Diagnosis and Management of Subarachnoid Hemorrhage

8/18/2019 Diagnosis and Management of Subarachnoid Hemorrhage

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Diagnosis andManagement ofSubarachnoidHemorrhage

Jose I. Suarez, MD, FNCS, FANA

ABSTRACT

Purpose of Review: The purposeof this article is to present the epidemiology, clinicalpresentation, and management of patients with subarachnoid hemorrhage (SAH). SAHis a neurologic emergency that carries high morbidity and mortality. Patients with SAHare at risk for several significant neurologic complications, including hydrocephalus, ce-rebral edema, delayed cerebral ischemia, rebleeding, seizures, and neuroendocrine ab-normalities that lead to impaired body regulation of sodium, water, and glucose.Recent Findings: The incidence of SAH has remained stable, but mortality of hos-pitalized patients has significantly declined over the past 3 decades. Many commontherapies for SAH have created controversy, and various recent neuroprotective clinicaltrials have produced negative results. However, the publication of two consensus guide-lines by theAmerican Heart Association/American StrokeAssociation and theNeurocriticalCare Society have provided a clarification for what should constitute best practice forpatients with SAH. The most important of those recommendations include the fol-lowing: admission of patients to high-volumecenters(defined as more than 35 patientswith SAH per year) under the management of a specialized and multidisciplinary team;

early identification and management of the bleeding source; evaluation and treatmentdecision for unsecured aneurysms by a multidisciplinary team made up of cerebrovas-cular neurosurgeons, endovascular practitioners, and neurointensivists; managementof patients in the neurocritical care unit with oral nimodipine, blood pressure control,euvolemia, and frequent monitoring for neurologic and systemic complications; anddelayed cerebral ischemia secondary to cerebral vasospasm should be treated withinduced hypertension and endovascular therapies once confirmed.Summary: SAH is a devastating neurologic disease. Management of patients with SAHshould adhere to currently available treatment guidelines. Several aspects of SAH man-agement remain controversial and need further studies to clarify their role in improvingpatient outcome.

Continuum (Minneap Minn) 2015;21(5):1263–1287.

INTRODUCTION

Nontraumatic subarachnoid hemor-rhage (SAH) represents about 3% of all strokes in the United States.1 The

worldwide incidence of SAH rangesfrom 2 to 16 per 100,000 people andhas not changed in the past 3 decades.2

Most epidemiologic studies have shown

that women are more likely to have SAHcompared to men (1.24:1.0) and thatminority groups (particularly African

American and Hispanic populations)are more frequently affected comparedto white Americans.1,2 The incidenceof SAH increases with age, with a typi-cal mean age of onset of 50 years or

Address correspondence toDr Jose I. Suarez, Baylor College of Medicine, OneBaylor Plaza, NB:302, Houston,TX 77030, [email protected].

Relationship Disclosure:Dr Suarez reports no disclosure.

Unlabeled Use of Products/Investigational Use Disclosure:Dr Suarez reports no disclosure.

* 2015, American Academy of Neurology.

1263Continuum (Minneap Minn) 2015;21(5):1263–1287 www.ContinuumJournal.com

Review Article

Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

mailto:[email protected]:[email protected]


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older.2 In about 80% of SAH cases, aruptured cerebral aneurysm is found.

However, neuroimaging techniquesmay show no source of bleeding in 15%of SAH cases or show other abnormali-ties (eg, arteriovenous malformation,

vasculitis) in the remaining 5% of cases.SAH causes significant morbidity and

mortality. Mortality rates vary widely among studies, ranging from 8% to 67%(median of 30% in the United States),

with the caveat that most of these studiesdid not account fully for prehospitaldeaths, which have been estimated to

be between 10% and 15%.

3

However,there has been a significant decrease incase-fatality rates of SAH across theglobe,3 which has been attributed to im-proved survival of hospitalized patientsand is most likely owing to changes inmanagement of patients with SAH, in-cluding neurocritical care, endovascular therapy, and more refined microsurgicaltechniques. Nevertheless, it is importantto emphasize that despite the decreasein case-fatality rates, about half of survi-

vors experience significant chronic reduc-

tions in health-related quality of life.4,5For example, a large proportion of survi-

vors do not return to their previous levelof employment, social independence andinteractions, or personal or family rela-tionships even 5 years after the event.This reduction in health-related qual-ity of life may be due to a combinationof factors, including impaired physicalfunctioning, cognitive deficits (partic-ularly executive function and memory),mood and emotional symptoms (eg, an-

xiety, depression, and posttraumaticstress disorder), and personality changes.Several risk factors for SAH have been

identified ( Table 1-1 ).2,6 Y 10 Whether any of these factors plays a predominantrole in an individual patient remains un-clear. Genetic and environmental fac-tors also can increase the risk of SAH,and some of these factors can interact.For instance, the size at which cerebral

aneurysms rupture may be smaller for those patients with concomitant hyper-

tension and cigarette smoking than for those with either factor alone.

SAHremains one of the topneurologicemergencies, and neurologists must fa-miliarize themselves with this devastatingdisease. This review discusses the mainfeatures of diagnosis and management of SAH. The main areas of emphasis whencaring for patients with SAH should in-clude the following: prompt evaluationand diagnosis,11 immediate transfer toappropriate centers,2,12 expeditious di-

agnosis and treatment of the bleedingsource,13,14 and overall good neurocrit-ical care adhering to available treat-ment guidelines.2,12

CLINICAL PRESENTATION

SAH typically presents with sudden andsevere headache (usually described as‘‘the worst headache ever’’) accompa-nied by nausea, vomiting, photophobia,neck pain, and loss of consciousness( Case 1-1A ).15 Physical examinationshould include determination of level

of consciousness, funduscopic evalua-tion, determination of meningeal signs,and presence of focal neurologic defi-cits ( Table 1-2 ). The latter are presentin about 10% of patients with SAH andare associated with worse prognosis whendue to the presence of thick subarach-noid clot or parenchymal hemorrhage.Transient elevation in the intracranialpres-sure (ICP) causes nausea, vomiting, andsyncope. However, more sustained andsevere increases in ICP can lead to coma

and brain death. Terson syndrome (vit-reous hemorrhage associated with SAH)can present in up to 40% of patients

with SAH.16,17 The sudden spike in ICPis thought to lead to preretinal hemor-rhages, which are associated with moresevere SAH and increased mortality.

Some patients with SAH can have amore atypical presentation.11,15 Occasion-ally, patients may present with seizures,

KEY POINTS

h Subarachnoid hemorrhage

is more frequent in

women than men and

more frequent in

minority populations

compared to

white Americans.

h Case-fatality rates of

hospitalized patients

with subarachnoid

hemorrhage have

decreased with the

advent of neurocriticalcare,

endovascular therapy,

and more refined

microsurgical techniques.

h The most important

points in the management

of patients with

subarachnoid hemorrhage

are prompt evaluation

and diagnosis, immediate

transfer to appropriate

centers, expeditious

diagnosis andtreatment of

the bleeding source, and

overall good neurocritical

care adhering to available

treatment guidelines.

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Subarachnoid Hemorrhage



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TABLE 1-1 Risk Factors for Subarachnoid Hemorrhage

b Nonmodifiable Risk Factors

Age

Female sex

Prior history of aneurysmal subarachnoid hemorrhage

Family history of subarachnoid hemorrhage

History of aneurysm in first-degree relatives (especially in two or more relatives)

b Modifiable Risk Factors

Hypertension

Cigarette smoking

Heavy alcohol use

Sympathomimetic drug use (eg, cocaine)

b Other

Certain genetic disorders (eg, autosomal dominant polycystic kidney disease,type IV Ehlers-Danlos syndrome)

Anterior circulation aneurysms are more likely to rupture in patients who areyounger than 55 years of age

Posterior circulation aneurysms are more likely to rupture in men

Significant financial or legal problems within the past 30 days

Cerebral aneurysms of more than 7 mm in diameter

Case 1-1AA 45-year-old right-handed woman presented to a primary stroke center with sudden onset of severeheadache accompanied by nausea, vomiting, and syncope, which developed 1 hour prior topresentation while she was moving furniture at her house. She had a past history of heavy smokingand cocaine use. Upon arrival to the emergency department, her blood pressure was 180/100 mm Hg,heart rate was 105 beats per minute, arterial oxygen saturation (SaO2) was 97% on room air, andher temperature was 36.5-C (97.7-F). Her examination revealed a Glasgow Coma Scale score of 15,normal cranial nerves, and no motor or sensory deficits. Her World Federation of Neurological SurgeonsScale (WFNSS) score was 1 and her modified Fisher Scale score was 3. She reported neck painthroughout the interview. She was treated with 4 mg of IV morphine sulfate and 10 mg of IV labetalolwithout much response. She was then started on a nicardipine drip to maintain a systolic blood pressureless than 160 mm Hg. A noncontrast head CT showed a subarachnoid hemorrhage (SAH) withpredominance in the anterior interhemispheric fissure (Figure 1-1A). The patient was immediatelytransferred by helicopter to a comprehensive stroke center for further care. Digital subtractionangiography (DSA) revealed an irregular, multilobed, and wide-neck anterior communicating arteryaneurysm (Figure 1-1B and 1-1C). After discussion among the neuroradiologist, the cerebrovascularneurosurgeon, and neurointensivists, the patient underwent surgical clipping of the unsecured aneurysm.Following surgery, the patient was transferred to the neurocritical care unit, where she received oralnimodipine, pain control, IV levetiracetam (seizure prophylaxis for 3 days), and fluids to maintain euvolemia.Nicardipine was discontinued, and she maintained her systolic blood pressure between 140 and 160 mm Hgspontaneously. Her neurologic examination remained unchanged and she was mobilized out of bed.

