Ebook Textbook of neurointensive care (2/E): Part 2

(BQ) Part 2 book Textbook of neurointensive care has contents: Diagnosis and treatment of altered mental status, complex spine surgery, elevated intracranial pressure, neuroradiological imaging, intraoperative neuroanesthesia, ethical issues in the neurointensive care unit,... and other contents.

A.J Layon et al (eds.), Textbook of Neurointensive Care,

DOI 10.1007/978-1-4471-5226-2_24, © Springer-Verlag London 2013

Abstract

Aneurysmal subarachnoid hemorrhage is a devastating condition with high mortality and morbidity rates for those that survive the initial hemorrhage There has been signifi cant research on aneurysmal subarachnoid hemor-rhage to better understand how we can diagnose, treat, and manage patients with this disease Cerebral vaso-spasm accounts for the majority of morbidity, mortality, and long-term disability in these patients, and a large volume of literature is dedicated to preventing and treat-ing vasospasm This chapter presents a simplifi ed, evi-dence-based review of the literature about the modes of diagnosis, medical and surgical management, and treat-ment options of patients with aneurysmal subarachnoid hemorrhage and cerebral vasospasm

Keywords

Cerebral aneurysm • Cerebral vasospasm • Evidence-based treatment • Hydrocephalus • Subarachnoid

hemorrhage

Introduction Aneurysmal subarachnoid hemorrhage (SAH) is a devas-tating condition accounting for about 5 % of all strokes, affecting about 30,000 people in the United States every year [ 1 , 2 ] The annual prevalence of aneurysmal SAH is likely higher than 30,000 due to misdiagnosis and those who do not receive medical care The incidence of aneu-rysmal SAH varies around the world and has been reported anywhere from 2 to 23 per 100,000 [ 3 , 4 ] Mortality rates range from 32 to 67 % [ 5 ] with a signifi cant degree of mor-bidity among those who survive the initial hemorrhage [ 6 7 ] Recent data have shown that there may be a declin-ing mortality rate after aneurysmal SAH with more recent treatment modalities [ 8 ] However, despite many advance-ments such as endovascular therapy for the treatment of Aneurysmal Subarachnoid Hemorrhage: Evidence-Based Medicine, Diagnosis, Treatment, and Complications Matthew M Kimball , Gregory J Velat , J D Mocco ,

and Brian L Hoh

24 M M Kimball , MD • B L Hoh , MD, FACS, FAHA, FAANS ( * )

Department of Neurological Surgery , University of Florida College of Medicine , 100265 , Gainesville , FL 32610 , USA e-mail: matthew.kimball@neurosurgery.ufl edu; brian.hoh@neurosurgery.ufl edu G J Velat , MD

Department of Neurosurgery , Lee Memorial Hospital , Fort Myers , FL 33901 , USA e-mail: gvelat@gmail.com J D Mocco , MD, MS, FAANS, FAHA

Department of Neurosurgery , Vanderbilt University Medical Center , 1161 21st Ave S, RM T4224 MCN , Nashville , TN 37232 , USA e-mail: j.mocco@vanderbilt.edu Contents Introduction 541

