRI)
MRI may be used to diagnose aneurysmal subarachnoid hemorrhage in patients with nondiagnostic CT
scan, although negative result still requires cerebrospinal fluid analysis (AHA Class IIb, Level of
Evidence C)(1)
MRI may also help in subsequent evaluations to(2)
assess for vascular malformation of brain, brainstem, or spinal cord if aneurysm not detected in
initial or repeat imaging
17/56
determine size of aneurysm, especially if partial thrombosis of aneurysm
Angiography
cerebral angiography
cerebral angiography may be used to detect an aneurysm in patients with negative results on head
CT and equivocal lumbar puncture(1, 2)
digital subtraction cerebral angiography (DSA) recommended if computed tomographic
angiography is inconclusive (AHA Class IIb, Level of Evidence C)(1)
3-dimensional rotational DSA recommended for detection of aneurysm in patients with SAH
if not previously diagnosed by noninvasive angiogram and for planning endovascular or
surgical treatment (AHA Class I, Level of Evidence B)(1)
3-dimensional DSA may also help delineate morphology of aneurysm
diagnostic cerebral angiography associated with neurologic complications in about 2.6% of
patients
based on retrospective study of 19,826 consecutive patients who had diagnostic cerebral
angiography
events occurring within 24 hours were considered complications
access-site hematoma was most common complication (4.2%)
522 patients (2.63%) had neurologic complications, including 27 (0.14%) with stroke with
permanent disability
12 patients (0.06%) died
Reference - Radiology 2007 Jun;243(3):812
CT angiography
perform vascular imaging of brain to assess cause of subarachnoid hemorrhage(3)
high-quality CT angiography may be preferred over catheter angiography for initial
assessment (CSBPR Evidence Level B)
if noninvasive vascular imaging negative, consider further additional imaging with catheter
angiography (CSBPR Evidence Level C)
CT angiography may be used to detect an aneurysm in patients with negative results on head CT
and equivocal lumbar puncture(1, 2)
can replace catheter cerebral angiography in most cases in older patients with degenerative
vascular disease when image quality is excellent
unreliable for aneurysms < 3 mm
digital subtraction cerebral angiography recommended if CT angiography inconclusive (AHA
Class IIb, Level of Evidence C)
computed tomographic angiography appears to have high sensitivity and specificity for
diagnosis of ruptured intracranial aneurysm in patients with acute subarachnoid hemorrhage
(level 2 [mid-level] evidence)
based on systematic review limited by clinical and statistical heterogeneity
systematic review of 50 diagnostic cohort studies evaluating CT angiography for ruptured
intracranial aneurysm in 4,097 patients with acute subarachnoid hemorrhage
reference standards included
surgery
selective cerebral angiography (such as during embolization procedure)
autopsy
digital subtraction angiography
37 studies used 4-detector row CT scanner
meta-analysis limited to patients with reference standard examination
diagnostic performance of CT angiography for ruptured intracranial aneurysm in meta-
analysis of 42 studies
18/56
pooled sensitivity 96% (95% CI 97%-99%, range 88%-100%), moderate statistical

heterogeneity
pooled specificity 100% (95% CI 97%-100%, range 50%-100%)
studies with higher quality scores had more heterogeneity
Reference - Radiology 2011 Jan;258(1):134 full-text, editorial can be found in Radiology
2011 Jan;258(1):15
computed tomographic angiography reported by neurosurgeons to be equal or superior to
catheter angiography in 83% of cases
100 consecutive patients with SAH were scheduled for angiography and CT angiography
80 patients had CT angiography
neurosurgeons assessed CT angiography as equal or superior to angiography in 83% cases
neurosurgeons reported willingness to perform surgery based on CT angiography alone in
74% cases
Reference - Radiology 1998 Aug;208(2):423, J Neurosurg 1999 Nov;91(5):761, J Neurosurg
1999 Nov;91(5):761
magnetic resonance angiography (MRA)
use of MRA limited in acute subarachnoid hemorrhage due to(1)
lack of routine availability
difficulties of scanning acutely ill patients
sensitivity to motion artifact
patient compliance
longer duration
cost
despite high sensitivity, negative MRA may not rule out intracranial aneurysm if high clinical
suspicion (BMJ 2001 Jun 2;322(7298):1347 full-text)
computed tomographic angiography and MRA have 87%-92% sensitivity and 86%-95% specificity
for detecting intracranial aneurysms compared to intra-arterial digital subtraction angiography
based on systematic review of studies with methodologic limitations
38 studies with 1,765 patients used DSA as a reference standard, had at least 10 subjects and
achieved quality score of at least 50%
most included studies had high prevalence of aneurysms so results not generalizable to screening of
asymptomatic patients
insufficient evidence regarding transcranial Doppler ultrasonography
Reference - Radiology 2000 Nov;217(2):361
Cerebrospinal fluid (CSF) analysis

CSF analysis not necessary if normal imaging as assessed by neuroradiologist with third generation or
higher CT scan within 6 hours of headache (CSBPR Evidence Level B)(3)
perform lumbar puncture and CSF analysis in patients with suspected hemorrhage if
equivocal or negative results on head computed tomography (CT)(2)
high clinical suspicion of subarachnoid hemorrhage and(3)
neuroradiologist not available to interpret third generation or higher CT scan (CSBPR
Evidence Level C)
normal reading on second or lower general CT scan
CT scan not read by an experienced radiologist(3)
CT scan performed ≥ 6 hours after headache onset(3)
patient is in altered state of consciousness(3)
sample protocol and findings(2)
collect CSF in 4 consecutive tubes with red cell count done in first and last tubes
typical findings on lumbar puncture for subarachnoid hemorrhage include
19/56
elevated opening pressure

elevated red cell count that does not decrease between tubes 1 and 4
xanthochromia (yellow range color), which may require > 12 hours to develop
if ≥ 12 hours after headache onset, xanthochromia evaluation may be more sensitive than other
assessments (although delay may not be practical or clinically appropriate) (CSBPR Evidence Level B)(3)
if results of lumbar puncture are equivocal or diagnostic, further diagnostic procedures may include CT
angiography or digital-subtraction cerebral angiography(2)
for technique on performing spinal tap, see Lumbar puncture
red blood cell count < 2,000 × 106 cells/L plus absence of xanthochromia on cerebrospinal fluid
analysis may rule out aneurysmal subarachnoid hemorrhage in patients presenting to emergency
department with acute nontraumatic headache (level 2 [mid-level] evidence)
based on diagnostic cohort study without external validation
1,739 alert patients > 15 years old presenting to emergency department with acute nontraumatic
headache had lumbar puncture at median 17 hours from headache onset
reference standard was blood in subarachnoid space on noncontrast brain computed tomography,
xanthochromia on cerebrospinal fluid (CSF) analysis, or red blood cells in final CSF tube and
aneurysm on cerebral angiography, plus either need for neurovascular intervention or death
0.9% had aneurysmal subarachnoid hemorrhage by reference standard
CSF was assessed for xanthochromia and red blood cell count
red blood cell count > 2,000 × 106 cells/L in final tube or presence of xanthochromia in any
tube interpreted as positive for hemorrhage
red blood cell count < 2,000 × 106 cells/L in final tube plus absence of xanthochromia in any
tube interpreted as negative
performance of cerebrospinal fluid analysis for diagnosis of aneurysmal subarachnoid hemorrhage
sensitivity 100%
specificity 91.2%
positive predictive value 21.4%
negative predictive value 100%
positive likelihood ratio 11.4
negative likelihood ratio 0
Reference - BMJ 2015 Feb 18;350:h568 full-text
CSF containing bilirubin may have variety of colors

based on analysis of 632 CSF samples
72 samples contained bilirubin based on spectrophotometric analysis
15 samples containing bilirubin without oxyhemoglobin appeared yellow (10 samples) or greenish
yellow (5 samples)
57 samples containing bilirubin and oxyhemoglobin appeared red to reddish-pink to orange
80% of CSF samples containing bilirubin were not perceived as being xanthochromic (yellow range
color)
Reference - N Engl J Med 2004 Oct 14;351(16):1695
cerebrospinal fluid xanthochromia by visual inspection may identify subarachnoid hemorrhage in
cases of normal CT results with sudden severe headache (level 2 [mid-level] evidence)
based on retrospective diagnostic cohort study
117 patients (mean age 45 years) alert, neurologically intact, with nontraumatic sudden severe
headache presenting to emergency room within 2 weeks of onset
mean clinical follow-up 28.8 months
eligibility criteria
noncontrast head CT negative for detection of blood or vascular malformation
lumbar puncture
4-vessel angiogram performed on all patients with xanthochromatic CSF by visual inspection
for detection of subarachnoid hemorrhage with positive CSF xanthochromia by visual inspection
20/56
93% sensitivity
95% specificity 95%
72% positive predictive value
sole patient with aneurysm detected without xanthochromia had large amount of red cells in
cerebrospinal fluid
Reference - Mayo Clin Proc 2008 Dec;83(12):1326
DynaMed commentary -- all patients in this study with subarachnoid hemorrhage had either
xanthochromia or large numbers of red cells in CSF but study size too small to safely consider a
negative test as ruling out possibility of subarachnoid hemorrhage
review of cerebrospinal fluid analysis can be found in Am Fam Physician 2003 Sep 15;68(6):1103 full-
text
Treatment
Treatment overview
urgent evaluation and treatment recommended by physician with expertise in stroke management due to
risk of rebleeding in first 24 hours (AHA Class I, Level of Evidence B , CSBPR Evidence Level B )(1, 3)
goals of treatment(2)
prevention of rebleeding (can be prevented with early treatment)
prevention and management of vasospasm
treatment of other medical and neurologic complications
medications
blood pressure control(1, 3)
control blood pressure with titratable agent to balance risk of stroke, hypertension-related
rebleeding, and maintenance of cerebral perfusion pressure (AHA Class I, Level of Evidence
B); if unsecured aneurysm, keep normotensive (CSBPR Evidence Level B)
decrease in systolic blood pressure to < 160 mm Hg is reasonable, though magnitude of blood
pressure control to reduce risk of rebleeding has not been established (AHA Class IIa, Level
of Evidence C)
treatment for high blood pressure should be started while aneurysm is unsecured, as it may
reduce risk of hypertension-induced rebleeding and maintain cerebral perfusion pressure
(CSBPR Evidence Level B)
nimodipine
should only be given orally; IV or parenteral use can cause serious adverse events, including
death
oral nimodipine associated with reduced death or dependence in patients with aneurysmal
subarachnoid hemorrhage (level 2 [mid-level] evidence)
endothelin receptor antagonists including clazosentan do not reduce poor functional outcomes (level
1 [likely reliable] evidence) and may not decrease mortality but appear to reduce delayed ischemic
neurologic deficit (level 2 [mid-level] evidence)
cilostazol may decrease risk of symptomatic cerebral vasospasm after neurosurgical clipping for
ruptured anterior circulation aneurysm
methylprednisolone improves 1-year functional outcomes in patients with aneurysmal subarachnoid
hemorrhage (level 1 [likely reliable] evidence)
antiplatelet agents might decrease composite of death or dependence in patients with aneurysmal
statins
statins do not appear to reduce delayed cerebral ischemia after aneurysmal subarachnoid
hemorrhage, but might reduce mortality (level 2 [mid-level] evidence)
simvastatin does not improve functional outcomes in patients with aneurysmal subarachnoid
21/56
perform surgical clipping or endovascular coiling of ruptured aneurysm as early as feasible in majority of
patients to reduce rate of rebleeding after aneurysmal subarachnoid hemorrhage (AHA Class I, Level of
Evidence B)
endovascular coiling preferred over surgical clipping for patients with ruptured aneurysm who are
candidates for either procedure (AHA Class I, Level of Evidence B)
endovascular coiling associated with decreased death or dependence at 2-3 months compared to
neurosurgical clipping in patients with subarachnoid hemorrhage in good clinical condition (level 2
[mid-level] evidence)
endovascular coiling may be effective for very small (≤ 3 mm) intracranial aneurysms (level 2 [mid-
level] evidence)
early goal-directed fluid therapy may reduce delayed cerebral ischemia and improve function in patients
with poor clinical grade subarachnoid hemorrhage (level 2 [mid-level] evidence)
follow-up
conduct regular neurologic assessments as part of regular vital sign evaluation using standardized
tools, ideally every 1-4 hours until patient is stable according to local protocols (CSBPR Evidence
Level C)
after aneurysmal subarachnoid hemorrhage, transcranial Doppler ultrasound may be used to monitor
for development of arterial vasospasm (AHA Class IIa, Level of Evidence B)
after aneurysmal repair, cerebrovascular imaging recommended for identification of aneurysm
remnants or recurrences requiring retreatment (AHA Class I, Level of Evidence B)
screening of first-degree relatives of patients with sporadic subarachnoid hemorrhage controversial; slight
increase in life expectancy offset by postoperative sequelae
Treatment setting
patients should be managed in centers with expertise in neurosurgical methods that regularly treat
aneurysms with endovascular and surgical techniques (CSBPR Evidence Level C)(3)
if patient initially seen in noncomprehensive stroke center, transfer to a tertiary center for ongoing
treatment once subarachnoid hemorrhage has been confirmed (CSBPR Evidence Level C)(3)
Fluid and electrolytes
maintenance of euvolemia and normal circulating blood volume is recommended to prevent delayed
cerebral ischemia (AHA Class I, Level of Evidence B)(1)
prophylactic hypervolemia before development of angiographic spasm is not recommended (AHA Class
III, Level of Evidence B)(1)
early goal-directed fluid therapy may reduce delayed cerebral ischemia and improve function in
patients with poor clinical grade subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on subgroup analysis of randomized trial without blinding
160 patients with subarachnoid hemorrhage treated with aneurysm obliteration within 24 hours were
randomized to 1 of 2 interventions and followed up to 3 months
early goal-directed fluid therapy (EGDT) guided by preload volume and cardiac output
standard therapy guided by fluid balance or central venous pressure
comparing EGDT vs. standard therapy
in overall analysis
delayed cerebral ischemia in 33% vs. 42% (not significant)
modified Rankin Scale score of 0-3 at 3 months in 67% vs. 57% (not significant)
in subgroup of 90 patients with poor clinical grade at baseline
delayed cerebral ischemia in 5% vs. 14% (p = 0.036, NNT 12)
modified Rankin Scale score of 0-3 at 3 months in 52% vs. 36% (P = 0.026, NNT 7)
median length of intensive care unit stay 14 days vs. 17 days (p = 0.043)
Reference - Stroke 2014 May;45(5):1280
22/56
bedside transpulmonary thermodilution monitoring after subarachnoid hemorrhage might reduce