Continued on page 1266




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Comment. This case delineates the initial management of a patient with SAH. The key issues toconsider include early identification, transfer to a high-volume center, admission to a specializedneurocritical care unit, identification and treatment of the bleeding source, and multidisciplinarydiscussion to undertake best treatment for an unsecured aneurysm. In addition, this patientunderwent blood pressure control prior to aneurysm treatment to prevent rebleeding, and receivedoral nimodipine, which has been shown to improve long-term outcomes in patients with SAH.

FIGURE 1-1 Initial imaging studies of the patient in Case 1-1. A, Nonenhanced head CTshows diffuse subarachnoid hemorrhage with predominance in anterior interhemisphericfissure without cerebral edema or significant hydrocephalus. B, A two-dimensional

digital subtraction angiogram shows an anterior communicating artery aneurysm on a lateralview (arrow ). C , A three-dimensional rotational digital subtraction angiogram reveals that theanterior communicating artery aneurysm is irregular and trilobed and has a wide neck ( arrow ).

Continued from page 1265





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acute encephalopathy, and concomitantsubdural hematoma and head trauma,making the underlying diagnosis of SAH

more elusive. A minority of patients may have a warning ‘‘sentinel’’ headache daysto weeks before an aneurysmal SAH,

which is thought to represent a small an-eurysmal leak.18,19 Regrettably, this pieceof information is only obtained retro-spectively as most of the time the head-ache is transient and head CT scanningis unrevealing in about 50% of cases.

DIAGNOSISHead CT Scan

The most appropriate initial diagnos-tic test for patients suspected of havingSAH is a noncontrast head CT scan( Figure 1-2 ) ( Case 1-1A ).15 The sen-sitivity of a CT scan has been reportedto be 98% to 100% for the detectionof subarachnoid blood within 12 hoursof symptom onset when compared tolumbar puncture. However, the sensi-tivity of a CT scan decreases to 93% at

24 hours and 50% at 7 days.20,21 Thecharacteristic appearance of extravasatedblood in the basal subarachnoid cisterns

is hyperdense ( Figure 1-1 A). Other loca-tions include the sylvian fissures; inter-hemispheric fissure; interpeduncular fossa; and suprasellar, ambient, andquadrigeminal cisterns. CT also can detectintracerebral hemorrhage, intraventricu-lar hemorrhage, and hydrocephalus.

Although MRI may be as sensitive as CTscan in the first 2 days of SAH presen-tation, it is rarely performed in this sce-nario because of logistical issues.22,23 MRI

with hemosiderin-sensitive sequences

(gradient echo and susceptibility-weightedimaging) or with fluid-attenuated inver-sion recovery (FLAIR) sequences is moresensitive than CT scan when performedseveral days after the onset of SAH.

Lumbar Puncture

A lumbar puncture is recommended inany patient with suspected SAH and neg-ative or equivocal results on head CT

KEY POINTS

h In some instances,

diagnosis of

subarachnoid hemorrhagecan be elusive owing to

atypical findings on

presentation such as

seizures at onset, acute

encephalopathy, and

concomitant subdural

hematoma and

head trauma.

h The sensitivity of CT for

detection of subarachnoid

blood may be 98% to

100% when obtained

within 12 hours of onsetof symptoms, compared

to lumbar puncture.

TABLE 1-2 Focal Physical Findings in Patients With Subarachnoid Hemorrhage

Findings Likely Cause

Third nerve palsy Usually posterior communicating aneurysm; also posterior cerebralartery and superior cerebellar artery aneurysms

Sixth nerve palsy Elevated intracranial pressure (false localizing sign)

Combination of hemiparesis andaphasia or visuospatial neglect

Middle cerebral artery aneurysm, thick subarachnoid clots, orparenchymal hematomas

Bilateral leg weakness and abulia Anterior communicating artery aneurysm

Ophthalmoplegia Internal carotid artery aneurysm impinging upon the cavernous sinus

Unilateral visual loss or bitemporalhemianopia

Internal carotid artery aneurysm compressing optic nerve or optic chiasm

Impaired level of consciousness andimpaired upward gaze

Pressure on the dorsal midbrain due to hydrocephalus

Brainstem signs Brainstem compression by basilar artery aneurysm

Neck stiffness Meningeal irritation by the presence of subarachnoid blood

Retinal and subhyaloid hemorrhages Sudden increase of intracranial pressure

Preretinal hemorrhages (Terson syndrome) Vitreous hemorrhage due to severe elevations of intracranial pressure




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scan ( Figure 1-2 ). CSF should be col-lected four consecutive tubes, and redblood cell count should be determinedin tubes one and four.11,15 The diagno-

sis of SAH is supported by the following:elevated opening pressure, elevated redblood cell count that does not signifi-cantly decrease from tube one to tubefour, and especially xanthochromia. Thelatter, which indicates red blood cellbreakdown, can be determined by visualinspection or by spectrophotometry.

Xanthochromia takes about 12 hours todevelop after SAH, and spectropho-

tometry seems to be more sensitivethan visual inspection. However, mosthospitals in the United States use visualinspection, and no well-conducted clin-

ical studies exist that allow clinicians toknow with certainty what the false-negative rate for xanthochromia is at var-ious time intervals from SAH onset.24

Identification of Bleeding Source

All patients with a diagnostic CT scan or with eitherequivocal or diagnostic lumbar puncture must undergo further imaging

with CT angiography (CTA) or cerebral

KEY POINT

h The diagnosis of


is supportedby thefinding

of xanthochromia in CSF.

FIGURE 1-2 Diagnostic algorithm for subarachnoid hemorrhage.

CT = computed tomography.

Reprinted with permission from Suarez JI,et al,N Eng J Med.15

B 2006 Massachusetts Medical Society. www.nejm.org/doi/full/10.1056/

NEJMra052732.




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digital subtraction angiography (DSA)( Figure 1-1 ).11,15 The latter has tradition-

ally been considered the ‘‘gold stan-dard’’ to elucidate the source of bleedingin SAH (particularly aneurysmal), butCTA has become widely available andis being commonly performed as first-line vascular imaging or even in lieu of DSA in some centers. CTA has a sensi-tivity and specificity ranging from 90%to 97% and 93% to 100%, respectively,depending on technique (16-detector rows versus 64-detector rows, slice thick-ness, and data processing algorithms)and the reader’s experience.25,26 CTA may not be reliable for the detection of smaller (ie, less than 4 mm) or distal an-eurysms. The decision to perform CTA or DSA will vary depending on resourceavailability and institutional practices.However, loss of consciousness at theonset of SAH may be a strong predictor for the detection of ruptured cerebralaneurysm on subsequent DSA.27 Thus,in those patients with a negative CTA,this presentation should still prompt aDSA. In the author’s institution, a com-

bination of two-dimensional and three-dimensional DSA are performed as thestandard diagnostic testing for aneurysmdetection in all SAH cases. Patients witha negative DSA should have a repeatstudy 7 to 14 days after initial presenta-tion, and if negative, MRI should be per-formed to uncover a possible vascular malformation of the brain, brainstem,or spinal cord.15,23

Misdiagnosis

Misdiagnosis of SAH is still common

because the classic findings may occur inconsistently or patients may present

with atypical findings. Misdiagnosis isassociated with significantly increasedmortality and disability (up to fourfold)in those patients presenting withoutneurologic deficits at their initial hospital

visit. Fortunately, the frequency of SAHmisdiagnosis has decreased from morethan 60% in the early 1980s to less than

15% more recently.28,29 Nevertheless, itis important to emphasize that practi-

tioners should have a high level of sus-picion for any patient presenting withnew-onset headache and understandthe possible pitfalls in the diagnosis of SAH ( Table 1-3 ). A recent study reported100% sensitivity to detect SAH in pa-tients older than 40 years of age usingclinical decision-making rules that in-clude any of the following factors: neck pain or stiffness, witnessed loss of con-sciousness, and symptom onset duringexertion plus thunderclap headacheand pain on neck flexion.30

Perimesencephalic SubarachnoidHemorrhage

As previously mentioned, in about 15%of patients with SAH, imaging studiesfail to demonstrate the source of bleed-ing. Approximately 38% of these patientshave nonaneurysmal perimesencephalicSAH.31 Most patients with nonaneurys-mal perimesencephalic SAH (about 54%)are male and have a low risk of com-plications and better outcomes than pa-

tients with aneurysmal SAH. A correctdiagnosis is important because of thecatastrophic consequences of missinga ruptured cerebral aneurysm. Nona-neurysmal perimesencephalic SAH isconfirmed in the presence of a nega-tive CTA or DSA in patients with thefollowing head CT scan pattern32: cen-ter of hemorrhage located immediately anterior to the midbrain, with or withoutextension of blood to the anterior partof the ambient cistern or to the basalpart of the sylvian fissures; no completefilling of the anterior interhemisphericfissure and no extension to the lateralsylvian fissures, except for minuteamounts of blood; and absence of frank intraventricular blood ( Figure 1-3 ).