Natural History of Aneurysmal SAH 542

Diagnosis and Initial Management 542

Presentation 542

Initial Evaluation and Imaging 542

Contrast Prophylaxis 545

Initial Stabilization and Management 546

Antifi brinolytics 547

Seizures 547

Hydrocephalus 548

Treatment Methods for Ruptured Cerebral Aneurysms 548

Surgical Treatment Options 548

Endovascular Treatment 550

Cerebral Vasospasm and SAH 551

Modalities for Identifying Cerebral Vasospasm 551

Vasospasm Prophylaxis and Management 552

Medical Complications of Subarachnoid Hemorrhage 556

Cardiac and Pulmonary Complications 556

Anemia and Transfusion 557

Hyponatremia 558

References 559

aneurysms and the ability to better diagnose and treat

cere-bral vasospasm, morbidity remains high

Aneurysmal SAH typically affects adults in the fi fth to

seventh decades of life and is about 1.6 times more common

in females than in males [ 9 , 10 ] Some genetic syndromes

have a higher risk of aneurysm formation and hemorrhage,

such as polycystic kidney disease [ 11 ] and Ehlers-Danlos

[ 12 ] syndrome Familial intracranial aneurysm syndrome is

when two or more fi rst- through third-degree relatives are

found to have intracranial aneurysms Those who have this

syndrome are more inclined to harbor multiple intracranial

aneurysms and experience aneurysmal SAH at a younger age

[ 13 ] Additional risk factors for developing aneurysmal SAH

include hypertension, smoking history, and alcohol abuse all

of which have been validated on multivariate analyses

[ 14 , 15 ] Cocaine use and other sympathomimetics have also

been shown to increase risk of SAH, particularly in younger

patients with SAH [ 16 ]

Natural History of Aneurysmal SAH

It is estimated that approximately 15 % of patients die at the

time of hemorrhage before receiving medical care About

30 % of those that survive the initial hemorrhage have

mod-erate to severe disability [ 5 ], and about two-thirds who

sur-vive to undergo successful aneurysm treatment never regain

their baseline quality of life [ 5 ] The overall mortality rate is

about 45 %, with most deaths occurring within the fi rst few

days following rupture In one series, the 30-day mortality

rate was 46 % [ 17 ], and in another study over half of the

patients died within 14 days of hemorrhage [ 18 ] For those

that survive the initial hemorrhage, approximately 8 % will

die from progressive deterioration [ 19 ] Rebleeding before

aneurysm treatment remains the major cause of morbidity

and mortality following the initial hemorrhage, supporting

the need for early treatment (within 72 h) of aneurysm

rup-ture For those who survive to undergo treatment, cerebral

vasospasm accounts for the majority of morbidity and

mor-tality Angiographic vasospasm occurs in 30–70 % of

patients between the fi fth and fourteenth days following

SAH [ 20 , 21 ] Approximately 50 % of patients with

angio-graphic vasospasm will develop delayed ischemic

neuro-logic defi cits (DINDS), and 15–20 % of these patients will

suffer major stroke or death despite intervention [ 22 , 23 ]

Bederson and coworkers [ 24 ] analyzed patient, aneurysm,

and institutional factors on clinical outcomes following

aneurysmal SAH They included patient factors as severity/

grade of initial hemorrhage, age, sex, time to treatment, and

medical comorbidities including hypertension, atrial fi

brilla-tion, congestive heart failure, coronary artery disease, and

renal disease Aneurysm factors included size and location

Institutional factors included availability of endovascular services, volume of SAH patients treated at a given institu-tion, and the type of facility in which the patient is fi rst evaluated

Rebleeding after the initial hemorrhage carries a very high mortality rate of approximately 70 % and is highest in the fi rst 24–48 h [ 25 ] The International Cooperative Study

on the Timing of Intracranial Aneurysm Surgery [ 26 ] found that patients who underwent aneurysm treatment in <72 h had a 5.6 % rebleed rate with 73 % of those occurring in the

fi rst 24 h Overall, they reported a rate of 4.1 % for the fi rst

24 h and 1 % per day for the fi rst two weeks More recent studies have shown that rebleeding may be more common in the fi rst 2–12 h [ 27 , 28 ] Current literature supports early securing of ruptured aneurysms through either microsurgical

or endovascular means to prevent rebleeding and improve overall patient outcomes

Diagnosis and Initial Management Presentation

The classic presentation of an awake patient with an mal SAH is the complaint of the worst headache of their life The headache may also be associated with nausea, vomiting, nuchal rigidity, photophobia, a brief loss of consciousness, cranial neuropathy, or other focal neurologic defi cits Although there has been a drastic improvement in diagnosis

aneurys-by primary care and emergency medical providers, there is still a reported misdiagnosis rate of about 12 %, in which the most common diagnostic error was failure to obtain a non-contrast computed tomographic (CT) scan of the head [ 24 ]