risk of complications in patients (level 2 [mid-level] evidence)
based on randomized trial without blinding
100 patients having surgical clipping within 24 hours of subarachnoid hemorrhage were randomized
to 1 of 2 groups
early goal-directed management with bedside transpulmonary thermodilution
standard care with pulmonary artery catheter
comparing transpulmonary thermodilution vs. standard care
delayed ischemic neurological deficit in 32% vs. 48% (p = 0.03, NNT 7)
vasospasm-related cerebral infarction in 6% vs. 14% (p = 0.049, NNT 13)
incidences of daily transcranial Doppler vasospasm in 50% vs. 66% (p = 0.03, NNT 7)
modified Rankin Scale score 0-3 in 56% vs. 44% (p = 0.06)
Reference - Stroke 2009 Jul;40(7):2368 full-text
previous Cochrane found insufficient evidence to support or refute use of circulatory volume expansion
therapy for aneurysmal subarachnoid hemorrhage (Cochrane Database Syst Rev 2004 Oct 18;
(4):CD000483)
hydroxyethyl starch hemodilution therapy reported to be associated with acquired type I von
Willebrand disease
based on case reports
6 cases of acquired type I von Willebrand disease reported in patients treated hydroxyethyl starch
hemodilution therapy for vasospasm due to subarachnoid hemorrhage
guidelines in France support limiting infusion to 33 mL/kg/day, limiting total dose to 80 mL/kg,
limiting treatment duration to 3 days, avoiding in patients with coagulation disorders, and
monitoring activated partial-thromboplastin time
Reference - N Engl J Med 2001 Aug 23;345(8):622
Medications
Nimodipine
nimodipine (Nimotop) should only be given ORALLY; IV or parenteral use can cause serious adverse
events, including death (FDA MedWatch 2006 Feb 15)
oral nimodipine should be given to all patients with aneurysmal subarachnoid hemorrhage (AHA Class I,
Level of Evidence A)(1)
nimodipine has been shown to improve neurologic outcomes, but not cerebral vasospasm
benefit of other calcium antagonists (orally or IV) is uncertain
if patient presents ≤ 96 hours after subarachnoid hemorrhage onset and has adequate blood pressure,
immediately start nimodipine for 14-21 days (CSBPR Evidence Level A) following local protocols for
dosing(3)
oral nimodipine associated with reduced death or dependence in patients with aneurysmal
based on Cochrane review limited by heterogeneity
systematic review of 16 randomized trials comparing calcium channel blockers to placebo or usual
care in 3,361 patients with aneurysmal subarachnoid hemorrhage
poor outcome defined as composite of death or dependence
oral nimodipine associated with reduced poor outcome in analysis of 4 trials with 853 patients
risk ratio 0.67 (95% CI 0.55-0.81)
NNT 6-14 with poor outcome in 40% of controls
results limited by significant heterogeneity
no significant differences in poor outcome with
nimodipine IV followed by orally in 2 trials with 535 patients
nicardipine IV in 1 trial with 886 patients
Reference - Cochrane Database Syst Rev 2007 Jul 18;(3):CD000277 (review updated 2008 Jul 23)
23/56
in patients with acute traumatic brain injury, nimodipine associated with reduced death or
disability if traumatic subarachnoid hemorrhage present (level 2 [mid-level] evidence)
based on subgroup analysis of Cochrane review
systematic review of 6 randomized trials comparing calcium channel blockers to placebo in
1,862 patients with acute traumatic brain injury
comparing nimodipine to placebo in overall analysis, no significant differences in
all-cause death in analysis of 3 trials with 1,291 patients
death or severe disability in analysis of 4 trials with 1,1816 patients
comparing nimodipine to placebo in subgroup of patients with traumatic subarachnoid
hemorrhage, nimodipine associated with reduced
all-cause death (risk ratio 0.59, 95% CI 0.37-0.94) in analysis of 2 trials with 331
patients
death or severe disability (risk ratio 0.67, 95% CI 0.46-0.98) in analysis of 3 trials with
460 patients
Reference - Cochrane Database Syst Rev 2003;(4):CD000565 (review updated 2008 Jun 7)
Magnesium sulfate
insufficient evidence to support routine administration of high-dose magnesium during acute stage
(CSBPR Evidence Level C)(3)
magnesium sulfate does not improve neurologic outcome (level 1 [likely reliable] evidence) but may
reduce risk of delayed cerebral ischemia (level 3 [lacking direct] evidence) in patients with
aneurysmal subarachnoid hemorrhage
systematic review of 13 randomized and nonrandomized trials comparing prophylactic magnesium
sulfate IV vs. control for prevention of delayed cerebral ischemia or radiographic vasospasm in
adults with aneurysmal subarachnoid hemorrhage
no significant differences in
good neurologic outcome in analysis of 12 trials with 2,315 patients (consistent results in 1
high-quality trial)
mortality in analysis of 11 trials with 2,092 patients
incidence of cerebral infarction in analysis of 5 trials with 572 patients
hypotension in analysis of 6 trials with 822 patients
radiographic vasospasm in analysis of 7 trials with 438 patients
magnesium sulfate associated with reduced risk of delayed cerebral ischemia in analysis of 10 trials
with 1,095 patients
risk ratio 0.73, 95% CI 0.56-0.96
NNT 8-87, with delayed cerebral ischemia in 29% of control group
Reference - J Crit Care 2013 Apr;28(2):173, commentary can be found in J Crit Care 2013
Dec;28(6):1101
magnesium sulfate does not reduce risk of dependence or death in patients with aneurysmal
subarachnoid hemorrhage (level 1 [likely reliable] evidence)
based on randomized trial
1,204 patients ≥ 18 years old and admitted to hospital within 4 days of aneurysmal
subarachnoid hemorrhage randomized to magnesium sulfate 64 mmol/day IV vs. placebo for
up to 20 days
all patients received nimodipine 360 mg/day orally
dependence (Rankin scale 4-5) or death in 26.2% with magnesium sulphate vs. 25.3% with
placebo (not significant)
Reference - MASH-2 trial (Lancet 2012 Jul 7;380(9836):44 full-text), corrections can be
found in Lancet 2012 Dec 8;380(9859):1994, Lancet 2012 Jul 7;380(9836):28, editorial can
24/56
be found in Lancet 2012 Jul 7;380(9836):9 (correction can be found in Lancet 2012 Jul
7;380(9836):28)
magnesium sulfate may reduce risk of delayed ischemic infarction in patients with aneurysmal
subarachnoid hemorrhage (level 3 [lacking direct] evidence)
based on nonclinical outcome in randomized trial
110 patients with aneurysmal subarachnoid hemorrhage randomized to magnesium sulfate 16
mmol IV bolus followed by infusion at 8 mmol/hour vs. equal amounts of normal saline and
followed for 6 months
magnesium sulfate infusion rates adjusted to maintain target level of 2-2.5 mmol/L for 10
days or until signs of vasospasm resolved and then tapered orally over 12 days
delayed ischemic infarction measured by computed tomography scan
comparing magnesium vs. control
delayed ischemic infarction in 22% vs. 51% (p = 0.002, NNT 4)
good outcome (Glasgow outcome scale score of ≥ 4 out of 5) reached in 63% vs. 51%
(not significant)
Reference - Crit Care Med 2010 May;38(5):1284, editorial can be found in Crit Care Med
2010 May;38(5):1382
magnesium sulfate may not reduce risk of poor neurologic outcome or delayed cerebral ischemia
regardless of treatment timing in patients with aneurysmal subarachnoid hemorrhage (level 2 [mid-
level] evidence)
based on subgroup analysis in systematic review of individual patient data
systematic review of individual patient data from 5 randomized trials comparing magnesium sulfate
IV vs. placebo in 1,981 patients with aneurysmal subarachnoid hemorrhage
patients were stratified by treatment timing (< 6 hours, 6-12 hours, 12-24 hours, and > 24
hours)
neurologic outcome assessed at 3 months (4 trials) or 6 months (1 trial)
comparing magnesium sulfate to placebo
no significant difference in risk of poor neurologic outcome in any timing group in analysis of
1,965 patients
magnesium sulfate within 6-12 hours of symptom onset associated with nonsignificant
increase in risk of delayed cerebral ischemia (risk ratio 2.09, 95% CI 0.99-4.39) in analysis of
169 patients, but no significant difference in any other timing groups
Reference - Stroke 2015 Nov;46(11):3190
Endothelin receptor antagonists
in patients with subarachnoid hemorrhage, endothelin receptor antagonists do not reduce poor
functional outcomes (level 1 [likely reliable] evidence) and may not decrease mortality but appear to
reduce delayed ischemic neurologic deficit (level 2 [mid-level] evidence)
based on 2 systematic reviews
endothelin receptor antagonists may decrease delayed ischemic neurologic deficit but may
increase risk of pneumonia in adults with subarachnoid hemorrhage (level 2 [mid-level]
evidence)
based on Cochrane review without significant differences in high-quality trials
systematic review of 4 randomized trials comparing endothelin receptor antagonists
(clazosentan in 3 trials, TAK-044 in 1 trial) vs. placebo in 2,024 adults with subarachnoid
hemorrhage
endothelin receptor agonists associated with
lower incidence of delayed ischemic neurologic deficit in analysis of 3 trials with 1,976
adults
risk ratio (RR) 0.8 (95% CI 0.67-0.95)
NNT 13-80 with delayed ischemic neurologic deficit in 25% in placebo group
25/56
analysis included 1 high-quality trial below (CONCSIOUS-2), but results in this

trial not significant
nonsignificant decrease in composite of death, persistent vegetative state, and severe
disability (RR 0.87, 95% CI 0.74-1.02) in analysis of 3 trials with 1,976 adults
increased risk of pneumonia in analysis of 3 trials with 1,976 adults
RR 1.56 (95% CI 1.23-1.97)
NNH 9-37 with pneumonia in 12% in placebo group
analysis included 1 high-quality trial, but results in this trial not significant
no significant difference in mortality in analysis of 4 trials with 2,010 adults, but wide
confidence interval does not rule out possibility of positive or negative effect (RR 1.05, 95%
CI 0.77-1.45)
Reference - Cochrane Database Syst Rev 2012 Sep 12;(9):CD008354
consistent results for delayed ischemic neurologic deficit in systematic review of 4
randomized trials comparing clazosentan to placebo, 3 of which were included in the
systematic review above (PLoS One 2012;7(10):e47778 full-text)
endothelin receptor antagonists do not reduce poor functional outcome (level 1 [likely reliable]
evidence) and may not reduce mortality (level 2 [mid-level] evidence) in patients with
based on systematic review with wide confidence intervals for mortality
systematic review of 5 randomized trials comparing endothelin receptor antagonist
(clazosentan or TAK-044) vs. placebo in 2,601 patients with aneurysmal subarachnoid
hemorrhage
poor functional outcome defined as Glasgow Outcome Scale score 1-3, extended Glasgow
Outcome Scale score 1-4, modified Rankin Scale score 4-6, or death or dependency if no
scale was provided
mortality in analysis of all trials (risk ratio 1.04, 95% CI 0.78-1.39)
poor functional outcome in analysis of 4 trials with 2,551 patients
new cerebral infarction in analysis of 3 trials with 1,596 patients
vasospasm-related cerebral infarction in analysis of 3 trials with 2,127 patients
consistent results in sensitivity analyses separately comparing clazosentan or TAK-044 to
placebo
Reference - Stroke 2012 Oct;43(10):2671 full-text
consistent results for mortality, poor functional outcome, and new cerebral infarction in
systematic review of 4 randomized trials comparing clazosentan to placebo, all of which were
included in the systematic review above (PLoS One 2012;7(10):e47778 full-text)
clazosentan
clazosentan reduces need for rescue therapy in patients with aneurysmal subarachnoid
systematic review of 4 randomized trials comparing clazosentan vs. placebo in 2,156 patients
with aneurysmal subarachnoid hemorrhage
comparing clazosentan to placebo
clazosentan associated with reduced
vasospasm-related delayed ischemic neurological deficits (risk ratio 0.76, 95% CI
0.62-0.92) in analysis of 3 trials with 2,127 patients
need for rescue therapy (risk ratio 0.62, 95% CI 0.49-0.79) in analysis of 2 trials
with 1,718 patients
no significant differences in mortality, poor functional outcome, or new cerebral
infarction
Reference - PLoS One 2012;7(10):e47778
clazosentan does not reduce poor functional outcomes (level 1 [likely reliable] evidence) and
may not reduce mortality (level 2 [mid-level] evidence) following surgical clipping for
26/56
based on 2 randomized trials with wide confidence intervals for mortality