INITIAL EVALUATION

Initial evaluation and managementof patients with SAH should focus on

KEY POINTS

h All patients with a

diagnostic CT scan or

with either equivocal or

diagnostic lumbar

puncture must undergo

further imaging with CT

angiography or digital

subtraction angiography.

h Any of the following

clinical factors should

prompt a workup for


in patients older than 40:

neck pain or stiffness,

witnessed loss of

consciousness, andsymptom onset during

exertion plus thunderclap

headache and pain on

neck flexion.




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stabilization of airway, breathing, andcirculation.2,12,15,22,23 Once patientsare deemed stable, a head CT scan mustbe performed. Patients who are unable toprotect their airway should be intubatedimmediately. The most common indica-tions for endotracheal intubation include

coma, hydrocephalus, seizure, and needfor sedation for significant agitation. Inaddition, extreme blood pressure valuesshould be avoided. Hypertension controlis predicated on the premise that it may precipitate rebleeding.33 No data fromrandomized controlled clinical trials exist,but usual practice and current recommen-dations are to maintain a mean arterialblood pressure of less than 110 mm Hg

or a systolic blood pressure of less than160 mm Hg until the ruptured aneu-rysm is secured, while using premorbidbaseline blood pressures to refine tar-gets and avoid hypotension. Commonly,pain control may be sufficient to achieveblood pressure control;otherwise, admin-

istration of IV labetalol (5 mg to 20 mg),hydralazine (5 mg to 20 mg), or continu-ous infusion of nicardipine (5 mg/h to15 mg/h) is preferred. Pain control isbest achieved with the administrationof short-acting opiates ( Case 1-1A ).

Disease Severity Scoring

The severity of neurologic impair-ment and the amount of subarachnoid

KEY POINT

h Mean arterial blood

pressure should be

maintained at less than

110 mm Hg or systolic

blood pressure at less

than 160 mm Hg until

the ruptured aneurysm

is secured, whileavoiding hypotension.

TABLE 1-3 Reasons for Misdiagnosis of Subarachnoid Hemorrhagea

b Failure to Recognize Spectrum of Presentation of Subarachnoid Hemorrhage

Not obtaining complete history from patients with unusual (for the patient) headaches(Was the onset abrupt? Is the quality different and severity greater than prior headaches?)

Failure to appreciate that the headache can improve spontaneously or with non-narcotic analgesics

Focusing on the secondary head injury resulting from syncope and fall or motor vehicle collision

Focusing on ECG findings

Focusing on elevated blood pressure

Overreliance on the classic presentation

Assuming symptoms may be related to other disorders (eg, viral syndrome, viral meningitis, migraine,tension-type headache, sinus-related headache, psychiatric disorder)

b Failure to Understand the Limitations of Head CT Scanning

Sensitivity decreases with increasing time from onset of headache

False-negative results with small-volume bleeds

Lack of experience of physician reader

Motion artifacts or lack of thin cuts of posterior fossa

False-negative results due to hematocrit of less than 30%

b Failure to Perform Lumbar Puncture or Interpret the CSF Findings Correctly

Failure to perform lumbar puncture in patients with negative or inconclusive CT scans

Failure to distinguish a traumatic tap from true subarachnoid hemorrhage

Failure to recognize that xanthochromia may be absent very early (less than 12 hours) and very late(more than 2 weeks)

CSF = cerebrospinal fluid; CT = computed tomography; ECG = electrocardiogram.a Data from Edlow JA, et al, J Emerg Med.11 www.jem-journal.com/article/S0736-4679(07)00729-9/abstract .




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bleeding on admission are the strongestpredictors of neurologic complicationsand outcome.15,23 Therefore, it isessential that patients with SAH bescored promptly after arrival and sta-bilization. There are several scoringsystems available. However, the World

Federation of Neurological SurgeonsScale (WFNSS) and the modified Fisher Scale are the most reliable and simple

to perform ( Table 1-415,34,35 ).23 Higher WFNSS and modified Fisher Sca lescores are associated with worse clin-ical outcome and a higher proportionof neurologic complications.

Admission to High-Volume

CentersThe next immediate steps are to transfer the patient to a high-volume center (if not

KEY POINT

h The severity of neurologic

impairment and the

amount of subarachnoid

bleeding on admission are

the strongest predictors

of neurologic complications

and outcome.

FIGURE 1-3 Noncontrast head CT scan of a patient with nonaneurysmal perimesencephalic subarachnoid hemorrhage.The center of the hemorrhage is located immediately anterior to the midbrain ( A and C , arrows) and extendsto the anterior part of the ambient cistern (B, arrow ).

TABLE 1-4 Clinical and Radiologic Grading Scales for Subarachnoid Hemorrhagea

World Federation of NeurologicalSurgeons Scale34 Modified Fisher Scale35

GradeGlasgowComa Scale

NeurologicExamination Grade

SubarachnoidHemorrhage

IntraventricularHemorrhage

1 15 No motor deficit 0 Absent Absent

2 13 Y 14 No motor deficit 1 Minimal Absent in both lateral ventricles

3 13 Y 14 Motor deficit 2 Minimal Present in both lateral ventricles

4 7 Y 12 With or withoutmotor deficit

3 Thickb Absent in both lateral ventricles

5 3 Y 6 With or withoutmotor deficit

4 Thickb Present in both lateral ventricles

a Modified with permissionfromSuarezJI, etal, N EnglJ Med.15 B 2006 Massachusetts Medical Society. www.nejm.org/doi/full/10.1056/NEJMra052732.b Thick is defined as a hemorrhage filling one or more cisterns or fissures out of a total of 10: interhemispheric fissure, the quadrigeminal

cistern, both suprasellar cisterns, both ambient cisterns, both basal sylvian fissures, and both lateral sylvian fissures.



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already in one), admit the patient to adedicatedneurocritical care unit, and have

the patient undergo a multidisciplinary evaluation for the management of an un-secured cerebral aneurysm ( Table 1-5 ).2,12

It has been shown that admission of pa-tients with SAH to low-volume centers

is associated with higher 30-day mor-tality compared to admission to high-

volume centers. In addition, admission

TABLE 1-5 Summary of Key Recommendations for the Management of Patients WithSubarachnoid Hemorrhage

TreatmentDecision

American Heart Association/AmericanStroke Association2,a Neurocritical Care Society12,b

Hospital/systemcharacteristics

Low-volume hospitals (eg, less than10 subarachnoid hemorrhage [SAH] casesper year) should consider early transfer ofpatients with SAH to high-volume centers(eg, more than 35 SAH cases per year) withexperienced cerebrovascular surgeons,endovascular specialists, andmultidisciplinary neurointensive careservices (Class I, Level B).

Patients with SAH should be treated athigh-volume centers (moderate qualityof evidence, strong recommendation).

After discharge, it is reasonable to referpatients with SAH for a comprehensiveevaluation, including cognitive, behavioral,and psychosocial assessments(Class IIa, Level B).

High-volume centers should haveappropriate specialty neurointensivecare units, neurointensivists, vascularneurosurgeons, and interventionalneuroradiologists to provide theessential elements of care(moderate quality of evidence,strong recommendation).

Aneurysm treatment Surgical clipping or endovascular coiling ofthe ruptured aneurysm should beperformed as early as feasible in the

majority of patients to reduce the rate ofrebleeding after SAH (Class I, Level B).

Early aneurysm repair should beundertaken, when possible and reasonableto prevent rebleeding (high quality of

evidence, strong recommendation).

For patients with ruptured aneurysms judged to be technically amenable to eitherendovascular coiling and neurosurgicalclipping, endovascular coiling should beconsidered (Class I, Level B).

An early, short course of antifibrinolytictherapy prior to early aneurysm repair(begun at diagnosis and continued up tothe point at which the aneurysm is securedor at 72 hours post ictus, whichever isshorter) should be considered (low qualityof evidence, weak recommendation).

Complete obliteration of the aneurysm isrecommended whenever possible(Class I, Level B).

Delayed (more than 48 hours after theictus) or prolonged (more than 3 days)antifibrinolytic therapy exposes patientsto side effects of therapy when the riskof rebleeding is sharply reduced andshould be avoided (high quality of

evidence, strong recommendation).

Stenting of a ruptured aneurysm is associatedwith increased morbidity and mortality(Class III, Level C).

For patients with an unavoidable delay inobliteration of aneurysm, a significant riskof rebleeding, and no compelling medicalcontraindications, short-term (less than72 hours) therapy with tranexamic acid oraminocaproic acid is reasonable to reducethe risk of early aneurysm rebleeding(Class IIa, Level B).






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TABLE 1-5 Summary of Key Recommendations for the Management of Patients WithSubarachnoid Hemorrhage Continued from page 1272

TreatmentDecision


Blood pressure control Between the time of SAH symptom onsetand aneurysm obliteration, blood pressureshould be controlled with a titratableagent to balance the risk of stroke,hypertension-related rebleeding, andmaintenance of cerebral perfusionpressure (Class I, Level B).