Initial Evaluation and Imaging

A noncontrasted head CT is the most important tool for nosis of a SAH (Fig 24.1a ) A CT scan is 98–100 % sensi-tive for the diagnosis of SAH if done within 12 h of hemorrhage The sensitivity decreases to about 93 % at 24 h and 85 % at 6 days after SAH [ 29 , 30 ] In a patient with a known aneurysm and a negative head CT or a patient with a concerning recent history for SAH and a negative head CT, lumbar puncture (LP) can be extremely valuable for diagnos-ing aneurysmal SAH It is extremely important that the per-son performing the lumbar puncture understands how to collect and handle the cerebrospinal fl uid (CSF), order the correct labs, and effectively communicate with the labora-tory personnel to achieve accurate test results It is important

diag-to know the relationship between the timing of the LP and onset of symptoms, to be able to interpret the results Lumbar

Fig 24.1 ( a – e ) Illustrative case 78-year-old woman with Hunt-Hess

grade 3, Fisher score 3 subarachnoid hemorrhage ( a ) Noncontrast head

computed tomographic (CT) scan demonstrates Fisher score 3

subarachnoid hemorrhage with hydrocephalus A right frontal

ventricu-lostomy drain catheter has been placed ( b ) Maximal intensity

projec-tion (MIP) reconstrucprojec-tions of CT angiography (axial on left, sagittal on

right) demonstrate a ruptured left posterior communicating artery

aneurysm with daughter sac ( arrowheads ) ( c ) Anteroposterior (AP,

left ) and lateral ( right ) projection cerebral angiography demonstrates a

ruptured left posterior communicating artery aneurysm with daughter

sac ( arrowheads ) A dime is superimposed on the lateral projection for

measurement calibration ( d ) Endovascular balloon-assisted coiling of

the ruptured left posterior communicating aneurysm is demonstrated on

AP ( left ) and lateral ( right ) projection roadmap cerebral angiography

(infl ated balloon, arrows ; coiling, arrowheads ) ( e ) Completed coil occlusion of the left posterior communicating artery aneurysm is demonstrated on AP ( left ) and lateral ( right ) projection cerebral angiography

a

b

c

puncture results in SAH have been well studied and are the

most sensitive test for SAH [ 31 , 32 ]

Lumbar puncture should be performed carefully, as some

believe that by removing a large volume of CSF, the

transmu-ral pressure gradient across the aneurysm dome may increase

leading to hemorrhage Measuring an opening pressure may

be helpful, particularly in the setting of hydrocephalus, but is

not diagnostic of aneurysmal SAH Occasionally, patients

with a remote history of SAH may present with symptoms of

hydrocephalus It is necessary to be able to differentiate

between a traumatic tap and a true SAH [ 33 ] (Table 24.1 )

The most critical data show the comparison of the red blood

cell (RBC) count in the fi rst and last tubes, and the presence

of xanthochromia in the supernatant fl uid Cerebrospinal

fl uid in SAH patients is typically bloody or grossly

xantho-chromic with a yellow or pink color but does not typically

clot when collected Traumatic taps commonly consist of gross blood and clot during collection The RBC count should remain fairly consistent between the fi rst and last tube, where

it will likely decline with a traumatic tap After the CSF is collected, it is spun down and a supernatant fl uid is collected and tested for xanthochromia, which is a discoloration of the CSF due to heme breakdown products from RBCs This is the most reliable means of differentiating aneurysmal SAH from a traumatic tap Although gross visual inspection can be helpful, spectrophotometry is much more accurate Timing of

LP and symptoms are very important Xanthochromia does not appear until 2–4 h after SAH but is present in 100 % of patients at 12 h and remains in the CSF in about 70 % of patients at 3 weeks but drops off signifi cantly between 3 and