1,157 patients aged 18-75 years with aneurysmal subarachnoid hemorrhage secured by
surgical clipping were randomized to clazosentan 5 mg/hour vs. placebo for up to 14 days
comparing clazosentan vs. placebo
mortality at 6 weeks 5% vs. 5% (not significant)
poor functional outcome (Glasgow scale score ≤ 4 out of 5) at 12 weeks in 29%
vs. 25% (not significant)
new cerebral infarct in 12% vs. 13% (not significant)
delayed ischemic neurological deficit in 15% vs. 18% (not significant)
rescue therapy in 11% vs. 16% (not significant)
Reference - CONSCIOUS-2 trial (Lancet Neurol 2011 Jul;10(7):618), editorial can be
found in Lancet Neurol 2011 Jul;10(7):593
577 patients (38% of planned enrollment) with aneurysmal subarachnoid hemorrhage secured
by surgical clipping were randomized to clazosentan 5 mg/hour vs. 15 mg/hour vs. placebo
for up to 14 days
trial terminated early due to results of CONSCIOUS-2 trial
no significant differences in poor outcome (Glasgow score ≤ 4)
25% with placebo
25% with clazosentan 5 mg/hour
28% with clazosentan 15 mg/hour
Reference - CONSCIOUS-3 trial (Stroke 2012 Jun;43(6):1463 full-text)
DynaMed commentary -- confidence intervals for mortality can be found in full-text of
systematic review above
clazosentan reported to reduce angiographic vasospasm after subarachnoid hemorrhage (level
3 [lacking direct] evidence)
based on randomized trial without randomization method or allocation concealment stated
413 patients with aneurysmal subarachnoid hemorrhage due to ruptured saccular aneurysm
randomized within 56 hours of hemorrhage to clazosentan (an IV epithelin receptor
antagonist) 1, 5, or 15 mg/hour vs. placebo for 14 days
aneurysmal clipping or coiling occurred within 12 hours of treatment initiation
clazosentan associated with reduced angiographic vasospasm compared to placebo (p < 0.02
for each clazosentan group)
no significant difference among groups in morbidity and mortality within 6 weeks of
Reference - CONSCIOUS-1 study (Stroke 2008 Nov;39(11):3015)
Antiplatelet agents
antiplatelet agents might decrease composite of death or dependence in patients with aneurysmal
based on Cochrane review with confidence intervals including clinically significant and
insignificant differences
systematic review of 7 randomized trials evaluating antiplatelet agents in 1,385 patients with
4 trials met criteria for good methodologic quality
poor outcome defined as death or dependence on help for activities of daily living
comparing any antiplatelet agent vs. control
antiplatelet agents associated with nonsignificant reduction in poor outcome (risk ratio 0.79,
95% CI 0.62-1.01) in analysis of 7 trials with 997 patients
mortality in analysis of 7 trials with 1,354 patients
clinical signs of secondary ischemia in analysis of 4 trials with 368 patients
intracranial hemorrhagic complications in analysis of 5 trials with 839 patients
aneurysmal rebleeding in analysis of 2 trials with 838 patients
27/56
ticlopidine associated with reduced poor outcome (risk ratio 0.37, 95% CI 0.14-0.98) in 1 trial with
133 patients
Reference - Cochrane Database Syst Rev 2007 Oct 17;(4):CD006184 (review updated 2008 Jul 22)
Corticosteroids
methylprednisolone may improve 1-year functional outcomes in patients with aneurysmal

based on randomized trial with confidence intervals including clinically unimportant differences
95 patients with aneurysmal subarachnoid hemorrhage randomized to methylprednisolone 16
mg//kg IV vs. placebo daily for 3 days and followed for 1 year
treatment started within 6 hours of confirmation of aneurysm rupture
comparing methylprednisolone vs. placebo
in living patients at 1 year, some or no restrictions (assessed by Functional Outcome Scale) in
85% vs. 66% (risk difference [RD] 19.3%, 95% CI 0.5%-37.9%, NNT 6, 95% CI 3-200)
good recovery based on Glasgow Outcome Scale in 70% vs. 54% (p = 0.08)
mortality at 1 year 18.3% vs. 17.3% (not significant)
Reference - J Neurosurg 2010 Mar;112(3):681
previous Cochrane review of 8 randomized or quasi-randomized trials found insufficient evidence
regarding effect of corticosteroids in subarachnoid hemorrhage due to small trial size and wide
confidence intervals (Cochrane Database Syst Rev 2005 Jul 20;(3):CD004583)
Other medications
addition of tirilazad to nimodipine decreases risk of symptomatic vasospasm (level 1 [likely reliable]
evidence) but may not improve mortality (level 2 [mid-level] evidence)
based on Cochrane review with wide confidence intervals for mortality
systematic review of 5 randomized placebo-controlled trials evaluating tirilazad started within 4
days of aneurysmal subarachnoid hemorrhage onset in 3,821 patients
oral or IV nimodipine used as background treatment in all patients
in analyses of all trials
tirilazad associated with lower risk of symptomatic vasospasm (defined as symptoms and
signs of ischemia not attributed to identifiable cause)
odds ratio 0.8 (95% CI 0.69-0.93)
NNT 13-16 assuming symptomatic vasospasm in 34% of controls
no significant difference between groups in
mortality (odds ratio 0.89, 95% CI 0.74-1.06)
poor outcome (death, vegetative state, or severe disability) (odds ratio 1.04, 95% CI
0.9-1.21)
Reference - Cochrane Database Syst Rev 2010 Feb 17;(2):CD006778
antifibrinolytic therapy
short-term (< 72 hours) tranexamic acid or aminocaproic acid is reasonable in patients with
unavoidable delay in obliteration of aneurysm and significant risk of rebleeding, if not
contraindicated, to reduce risk of early aneurysm rebleeding (AHA Class IIa, Level of Evidence B)
(1)
antifibrinolytic therapy may decrease rebleeding but increase ischemia in patients with
based on Cochrane review limited by heterogeneity
systematic review of 10 randomized trials comparing antifibrinolytic therapy vs. placebo or
control treatment in 1,904 patients with subarachnoid hemorrhage
antifibrinolytics included tranexamic acid (9 trials) and epsilon-amino-caproic acid (1 trial)
only 2 trials included intervention for ischemia prevention
antifibrinolytic therapy associated with
28/56
decreased rebleeding in analysis of 10 trials with 1,904 patients, but results limited by
significant heterogeneity
risk ratio (RR) 0.65 (95% CI 0.44-0.97)
NNT 9-152 with rebleeding in 22% of control group
increased cerebral ischemia in analysis of 6 trials with 1,671 patients, but results limited
by significant heterogeneity
RR 1.41 (95% CI 1.04-1.91)
NNH 5-125 with cerebral ischemia in 20% of control group
mortality in analysis of all trials
hydrocephalus in analysis of 5 trials with 1,179 patients
Reference - Cochrane Database Syst Rev 2013 Aug 30;(8):CD001245
statins
do not routinely start statin therapy during acute stage if patient not on statin therapy before
hospitalization (CSBPR Evidence Level A)(3)
statins do not appear to reduce delayed cerebral ischemia after aneurysmal subarachnoid
hemorrhage, but might reduce mortality (level 2 [mid-level] evidence)
based on systematic review of moderate quality trials
systematic review of 4 trials comparing statins vs. placebo for treatment of aneurysmal
subarachnoid hemorrhage with 190 patients
statins associated with nonsignificant reduction in mortality in analysis of 3 trials with 151
patients
risk ratio (0.37, 95% CI 0.13-1.1)
few events reported overall
delayed cerebral ischemia in analysis of 4 trials with 190 patients, results limited by
heterogeneity
poor outcomes in analysis of 3 trials with 151 patients
vasospasm (detected by transcranial Doppler) in analysis of 3 trials with 151 patients,
results limited by heterogeneity
Reference - Stroke 2010 Jan;41(1):e47
Cochrane review evaluating cholesterol-reducing agents for aneurysmal subarachnoid
hemorrhage with treatment duration 14 days found 1 trial (included in systematic review
above) and reported reduced vasospasm on clinical assessment (Cochrane Database Syst Rev
2013 Apr 30;(4):CD008184)
simvastatin does not improve functional outcomes in patients with aneurysmal subarachnoid
based on randomized trial
803 patients with radiologically confirmed aneurysmal subarachnoid hemorrhage presenting <
96 hours from ictus were randomized to simvastatin 40 mg vs. placebo once daily for up to 21
days and followed for 6 months
study drug discontinued upon patient discharge from neurosurgical unit
patients taking statin therapy at presentation were excluded
97% had follow-up data at 6 months
comparing simvastatin vs. placebo
modified Rankin Scale score of 0-2 at discharge in 60% vs. 62% (not significant)
modified Rankin Scale score of 0-2 at 6 months in 72% vs. 72% (not significant)
death at 6 months in 10% vs. 9% (not significant)
serious adverse events in 18% vs. 18% (not significant)
Reference - STASH trial (Lancet Neurol 2014 Jul;13(7):666)
aggressive hyperglycemia management protocol may not reduce poor outcome in patients with
based on retrospective cohort study
29/56
332 patients admitted to intensive care unit with subarachnoid hemorrhage evaluated
166 patients treated with aggressive hyperglycemia management protocol upon admittance
166 patients treated with standard protocol upon admittance
modified Rankin scale ≥ 4 (poor outcome) at 3-6 months in 28.3% with aggressive hyperglycemia
management vs. 40.4% with standard protocol (not significant)
in aggressively managed patients, patients with good glucose control associated with reduced risk of
poor outcome (odds ratio 0.25, 95% CI 0.08-0.8)
Reference - Stroke 2009 May;40(5):1644 full-text
anticonvulsants
if no seizures, prophylactic anticonvulsants not recommended (CSBPR Evidence Level B)(3)
no randomized trials found evaluating antiepileptics for primary or secondary prevention of
seizures in patients with subarachnoid hemorrhage
based on Cochrane review
Reference - Cochrane Database Syst Rev 2013 Jun 5;(6):CD008710
Surgery and procedures
American Heart Association/American Stroke Association (AHA/ASA) recommendations(1)