Treat extreme hypertension in patientswith an unsecured, recently rupturedaneurysm. Modest elevations in bloodpressure (mean blood pressure of less than110 mm Hg) do not require therapy.Premorbid baseline blood pressures shouldbe used to refine targets and hypotensionshould be avoided (low quality of evidence,strong recommendation).

The magnitude of blood pressure controlto reduce the risk of rebleeding has notbeen established, but a decrease in systolic

blood pressure to less than 160 mm Hgis reasonable (Class IIa, Level C).

Intravascularvolume status

Maintenance of euvolemia and normalcirculating blood volume is recommendedto prevent delayed cerebral ischemia(Class I, Level B).

Intravascular volume management shouldtarget euvolemia and avoid prophylactichypervolemic therapy. In contrast, there isevidence for harm from aggressiveadministration of fluid aimed at achievinghypervolemia (moderate qualityof evidence, strong recommendation).

Cardiopulmonarycomplications

No recommendations given. Baseline cardiac assessment with serialenzymes, ECG, and echocardiography isrecommended, especially in patientswith evidence of myocardial dysfunction(low quality of evidence, strong

recommendation).

Monitoring of cardiac output may be usefulin patients with evidence of hemodynamicinstability or myocardial dysfunction(low quality of evidence, strongrecommendation).

Seizures The use of prophylactic anticonvulsantsmay be considered in the immediateposthemorrhagic period (Class IIb, Level B).

Routine use of anticonvulsant prophylaxiswith phenytoin is not recommendedafter SAH (low quality of evidence,strong recommendation).

The routine long-term use of anticonvulsantsis not recommended (Class III, Level B). If anticonvulsant prophylaxis is used, a short

course (3 Y 7 days) is recommended (lowquality of evidence, weak recommendation).

Continuous EEG monitoring should beconsidered in patients with poor-gradeSAH who fail to improve or who haveneurologic deterioration of undeterminedetiology (low quality of evidence,strong recommendation).





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TreatmentDecision


Fever treatment Aggressive control of fever to a target ofnormothermia by use of standard oradvanced temperature-modulating systemsis reasonable in the acute phase of SAH(Class IIa, Level B).

During the period of risk for delayed cerebralischemia, control of fever is desirable;intensity should reflect the individualpatient’s relative risk of ischemia (lowquality of evidence, strong recommendation).

Surface cooling or intravascular devicesaremore effective andshould be employedwhen antipyretics fail in cases where fevercontrol is highly desirable (high quality ofevidence, strong recommendation).

Glucose control Careful glucose management with strictavoidance of hypoglycemia may beconsidered as part of the general criticalcare management of patients with SAH(Class IIb, Level B).

Hypoglycemia (serum glucose of less than80 mg/dL) should be avoided (high qualityof evidence, strong recommendation).

Serum glucose should be maintainedbelow 200 mg/dL (moderate quality ofevidence, strong recommendation).

Deep venousthrombosisprophylaxis

Heparin-induced thrombocytopenia anddeep venous thrombosis are relativelyfrequent complications after SAH. Earlyidentification and targeted treatment arerecommended,but further research is neededto identify the ideal screening paradigms(Class I, Level B).

Measures to prevent deep venousthrombosis should be employed in allpatients with SAH (high quality of evidence,strong recommendation).

The use of unfractionated heparin forprophylaxis could be started 24 hoursafter undergoing aneurysm obliteration

(moderate quality of evidence,strong recommendation).

Delayed cerebralischemia

Oral nimodipine should be administered toall patients with SAH (Class I, Level A).

Oral nimodipine (60 mg every 4 hours)should be administered after SAH fora period of 21 days (high quality ofevidence, strong recommendation).

Maintenance of euvolemia and normalcirculating blood volume is recommendedto prevent delayed cerebral ischemia(Class I, Level B).

The goal should be maintainingeuvolemia, rather than attemptinghypervolemia (moderate qualityof evidence, strong recommendation).

Prophylactic hypervolemia or balloonangioplasty before the development ofangiographic spasm is not recommended(Class III, Level B).

Transcranial Doppler may be used formonitoring and detection of large arteryvasospasm with variable sensitivity(moderate quality of evidence,strong recommendation).

Transcranial Doppler is reasonable tomonitor for the development of arterialvasospasm (Class IIa, Level B).

Digital subtraction angiography is thegold standard for detection of largeartery vasospasm (high quality of evidence,strong recommendation).

Perfusion imaging with CT or MRI can beuseful to identify regions of potentialbrain ischemia (Class IIa, Level B).






13/25

to dedicated neurocritical care units st-affed by dedicated neurointensivists isassociated with decreased in-hospitalmortality.36

Treatment of UnsecuredAneurysms

Treatment of unsecured aneurysms has

evolved, and two accepted efficacious

management modalities currently exist:

surgical clipping and endovascular coil-

ing. The choice of treatment depends

on several factors, including the pa-

tient’s age and aneurysm location,

morphology, and relationship to ad-

jacent vessels. Because of the complex-

ity of determining the most appropriate

treatment for individual patients, it

is recommended that a multidisciplin-

ary team made up of cerebrovascular

neurosurgeons, endovascular practi-

tioners, and neurointensivists confer


TreatmentDecision


Induction of hypertension is recommendedfor patients with delayed cerebral ischemiaunless blood pressure is elevated atbaseline or cardiac status precludes it(Class I, Level B).

Patients clinically suspected of delayedcerebral ischemia should undergo atrial of induced hypertension(moderate quality of evidence,strong recommendation).

Cerebral angioplasty and/or selectiveintra-arterial vasodilator therapy isreasonable in patients with symptomaticvasospasm, particularly those who arenot responding to hypertensive therapy

(Class IIa, Level B).

Endovascular treatment usingintra-arterial vasodilators and/orangioplasty may be considered forvasospasm-related delayed cerebralischemia (moderate quality of evidence,

strong recommendation).

Anemia andtransfusion

The use of packed red blood celltransfusion to treat anemia might bereasonable in patients with SAH whoare at risk of cerebral ischemia. Theoptimal hemoglobin goal is still to bedetermined (Class IIb, Level B).

Patients should receive packed red bloodcell transfusions to maintain hemoglobinconcentration above 8 Y 10 g/dL (moderatequality of evidence, strongrecommendation).

Hyponatremia The use of fludrocortisone acetate andhypertonic saline solution is reasonablefor preventing and correctinghyponatremia (Class IIa, Level B).

Fluid restriction should not be used totreat hyponatremia (weak quality ofevidence, strong recommendation).

Early treatment with hydrocortisoneor fludrocortisone may be used tolimit natriuresis and hyponatremia

(moderate quality of evidence,weak recommendation).

Mild hypertonic saline solutions can be usedto correct hyponatremia (very low qualityof evidence, strong recommendation).

CT = computed tomography; ECG = electrocardiogram; EEG = electroencephalogram; MRI = magnetic resonance imaging.a American Heart Association / American Stroke Association recommendations follow the American Heart Association Stroke

Council’s methods of classifying the level of certainty of the treatment effect and the class of evidence.b For the Neurocritical Care Society’s guidelines, the quality of the data was assessed and recommendations developed using the

Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system.

KEY POINT

h Admission of patients

with subarachnoidhemorrhage to

low-volume centers is

associated with higher

30-day mortality

compared to admission

to high-volume centers.




14/25

to reach a consensus.2,12,15,22,23,29 The

International Subarachnoid Aneurysm

Trial (ISAT) was a prospective random-ized controlled clinical trial that evalu-

ated patients with unsecured aneurysms

who were considered suitable for either

endovascular coiling or surgical clip-

ping.13,14 Patients assigned to the endo-

vascular coiling group had a significantly

higher favorable outcome (defined as

survival free of disability at 1 year)

and lower risk of epilepsy compared

to those assigned to the surgical clip-

ping group. However, the risk of

rebleeding and partial occlusion of aneurysms was lower with surgical

clipping. Overall, endovascular coil-

ing should be preferred over surgical

clipping whenever possible; however,

many aneurysms are not equally suit-

able for either surgical clipping or endo-

vascular coiling ( Table 1-6 ) ( Case 1-1A ).

Regardless of the treatment modality

chosen, unsecured aneurysms must be

treated as soon as possible to prevent

rebleeding ( Table 1-5 ). In the author’s

institution, the median time for aneu-rysm treatment is 7 hours from initial

hospital arrival.

INTENSIVE CARE UNITMANAGEMENT

SAH is often accompanied by more se-

vere initial systemic and intracranial re-

sponses than other cerebral insults.37 Y 40

More than 75% of patients with SAH

experience systemic inflammatory re-

sponse syndrome (SIRS), which is likely

related to elevated levels of inflammatory

cytokines. SIRS has been associated with

permanent neurocognitive dysfunction.In addition, patients with SAH are at risk

for several significant neurologic com-

plications, including hydrocephalus, cere-

bral edema, delayed cerebral ischemia,

rebleeding, seizures, and neuroendo-

crine abnormalities that lead to impaired

body regulation of sodium, water, and

glucose. Furthermore, SAH unleashes

hypothalamic-mediated changes, includ-

ing increased sympathetic and parasym-pathetic drive, that result in cardiac and

pulmonary complications. For example,

increased circulating catecholamines are

thought to be the cause for several cardiac

manifestations, including ECG changes,

arrhythmias, impaired cardiac contrac-

tility (eg, Takotsubo cardiomyopathy),

troponinemia, and myocardial necrosis.