4 weeks If a patient has a normal noncontrasted head CT and CSF profi le, aneurysmal SAH is essentially ruled out

d

e

Fig 24.1 (continued)

Magnetic resonance imaging is currently of little

diagnos-tic value for acute aneurysmal SAH due to poor sensitivity to

detect methemoglobin molecules in the fi rst 24–48 h

follow-ing rupture Patient compliance, duration of time needed to

obtain the scan, and increased cost compared to CT scanning

have relegated MR imaging in the diagnosis of aneurysmal

SAH Magnetic resonance angiography (MRA) may be used

in patients with renal insuffi ciency, acute renal failure, or

pregnant patients to diagnose intracranial aneurysms with

reduced sensitivity and specifi city compared to CT

angiogra-phy (CTA) MRA sensitivity ranges from 85 to 100 % for

aneurysms >5 mm but drops to approximately 56 % for

aneurysms ≤5 mm [ 34 , 35 ] MRI and MRA may be helpful

when looking for other causes of SAH such as cervical

spi-nal arteriovenous malformations that may be missed by

con-ventional CTA

The most useful noninvasive imaging modality in acute

SAH is CTA (Fig 24.1b ) It can be obtained quickly,

pro-vides excellent three-dimensional reconstructions, shows

relationship of aneurysms to bony landmarks, may show

thrombus or calcifi cation within the aneurysm, is

noninva-sive, and has a high sensitivity and specifi city Sensitivity of

CTA for aneurysms ranges from 95 to 100 % for

aneu-rysms ≥5 mm but drops off to 64–83 % for aneurysms ≤5 mm

[ 36 – 38 ] CTA sensitivity diminishes with small aneurysms,

increased blood products, and may vary in accordance with

experience of the interpreting neuroradiologist Potential

disadvantages of CTA include the inability to adjust the

con-trast dose and/or concentration for patients at risk of renal

dysfunction, artifact from previous aneurysm clips or

embolic material may obstruct aneurysm diagnosis, and

small distal vessels may not be well visualized Currently,

CTA is the diagnostic imaging study of choice for initial

detection of intracranial aneurysms

Cerebral angiography, the traditional gold standard

diag-nostic test for intracranial aneurysms, is typically performed

if CT angiography fails to reveal a potential bleeding source

Cerebral angiography holds many advantages over other

diagnostic imaging techniques First, it allows for

methodi-cal evaluation of the intracranial vasculature via selective

injection of intracranial arteries PA and lateral projections

are obtained simultaneously to better characterize the exact

location and morphology of intracranial aneurysms (Fig 24.1c ) Three-dimensional reconstructions can be read-ily obtained In addition, cerebral vasculature surrounding an intracranial aneurysm is delineated Endovascular interven-tion may be pursued at the time of cerebral angiography, effectively streamlining aneurysm treatment Contrast load can also be altered, which may benefi t patients with renal insuffi ciency Despite the improved sensitivity of cerebral angiography for the diagnosis of intracranial aneurysms or other vascular malformation causing SAH, in about 20–25 %

a source of hemorrhage will not be found Many centers repeat a diagnostic cerebral angiogram 1 week after the ini-tial angiogram to evaluate for a small aneurysm that was unable to be visualized on the initial study In about 1–2 % of patients, an aneurysm is found after repeat angiogram [ 39 ] It

is controversial whether the small percentage of aneurysms found on repeat angiography warrants a repeat angiogram on all patients with a single negative diagnostic cerebral angio-gram We feel that the small morbidity of a diagnostic cere-bral angiogram of about 1–2 % versus the morbidity and mortality of a re-ruptured undiagnosed aneurysm warrants a repeat angiogram