for surgical and endovascular treatment of ruptured cerebral aneurysms
perform surgical clipping or endovascular coiling of ruptured aneurysm as early as feasible in
majority of patients to reduce rate of rebleeding after aneurysmal subarachnoid hemorrhage
(SAH) (AHA Class I, Level of Evidence B)
endovascular coiling preferred over surgical clipping for patients with ruptured
aneurysm who are candidates for either procedure (AHA Class I, Level of Evidence B)
ensure complete obliteration of aneurysm whenever possible (AHA Class I, Level of
Evidence B)
specific aneurysm treatment as judged by experienced cerebrovascular surgeons and
endovascular specialists should be a multidisciplinary decision based on characteristics of
patient and aneurysm (AHA Class I, Level of Evidence C)
except in cases of compelling contraindication, patients having coiling or clipping of ruptured
aneurysm should have delayed follow-up vascular imaging, and retreatment (either repeat
coiling or microsurgical clipping) should be strongly considered when there is a clinically
significant remnant (AHA Class I, Level of Evidence B)
microsurgical clipping may have increased consideration in patients presenting with large (>
50 mL) intraparenchymal hematomas and middle cerebral artery aneurysms, whereas
endovascular coiling may have increased consideration in patients > 70 years old, those
presenting with poor-grade (World Federation of Neurological Surgeons classification IV/V)
aneurysmal subarachnoid hemorrhage, and in those with aneurysms of basilar apex (AHA
Class IIb, Level of Evidence C)
stenting of ruptured aneurysm associated with increased morbidity and mortality, and should
only be considered when less risky options have been excluded (AHA Class III, Level of
Evidence C)
for anesthetic management during surgical and endovascular treatment
minimization of degree and duration of intraoperative hypotension during aneurysm surgery
is probably indicated (AHA Class IIa, Level of Evidence B)
prevention of intraoperative hyperglycemia during aneurysm surgery is probably indicated
(AHA Class IIa, Level of Evidence B)
use of general anesthesia during endovascular treatment of ruptured cerebral aneurysms can
be beneficial in selected patients (AHA Class IIa, Level of Evidence C)
insufficient data on pharmacologic strategies and induced hypertension during temporary
vessel occlusion to make specific recommendations, but there are instances when their use
may be considered reasonable (AHA Class IIb, Level of Evidence C)
30/56
induced hypothermia during aneurysm surgery not routinely recommended but may be
reasonable option in selected cases (AHA Class III, Level of Evidence B)
prophylactic balloon angioplasty before development of angiographic spasm is not recommended
(AHA Class III, Level of Evidence B)
Canadian Stroke Best Practice Recommendations (CSBPR)(3)
if aneurysmal SAH
urgently secure aneurysm with endovascular coiling or microsurgical clipping (ideally within
24-48 hours) (CSBPR Evidence Level B)
if symptomatic hydrocephalus on CT, urgently place external ventricular drain (CSBPR
Evidence Level B)
if decreased consciousness level and large intraparenchymal extension at time aneurysm is secured,
consider urgent evacuation of hematoma (CSBPR Evidence Level C)
if patient eligible for both endovascular and microsurgical therapy, endovascular therapy is
preferred (CSBPR Evidence Level A)
treatment choice should be based on patient-specific characteristics, including (CSBPR
Evidence Level B)
patient age and comorbid conditions
hemorrhage severity, size, and location
aneurysm morphology
institutional resources and experience
to determine most appropriate treatment, consider(2)
patient's age
overall medical condition
location of aneurysm
morphology of aneurysm
relationship of aneurysm to adjacent vessels
delay in treatment of aneurysm after subarachnoid hemorrhage associated with increased risk of
death or dependence (level 2 [mid-level] evidence)
based on cohort analysis of data from randomized trial
2,106 patients (98%) from ISAT trial were included in analysis comparing treatment for ruptured
aneurysm within 2 days of subarachnoid hemorrhage to treatment ≥ 3 days after subarachnoid
hemorrhage
treatment for ruptured aneurysm was either endovascular coiling or neurosurgical clipping
risk factors for poor outcome (modified Rankin scale score ≥ 3 or death)
at 2 months
clipping at 5-10 days (adjusted odds ratio [OR] 1.46, 95% CI 1.02-2.08)
clipping at ≥ 11 days (adjusted OR 1.61, 95% CI 1.07-2.41)
coiling at ≥ 11 days (adjusted OR 1.73, 95% CI 1.06-2.81)
no significant differences with clipping at 3-4 days, or coiling at 3-10 days
at 1 year
coiling at ≥ 11 days (adjusted OR 2.5, 95% CI 1.55-4.03)
no significant differences with clipping at any time, or coiling at 3-10 days
risk factors for delayed cerebral ischemia
coiling at 5-10 days (adjusted OR 1.68, 95% CI 1.17-2.43)
no significant differences with clipping at any time, or coiling at 3-4 days or ≥ 11 days
Reference - Stroke 2012 Aug;43(8):2126 full-text
endovascular coil embolization associated with decreased mortality compared to neurosurgical clipping
endovascular coiling associated with decreased death or dependence compared to
neurosurgical clipping in patients with subarachnoid hemorrhage in good clinical condition
based on Cochrane review of trials without blinding of outcome assessors and 1 separate
randomized trial without blinding of outcome assessors
systematic review of 3 randomized trials comparing endovascular coiling to neurosurgical
clipping in 2,272 patients with subarachnoid hemorrhage
31/56
most patients in good clinical condition and had aneurysm of anterior circulation
endovascular coiling associated with reduced risk of death or dependence at 2-3 months
in analysis of all trials
risk ratio 0.71 (95% CI 0.63-0.81)
NNT 8-15 with death or dependence at 2-3 months in 36% of controls
analysis dominated by 1 large trial with 2,143 patients (summarized below)
Reference - Cochrane Database Syst Rev 2005 Oct 19;(4):CD003085
consistent results in analysis of randomized trials from systematic review of 4
randomized trials and 23 observational studies comparing coiling to clipping in 11,568
patients with subarachnoid hemorrhage (Stroke 2013 Jan;44(1):29 full-text)
endovascular coiling associated with decreased death or dependence compared to
neurosurgical clipping in patients with aneurysmal subarachnoid hemorrhage
2,143 patients with subarachnoid hemorrhage and ruptured intracranial
aneurysms were randomized to endovascular coiling (detachable coiled placed
endoscopically) vs. neurosurgical clipping (craniotomy)
trial recruitment stopped early after planned interim analysis
comparing endovascular coiling vs. neurosurgical clipping at 1 year
death or dependence in 23.7% vs. 30.6% (p = 0.0019, NNT 15)
mortality 8.1% vs. 10.1% (not significant)
Reference - ISAT trial (Lancet 2002 Oct 26;360(9342):1267), editorial can be
found in Lancet 2002 Oct 26;360(9342):1262, commentary can be found in
Lancet 2003 Feb 1;361(9355):430, Lancet 2003 Mar 1;361(9359):783
consistent results in analysis of complete 1-year outcomes (Lancet 2005 Sep
3;366(9488):809), editorial can be found in Lancet 2005 Sep 3-9;366(9488):783
endovascular coiling associated with decreased 5-year mortality compared to
clipping of intracranial aneurysm (level 2 [mid-level] evidence)
based on follow-up of ISAT trial at mean 9 years
813 (76%) patients in coiling group vs. 769 (72%) patients in clipping
group were followed for 6-14 years
5-year mortality 11% with endovascular coiling vs.14% clipping (p = 0.03)
Reference - Lancet Neurol 2009 May;8(5):427 full-text, editorial can be
found in Lancet Neurol 2009 May;8(5):414
endovascular coiling associated with greater likelihood of independent
survival at 10 years (level 2 [mid-level] evidence)
based on follow-up of ISAT trial
1,644 patients had follow-up of 10-18.5 years, and 1,003 patients
completed questionnaires regarding disability at 10 years
comparing endovascular coiling vs. neurosurgical clipping at 10 years
mortality 17% vs. 21% (p < 0.05, NNT 20)
functional independence (modified Rankin score 0-2) in 82% vs.
78% (not significant)
endovascular coiling associated with greater likelihood of independent
survival at 10 years (odds ratio 1.34, 95% CI 1.07-1.67)
Reference - Lancet 2015 Feb 21;385(9969):691, correction can be found in
Lancet 2015 Mar 14;385(9972):946, editorial can be found in Lancet 2015
Feb 21;385(9969):666
472 patients with subarachnoid hemorrhage were randomized to endovascular coiling vs.
surgical clipping
mean Hunt and Hess grade 2.6 at baseline
death or dependence defined as modified Rankin score > 2
17% crossed over to alternate treatment group, but were analyzed according to original
treatment allocation
32/56
13% did not receive study intervention due to death before treatment (1.2%) or no
source of hemorrhage identified on angiography (12%)
death or dependence in 23.2% with endovascular coiling vs. 33.7% with surgical
clipping at 1 year (p = 0.02, NNH 9)
consistent results in as-treated analysis
Reference - BRAT trial (J Neurosurg 2012 Jan;116(1):135), editorial can be found in J
Neurosurg 2012 Jan;116(1):133
no significant difference in rate of death or dependence between endovascular coiling
and surgical clipping at 3 years in analysis of 349 evaluable patients (74% of those
randomized) who received treatment (J Neurosurg 2013 Jul;119(1):146), editorial can
be found in J Neurosurg 2013 Jul;119(1):139
endovascular coiling associated with reduced risk of seizure compared to clip occlusion in
patients with ruptured cerebral aneurysm (level 2 [mid-level] evidence)
based on secondary analysis of ISAT trial
2,143 patients with subarachnoid hemorrhage and ruptured intracranial aneurysm were
randomized to endovascular coil embolization vs. neurosurgical clip occlusion
seizure in 8.3% with coil embolization vs. 13.6% with clip occlusion (p = 0.014, NNT 19)
factors associated with increased risk of seizure
younger age (hazard ratio [HR] 1.54, 95% CI 1.14-2.13)
delayed ischemic neurologic deficit due to vasospasm (HR 2.1, 95% CI 1.49-2.94)
thromboembolic complications (HR 5.08, 95% CI 3-8.61)
middle cerebral artery (HR 2.23, 95% CI 1.57-3.17)
Reference - J Neurosurg 2011 Dec;115(6):1159
endovascular treatment may be associated with lower rate of stroke lesions at 1 year
compared to surgical clipping (level 2 [mid-level] evidence)
based on randomized trial with allocation concealment not stated
168 patients with SAH were randomized to surgical clipping vs. endovascular treatment of
ruptured aneurysm
138 patients had magnetic resonance examinations 1 year after aneurysmal SAH
comparing surgical vs. endovascular treatment
stroke lesions found in
frontal lobe 70.4% vs. 50.7% (p = 0.018)
temporal lobe 47.9% vs. 22.4% (p = 0.002)
ischemic stroke lesions in parental artery territory 46.5% vs. 22.4% (p = 0.003), with
corresponding mean lesion volumes of 20.9 vs. 17.6 cm (p = 0.209)
subtentorial stroke lesions 0% vs. 6% (p = 0.037)
no significant difference between groups in size and frequency of ischemic stroke
lesions in remote vascular territories
retraction injuries in 56.3% vs. 14.9% of patients (p < 0.001)
in 114 patients who had neuropsychological examination, correlations found between focal
parenchymal stroke lesion volume and neuropsychological test score
Reference - Radiology 2008 Feb;246(2):543 full-text
coiling not associated with higher long-term risk of recurrent subarachnoid hemorrhage
compared to clipping (level 2 [mid-level] evidence)
based on cohort of patients with ruptured intracranial aneurysm treated by coiling (283
patients) vs. clipping (748 patients)
cumulative incidence of recurrent subarachnoid hemorrhage within 8 years of treatment 0.4%
coiled vs. 2.6% clipped (not significant)
Reference - Stroke 2009 May;40(5):1758
cost-effectiveness analysis of endovascular vs. neurosurgical treatment for ruptured intracranial
aneurysms in the United States can be found in J Neurosurg 2009 May;110(5):880
review of endovascular treatment of cerebrovascular diseases (including intracranial aneurysm) and
intracranial neoplasms can be found in Lancet 2004 Mar 6;363(9411):804
33/56
American Heart Association recommendations for endovascular treatment of intracranial aneurysms

can be found in Stroke 2002 Oct;33(10):2536
perioperative antiplatelets
modified antiplatelet preparation may reduce risk of thromboembolic events compared to
standard preparation in patients with high on-treatment platelet reactivity having coil
embolization for unruptured intracranial aneurysm (level 2 [mid-level] evidence)
228 patients with unruptured intracranial aneurysm scheduled for coil embolization were
assessed for platelet function
126 patients with high on-treatment platelet reactivity (HTPR) (defined as ≥ 550 aspirin
reaction units or > 213 P2Y12 reaction units) were randomized to modified vs. standard
antiplatelet preparation regimen and followed for 30 days after embolization
modified antiplatelet preparation administered ≥ 4 hours before coiling and consisted of
aspirin 300 mg plus clopidogrel 75 mg orally for patients with HTPR to aspirin
cilostazol 200 mg loading dose plus standard antiplatelet regimen for patients
with HTPR to clopidogrel
standard antiplatelet preparation consisted of aspirin 100 mg plus clopidogrel 75
mg/day orally for > 5 days
102 patients without HTPR were treated with standard antiplatelet preparation
comparing modified vs. standard antiplatelet preparation
thromboembolic event within 7 days after embolization in 1.6% vs. 11.1% (p = 0.02,
NNT 11)
bleeding in 9.5% vs. 6.3% (not significant)
no additional incident thromboembolic events reported at 30 days (1 patient in standard
antiplatelet preparation group had recurrent thromboembolic event)
1% in non-HTPR group had thromboembolic event within 7 days after embolization
Reference - JAMA Neurol 2015 Jul;72(7):764
cilostazol may decrease risk of symptomatic cerebral vasospasm after neurosurgical clipping
for ruptured anterior circulation aneurysm (level 2 [mid-level] evidence)
109 patients (mean age 61 years) with subarachnoid hemorrhage due to ruptured anterior
circulation aneurysm who had neurosurgical clipping within 72 hours of onset were
randomized to cilostazol 100 mg orally twice daily vs. usual care for 2 weeks and followed
for 6 months
cilostazol was begun within 96 hours after onset of hemorrhage and within 48 hours
postoperatively
symptomatic vasospasm defined as 1 of
new focal or global neurological deficit
≥ 2-point decrease in Glasgow Coma Scale not attributable to initial hemorrhage,
rebleeding, hydrocephalus, surgical complications, fever, infections, or electrolyte or
metabolic disturbances
comparing cilostazol vs. usual care at 2 weeks
symptomatic vasospasm in 13% vs. 40% (p = 0.0021, NNT 4)
angiographic vasospasm in 50% vs. 76% (p = 0.006)
new cerebral infarction on neuroimaging in 11% vs. 29% (p = 0.03)
no significant differences in hospital stay, 6-month mortality, or in modified Rankin scale
scores at 1, 3, or 6 months
Reference - J Neurosurg 2013 Jan;118(1):121
perioperative hypothermia for cerebral protection
perioperative hypothermia might reduce death or severe disability in patients having brain
surgery (level 2 [mid-level] evidence)
based on Cochrane review with confidence interval including clinically important and
unimportant differences
34/56
systematic review of 4 randomized trials comparing induced hypothermia for cerebral

protection vs. normothermia in 1,219 patients having brain surgery
2 trials evaluated hypothermia during surgery and 2 trials evaluated hypothermia after surgery
most patients had subarachnoid hemorrhage
hypothermia associated with nonsignificant decrease in death, persistent vegetative state, or
severe disability (risk ratio 0.8, 95% CI 0.61-1.04) in analysis of all trials
mortality in analysis of all trials
intracranial hemorrhage in 1 trial with 1,000 patients
Reference - Cochrane Database Syst Rev 2015 Jan 28;(1):CD006638
mild intraoperative hypothermia might reduce postoperative death or dependency in patients
with good-grade aneurysmal subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on Cochrane review with confidence interval including clinically important and
unimportant differences
systematic review of 3 randomized trials comparing mild intraoperative hypothermia (32-35
degrees C [89.6-95 degrees F]) vs. no hypothermia in 1,158 patients with intracranial
aneurysms
93.8% had good-grade aneurysmal subarachnoid hemorrhage
no significant difference in death or dependency (risk ratio 0.82, 95% CI 0.62-1.09) in
analysis of 3 trials with 1,158 patients
Reference - Cochrane Database Syst Rev 2016 Mar 22;(3):CD008445
postoperative intra-aortic balloon counterpulsation may not reduce risk of poor outcome compared
to hypervolemic therapy in patients with subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on randomized trial with inadequate statistical power
71 patients with subarachnoid hemorrhage at high risk of vasospasm due to large volume of
hemorrhage were randomized to postoperative intra-aortic balloon counterpulsation vs.
conventional hypervolemic therapy
intra-aortic balloon counterpulsation involves implantation of balloon catheter to augment diastolic
pressure and increase cardiac output
intra-aortic balloon counterpulsation associated with lower cardiac output (p = 0.002) and higher
systemic vascular resistance (p = 0.005)
no significant differences in Glasgow Outcome Scores, quality of life, or incidence of delayed
ischemic neurological deficits at 6 months
complications reported following intra-aortic balloon counterpulsation procedure included bleeding
from insertion site in 2 patients and thromboembolism necessitating femoral embolectomy in 1
patient
authors reported rates of poor outcome to be lower than rates used for power calculation in planning
trial size
Reference - Stroke 2013 Jan;44(1):224 full-text
Consultation and referral
urgent expert consultation recommended for all patients(3)