Pulmonary complications, such as neu-

rogenic pulmonary edema, most likely

have a similar underlying pathophysi-

ologic mechanism. It is important torecognize and treat all these systemic

complications as they are associated

with increased risk for delayed cerebral

ischemia and poor neurologic outcome

after SAH.

Neurologic Complications

Rebleeding. Rebleeding is a major dis-

abling complication of SAH, which car-

ries high mortality and morbidity. In

the first 24 hours, 4% to 15% of pa-

tients will rebleed, with the highest risk occurring less than 6 hours from symp-tom onset.33 Rebleeding risk decreasesover the following 2 weeks. The mainrisk factors associated with rebleeding

include high systolic blood pressure

(ie, greater than 160 mm Hg), poor neu-

rologic grade, intracerebral or intraven-

tricular hematomas, ruptured posterior

circulation aneurysms, and aneurysms

of greater than 10 mm in size.33

The best measure to reduce the risk

of rebleeding is the early treatment of unsecured aneurysms ( Table 1-5 ).2,12

However, in some instances there may be a delay in surgical clipping or endo-

vascular coiling of the aneurysm, andshort-term (ie, less than 72 hours) treat-ment with tranexamic acid or amino-caproic acid has been recommended if no contraindications exist. The use of these antifibrinolytic agents is based

KEY POINTS

h Overall, when

considering treatment of

unruptured aneurysms,

endovascular coiling

should be preferred over

surgical clipping

whenever possible.

h Patients with

subarachnoid

hemorrhage are at risk

for several significant

neurologic complications,

including hydrocephalus,

cerebral edema,

delayed cerebral ischemia,

rebleeding, seizures,and neuroendocrine

abnormalities.

h The best measure to

reduce the risk of

rebleeding is the

early treatment of

unsecured aneurysms.





15/25

on the premise that early risk for re-bleeding is a consequence of activatedfibrinolysis and reduced clot stability during the first 6 hours. In addition,

blood pressure control is also very im-portant to prevent rebleeding prior toaneurysm obliteration, as previously mentioned. Patients suspected of re-bleeding should be evaluated promptly,have a follow-up head CT scan and DSA (if not already done), and immediately undergo aneurysm obliteration. Endo-

vascular treatment of ruptured cere-bral aneurysms should include coilingonly. Stenting of cerebral aneurysms inthe setting of SAH should be avoidedas it is associated with higher bleedingcomplications and poor outcome.2

Hydrocephalus. Acute symptomatic

hydrocephalus occurs in about 20% of

patients with SAH, usually within the

first few days after symptom onset.2,15,22

Patients manifestdecreased levels of con-

sciousness and other signs of increasedICP, such as impaired upward gaze andhypertension. An immediate follow-up

head CT scan is warranted in any patient with suspected symptomatic hydroceph-alus and must be followed by insertion

of an external ventricular drain (EVD).

Some centers perform lumbar drain in-sertion instead of EVD in patients withSAH who have communicating hydro-cephalus. Weaning the patient of an EVD

should begin shortly after aneurysm ob-literation or within 48 hours of insertionif the patient is neurologically stable. A rapid weaning protocol is preferred.

About 60% of patients with SAH who

undergo EVD insertion will have suc-cessful weaning, and the others may require chronic ventriculoperitoneal

shunt insertion ( Case 1-1B ).Seizures. Delineating the true fre-quency of seizures in patients with SAHhas been difficult and controversial asmany patients (20% to 26%) present withseizurelike episodes that are not easy tocharacterize as many of them occur atthe time of symptom onset.2,12 Y 15 Ingeneral, patients with middle cerebralartery (MCA) aneurysms, concomitant

KEY POINT

h About 60% of patients

with subarachnoid

hemorrhage who undergo

external ventricular drain

insertion will have

successful weaning and

the others may require

chronic ventriculoperitoneal

shunt insertion.

TABLE 1-6 Preferences for Treatment of Unsecured Aneurysms

CharacteristicsPreferred TreatmentModality

Advanced age Endovascular coiling

Poor clinical grade Endovascular coiling

Multiple underlying systemic conditions Endovascular coiling

Aneurysms with wide neck-to-body ratio Surgical clipping

Normal arterial branches arising from dome or bodyof aneurysm

Surgical clipping

Middle cerebral artery aneurysm Surgical clipping

Top-of-the-basilar aneurysm Endovascular coiling

Aneurysm associated with large parenchymal hematoma Surgical clipping

High surgical risk Endovascular coiling

Patient preference Endovascular coiling

Clinical equipoisea Endovascular coiling

a Unsecured aneurysm is considered equallysuitable for either endovascular coiling or surgical clipping.




16/25

intraparenchymal hematomas, and poor clinical grade are at higher risk for sei-

zures, whereas patients treated withendovascular coiling have lower ratesof seizures. Long-term risk for epilepsy is low.

The administration of prophylacticanticonvulsants in patients with SAH wascommon practice; however, anticonvul-sant administration (particularly phenyt-oin) has been associated with worseclinical outcome and a high frequency of medication-related complications.2,12

Current recommendations are to avoidphenytoin, and, if desirable, short-termanticonvulsant administration for 3 to7 days could be administered. In addi-tion, concern exists that the frequency of subclinical seizures may be high inpatients with poor-grade SAH, and con-tinuous EEG has been recommended inthis setting.12

Delayed cerebral ischemia. Delayed

cerebral ischemia is one of the most

dreaded complications after SAH and isthe most important factor impacting func-

tional outcome.39 Y 41 Delayed cerebral

ischemia occurs in about 30% of pa-

tients with SAH, usually between 4 and

14 days after the onset of symptoms.

Delayed cerebral ischemia is defined as

any neurologic deterioration (focal or

global) presumed secondary to cerebral

ischemia that persists for more than 1

hour and cannot be explained by any

other neurologic or systemic condition.

The latter implies an absence of signif-icant hydrocephalus, sedation, hypox-

emia, seizures, and electrolyte or renal or

hepatic impairment. Thus, delayed cere-

bral ischemia is a diagnosis of exclusion.Several factors have been impli-

cated in the pathogenesis of delayed

KEY POINTS

h Anticonvulsant

administration

(particularly phenytoin)

has been associated

with worse

clinical outcome.

h Delayed cerebral ischemia

is defined as any

neurologic deterioration

(focal or global) presumed

secondary to cerebral

ischemia that persists for

more than 1 hour and

cannot be explained by

any other neurologic or

systemic condition.

Case 1-1BThe patient discussed in Case 1-1A continued to evolve satisfactorily with normal mean cerebral bloodflow velocities by transcranial Doppler (TCD). On postbleed day 6, TCD revealed an increase in mean

cerebral blood flow velocity in the right middle cerebral artery (MCA) to 160 cm/s from 80 cm/s onday 5. The next morning, the patient developed a sudden onset of left hemiparesis and confusion.A head CT scan revealed no rebleeding, cerebral edema, or hydrocephalus. She was given anIV bolus of 500 mL of 0.9% saline and was started on a norepinephrine drip with some improvementof her left hemiparesis but without complete resolution. The patient’s electrolytes, blood urea nitrogen,creatinine, and liver function tests were normal, and her white blood cell count was 14,000 cells/mm 3.A follow-up TCD after neurologic deterioration showed a further increase in mean cerebral blood flowvelocity of her right MCA to 220 cm/s and a Lindegaard ratio (MCA/extracranial internal carotidartery mean blood flow velocities) of 6. Digital subtraction angiography (DSA) was performed 90 minutesafter symptom onset, showing severe vasospasm of her right MCA and anterior cerebral artery (ACA)(Figure 1-4A). She underwent balloon angioplasty of the right MCA and subsequent intra-arterialinfusion of nicardipine in both the right MCA and ACA with radiologic and clinical improvement(Figure 1-4B). The patient’s neurologic examination normalized, and her systolic blood pressure wasmaintained at greater than 180 mm Hg for 3 more days. Her TCD showed improvement in meancerebral blood flow velocities to less than 100 cm/s by day 9, and the patient was slowly weaned offnorepinephrine by day 10. On day 11 she developed a decreased level of consciousness without focalneurologic findings except for limited upward gaze. A follow-up head CT scan showed communicatinghydrocephalus, and an external ventricular drain (EVD) was inserted (Figure 1-4C). Several attempts atweaning the patient off the EVD failed and, therefore, she underwent programmable ventriculoperitonealshunt placement (Figure 1-4D) on day 15, after which she was transferred to the regular floor. Thepatient was discharged to home on day 17, after clearance by physical and occupational therapies, withinstructions to continue nimodipine for 4 more days and schedule follow-up in vascular neurology andneurosurgery outpatient clinics.