Contrast Prophylaxis

The number of diagnostic and therapeutic spinal and cerebral angiograms has gone up exponentially in the last 20 years and therefore the use of iodinated contrast media Although newer and safer contrast media have been developed and used over recent years, we need to understand the risks of using these agents The majority of the literature on these agents comes from the cardiology literature where there is a much higher patient population to study Low-osmolality agents have been in use since the 1980s and have had a direct reduction in the pain associated with administration as well

as adverse events These agents have been proven to be safe but are associated with a small percentage of adverse reac-tions ranging from rash and fl ushing to angioedema, vaso-motor collapse, and death The risk for adverse reactions increases with higher osmolarity and ionicity The risk for all adverse reactions ranges from 4 to 12 % with ionic agents

Table 24.1 CSF results in SAH versus traumatic LP

Red blood cell count (RBC) Usually >100,000 RBC/mm 3

(little change between fi rst and last tube)

RBC should decrease between fi rst and last tube

Fluid appearance (gross) Xanthochromia (yellow/pink) Bloody

Supernatant appearance (spun) Xanthochromia Clear

compared to 1–3 % with nonionic agents [ 40 ] The risk for

severe reactions such as anaphylaxis and vasomotor collapse

was signifi cantly lower for low-osmolality agents 0.03 %

compared with 0.16 % for high-osmolality agents [ 41 ] The

strongest risk factors for predicting an adverse reaction to

contrast are a previous history of contrast reaction and atopic

conditions such as asthma A previous history of a contrast

reaction gives a 17–35 % risk of future reaction [ 42 ] Asthma

increases the risk of reaction by approximately six times the

general population [ 43 ] Other risk factors reported for

con-trast reactions include underlying heart disease, renal

dis-ease, diabetes mellitus, myeloma, sickle cell disdis-ease,

polycythemia, food or medication allergies, hay fever,

non-steroidal anti-infl ammatory drug use, beta-blocker use, age

greater than 60, and female gender [ 44 ] There has been a

long debated argument as to risk of a contrast reaction in a

patient with a known shellfi sh allergy There has never been

a reported case of shellfi sh allergy where iodine was

impli-cated, and the reaction to radiocontrast media has never been

proven to be related in any way to the iodine content in a

preparation Routine premedication for contrast reaction

prior to contrast is not supported by the evidence currently

available in the literature for those with shellfi sh allergy Two

major prophylaxis regimens are approved by the American

College of Radiology and include:

Pretreatment Protocol 1 :

(a) Prednisone 50 mg orally 13, 7, and 1 h prior to

procedure

(b) Diphenhydramine 25–50 mg intravenously,

intramus-cularly, or orally 1 h prior to procedure

(c) Nonionic low-osmolality contrast medium

Pretreatment Protocol 2 :

(a) Methylprednisolone 32 mg orally 12 and 2 h prior to

procedure

(b) Diphenhydramine 25–50 mg intravenously,

intramus-cularly, or orally 1 h prior to procedure

(c) Nonionic low-osmolality contrast medium

The use of these preventative protocols has reduced the

incidence of severe reactions and should be used in the

appropriate populations In the instance that waiting the

12–13 h is not reasonable for diagnosis or treatment by CTA

or cerebral angiogram, a single dose of 100 mg of

hydrocor-tisone sodium succinate can be given intravenously at the

time of the procedure

Initial Stabilization and Management

The patient should be transferred out of the emergency

medi-cal setting to a neurosurgimedi-cal ICU setting as soon as possible

The admission Hunt-Hess grade (Table 24.2 ), Fisher score

(Table 24.3 ), and World Federation of Neurologic Surgeons

(WFNS) grade (Table 24.4 ) should also be reported, as it

may aid treatment, prognosis, and risk of vasospasm The Airway management, breathing, and hemodynamic stability are the fi rst priority All of these should be managed with the understanding that manipulation of the airway may induce gag or cough refl exes, elevations in PCO 2 , and intubation may elevate blood pressure, acutely placing the patient at high risk for rebleeding Preoxygenation should be done prior to intubation The gag and cough refl ex, and refl ex cardiac dysrhythmias can be avoided by appropriate phar-macologic agents Although bed rest and a low-stimulation environment have been accepted as common management for an unsecured aneurysm, there are no data to support that

it lowers the risk of early rebleeding; however, it causes

no harm to the patient and should probably be followed There is a large amount of literature in regard to treatment

of hypertension in the acute period for an unsecured rysm; however, no well-controlled studies have been done

aneu-to show that strict blood pressure control has any effect on rebleeding rates A retrospective study has shown that there appears to be a lower risk of rebleeding in those treated with