aneurysmal subarachnoid hemorrhage is an emergency that should be assessed and treated
immediately by physician with expertise in stroke management (CSBPR Evidence Level B)
urgent consultation with neurosurgeon recommended (CSBPR Evidence Level B)
Other management
elevate head 30 degrees for ≥ 24-48 hours (CSBPR Evidence Level B)(3)
treat elevated temperatures to achieve normothermia (CSBPR Evidence Level B)(3)
administer venous thromboembolic prophylaxis (CSBPR Evidence Level A)(2, 3)
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consider sequential compression devices prior to securing aneurysm (CSBPR Evidence Level B)
see Stroke section in Venous thromboembolism (VTE) prophylaxis for medical patients or Deep
vein thrombosis (DVT) for additional information
cerebrospinal fluid (CSF) drainage
addition of cerebrospinal fluid drainage to standard care may reduce short-term but not long-
term disability in patients with aneurysmal subarachnoid hemorrhage (level 2 [mid-level]
evidence)
based on randomized trial with incomplete blinding
210 patients (median age 54 years) with aneurysmal subarachnoid hemorrhage randomized to
lumbar drainage of CSF plus standard care vs. standard care alone
all patients had World Federation of Neurological Surgeons Grade 1-3 aneurysmal
subarachnoid hemorrhage and modified Fisher Grade 2, 3, 4, or 3+4 on initial computed
tomography scan
delayed ischemic neurological deficit defined as drop in consciousness (1 motor score or 2
eye/verbal scores of Glasgow Coma Score) or new focal neurological deficit ≥ 96 hours post
hemorrhage not present immediately after aneurysm treatment and after exclusion of other
causes
comparing CSF drainage plus standard care vs. standard care alone
delayed ischemic neurological deficit in 21% vs. 35.2% (p = 0.021, NNT 7)
10-day posthemorrhage modified Rankin Scale score of 4, 5, or 6 in 44.8% vs. 62.5%
(p = 0.009, NNT 6)
6-month posthemorrhage modified Rankin score of 4, 5, or 6 in 19.8% vs. 18.6% (not
significant)
Reference - Stroke 2012 Mar;43(3):677 PDF
continuous cerebral spinal fluid drainage with intermittent intracranial pressure monitoring
may increase risk of complications compared to intermittent drainage with continuous
monitoring in patients with subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on randomized trial with early termination
60 adults with subarachnoid hemorrhage and external ventricular drain within 72 hours of
admission were randomized to continuous CSF drainage with intermittent intracranial
pressure (ICP) monitoring vs. with intermittent CSF drainage with continuous ICP monitoring
trial had planned to recruit 100 patients but was terminated early following unplanned interim
analysis showing increase in complications (CSF leak, self-device removal, hemorrhage,
ventriculitis, or nonpatient or clogged drain) in continuous drainage group
comparing continuous drainage vs. intermittent drainage
complications in 52.9% vs. 23.1% (p = 0.022, NNH 3)
vasospasm (clinically symptomatic and present on transcranial Doppler) in 61.7% vs.
69.2% (not significant)
Reference - J Neurosurg 2013 Oct;119(4):974
addition of intraventricular fibrinolysis plus low-frequency rotation to usual care does not appear to
improve functional outcomes in patients with subarachnoid hemorrhage (level 2 [mid-level]
evidence)
based on randomized trial with possible baseline differences
60 patients with subarachnoid hemorrhage (78% with severe hemorrhage) randomized to
intraventricular recombinant tissue-type plasminogen activator plus lateral rotational therapy vs.
usual care and followed for 3 months
all patients had prior surgical or endovascular aneurysm repair
World Federation of Neurosurgical Societies (WFNS) grade 4 or 5 injury in 67% of fibrinolysis
group and 90% of controls
no significant difference in functional outcomes (on Glasgow Outcome Scale), incidence of delayed
cerebral ischemia, or hydrocephalus
intraventricular fibrinolysis plus low-frequency rotation associated with increased clot clearance
rates (p < 0.001 for each)
Reference - Stroke 2013 Aug;44(8):2162
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no randomized trials found comparing early vs. delayed mobilization in patients with aneurysmal
based on Cochrane review
Reference - Cochrane Database Syst Rev 2013 May 31;(5):CD008346
if poor prognosis for neurological recovery(3)
consider initial course of supportive nonsurgical management (CSBPR Evidence Level B)
establish goals early after hospital arrival with patient and/or designated decision-maker (CSBPR
Evidence Level B)
patients with Do Not Resuscitate (DNR) status should receive all other appropriate medical and
surgical interventions unless explicitly indicated not to (CSBPR Evidence Level C)
Follow-up
conduct regular neurological assessments as part of regular vital sign evaluation using standardized tools,
ideally every 1-4 hours until patient is stable according to local protocols (CSBPR Evidence Level C);
adjust frequency of assessments according to clinical condition, such as increasing frequency during
vasospasm(3)
monitor comatose patients with electroencephalography for nonconvulsive seizures(2)
if no seizures, prophylactic anticonvulsants are not recommended (CSBPR Evidence Level B)(3)
after aneurysmal subarachnoid hemorrhage, transcranial Doppler ultrasound is reasonable to monitor for
development of arterial vasospasm (AHA Class IIa, Level of Evidence B)(1)
arterial vasospasm typically develops 7-10 days after hemorrhage, and often resolves spontaneously
after 21 days(1)
transcranial Doppler ultrasound may be performed daily or every other day to monitor for
vasospasm in patients considered at risk(2)
best predictor of vasospasm is amount of blood on initial head computed tomography (CT) scan(2)
after aneurysmal repair, cerebrovascular imaging recommended for identification of aneurysm remnants or
recurrences requiring retreatment (AHA Class I, Level of Evidence B)(1)
reasonable to refer patients for comprehensive assessment after discharge including cognitive, behavioral,
and psychosocial evaluation (AHA Class IIa, Level of Evidence B)(1)
long-term care and planning may include(2)
rehabilitation
treatment of depression
treatment of chronic headaches
neuropsychological evaluation
see Long-term management of stroke and Stroke rehabilitation in adults for additional information
magnetic resonance angiography has 80%-88% sensitivity for detecting residual flow following coil
occlusion of cerebral aneurysm (level 1 [likely reliable] evidence)
based on prospective diagnostic cohort study
167 cerebral aneurysms treated by coil occlusion in 149 patients (median age 53 years) were
evaluated with magnetic resonance angiography (MRA) and 2-dimensional cranial digital
subtraction angiogram (DSA) > 6 months after coil occlusion
magnetic resonance angiography included time-of-flight (TOF) sequences followed by contrast-
enhanced (CE) sequences (neuroradiologist not blinded to TOF sequences)
DSA (reference standard) showed residual flow in 60%
class 2 (small remnant) in 33%
class 3 (residual neck) in 27%
interrater concordance 81%
CE MRA detected any residual flow (class 2 or 3) with
sensitivity 88%
specificity 79%
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positive predictive value 86%

CE MRA detected residual flow in the sac (class 3) with
sensitivity 80%
specificity 85%
positive predictive value 67%
CE MRA performance for class 3 residual flow comparing aneurysms of 2-6 mm vs. > 6 mm
sensitivity 54% vs. 90%
specificity 92% vs. 74%
Reference - Stroke 2012 Mar;43(3):740 full-text
Complications and Prognosis

Complications
cognitive impairment
> 50% of subarachnoid hemorrhage survivors report some cognitive impairment including problems
with memory, mood, or neuropsychologic function(2)
20% of patients with aneurysmal subarachnoid hemorrhage have global cognitive impairment,
which is associated with poorer functional recovery and reduced quality of life(1)
aneurysmal subarachnoid hemorrhage associated with impaired memory, executive function,
language function, and day-to-day functioning in systematic review of 69 observational studies
(Stroke 2010 Aug;41(8):e519 full-text)
cerebral vasospasm and delayed cerebral ischemia
major cause of death and disability in patients with subarachnoid hemorrhage(1)
best predictor of vasospasm is amount of blood seen on initial computerized tomography scan(2) ;
see modified Fisher score below
angiographic vasospasm (with or without symptoms) is found in about 66% of patients(2)
angiographic vasospasm leads to ischemic symptoms (delayed cerebral ischemia) in about 50% of
patients with subarachnoid hemorrhage(1, 2)
typically usually occurs between 7 and 10 days after subarachnoid hemorrhage and often
spontaneously resolve after 21 days(1)
no effective preventative treatment(1)
prophylactic hyperdynamic therapy or balloon angioplasty to prevent symptomatic vasospasm not
recommended (CSBPR Evidence Level B)(3)
treatment for delayed cerebral ischemia includes
hemodynamic augmentation
maintaining euvolemia and induced hypertension(1)
maintaining euvolemia is preferred over hypervolemia to prevent or treat symptomatic
vasospasm (CSBPR Evidence Level B)(3)
guidelines support using induced hypertension for treatment of delayed cerebral
ischemia
if ruptured aneurysm treated and no cardiac contraindication, first treat
symptomatic vasospasm with induced hypertension (with target blood pressure
based on neurological response) (CSBPR Evidence Level C)(3)
use induced hypertension unless blood pressure is elevated at baseline or cardiac
status precludes its use (AHA Class I, Level of Evidence B)(1)
agents for induced hypertension can include phenylephrine, norepinephrine, or
dopamine(2)
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for patients who do not improve with hemodynamic augmentation

treatment options include(1)
balloon angioplasty for accessible lesions
intra-arterial vasodilator infusion for lesions not accessible (commonly used
vasodilators include calcium channel blockers and nitric oxide)
cerebral angioplasty and/or selective intra-arterial vasodilator therapy reasonable if
symptomatic cerebral vasospasm, particularly if no response to hypertensive therapy
(AHA Class IIa, Level of Evidence B)(1)
if induced hypertension contraindicated or not effective, consider mechanical or
chemical endovascular treatment (CSBPR Evidence Level C)(3)
other neurologic complications
seizures
seizures or seizure-like episodes reported in up to 26% of patients(1)
most commonly occur within 24 hours of aneurysmal subarachnoid hemorrhage(1)
frequency of nonconvulsive seizures may be up to 20% in comatose patients(2)
epilepsy diagnosed in about 13% of patients after subarachnoid hemorrhage due to
saccular intracranial aneurysm
876 patients with subarachnoid hemorrhage due to saccular intracranial aneurysm
admitted to hospital in Finland who were alive 2 weeks after admission were assessed
during median 76-month follow-up
12.9% diagnosed with epilepsy, with median time from admission to epilepsy
diagnosis 8 months
22.8% died
cumulative incidence of epilepsy was 8% at 1 year and 12% at 5 years
factors associated with increased risk of epilepsy included
intracerebral hemorrhage > 15 cm3 at admission (hazard ratio [HR] 1.9, 95% CI
1.1-3.6)
seizure within 1 week of subarachnoid hemorrhage (HR 2.3, 95% CI 1.5-3.8)
Hunt and Hess subarachnoid hemorrhage grade III at admission (HR 2.2, 95% CI
1.2-3.7)
Hunt and Hess subarachnoid hemorrhage grade IV-V at admission (HR 2.6, 95%
CI 1.4-4.8)
Reference - Neurology 2015 Jun 2;84(22):2229
aneurysm rebleeding
aneurysm rebleeding reported in 4%-14% of patients in first 24 hours(1)
risk greatest in first 2-12 hours(1)
hydrocephalus reported in patients with aneurysmal subarachnoid hemorrhage, including both acute
and chronic shunt dependent hydrocephalus(1)
other complications
pulmonary edema reported in 23% of patients(2)
cardiac arrhythmias reported in 35% of patients(2)
hyponatremia reported in 10%-30% of patients(1)
heparin-induced thrombocytopenia reported in 5% of patients, likely due to heparin used in
angiographic procedures(1)
deep vein thrombosis (DVT), especially in immobilized patients(1)
Prognosis
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determine initial clinical severity of aneurysmal subarachnoid hemorrhage using simple validated scales
(for example, Hunt and Hess or World Federation of Neurological Surgeons), as these validated scales are
the most useful indicator of patient outcome (AHA Class I, Level of Evidence B)(1)
determination of prognosis includes(1)
patient factors
severity of initial hemorrhage
age
sex
time to treatment
medical comorbidities
blood pressure at admission
aneurysm factors
size
location
morphology
institutional factors
availability of endovascular treatment
number of subarachnoid hemorrhage (SAH) cases treated
type of facility in which patient is first evaluated
Mortality
mortality rates following aneurysmal subarachnoid hemorrhage