17/25


18/25

cerebral ischemia, including cerebral va-

sospasm, microcirculatory constriction,

microthrombosis, cortical spreadingdepression, and delayed cellular apo-

ptosis.39 Most likely, the main driver of

all these processes is the release of oxy-

hemoglobin and erythrocyte contents

through hemolysis, which unleashes a

host of inflammatory and proapoptotic

factors. The risk for cerebral vasospasm

increases with the thickness, density,

location, and persistence of the sub-

arachnoid blood. In addition, poor

clinical grade, loss of consciousness at

ictus, cigarette smoking, cocaine use,SIRS, hyperglycemia, and hydrocepha-

lus also increase the risk of delayed

cerebral ischemia and poor neurologic

outcome.39,40 However, predicting who

will develop delayed cerebral ischemia

has proven very difficult. The latter has

important implications for the reduc-

tion of level of monitoring in patients

with SAH who are at low risk for delayed

cerebral ischemia, thus avoiding poten-

tial adverse effects of aggressive man-

agement and potentially decreasingresource utilization. The best predic-

tors for patients requiring less frequent

monitoring include older age (more than

65 years), a WFNSS score of 1 to 3, and

a modified Fisher Scale score less than

3 ( Table 1-5 ).39

Prophylaxis. The best studied of theavailable interventions aimed at prevent-ing delayed cerebral ischemia are calciumchannel blockers and intravascular vol-ume status. The use of nimodipine to

decrease the risk of delayed cerebralischemia and poor functional outcomeis well supported and recommended( Table 1-5 ).2,12,23,39 Nimodipine is ad-ministered by enteral route at 60 mgevery 4 hours for 21 days. Nimodipineaffords neuroprotection without decreas-ing the frequency of angiographic vaso-spasm. The most common adverse effectsof nimodipine include constipation and

hypotension. The latter could be prob-lematic as it could lead to hypoperfusion

due to decreased cerebral perfusion pres-sure (CPP). Therefore, it is important thatsystolic blood pressure not be compro-mised when administering nimodipine.One solution employed by the author isto half the nimodipine dose to 30 mgevery 2 hours while maintaining ade-quate intravascular volume.

Patients with SAH frequently experi-ence decreased intravascular volume andnegative fluid balance, which have beenassociated with higher incidence of cere-

bral infarction and poor neurologic out-come. These findings led to the institutionof prophylactic hypervolemic therapy.However, this strategy hasnotbeen shownto improve cerebral blood flow (CBF) or decrease the frequency of cerebral vaso-spasm or delayed cerebral ischemia, andit increases the frequency of cardiopul-monary complications. Therefore, pro-phylactic hypervolemia should not bepursued. Current recommendations areto maintain euvolemia at all times after SAH.2,12 It is important to emphasize

that controversy still exists about themethodology to follow to determineeuvolemia. Many neurointensivists use acombination of methods, including strictmonitoring of fluid balance, central

venous pressure, echocardiogram, andstroke volume variation, among others.In practice, maintenance of euvolemiacan generally be ensured by replacingurine output and even administeringfludrocortisone or hydrocortisone in pa-tients with significant diuresis ( Table 1-5 ).

Diagnosis and monitoring. Diagnos-ing delayed cerebral ischemia is not easy.However, the combination of neurologicexamination and imaging studies canenhance the chances of early detectionandmanagement. Patients with SAHmustbe in the neurocritical care unit wherethey can be examined very frequently,preferably at least every 2 hours. Delayedcerebral ischemia must be suspected

KEY POINTS

h Possible underlying

conditions implicated

in the pathogenesis

of delayed cerebral

ischemia include

cerebral vasospasm,

microcirculatory

constriction,

microthrombosis, cortical

spreading depression, and

delayed cellular apoptosis.

h Nimodipine should be

administered to all

patients with

subarachnoid

hemorrhage to decreasethe risk of delayed

cerebral ischemia

and poor

functional outcome.

h Euvolemia should be

maintained at all times,

while prophylactic

hypervolemia should

be avoided.





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when patients with SAH develop focalneurologic impairment or a decrease

of at least 2 points on the Glasgow ComaScale that lasts for more than 1 hour and cannot be explained by any other cause. In addition, all patients with SAHshould undergo head CT or MRI 24 to48 hours after aneurysm occlusion.Therefore, any new hypodensities onCT imaging after this period not attri-butable to EVD insertion or intra-parenchymal hematoma should beregarded as cerebral infarctions fromdelayed cerebral ischemia regardless of

clinical signs.

41

The general consensus among prac-titioners indicates that patients with SAHshould undergo additional imaging and/or physiologic monitoring routinely duringthe risk period for delayed cerebral isch-emia ( Table 1-5 ).2,12 Such monitoring isusually multimodal and includes ICP,CPP, CBF, EEG, transcranial Doppler (TCD), DSA, CTA, CT perfusion (CTP),and brain tissue oxygenation. TCD hasbeen the longest and best studied of allthe monitoring modalities. TCD has

adequate sensitivity and specificity todetect delayed cerebral ischemia sec-ondary to cerebral vasospasm in largearteries compared to DSA, but is limitedby the operator’s experience and thepatient’s cranial windows.42 TCD thresh-olds for vasospasm are the following:mean cerebral blood flow velocities of less than 120 cm/s for absence and morethan 200 cm/s or a Lindegaard ratio (MCA mean cerebral blood flow velocity/extra-cranial internal carotid artery mean

cerebral blood flow velocity) of greater than 6 for presence. In addition, meancerebral blood flow velocity increases by more than 50 cm/s within 24 to 48 hoursalso have been associated with delayedcerebral ischemia.

DSA is the gold standard for detectionof large artery vasospasm.2,12 CTA hasbecome more widely available and may replace DSA for screening of vasospasm

with a high degree of specificity. CTPfindings of an elevated mean transit time

(MTT) of greater than 6.4 seconds may be additive to CTA in predicting delayedcerebral ischemia and has been recom-mended as a threshold for decreasedcerebral perfusion. Qualitative visual in-terpretation of CTP can also be useful.Brain tissue oxygenation and CBF moni-toring can provide additional information

when used in the context of a multimo-dality approach, bearing in mind their limitations, such as limited tissue sam-pling and location in relation to pathology.

Continuous EEG offers the advantage of being able to monitor broad regions of the brain to detect epileptiform dis-charges noninvasively. Continuous EEGis particularly useful in patients with poor-grade SAH where neurologic examina-tion is limited.

Some variability exists regarding the

timing and frequency of use of the var-

ious neuromonitoring techniques men-tioned above. The author’s institution

follows an algorithm for identifying andtreating subarachnoid hemorrhage sim-

ilar to the one proposed by Macdonaldas shown in Figure 1-5.39 Patients with

SAH are stratified into low risk (ie, older age, a WFNSS score of 1 to 2, and a mod-

ified Fisher Scale score of less than 3),

high risk (ie, a WFNSS score of 1 to 3

and a modified Fisher Scale score of 3),and high risk with poor neurologic

status (ie, clouded examination due tosedation, a WFNSS score of 3 to 5, anda modified Fisher Scale score of 4). Allpatients with aneurysmal SAH undergo

TCD (daily or every other day) and headCT/CTA/CTP on admission and on days3 to 5 and days 7 to 10 for screening of decreased cerebral perfusion or vaso-spasm. DSA also can be performed inlieu of CTA/CTP. High-risk patients

with poor neurologic status undergoadditional neuromonitoring, includ-ing EEG, brain tissue oxygenation, andCBF determination.

KEY POINTS

h Delayed cerebral

ischemia must be

suspected when patients

with subarachnoid

hemorrhage develop

focal neurologic

impairment or a decrease

of at least 2 points on

the Glasgow Coma Scale

that lasts for more than

1 hour and cannot

be explained

by any other cause.

h Any new hypodensities

on CT imaging 24 to

48 hours after aneurysmtreatment should be

regarded as cerebral

infarctions from delayed

cerebral ischemia.

h Transcranial Doppler

thresholds for vasospasm

include mean cerebral

blood flow velocities of

less than 120 cm/s for

absence and more than

200cm/s or a Lindegaard

ratio of greater than

6 for presence.

h Digital subtraction

angiography is the gold

standard for detection of

large artery vasospasm.

h CT perfusion findings of

elevated mean transit

time of greater than

6.4 seconds may be

additive to CT angiography

in predicting delayed

cerebral ischemia and

has been recommended

as a thresholdfor decreasedcerebral perfusion.




20/25

Management. All of the patients withSAH in the author’s institution are treated

with nimodipine and euvolemia as men-tioned above ( Table 1-5 ) ( Figure 1-5 ).

Low-risk patients whose neurologic ex-

amination remains unchanged along with absence of vasospasm and hypo-

perfusion on TCD and CTA/CTP are

considered for transfer to a lower level

of care as early as 5 days post ictus.

High-risk patients who have good

neurologic status and whose neurologic

examination remains unchanged along

with normal TCD and CTA/CTP aretransferred out of the neurocritical care

unit as early as 7 days after symptom

onset. High-risk patients with poor

neurologic status, whose examination

FIGURE 1-5 Management approach to delayed cerebral ischemia.

BP = blood pressure; CPP = cerebral perfusion pressure; CT = computed tomography; CTA = computedtomography angiography; CTP = computed tomography perfusion; DCI = delayed cerebral ischemia;

ICP = intracranial pressure; IVH = intraventricular hemorrhage; MTT = mean transit time; SAH = subarachnoid hemorrhage;TCD = transcranial Doppler; WFNSS = World Federation of Neurological Surgeons Scale.