Table 24.2 Hunt-Hess classifi cation

Grade Description

1 Asymptomatic or minimal headache and slight nuchal

rigidity

2 Moderate to severe headache, nuchal rigidity, no

neurologic defi cit except cranial nerve palsy

3 Drowsy, minimal neurologic defi cit

4 Stuporous, moderate to severe hemiparesis, early

decerebrate rigidity

5 Deep coma, decerebrate rigidity, moribund Reproduced with permission from Hunt and Hess [ 45 ]

Table 24.3 Fisher score

Fisher grade Appearance of blood on CT scan

1 No hemorrhage evident

2 Subarachnoid hemorrhage less than 1 mm thick

3 Subarachnoid hemorrhage more than 1 mm thick

4 Subarachnoid hemorrhage of any thickness with

intraventricular hemorrhage or intraparenchymal hemorrhage

Modifi ed with permission from Fisher et al [ 46 ]

Table 24.4 World Federation of Neurologic Surgeons (WFNS) grade

WFNS grade Glasgow coma score Major focal defi cit

antihypertensive medications, but in this study those treated

had higher blood pressures than those not treated, and there

did not appear to be a correlation with a lower blood

pres-sure [ 48 ] Another study had stated that rebleeding may be

related to greater variations in blood pressure and not an

absolute value [ 49 ] A specifi c goal systolic blood pressure

(SBP) remains controversial and variable, but most would

agree that a SBP goal <150 mmHg would be safe When

treating elevated SBP, short-acting agents given by

continu-ous infusion are ideal as they can be titrated easily to

pre-vent large fl uctuations Beta-blockers such as labetalol and

esmolol and calcium channel blockers such as nicardipine

may be used safely with minimal side effects and easy to

titrate Hydralazine can be given intravenously as needed for

patients with bradycardia Sodium nitroprusside should be

avoided or used for less than 24 h as it can raise intracranial

pressure by direct vasodilation, having greater effect on the

arterial than the venous system It can also cause toxicity by

its breakdown products thiocyanate and cyanide It should

be used for acute management until other medications can

be titrated to control blood pressure Blood pressure

con-trol should be balanced between preventing rebleeding and

hypotensive episodes that reduce cerebral perfusion pressure

(CPP) and risk of ischemic events

Antifi brinolytics

The use of antifi brinolytics for the prevention of early

rehem-orrhage has been studied since the late 1960s and early

1970s Early studies showed similar results which included a

signifi cant reduction in the incidence of early rebleeding;

however, this was offset by an increased risk of cerebral

infarction and DINDs The two major medications used are

tranexamic acid and epsilon-aminocaproic acid (EACA) In

1981, Torner [ 50] reported results from the Cooperative

Aneurysm Study in regards to a randomized, double-blinded,

placebo-controlled trial using tranexamic acid use for

patients after SAH A slightly greater than 60 % reduction

was seen in rebleeding in the treatment group, but there was

a signifi cant increased risk of cerebral infarction in the

treat-ment group In 1984, Kassel [ 51 ] gave a report from the

Cooperative Aneurysm Study, which showed a 40 %

reduction in rebleeding among those patients receiving an antifi

-brinolytic but a 43 % increase in focal neurologic defi cits

Because of the decrease in rebleeding rates but the increase

in neurologic defi cits, it was believed that, if the antifi

brino-lytic was used for a short time period until securing of the

aneurysm and stopped before the vasospasm period, the

increased ischemic complications might decrease

Since 2002, there have been 3 major studies comparing

the use of short-term antifi brinolytics during SAH to prevent

rebleeding: 1 randomized controlled trial and 2 retrospective

cohort trials A randomized trial by Hillman [ 52 ] included

505 patients of which 254 were treated with tranexamic acid within 48 h of SAH A signifi cant reduction in rebleeding from 10.8 to 2.4 % was seen among the two groups and a nonsignifi cant 19 % reduction in poor outcome, and a 4 % increase in good outcome was also noted A cohort- controlled study by Starke [ 53 ] consisted of 72 patients who received EACA on admission that was continued for <72 h, compared