reported mortality about 50%(2)
most deaths occur within first 2 weeks after hemorrhage(2)
10%-12% of deaths occur before patient receives medical attention(1, 2)
25% of deaths occur during first 24 hours after event(2)
30-day mortality due to subarachnoid hemorrhage decreased by about 20% from 1980 to 2005
systematic review of 31 cohort studies evaluating case-fatality rates in patients with
30-day mortality decreased by 0.9% per year (95% CI 0.3%-1.5% per year) in unadjusted
analysis of all studies, from 55% to 35% (percentages estimated from figure)
Reference - Neurology 2010 May 11;74(19):1494 full-text, editorial can be found in
Neurology 2010 May 11;74(19):1486
risk prediction models
Subarachnoid Hemorrhage International Trialists (SAHIT) models predict risk of
unfavorable outcome and mortality at 3 months in patients with subarachnoid hemorrhage
(level 1 [likely reliable] evidence)
based on retrospective prognostic cohort study with independent derivation and validation
cohorts
online calculator can be found at SAHIT and includes
age, World Federation of Neurosurgical Societies score, history of hypertension in core
model
neuroimaging findings in neuroimaging model
treatment modality (clip, coil, or not repaired) in full model
derivation cohort included 10,936 patients (median age 53 years) from 7 randomized trials
and 2 prospective hospital registries who had subarachnoid hemorrhage due to ruptured
intracranial aneurysms
validation cohort included similar 3,355 patients (median age 55 years) from 3 randomized
trials and 4 hospital registries
mortality 13% of patients in derivation cohort and 17% of patients in validation cohort
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unfavorable outcome (Glasgow Outcome Scale score 1-3) in 29% in derivation cohort and
28% of patients in validation cohort
in validation cohort, all 3 SAHIT models had good discrimination and good calibration for
risk of unfavorable outcome and mortality based on retrospective prognostic cohort study
with independent derivation and validation cohorts
Reference - BMJ 2018 Jan 18;360:j5745 full-text
admission bioclinical score (ABC score) may predict 1-year mortality in patients having
endovascular coiling after subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on derivation and validation cohort study without external validation at independent
research center
derivation cohort included 368 patients (mean age 50 years) with subarachnoid hemorrhage
who were treated with endovascular coiling and validation cohort included 158 similar
patients
1-year mortality was 17.4% in derivation cohort and 18.4% in validation cohort
predictors of 1-year mortality were identified in derivation cohort at admission to
neurosurgical intensive care unit
risk factors significantly associated with 1-mortality and points assigned to derive admission
bioclinical score (ABC score) (0-6 total points)
Glasgow Coma Scale (GCS) score - 1 point if GCS score = 14, 2 points if GCS score =
13, 3 points if GCS < 13
troponin 1 > 0.5 mcg/L - 1 point
S100beta > 0.5 mcg/L - 2 points
probability of 1-year mortality in derivation cohort by ABC score
Results:
Total Score 1-year Mortality
0 points 4.7%
1 point 8.4%
2 points 14.7%
3 points 24.5%
4 points 37.9%
5 points 53.5%
6 points 68.3%
in validation cohort, ABC score was significantly more accurate for predicting 1-year
mortality than Glasgow Coma scale, World Federation of Neurosurgical Societies score, and
Fisher score in receiver operator curve analysis
Reference - Stroke 2012 May;43(5):1253 full-text
risk factors associated with mortality
some cardiac abnormalities after aneurysmal subarachnoid hemorrhage may be associated
with death and delayed cerebral ischemia (level 2 [mid-level] evidence)
based on systematic review limited by heterogeneity
systematic review and meta-analysis of 25 cohort studies evaluating association of various
cardiac markers with outcomes in 2,690 patients (mean age 53 years) who had aneurysmal
risk of death associated with
elevated brain natriuretic peptide levels in 1 trial with 235 patients (relative risk 11.1)
tachycardia in 1 trial with 76 patients (relative risk 3.9)
elevated troponin in 2 trials with 278 patients (relative risk 2)
echocardiographic wall motion abnormalities in 3 trials with 486 patients (relative risk
1.9)
T wave abnormalities in 7 trials with 741 patients (relative risk 1.8)
Q wave in 3 trials with 511 patients (relative risk 2.9)
ST-segment depression in 3 trials with 511 patients (relative risk 2.1)
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cardiac markers associated with risk of delayed cerebral ischemia

creatine kinase MB in 4 trials with 177 patients
ST-segment depression in 1 trial with 121 patients
wall motion abnormalities in 1 trial with 72 patients
brain natriuretic peptide levels in 2 trials with 51 patients
elevated troponin in 3 trials with 335 patients
Reference - Neurology 2009 Feb 17;72(7):635
history of blood transfusion associated with increased risk for mortality due to subarachnoid
hemorrhage
based on population-based prospective cohort study
209,293 persons aged 40-79 years in Japan followed for 9 years
history of blood transfusion associated with increased risk (odds ratio 4.2) in multivariate
analysis
Reference - Stroke 2003 Dec;34(12):2781 full-text
Symptomatic vasospasm
modified Fisher scale for predicting risk of symptomatic vasospasm

Fisher computed tomography (CT) grading scale was developed to assess subarachnoid hemorrhage
to evaluated risk of developing symptomatic vasospasm, a serious potential complication
(Neurosurgery 1980 Jan;6(1):1)
Fisher scale was modified in 2006 (see below) to account for patients with thick cisternal blood and
concomitant intraventricular or intraparenchymal blood
scoring
Modified Fisher Scale for Prediction of Symptomatic Vasospasm:
Subarachnoid Hemorrhage Classification Points
IVH present - 4 points
Diffuse thick SAH*
IVH absent - 3 points
Localized thick SAH
Diffuse thin SAH
IVH absent - 1 point
Localized thin SAH
IVH absent - 1 point
No SAH
*Abbreviations: SAH, subarachnoid hemorrhage; IVH, intraventricular hemorrhage
score range 1-4 points with increasing risk of incident symptomatic vasospasm with
increasing score
Reference - Surgical neurology international
modified Fisher scale appears to predict risk of developing symptomatic vasospasm in patients
after subarachnoid hemorrhage (level 2 [mid-level] evidence)
based on retrospective prognostic cohort study
1,355 patients with subarachnoid hemorrhage (SAH) had computed tomography (CT) images
and clinical outcomes evaluated
all patients had been enrolled in placebo arms of 1 of 4 randomized trials
symptomatic vasospasm defined as clinical symptoms at day 5-12 post-SAH including
worsening headache, stiff neck, insidious onset of confusion or consciousness-level decline,
or focal deficits not attributable to other causes
Fisher CT grading scale modified by allowing for identification of patients with thick
cisternal clot and intraventricular hemorrhage
odds ratios were adjusted for other variables associated with symptomatic vasospasm
42/56
modified Fisher scale scoring (range 0-4 with higher scores denoting higher risk)
focal or diffuse thin SAH, no intraventricular hemorrhage (IVH) - 1 point
focal or diffuse thin SAH, with IVH - 2 points
thick SAH without IVH - 3 points
thick SAH with IVH - 4 points
33% of patients developed symptomatic vasospasm
higher grade of modified Fisher scale was associated with increased risk of symptomatic
vasospasm; patients with
2 points had odds ratio (OR) 1.58, 95% CI 1.02-2.46
3 points had OR 1.59, 95% CI 1.14-2.22
4 points had OR 2.2, 95% CI 1.58-3.05
adjusted OR for incremental risk of symptomatic vasospasm for each point level is OR 1.28,
95% CI 1.06-1.54
Reference - Neurosurgery 2006 Jul;59(1):21-7
Recurrent subarachnoid hemorrhage
risk of aneurysm rebleeding associated with degree of aneurysm occlusion after treatment
based on secondary analysis of CARAT study
1,001 patients with subarachnoid hemorrhage treated with coil embolization or surgical clipping
were followed for mean of 3.6 years (range 0-9.6 years)
19 postprocedural reruptures occurred
risk of rerupture by degree of aneurysm occlusion after treatment (p < 0.0001 for trend)
1.1% after complete occlusion
2.9% after 91%-99% occlusion
5.9% after 70%-90% occlusion
17.6% after < 70% occlusion
overall risk of rerupture was 2.2% in first year, 0.2% in second year, and 0% after 2 years
no reruptures occurred after retreatment
Reference - Stroke 2008 Jan;39(1):120 full-text, commentary can be found in Nat Clin Pract Neurol
2008 Jun;4(6):302, Stroke 2008 Jul;39(7):e121
6.9% rate of aneurysm rebleeding
based on prospective inception cohort study
of 574 patients with subarachnoid hemorrhage, rebleeding occurred in 40 (6.9%)
73% of rebleeding cases occurred within 3 days
Reference - Arch Neurol 2005 Mar;62(3):410
prior cocaine use associated with increased hospital mortality and rate of aneurysm rerupture in
patients with aneurysmal subarachnoid hemorrhage
1,134 patients with aneurysmal subarachnoid hemorrhage were analyzed
142 patients (12.5%) had prior cocaine use
comparing cocaine use vs. no cocaine use
hospital mortality 26% vs. 17% (p < 0.05)
aneurysm rerupture in 7.7% vs. 2.7% (p < 0.05)
no significant between-group difference in functional outcome as assessed by Glasgow Outcome
Scale
Reference - Stroke 2013 Jul;44(7):1825 full-text
Neurologic outcomes
nonaneurysmal subarachnoid hemorrhage has good prognosis and neurologic complications uncommon(2)
review of 24 patients with pretruncal nonaneurysmal subarachnoid hemorrhage can be found in
Mayo Clin Proc 1998 Aug;73(8):745
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cognitive impairment following aneurysmal subarachnoid hemorrhage(2)

up to 46% of survivors have long-term cognitive impairment, with effect on functional status and
quality of life
one-half to two-thirds of survivors return to work after 1 year
Montreal cognitive assessment (MoCA) may be useful for long-term assessment of mild cognitive
impairment in patients with history of subarachnoid hemorrhage
Montreal Cognitive Assessment (MoCA) freely available in multiple languages; can be
downloaded at www.mocatest.org (no-fee registration required)
MoCA
10-minute cognitive screening test designed as a first-line tool to assist physicians in
the diagnosis of mild cognitive impairment (MCI)
initial version covered 10 cognitive domains but was pared down to 8 cognitive
domains in revised versions, including
short-term memory recall
visuospatial abilities
executive functions
attention
concentration
working memory
language
orientation to time and place
1 point added if patient had ≤ 12 years of education to adjust for education effects
max score 30 points
cutoff score of < 26 points associated with high sensitivity for detecting mild cognitive
impairment
also available in several versions, which can decrease learning effects if testing
repeated every 3 months or less (www.mocatest.org)
Reference - J Am Geriatr Soc 2005 Apr;53(4):695
MoCA appears more helpful for detecting cognitive impairment than MMSE in patients
with subarachnoid hemorrhage at both 2-4 weeks and 1 year post-hemorrhage (level 2
[mid-level] evidence)
based on prospective diagnostic cohort study
80 patients aged 21-75 years with aneurysmal subarachnoid hemorrhage (aSAH) in
Hong Kong were assessed for cognitive impairment 2-4 weeks and 1 year post-
hemorrhage
all patients were admitted to hospital within 96 hours of hemorrhage
patients were assessed with both Montreal Cognitive Assessment (MoCa) and Mini-
Mental State Examination (MMSE); which were compared to reference standard of
tests evaluating 5 cognitive domains (verbal memory, visuospatial skill and memory,
executive function and psychomotor speed, and language)
cognitive domain deficit defined as domain score < -1.65 (below fifth percentile);
cognitive impairment defined as ≥ 2 cognitive domain deficits
16% of patients had cognitive impairment at 2-4 weeks, and 15% of patients had
cognitive impairment at 1 year
for detection of cognitive impairment at 2-4 weeks post-hemorrhage
MoCA with cutoff of 17/18 points had
sensitivity 75% and specificity 95%
positive predictive value 75% and negative predictive value 95%
MMSE with cutoff of 23/24 points had
for detection of cognitive impairment at 1 year post-hemorrhage
MoCA with cutoff 21/22 points had
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MMSE with cutoff 23/24 points had
Reference - PLoS One 2013;8(4):e59946 full-text
5-category prognostic scale based on Glasgow Coma Scale may predict poor outcomes following
632 patients ≥ 16 years old admitted to hospital within 4 days of subarachnoid hemorrhage who had
Glasgow Coma Scale (GCS) assessment at admission were analyzed
patients stratified to 5 categories for risk of poor outcome by GCS score
poor outcome defined as 1 of
Glasgow Outcome Scale score 1-3
Rankin score 4-5
death
poor outcomes by risk category
14.8% in lowest risk group (GCS = 15)
41.3% in low risk (GCS = 11-14)
74.4% in moderate risk (GCS = 8-10)
84.7% in high risk (GCS = 4-7)
93.9% in highest risk (GCS = 3)
Reference - Stroke 2008 Apr;39(4):1347
elevated blood sugars associated with higher risk of poor outcomes
hyperglycemia on admission associated with higher risk of poor outcome in patients with
aneurysmal subarachnoid hemorrhage (level 2 [mid-level] evidence)
systematic review of 17 studies evaluating effect of admission glucose level on outcomes
after aneurysmal subarachnoid hemorrhage in 4,095 patients
admission hyperglycemia defined as mean glucose level 5.7-12 mmol/L (103-216 mg/dL) was
associated with greater likelihood of poor outcome (odds ratio 3.1, 95% CI 2.3-4.3)
Reference - Stroke 2009 Jun;40(6):e424
intraoperative hyperglycemia may be associated with impaired cognition in patients having
surgery for subarachnoid hemorrhage caused by aneurysm (level 2 [mid-level] evidence)
based on post hoc analysis of randomized trial (IHAST trial)
1,000 patients with subarachnoid hemorrhage had surgery for aneurysm clipping within 14
days
gross neurologic and neuropsychological function evaluated at 3 months postsurgery
intraoperative blood glucose concentrations ≥ 129 mg/dL (7.2 mmol/L) associated with
impaired cognition (p = 0.03)
longer length of intensive care unit stay (but not overall hospital stay) (p < 0.002)
intraoperative glucose concentrations ≥ 152 mg/dL (8.4 mmol/L) more likely to develop
deficits in gross neurologic function on 1 of 4 scales (p < 0.05)
Reference - Mayo Clin Proc 2008 Apr;83(4):406, editorial can be found in Mayo Clin Proc
2008 Apr;83(4):394
neurologic deterioration after surgery for ruptured intracranial aneurysm is common and is
associated with increased risk of poor outcome (level 1 [likely reliable] evidence)
based on analysis of randomized trial (IHAST trial)
1,000 patients with ruptured intracranial aneurysm were assessed with National Institutes of Health
Stroke Scale preoperatively, at 24 and 72 hours postoperatively, and at discharge
42.6% had acute postoperative neurological deterioration 24 hours after surgery
good outcome (Glasgow Outcome Scale score of 1) at 3 months in 46.2% of patients with
postoperative neurological deterioration at 24 hours vs. 77.7% of patients without postoperative
neurological deterioration at 24 hours (p < 0.05)
factors associated with risk of postoperative neurological deterioration included
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older age
higher Fisher grade on first head computed tomography (CT) scan (diffuse blood, localized
clot or thick layer of blood, or intraparenchymal or ventricular clot)
ventriculostomy prior to aneurysm surgery
increased systolic blood pressure during surgery
delay in timing of surgery (≥ 4 days)
ST-segment depression during surgery
history of abnormality in cardiac valve function
use of intentional hypotension during surgery (mean arterial pressure < 60 mm Hg for ≥ 15
minutes)
increased duration of anterior cerebral artery occlusion
duration of temporary clip application of ≥ 20 minutes
increased intraoperative blood loss
increased difficulty of aneurysm exposure
Reference - J Neurosurg 2012 Jun;116(6):1267
fever of noninfectious origin associated with poorer cognitive outcome(1)
perioperative fever associated with worsened surgical outcomes
based on analysis of patients enrolled in Intraoperative Hypothermia for Aneurysm Surgery
Trial
1,000 patients with World Federation of Neurological Surgeons grades I-III subarachnoid
hemorrhage having clipping of intracranial aneurysms after subarachnoid hemorrhage were
assessed for fever between hospital admission and discharge
fever reported between hospital admission and discharge in 41% of patients
functional and neuropsychiatric outcomes measured at 3 months postoperatively
patients having fever during hospitalization had significantly worse outcomes for all outcome
measures
Reference - Neurosurgery 2009 May;64(5):897
apolipoprotein E genotype associated with higher risk of negative outcome and delayed ischemia
based on systematic review of 8 studies with 696 patients with subarachnoid hemorrhage
Reference - Neurology 2007 Aug 21;69(8):766
Prevention and Screening