Reprinted with permission from Macdonald RL, Nat Rev Neurol.39

B 2014 Macmillan Publishers Limited. www.nature.com/nrneurol/journal/v10/n1/full/

nrneurol.2013.246.html .




http://www.nature.com/nrneurol/journal/v10/n1/full/nrneurol.2013.246.htmlhttp://www.nature.com/nrneurol/journal/v10/n1/full/nrneurol.2013.246.htmlhttp://www.nature.com/nrneurol/journal/v10/n1/full/nrneurol.2013.246.htmlhttp://www.nature.com/nrneurol/journal/v10/n1/full/nrneurol.2013.246.htmlhttp://www.nature.com/nrneurol/journal/v10/n1/full/nrneurol.2013.246.html


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remains unchanged, and all neuro-

monitoring values remain within normal

limits, are considered for transfer to alower level of care 14 days after SAH. If at any given time low-risk or high-risk patients develop elevated TCD mean ce-rebral blood flow velocities or abnormalCTA/CTP, the intensity and frequency of neurologic monitoring is escalated.

Once patients experience neuro-

logic deterioration suggestive of delayed

cerebral ischemia, rescue therapies are

initiated. Current guidelines indicate

that induced hypertension is indicated

( Table 1-5 ) ( Figure 1-5 ).

2,12

At the au-thor’s institution, typically, an IV fluid

bolus (1 to 2 liters of 0.9% saline) is ad-

ministered and hypertension is induced

with norepinephrine as our drug of

choice. Blood pressure augmentation

progresses in stepwise fashion with fre-

quent assessment of neurologic functionat each 10 mm Hg change in systolic(up to 200 mm Hg) or mean arterialblood pressures to determine whether a higher blood pressure target is needed.The author’s institution reserves the use

of inotropes (dobutamine or milrinone)for those patients with known poor car-diac function. If neurologic deficits per-sist, then the patient undergoes CT/CTA/ CTP or DSA with subsequent endovas-cular therapy once cerebral vasospasmis confirmed. Endovascular treatmentusing intra-arterial vasodilators and/or angioplasty is supported by prospectiveand retrospective observational data andis currently recommended ( Table 1-5 ).2,12

Induced hypertension is maintained

for at least 72 hours or until stability isachieved and is slowly weaned off after that. We do not perform prophylacticangioplasty when cerebral vasospasmis discovered during the screeningCT/CTA/CTP or DSA without neurologicdeterioration because this practice isassociated with higher complicationrates.2,12 In high-risk patients with poor neurologic status, diagnosis and treat-

ment of delayed cerebral ischemia may be somewhat subjective and mostly

based on neuromonitoring findings.The protocol at the author’s institu-tion dictates induced hypertensionand CT/CTA/CTP or DSA when thesepatients experience elevated TCD meancerebral blood flow velocities indica-tive of vasospasm, abnormal brain tis-sue oxygenation, or CBF ( Figure 1-5 ).

Medical Complications

Cardiopulmonary. Cardiopulmonary al-

terations are among the most common

systemic complications of SAH and canrange from minor ECG changes to se-

vere dilated cardiomyopathy and acute

respiratory distress syndrome (ARDS).38

ECG alterations and cardiac enzyme

(troponin T) elevations are quite frequent

after SAH and, depending on their se-

verity, are also significant surrogates for

clinical outcome. ECG changes include

sinus tachycardia, peaked T waves, T-wave

inversions, ST segment depression or

elevation, and QT prolongation. Tro-

ponin elevation can be seen in up to30% of patients. The exact pathogenesis

behind cardiac abnormalities is not com-

pletely understood but may reflect a

catecholamine-related myocardial injury.

Echocardiogram can help differentiate

patients with diffuse cardiac dysfunction

related to SAH from those with underly-

ing cardiac ischemia showing regional

wall motion abnormalities restricted to

the territory of a coronary vessel. Clin-

ically, patients with SAH can develop sig-

nificant cardiac dysfunction manifestingas left ventricular failure, with impairedcardiac output, hypotension, and pul-

monary edema. These cardiovascular

dysfunctions can lead to severe hypo-

perfusion, reduced CPP or brain tissue

oxygenation, with added catastrophic

consequences for an already-injured

brain prone to delayed cerebral ische-

mia and poor neurologic outcome.

KEY POINTS

h Once patients experience

neurologic deterioration

suggestive of delayed

cerebral ischemia, rescue

therapies are initiatedwith

induced hypertension as

first-line modality.

h In high-risk patients

with poor neurologic

status, diagnosis and

treatment of delayed

cerebral ischemia may

be somewhat subjective

and mostly based on

neuromonitoring findings.

h Cardiopulmonary

alterations are

among the most

common systemic

complications of

subarachnoidhemorrhage.




22/25

The term stunned myocardium hasbeen applied to patients with SAH who

present with hypoxemia and cardiogenicshock with pulmonary edema withinhours of disease onset. Takotsubo cardio-myopathy (typically characterized by apicalballooning on echocardiogram) can beseen in those patients with poor neuro-logic status and increases the risk of

delayed cerebral ischemia.12 Current rec-

ommendations for the treatment of pul-

monary edema or ARDS in patients with

SAH are to avoid excessive fluid intake

and to use diuretics judiciously to target

euvolemia. In addition, standard man-

agement of heart failure is indicated,

keeping in mind that CPP should be main-

tained within normal limits.12 Although

lung-protective mechanical ventilation

should be tried whenever possible, hy-

percarbia should be closely monitored

and managed to avoid ICP elevations.

Cardiopulmonary function should be

supported, even with the insertion of an

intra-aortic balloon pump if necessary,as these abnormalities usually improve

a few days after onset.

Fever. Fever is the most common non-neurologic complication of SAH, occur-ring in up to 70% of patients during their hospitalization.2,12 Fever is more likely to occur in patients with poor neuro-logic status and higher modified Fisher Scale scores. Fever in SAH has been as-sociated with poor clinical outcome andis more likely related to SIRS rather thaninfectious in origin. There is currently no clear evidence indicating that fever control is beneficial for patients with

SAH. However, current recommenda-tions are to monitor body temperaturefrequently and to seek and treat infec-tious processes. In addition, during theperiod of risk for delayed cerebral ische-mia, fever control should be achieved ina stepwise fashion starting with standardantipyretic medications and escalating tosurface cooling or intravascular devices

while avoiding shivering.

Thromboembolism. The incidenceof deep venous thrombosis (DVT) after

SAH ranges from 2% to 20% dependingon the screening methodology used.12

The risk of DVT is higher in patients withpoor neurologic status. Because of thehigh incidence of DVT and its potentiallife-threatening consequences, prophy-laxis should be administered to allpatients with SAH. Sequential compres-sion devices are recommended for allpatients with SAH ( Table 1-5 ). The useof unfractionated heparin for prophy-laxis is indicated after aneurysm obliter-

ation and can be started 24 hours after the procedure.Glucose abnormalities. Hyperglyce-

mia is a common phenomenon follow-ing SAH. Its real impact is still unclear,but hyperglycemia has been associated

with the development of delayed cere-bral ischemia and poor clinical outcome.Hypoglycemia also is associated with

worse clinical outcome. The methods,timing, and aggressiveness of glucosecontrol are not well studied in patients

with SAH. Current recommendations

are to maintain a blood glucose between80 mg/dL and 200 mg/dL pending further investigations ( Table 1-5 ).12

Hyponatremia. Hyponatremia is themost common electrolyte disorder inSAH and can occur in about 30% of pa-tients.2,12,15 Hyponatremia has been as-sociated with development of delayedcerebral ischemia and poor clinical out-come. Hyponatremia can be secondary to cerebral salt wasting or inappropriatesecretion of antidiuretic hormone. Tra-

ditionally, in patients without SAH, theformer is treated with volume infusionand the latter with fluid restriction. How-ever, because determination of fluid statuscan be difficult in the neurocritical careunit and because hypovolemia is asso-ciated with poor clinical outcome, fluidrestriction should be avoided in patients

with SAH. Treatment goals for hypona-tremia in SAH should be oral free water

KEY POINTS

h Pulmonary edema or

acute respiratory distress

syndrome in patients

with subarachnoid

hemorrhage should be

treated with judicious

use of diuretics and other

standard heart failure

therapies targeting

euvolemia and normal

cerebral perfusion pressure.

h Fever is the most

common non-neurologic

complication in

patients with

subarachnoid hemorrhage.

h Fever in patients with


has been associated with

poor clinical outcome.

h Deep venous thrombosis

prophylaxis should be

administered to all

patients with

subarachnoidhemorrhage.





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restriction while maintaining euvolemia.Patients can be treated with continuous

infusion of hypertonic saline (1.5% to 3%)and fludrocortisone if diuresis is activeand impedes maintenance of adequate

fluid balance. It is important to test for

thyroid and adrenal dysfunction, partic-

ularly in those patients with SAH who

require vasopressors to maintain blood

pressure goals.

Hemoglobin. The majority of patients with SAH experience a drop in hemo-globin during hospitalization, which couldbe due to several factors, including ex-

cessive blood draws, blood loss for other reasons, or systemic inflammation.12 Ane-mia has been associated with delayedcerebral ischemia and poor clinical out-come in patients with SAH. However,the optimal hemoglobin concentrationin patients with SAH has not been deter-mined, and whether blood transfusionimproves clinical outcome remains tobe proven. Current recommendationsare to minimize blood loss from blooddrawing and to maintain a hemoglobinconcentration of above 8 g/dL to 10 g/dL

( Table 1-5 ).