to 175 patients that did not receive an antifi brinolytic A nifi cant reduction in rebleeding was seen in the EACA- treated group 2.7 % versus 11.4 % in the non-treated group

sig-No signifi cant difference was seen between ischemic cations between the two groups; however, an 8-fold increase

compli-in deep venous thrombosis (DVT) was found compli-in the treated group without a difference in pulmonary embolism (PE) incidence A retrospective review by Harrigan [ 54 ] of

EACA-356 patients compared to historical controls and determined short-term administration of EACA is associated with rates

of rehemorrhage, ischemic stroke, and symptomatic spasm that compare favorably with historical controls Overall, it appears that there is signifi cant decrease in the incidence of early rehemorrhage with early use of antifi bri-nolytics which should be discontinued in less than 72 h to decrease the risk of embolic and ischemic complications

Seizures

There has always been an association between SAH and zures; however, the true incidence and its effect on clinical outcome are debated In a study by Lin [ 55 ], 217 patients with aneurysmal SAH were reviewed for incidence and tim-ing of seizures and followed for 2 years Overall, 21 % of all patients experienced one seizure, with 37 % of those being at onset of SAH, 11 % preoperative seizures, and 46 % had at least one seizure after the fi rst week In total, 6.9 % of the

sei-217 patients developed late epilepsy, but only 3.8 % of patients who had a seizure during the hospitalization devel-oped late epilepsy

There has been a signifi cant amount of debate in regards

to whether seizures associated with SAH have an effect on outcome Antiepileptic drugs (AEDs) have side effects as well, and some argue that the medications themselves can have an effect on outcome after SAH A study [ 56 ] using the Nationwide Inpatient Sample Database (NISD) reported that generalized convulsive status epilepticus (GCSE) was independently associated with higher in-hospital mortality, longer hospital stays, and higher costs Literature on non-convulsive status epilepticus (NCSE) is poor, and the inci-dence is probably higher than reported There have been some retrospective studies showing a relationship between phenytoin use in SAH and poor outcome, but because of the retrospective nature and diffi culty in interpretation of the

data, no recommendations can be made at this time A study

by Chumnanvej [ 57 ] reported that 3 days of phenytoin after

SAH was adequate for seizure prophylaxis They compared

79 patients who had previously undergone multi-week

phe-nytoin prophylaxis after SAH versus 370 patients in which

only 3 days of phenytoin were given and then discontinued

There was a signifi cant reduction in phenytoin-related

com-plications such as hypersensitivity reactions, but the

percent-age of patients who had seizures, short or long term, did

not change signifi cantly between the two groups Although

this study is not a prospective randomized trial, it may be

benefi cial to provide a 3-day regimen of phenytoin

prophy-laxis after SAH to minimize medication side effects such as

hypersensitivity reactions, cognitive effects, and interaction

with other medications while providing seizure prophylaxis

Hydrocephalus

Acute hydrocephalus occurs in 15–87 % [ 58 – 60 ] of patients

that present with aneurysmal SAH Of those patients,

how-ever, only 8.9–48 % [ 58 – 60] develop chronic shunt-

dependent hydrocephalus The management of acute

hydrocephalus secondary to aneurysmal SAH is usually

managed by external ventricular drainage (EVD) or lumbar

drainage (LD) Treatment of acute hydrocephalus with an

EVD is associated with neurologic improvement [ 61 – 63 ]