Prevention
consider morphologic and hemodynamic characteristics along with size and location of aneurysm, patient
age, and health in determining risk of aneurysm rupture (AHA Class IIb, Level of Evidence B)(1)
treat hypertension to reduce risk of aneurysmal subarachnoid hemorrhage (AHA Class I, Level of
Evidence B)(1)
avoid smoking and alcohol misuse to reduce risk of aneurysmal subarachnoid hemorrhage (AHA Class I,
Level of Evidence B)(1)
diets rich in vegetables may reduce risk of subarachnoid hemorrhage (AHA Class IIb, Level of Evidence
B)(1)
American Heart Association/American Stroke Association (AHA/ASA) recommendations for
management of unruptured intracranial aneurysms
surgical clipping
effective treatment for unruptured intracranial aneurysms, where treatment is indicated
(AHA/ASA Class I, Level B)
perioperative considerations
when considering surgical clipping, several factors must be considered, such as patient
age and location and size of aneurysm (AHA/ASA Class I, Level B)
fully inform patients about risks and benefits (AHA/ASA Class I, Level B)
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surgical treatment should be performed at centers that perform > 20 cases/year

consider using specialized intraoperative tools and techniques to avoid vessel
compromise or residual aneurysms (AHA/ASA Class IIb, Level C)
follow-up
imaging after surgical intervention recommended to document aneurysm obliteration
(differential risk of growth and hemorrhage for aneurysms that are completely vs.
incompletely obliterated) (AHA/ASA Class I, Level B)
consider long-term follow-up imaging after surgical clipping due to combined risk of
aneurysm recurrence and de novo aneurysm formation (AHA/ASA Class IIb, Level B)
long-term follow-up may be especially important for incompletely obliterated
aneurysms during initial treatment (AHA/ASA Class IIb, Level B)
endovascular coiling
effective treatment for unruptured intracranial aneurysms, where treatment is indicated
associated with reduction in procedural morbidity and mortality compared to surgical clipping
in selected cases, but has an overall higher risk of recurrence (AHA/ASA Class IIb, Level B)
perioperative considerations
fully inform patients about risks and benefits (AHA/ASA Class I, Level B), including
explicit review of procedural risk of radiation exposure (AHA/ASA Class I, Level C)
surgical treatment should be performed at centers that perform > 20 cases/year
use of coated coils is not beneficial compared to bare-metal coils (AHA/ASA Class III,
Level A)
newer endovascular techniques
may be considered in carefully selected cases, such as
endoluminal flow diversion (AHA/ASA Class IIb, Level B)
liquid embolic agents (AHA/ASA Class IIb, Level C)
strict adherence to United States FDA indications for use probably indicated until additional
trial data demonstrate an incremental improvement in safety and efficacy over existing
technologies (AHA/ASA Class IIa, Level C)
Reference - AHA/ASA guidelines on management of patients with unruptured intracranial
aneurysms (Stroke 2015 Aug;46(8):2368), commentary can be found in Nat Rev Neurol 2015
Sep;11(9):490
observation of small unruptured intracranial aneurysms for signs of growth and symptoms reported
to be associated with low rate of rupture prior to treatment (level 3 [lacking direct] evidence)
based on case series
292 patients (mean age 55 years, 77% female) with 368 newly diagnosed small unruptured
intracranial aneurysms initially managed by observation were assessed for aneurysm treatment,
rupture, and death for up to 12 years
all patients were asymptomatic without major risk factors
all patients had ≥ 1 diagnosis of
anterior circulation aneurysm < 7 mm
internal carotid artery intracavernous segment aneurysm of any size
posterior circulation aneurysm < 4 mm (including location in posterior communicating
artery segment of the internal carotid artery)
during mean follow-up 3.2 years
annual rate of unexpected rupture prior to treatment 0.24%
annual mortality 0.078%
treatment due to change in aneurysm morphology, ruptured dome, or patient request given in
10.2%
aneurysm growth in 7.9%
Reference - J Neurol Neurosurg Psychiatry 2016 Dec;87(12):1277
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neurosurgical referral unwarranted for small (< 10 mm) cerebral aneurysms in asymptomatic patients,
since risk of rupture very low (J Fam Pract 2003 Jul;52(7):560), commentary can be found in J Fam Pract
2004 Jan;53(1):52
Screening
may be reasonable to offer noninvasive screening to patients with familial (≥ 1 first-degree relative)
aneurysmal subarachnoid hemorrhage (SAH) and/or a history of aneurysmal subarachnoid hemorrhage to
evaluate for de novo aneurysms or late regrowth of treated aneurysm (AHA Class IIb, Level of Evidence
B)(1)
screening of first-degree relatives of patients with sporadic subarachnoid hemorrhage controversial;
slight increase in life expectancy offset by postoperative sequelae
626 first-degree relatives of 160 patients with sporadic subarachnoid hemorrhage were screened
with magnetic resonance angiography, conventional angiography if patients thought to have
aneurysms
aneurysms found in 25 (4%) relatives
18 had surgery with decreased functioning in 11
surgery increased estimated life expectancy by 2.5 years at expense of 19 years of decreased
function
149 patients would have to be screened to prevent 1 subarachnoid hemorrhage
298 patients would have to be screened to prevent 1 fatal subarachnoid hemorrhage
Reference - N Engl J Med 1999 Oct 28;341(18):1344; safer endovascular therapies may make
screening warranted (J Watch 1999 Dec 1;19(23);186), commentary can be found in J Fam Pract
2000 Feb;49(2):184, N Engl J Med 2000 Mar 9;342(10):739
universal screening for intracranial aneurysms not currently recommended in patients with autosomal
dominant polycystic kidney disease (AJNR Am J Neuroradiol 2013 Aug;34(8):1556), commentary can be
found in AJNR Am J Neuroradiol 2013 Aug;34(8):1560
screening may be appropriate in patients > 45 years old with autosomal dominant polycystic
kidney disease
based on study of 83 adults with autosomal dominant polycystic kidney disease (predialysis-
phase) who were screened for intracranial aneurysms with magnetic resonance angiography
of the brain
16.9% prevalence of intracranial aneurysms
all were < 9 mm and localized in anterior circulation
6% required neurosurgical intervention
frequency increased with age
arachnoid cysts identified in 4.8% of patients
Reference - AJNR Am J Neuroradiol 2013 Aug;34(8):1556, commentary can be found in
AJNR Am J Neuroradiol 2013 Aug;34(8):1560
Guidelines and Resources

Guidelines
United States guidelines
American Heart Association/American Stroke Association (AHA/ASA) guideline on management of

aneurysmal subarachnoid hemorrhage can be found in Stroke 2012 Jun;43(6):1711 PDF
American Heart Association/American Stroke Association (AHA/ASA) guideline on management of

spontaneous intracerebral hemorrhage in adults can be found in Stroke 2015 Jul;46(7):2032 full-text
48/56
American Heart Association/American Stroke Association (AHA/ASA) guidelines on management of

patients with unruptured intracranial aneurysms can be found in Stroke 2015 Aug;46(8):2368 PDF
American Heart Association/American Stroke Association (AHA/ASA) statement on updated definition

of stroke for 21st century can be found in Stroke 2013 Jul;44(7):2064 full-text
American Heart Association (AHA) scientific statement on indications for performance of intracranial
endovascular neurointerventional procedures can be found in Circulation 2018 May 22;137(21):e661
Neurocritical Care Society (NCS) recommendations on critical care management of patients following
aneurysmal subarachnoid hemorrhage can be found in Neurocrit Care 2011 Sep;15(2):211 PDF,
commentary can be found in Neurocrit Care 2012 Apr;16(2):343
American College of Radiology (ACR) Appropriateness Criteria for focal neurologic deficit can be found
at ACR 2012 PDF
American Society of Neurophysiological Monitoring (ASNM) position statement on intraoperative

monitoring using somatosensory evoked potentials can be found at ASNM 2010 PDF
American Academy of Neurology/American Clinical Neurophysiology Society (AAN/ACNS) guideline
on intraoperative spinal monitoring with somatosensory and transcranial electrical motor evoked
potentials can be found in Neurology 2012 Feb 21;78(8):585 full-text
American Academy of Neurology (AAN) guideline on transcranial Doppler ultrasonography can be found
in Neurology 2004 May;62(9):1468
American College of Radiology (ACR) Appropriateness Criteria for cerebrovascular disease can be found
at ACR 2016 PDF
United Kingdom guidelines
Royal College of Physicians (RCP) national clinical guideline on stroke can be found at RCP 2016 Oct 3
PDF
Canadian guidelines
Canadian Stroke Best Practice Recommendations (CSBPR) on

stroke recognition and response can be found at CSBPR 2015 Jan PDF
secondary prevention of stroke can be found at CSBPR 2017 Oct
hyperacute stroke care can be found at CSBPR 2015 Jun [French] or in Int J Stroke 2015
Aug;10(6):924
acute inpatient stroke care can be found at CSBPR 2015 Oct or in Int J Stroke 2016 Feb;11(2):239
stroke rehabilitation can be found at CSBPR 2015or in Int J Stroke 2016 Jun;11(4):459
transitions of care can be found at CSBPR 2015
mood, cognition, and fatigue can be found at CSBPR 2015 Jun or in Int J Stroke 2015
Oct;10(7):1130
Telestroke can be found at CSBPR 2017 Apr or in Int J Stroke 2017 Oct;12(8):886
Registered Nurses Association of Ontario (RNAO) guideline on stroke assessment across continuum of
care can be found at RNAO 2005 Jun PDF, supplement can be found at RNAO 2011 Aug PDF
European guidelines
Croatian expert recommendations on management of aneurysmal subarachnoid hemorrhage can be found

in Acta Clin Croat 2014 Mar;53(1):139
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European Stroke Organization (ESO) guidelines for the management of intracranial aneurysms and
subarachnoid haemorrhage can be found in Cerebrovasc Dis 2013;35(2):93 full-text
Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor (Spanish Society of
Anesthesiology, Reanimation and Pain Therapy [SEDAR]) guidelines on
subarachnoid hemorrhage: epidemiology, social impact and multidisciplinary approach can be found
in Rev Esp Anestesiol Reanim 2010 Dec;57 Suppl 2:S4 [Spanish]
neurologic complications of subarachnoid hemorrhage due to intracranial aneurysm rupture can be
found in Rev Esp Anestesiol Reanim 2010 Dec;57 Suppl 2:S44 [Spanish]
systemic complications of subarachnoid hemorrhage from spontaneous rupture of cerebral
aneurysm can be found in Rev Esp Anestesiol Reanim 2010 Dec;57 Suppl 2:S63 [Spanish]
Asian guidelines
Japanese Society on Surgery for Cerebral Stroke evidence-based guidelines on management of aneurysmal
subarachnoid hemorrhage can be found in Neurol Med Chir (Tokyo) 2012;52(6):355
Joint Committee of Japan Stroke Society (JStS) guideline on management of stroke can be found at JStS
2009 PDF [Japanese 日本語]
Review articles
review can be found in Lancet 2007 Jan 27;369(9558):306, commentary can be found in Lancet 2007 Mar
17;369(9565):903
review can be found in BMJ 2006 Jul 29;333(7561):235 full-text, commentary can be found in BMJ 2006
Aug 19;333(7564):396 (commentary can be found in BMJ 2006 Sep 9;333(7567):550)
review of vascular anomalies classification can be found in Pediatrics 2015 Jul;136(1):e203
review of recognition and evaluation of nontraumatic subarachnoid hemorrhage and ruptured cerebral
aneurysm can be found in Am Fam Physician 2013 Oct 1;88(7):451
review of nonaneurysmal subarachnoid hemorrhage can be found in J Neurosci Nurs 2007 Jun;39(3):135
review of perioperative management of aneurysmal subarachnoid hemorrhage can be found in Curr Pharm
Des 2013;19(32):5792
review of neurointensive care for subarachnoid hemorrhage can be found in Mayo Clin Proc 2005
Apr;80(4):550
review of triggers for aggressive interventions in subarachnoid hemorrhage can be found in Neurocrit
Care 2011 Sep;15(2):324
review of critical care guidelines on endovascular management of cerebral vasospasm can be found in
Neurocrit Care 2011 Sep;15(2):336
review of unruptured intracranial aneurysms can be found in Mayo Clin Proc 2004 Dec;79(12):1572
review of transcranial Doppler can be found in J Am Board Fam Med 2007 Jan-Feb;20(1):65 full-text
case presentation can be found in BMJ 2009 Aug 21;339:b2874
case series of posterior cerebral artery aneurysms can be found in J Neurosurg 2003 Jul;99(1):15
case presentation of subarachnoid hemorrhage in woman with migraines can be found in Am Fam
Physician 2009 Mar 1;79(5):374 full-text
MEDLINE search
to search MEDLINE for (Subarachnoid hemorrhage) with targeted search (Clinical Queries), click
therapy, diagnosis, or prognosis
Patient Information
handout from American Academy of Neurology PDF
50/56
handout from Brain and Spine Foundation PDF

handout from Brain Aneurysm Foundation
technical information from Patient Plus PDF
handout from Internet Stroke Center
handout from Mount Sinai Hospital
handout from University of Michigan Health System PDF
handout on subarachnoid hemorrhage and vasospasm from Mayfield Clinic and Spine Institute PDF
handout on brain aneurysm from Mayo Clinic
ICD-9/ICD-10 Codes
ICD-9 codes
430 subarachnoid hemorrhage