CONCLUSION

SAHis a neurologic emergency associated

with high morbidity and mortality. SAHis more frequent in women than menand more frequent in minority popula-tions compared to white Americans. Themain areas of emphasis when caring for

patients with SAH should be the fol-lowing: prompt evaluation and diagnosis,immediate transfer to appropriate centers,

expeditiousdiagnosis and treatment of thebleeding source, and overall good neuro-

critical care adhering to available treatmentguidelines. The main neurologic com-plications of SAH include hydrocephalus,seizures, cerebraledema, delayed cerebral

ischemia, and neuroendocrine disorders.Patients with SAH frequently experiencecardiopulmonary complications, whichcan be life threatening.

REFERENCES1. Go AS, Mozaffarian D, Roger VL, et al. Heart

disease and stroke statistics V 2014 update:a report from the AmericanHeart Association.

Circulation 2014;129(3):e28 Y e292.

doi:10.1161/01.cir.0000441139.02102.80.

2. Connolly ES Jr, Rabinstein AA, Carhuapoma JR,

et al Guidelines for the management

of aneurysmal subarachnoid hemorrhage: a

guideline for healthcare professionals from

the American Heart Association/American

Stroke Association. Stroke 2012;43(6):1711 Y 1737.

doi:10.1161/STR.0b013e3182587839.

3. Lovelock CE, Rinkel GJ, Rothwell PM. Time

trends in outcome of subarachnoid hemorrhage:

population-based study and systematic review.

Neurology 2010;74(19):1494 Y 1501. doi:10.1212/

WNL.0b013e3181dd42b3.

4. Tjahjadi M, Heinen C, Konig R, et al.

Health-related quality of life after

spontaneous subarachnoid hemorrhage

measured in a recent patient population.

World Neurosurg 2013;79(2):296 Y 307.

doi:10.1016/j.wneu.2012.10.009.

5. Lo B, Macdonald RL. Health-related quality of

life after aneurysmal subarachnoid hemorrhage:

new data from a large series in Germany.

World Neurosurg 2013;79(2):243 Y 244.

doi:10.1016/j.wneu.2012.12.025.

6. Broderick JP, Brown RD Jr, Sauerbeck L,

et al. Greater rupture risk for familial as

compared to sporadic unruptured intracranial

aneurysms. Stroke 2009;40(6):1952 Y 1957.

doi:10.1161/STROKEAHA.108.542571.

7. Lindner SH, Bor AS, Rinkel GJ. Differences in risk

factors according to the site of intracranial

aneurysms.J Neurol NeurosurgPsychiatry 2010;

81(1):116 Y 118. doi:10.1136/jnnp.2008.163063.

8. Etminan N, Beseoglu K, Steiger HJ, Hanggi D.

The impact of hypertension and nicotine on

the size of ruptured intracranial aneurysms.

J Neurol Neurosurg Psychiatry 2011;82(1):4 Y 7.

doi:10.1136/jnnp.2009.199661.

9. Shiue I, Arima H, Anderson CS; ACROSS

Group. Life events and risk of subarachnoid

hemorrhage: the Australasian Cooperative

Research on Subarachnoid Hemorrhage Study

(ACROSS). Stroke 2010;41(6):1304 Y 1306.

doi:10.1161/STROKEAHA.109.575282.

10. Andreasen TH, Bartek J Jr, Andresen M,

et al. Modifiable risk factors for aneurysmal

subarachnoid hemorrhage. Stroke 2013;

44(12):3607 Y 3612. doi:10.1161/STROKEAHA.

113.001575.

11. Edlow JA, Malek AM, Ogilvy CS. Aneurysmal

subarachnoid hemorrhage: update for

emergency physicians. J Emerg Med 2008;

34(3):237 Y 251. doi:10.1016/j.jemermed.

2007.10.003.

KEY POINTS

h Fluid restriction should

be avoided in patients

with subarachnoid

hemorrhage, and

hyponatremia should be

treated with oral free

water restriction while

maintaining euvolemia.

h Anemia in patients with

subarachnoidhemorrhage

has been associated

with delayed cerebral

ischemia and worse

clinical outcome.




24/25

12. Diringer MN, Bleck TP, Claude Hemphill J 3rd,

et al. Critical care management of patients

following aneurysmal subarachnoid

hemorrhage: recommendations from theNeurocritical Care Society’s Multidisciplinary

Consensus Conference. Neurocrit Care

2011;15(2):211 Y 240. doi:10.1007/

s12028-011-9605-9.

13. Molyneux A, Kerr R, Stratton I, et al.

International Subarachnoid Aneurysm Trial

(ISAT) of neurosurgical clipping versus

endovascular coiling in 2143 patients with

ruptured intracranial aneurysms: a randomized

trial. Lancet 2002;360(9342):1267 Y 1274.

doi:10.1016/S0140-6736(02)11314-6.

14. Molyneux AJ, Kerr RS, Yu LM, et al.

International Subarachnoid Aneurysm Trial

(ISAT) of neurosurgical clipping versus

endovascular coiling in 2143 patients withruptured intracranial aneurysms: a randomised

comparison of effects on survival, dependency,

seizures, rebleeding, subgroups, and

aneurysm occlusion. Lancet 2005;366(9488):

809 Y 817. doi:10.1016/S0140-6736(02)11314-6.

15. Suarez JI, Tarr RW, Selman WR. Aneurysmal

subarachnoid hemorrhage. N Engl J Med

2006;354(4):387 Y 396. doi:10.1056/

NEJMra052732.

16. Hassan A, Lanzino G, Wijdicks EF, et al.

Terson’s syndrome. Neurocrit Care 2011;15(3):

554 Y 558. doi:10.1007/s12028-011-9555-2.

17. McCarron MO, Alberts MJ, McCarron P. A

systematic review of Terson’s syndrome:

frequency and prognosis after subarachnoidhemorrhage. J Neurol Neurosurg Psychiatry

2004;75(3):491 Y 493. doi:10.1136/

jnnp.2003.016816.

18. Linn FH, Wijdicks EF, van der Graaf Y, et al.

Prospective study of sentinel headache in

aneurysmal subarachnoid haemorrhage.

Lancet 1994;344(8922):590 Y 593. doi:10.1016/

S0140-6736(94)91970-4.

19. Leblanc R. The minor leak preceding

subarachnoid hemorrhage. J Neurosurg

1987;66(1):35 Y 39.

20. Sames TA, Storrow AB, Finkelstein JA,

Magoon MR. Sensitivity of new-generation

computed tomography in subarachnoid

hemorrhage. Acad Emerg Med 1996;3(1):16 Y 20.doi:10.1111/j.1553-2712.1996.tb03296.x.

21. Boesiger BM, Shiber JR. Subarachnoid

hemorrhage diagnosis by computedtomography

and lumbar puncture: are fifth generation CT

scanners better at identifying subarachnoid

hemorrhage? J Emerg Med 2005;29(1):23 Y 27.

doi:10.1016/j.jemermed.2005.02.002.

22. Raya AK, Diringer MN. Treatment of

subarachnoid hemorrhage. Crit Care Clin 2014;

30(4):719 Y 733. doi:10.1016/j.ccc.2014.06.004.

23. Rabinstein AA, Lanzino G, Wijdicks EF.

Multidisciplinary management and emerging

therapeutic strategies in aneurysmal

subarachnoid haemorrhage. Lancet Neurol2010;9(5):504 Y 519. doi:10.1016/

S1474-4422(10)70087-9.

24. Perry JJ, Sivilotti ML, Stiell IG, et al. Should

spectrophotometry be used to identify

xanthochromia in the cerebrospinal fluid

of alert patients suspected of having

subarachnoid hemorrhage? Stroke

2006;37(10):2467 Y 2472. doi:10.1161/

01.STR.0000240689.15109.47.

25. McKinney AM, Palmer CS, Truwit CL, et al.

Detection of aneurysms by 64-section

multidetector CT angiography in patients

acutely suspected of having an intracranial

aneurysm and comparison with digital

subtraction and 3D rotational angiography.AJNR Am J Neuroradiol 2008;29(3):594 Y 602.

doi:10.3174/ajnr.A0848.

26. Donmez H, Serifov E, Kahriman G, et al.

Comparison of 16-row multisliceCT angiography

with conventional angiography for detection

and evaluation of intracranial aneurysms.

Eur J Radiol 2011;80(2):455 Y 461. doi:10.1016/

j.ejrad.2010.07.012.

27. DupontSA, Lanzino G, Wijdicks EF,Rabinstein AA.

The use of clinical and routine imaging data

to differentiate between aneurysmal and

nonaneurysmal subarachnoid hemorrhage

prior to angiography. Clinical article.

J Neurosurg 2010;113(4):790 Y 794.

doi:10.3171/2010.4.JNS091932.

28. Kowalski RG, Claassen J, Kreiter KT, et al.Initial misdiagnosis and outcome after

subarachnoid hemorrhage. JAMA 2004;291(7):

866 Y 869. doi:10.1001/jama.291.

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Diagnosis and Management of Subarachnoid Hemorrhage