772.2 subarachnoid hemorrhage of newborn
852.0 subarachnoid hemorrhage following injury without mention of open intracranial wound
852.00 subarachnoid hemorrhage following injury, without mention of open intracranial wound,
with state of consciousness unspecified
with no loss of consciousness
with brief (less than one hour) loss of consciousness
with moderate (1-24 hours) loss of consciousness
with prolonged (more than 24 hours) loss of consciousness and return to pre-existing conscious
level
with prolonged (more than 24 hours) loss of consciousness, without return to pre-existing conscious
level
with loss of consciousness of unspecified duration
with concussion, unspecified
852.1 subarachnoid hemorrhage following injury with open intracranial wound
852.10 subarachnoid hemorrhage following injury, with open intracranial wound, with state of
consciousness unspecified
852.11 subarachnoid hemorrhage following injury, with open intracranial wound, with no loss of
consciousness
852.12 subarachnoid hemorrhage following injury, with open intracranial wound, with brief (less
than one hour) loss of consciousness
852.13 subarachnoid hemorrhage following injury, with open intracranial wound, with moderate (1-
24 hours) loss of consciousness
852.14 subarachnoid hemorrhage following injury, with open intracranial wound, with prolonged
(more than 24 hours) loss of consciousness and return to pre-existing conscious level
852.15 subarachnoid hemorrhage following injury, with open intracranial wound, with prolonged
(more than 24 hours) loss of consciousness, without return to pre-existing conscious level
852.16 subarachnoid hemorrhage following injury, with open intracranial wound, with loss of
consciousness of unspecified duration
852.19 subarachnoid hemorrhage following injury, with open intracranial wound, with concussion,
unspecified
ICD-10 codes
51/56
I60 subarachnoid haemorrhage

I60.0 subarachnoid haemorrhage from carotid siphon and bifurcation
I60.1 subarachnoid haemorrhage from middle cerebral artery
I60.2 subarachnoid haemorrhage from anterior communicating artery
I60.3 subarachnoid haemorrhage from posterior communicating artery
I60.4 subarachnoid haemorrhage from basilar artery
I60.5 subarachnoid haemorrhage from vertebral artery
I60.6 subarachnoid haemorrhage from other intracranial arteries
I60.7 subarachnoid haemorrhage from intracranial artery, unspecified
I60.8 other subarachnoid haemorrhage
I60.9 subarachnoid haemorrhage, unspecified
I67.1 cerebral aneurysm, nonruptured
I69.0 sequelae of subarachnoid haemorrhage
P10.3 subarachnoid haemorrhage due to birth injury
P52.5 subarachnoid (nontraumatic) haemorrhage of fetus and newborn
S06.6 traumatic subarachnoid haemorrhage
ICD-10-CA modification in Canada
S06.60 without loss of consciousness
S06.61 with brief loss of consciousness
S06.62 with moderate loss of consciousness
S06.63 with prolonged loss of consciousness with return to pre-existing level of
consciousness
S06.64 with prolonged loss of consciousness without return to pre-existing level of
consciousness
S06.69 with loss of consciousness of unspecified duration
additionally, a sixth digit was added
0 without open intracranial wound
1 with open intracranial wound
References
General references used
1. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council,
Council on Cardiovascular Radiology and Intervention, Council on Cardiovascular Nursing, Council on
Cardiovascular Surgery and Anesthesia, Council on Clinical Cardiology. Guidelines for the management
of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American
Heart Association/American Stroke Association. Stroke. 2012 Jun;43(6):1711-37 full-text
2. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006 Jan
26;354(4):387-96, commentary can be found in N Engl J Med 2006 Apr 20;354(16):1755
3. Casaubon LK, Boulanger JM, Blacquiere D, et al; on behalf of Heart and Stroke Foundation of Canada
Canadian Stroke Best Practices Advisory Committee. Canadian Stroke Best Practice Recommendations:
Hyperacute Stroke Care Guidelines, Update 2015. Int J Stroke 2015 Aug;10(6):924-40 full-text
Recommendation grading systems used
American Heart Association (AHA) grading system for recommendations

classes of evidence
Class I - evidence for and/or general agreement that procedure or treatment is useful and
effective
Class II - conflicting evidence and/or divergence of opinion regarding usefulness/efficacy of
procedure or treatment
Class IIa - weight of evidence or opinion is in favor of procedure or treatment
52/56
Class IIb - usefulness/efficacy less well established by evidence or opinion

Class III - evidence and/or general agreement that procedure or treatment is not
useful/effective and in some cases may be harmful
therapeutic recommendations
Level of Evidence A - derived from multiple randomized clinical trials or meta-analyses
Level of Evidence B - derived from single randomized trial or nonrandomized studies
Level of Evidence C - consensus expert opinion
diagnostic/prognostic recommendations
Level of Evidence A - derived from multiple prospective cohort studies using reference
standard applied by blinded evaluator
Level of Evidence B - derived from single grade A study or ≥ 1 case-control study or studies
using reference standard applied by evaluator without blinding
Level of Evidence C - consensus expert opinion
Reference - AHA guidelines on management of aneurysmal subarachnoid hemorrhage (Stroke 2012
Jun;43(6):1711 full-text)
American Heart Association/American Stroke Association (AHA/ASA) grading system for
recommendations
classifications of recommendations
Class I - benefits clearly outweigh risks; procedure or treatment should be performed or
administered
Class IIa - benefits outweigh risks; reasonable to perform procedure or administer treatment,
but additional studies with focused objectives needed
Class IIb - benefits and risks are closely balanced; procedure or treatment may be considered;
additional studies with broad objectives needed, additional registry data would be useful
Class III - procedure or treatment should not be performed or administered because it is not
helpful or may be harmful
Class III ratings may be subclassified as Class III No Benefit or Class III Harm
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses
Level B - data derived from single randomized trial or nonrandomized studies
Level C - only consensus opinions of experts, case studies, or standard of care
Reference - AHA/ASA guidelines on management of patients with unruptured intracranial
aneurysms (Stroke 2015 Aug;46(8):2368)
Canadian Stroke Best Practice Recommendations (CSBPR) levels of evidence

Evidence Level A
meta-analysis of randomized controlled trials or consistent findings from ≥ 2 randomized
trials
desirable effects clearly outweigh undesirable effects or vice versa
Evidence Level B
single randomized controlled trial or consistent findings from ≥ 2 well-designed
nonrandomized and/or uncontrolled trials, and large observational studies
desirable effects outweigh or are closely balanced with undesirable effects or vice versa
Evidence Level C
writing group consensus and/or supported by limited research evidence
desirable effects outweigh or are closely balanced with undesirable effects or vice versa
Reference - CCSBPR Overview and Methodology (CSBPR 2014 PDF)
Synthesized Recommendation Grading System for DynaMed Plus

DynaMed systematically monitors clinical evidence to continuously provide a synthesis of the most valid
relevant evidence to support clinical decision-making (see 7-Step Evidence-Based Methodology).
Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow DynaMed users to quickly see
53/56
where guidelines agree and where guidelines differ from each other and from the current evidence.
In DynaMed Plus (DMP), we synthesize the current evidence, current guidelines from leading authorities,
and clinical expertise to provide recommendations to support clinical decision-making in the Overview &
Recommendations section.
We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to classify
synthesized recommendations as Strong or Weak.
Strong recommendations are used when, based on the available evidence, clinicians (without
conflicts of interest) consistently have a high degree of confidence that the desirable consequences
(health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs,
burdens).
Weak recommendations are used when, based on the available evidence, clinicians believe that
desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about
the magnitude of expected consequences (benefits and harms). Weak recommendations are used
when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in
their judgments. Weak recommendations are also used when the range of patient values and
preferences suggests that informed patients are likely to make different choices.
DynaMed Plus (DMP) synthesized recommendations (in the Overview & Recommendations section) are
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Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
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use "should do" phrasing, or phrasing implying an expectation to perform the recommended action
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Recommendations are explicitly labeled as Strong recommendations or Weak recommendations
when a qualified group has explicitly deliberated on making such a recommendation. Group
deliberation may occur during guideline development. When group deliberation occurs through
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Clinical questions will be formulated using the PICO (Population, Intervention, Comparison,
Outcome) framework for all outcomes of interest specific to the recommendation to be
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Systematic searches will be conducted for any clinical questions where systematic searches
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Evidence will be summarized for recommendation panel review including for each outcome,
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Recommendation panel members will be selected to include at least 3 members that together
have sufficient clinical expertise for the subject(s) pertinent to the recommendation,
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All recommendation panel members must disclose any potential conflicts of interest
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significant conflict exists for the recommendation in question.
Panel members will make Strong recommendations if and only if there is consistent
agreement in a high confidence in the likelihood that desirable consequences outweigh
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Panel members will make Weak recommendations if there is limited confidence (or
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recommendation drafting or development, with explicit confirmation that Strong recommendations
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DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
All editorial team members and reviewers have declared that they have no financial or other competing
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DynaMed provides Practice-Changing DynaMed Updates, with support from our partners, McMaster
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Special acknowledgements
Alexander Rae-Grant, MD, FRCP(C), FAAN (Deputy Editor, Neurology DynaMed Plus; Neurologist,
Cleveland Clinic; Ohio, United States)
Dr. Rae-Grant declares no relevant financial conflicts of interest.
Esther Jolanda van Zuuren, MD (Head of Allergy, Dermatology, and Venereology, Leiden University
Medical Centre; Netherlands; Editor, Cochrane Skin Group)
Dr. van Zuuren declares no relevant financial conflicts of interest.
Alan Ehrlich, MD (Executive Editor; Associate Professor of Family Medicine, University of

Massachusetts Medical School; Massachusetts, United States)
Dr. Ehrlich declares no relevant financial conflicts of interest.
DynaMed Plus topics are written and edited through the collaborative efforts of the above individuals.
Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice.
Recommendations Editors are actively involved in development and/or evaluation of guidelines.
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DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No.
116453, Subarachnoid hemorrhage; [updated 2018 Jun 06, cited place cited date here]; [about 34
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11/10/2018 DynaMed Plus: Subarachnoid hemorrhage

Other medications to consider include:

for nontraumatic subarachnoid hemorrhage(2)

for aneurysmal hemorrhage

aneurysmal hemorrhage incidence rates vary widely with world region(1, 2)

Likely risk factors

Ehlers-Danlos syndrome (EDS) (type IV)

Modifiable risk factors

Other risk factors

Possible risk factors

Factors not associated with increased risk

multiple cerebral aneurysms in about 15% of patients with aneurysmal hemorrhage(2)

Etiology and Pathogenesis

History and Physical

Chief concern (CC)

acute onset of severe headache(1, 2)

History of present illness (HPI)

Past medical history (PMH)

ask about history of high blood pressure or hypertension(1)

Family history (FH)

ask about family history of intracranial aneurysms or subarachnoid hemorrhage(1, 2)

Social history (SH)

ask about smoking, alcohol, and drug use(1)

may have altered level of consciousness(2)

look for retinal hemorrhages(2)

Subhyaloid hemorrhage: Characteristic boat-shaped subhyaloid hemorrhages on funduscopic exam

check for meningismus, nuchal rigidity(2)

adjust frequency of assessments according to clinical condition

National Institutes of Health Stroke Scale (NIHSS)

focal neurological signs most commonly include(2)

neuroimaging of "first" or "worst" headache reduces risk of misdiagnosing subarachnoid hemorrhage(1, 2)

detecting subarachnoid hemorrhage

Clinical prediction rules

Computed tomography (CT) imaging

sensitivity 98.6% (95% CI 95.1%-99.6%)

Intracranial hemorrhage: CT brain showing subarachnoid hemorrhage

Magnetic resonance imaging (MRI)

determine size of aneurysm, especially if partial thrombosis of aneurysm

pooled sensitivity 96% (95% CI 97%-99%, range 88%-100%), moderate statistical

Cerebrospinal fluid (CSF) analysis

elevated opening pressure

CSF containing bilirubin may have variety of colors

Fluid and electrolytes

bedside transpulmonary thermodilution monitoring after subarachnoid hemorrhage might reduce

Endothelin receptor antagonists

analysis included 1 high-quality trial below (CONCSIOUS-2), but results in this

based on 2 randomized trials with wide confidence intervals for mortality

methylprednisolone may improve 1-year functional outcomes in patients with aneurysmal

Surgery and procedures

American Heart Association/American Stroke Association (AHA/ASA) recommendations(1)

American Heart Association recommendations for endovascular treatment of intracranial aneurysms

systematic review of 4 randomized trials comparing induced hypothermia for cerebral

Consultation and referral

urgent expert consultation recommended for all patients(3)

positive predictive value 86%

Complications and Prognosis

for patients who do not improve with hemodynamic augmentation

mortality rates following aneurysmal subarachnoid hemorrhage

cardiac markers associated with risk of delayed cerebral ischemia

modified Fisher scale for predicting risk of symptomatic vasospasm

Recurrent subarachnoid hemorrhage

cognitive impairment following aneurysmal subarachnoid hemorrhage(2)

positive predictive value 41% and negative predictive value 100%