There has been some concern about the risk of rebleeding after

placement of an EVD Three retrospective case series have

evaluated this topic One study found that there was an

increased risk of rebleeding with EVD placement [ 64 ], and the

other two found no increased risk [ 65 , 66 ] Lumbar drainage

for the treatment of SAH-associated hydrocephalus has only

been evaluated in retrospective studies and has been found to

be safe and not increase the risk for rebleeding [ 67 – 70 ] There

has been suggestion that lumbar drainage decreases the

inci-dence of vasospasm but has only been studied in

retrospec-tive series [ 68 ] Serial lumbar puncture for management of

SAH-associated hydrocephalus has also been described as

safe and not increasing the risk of rebleeding, but only in

small retrospective series [ 71 ]

The management of chronic hydrocephalus associated

with aneurysmal SAH is usually managed by ventricular shunt

placement External ventricular drainage weaning can be done

in a variety of ways A small single-center prospective

ran-domized control trial studied a method for determining which

patients would require permanent ventricular shunt placement

[ 72 ] Forty-one patients were randomized to rapid EVD

wean-ing (<24 h), and 40 patients were randomized to gradual EVD

weaning (96 h weaning period) There was no difference in

rate of shunt placement between the two groups, but the

grad-ual wean group had 2.8 more days in the intensive care unit

( p = 0.0002) and 2.4 more days in the hospital ( p = 0.031)

Several factors have been studied to attempt to identify factors predictive of SAH-associated shunt-dependent hydro-cephalus One factor that has been studied is whether clipping versus coiling affects the incidence of shunting A meta-anal-ysis [ 60 ] of fi ve non-randomized with 1,718 patients (1,336 clipped, 382 coiled) studies showed that the rate of shunt dependency was lower in the clipping group when compared

to the coiling group ( p = 0.01); however, only one of the fi ve

studies when evaluated independently showed a signifi cant difference [ 73] Fenestration of the lamina terminalis has been suggested to reduce the incidence of shunt-dependent hydrocephalus A meta-analysis of 11 non- randomized stud-ies including 1,973 patients (975 fenestrated, 998 non-fenes-trated) found no signifi cant difference in shunt-dependent hydrocephalus between the two groups [ 74 ]

Subarachnoid-associated acute hydrocephalus can safely

be managed by external ventricular drainage or lumbar drainage It may potentially improve the neurologic exam and may slightly increase the risk of rebleeding Although the benefi t of neurologic improvement has only been shown

in retrospective series, it has been consistently shown in these studies, and the slight risk of rebleeding with place-ment is not greatly supported in the literature Chronic hydrocephalus from SAH can be treated with ventricular shunt placement Determination of shunt dependency by weaning of EVDs within a <24-h period can be done safely without increasing the rate of shunt placement There is no clear evidence that the modality of aneurysm treatment (clip-ping versus coiling) is associated with the development of shunt-dependent hydrocephalus It is unlikely that lamina terminalis fenestration decreases the rate of shunt-dependent hydrocephalus

Treatment Methods for Ruptured Cerebral Aneurysms

Two basic treatment options exist for ruptured cerebral rysms: open surgical clipping or wrapping and endovascular coil embolization Whether done from inside or outside of the vessel, the goal is to exclude the aneurysm from the cere-bral circulation Ruptured aneurysms should ideally be treated as early as possible, within the fi rst 24 h, to prevent rebleeding

Surgical Treatment Options

Surgical treatment of aneurysms may involve clipping with titanium clips, wrapping with synthetic substances, or liga-tion of the feeding vessel Surgical treatment for ruptured cerebral aneurysms is seated in a long history of courageous and intelligent pioneers developing new ways to treat this

deadly pathology Surgery for ruptured aneurysms fi rst began

with what were considered “passive” strategies Victor

Horsley was given credit for successfully treating the fi rst

ruptured cerebral aneurysm in 1885 by ligating the ipsilateral

cervical carotid artery [ 75] In 1931, Dott developed the

technique of reinforcing the aneurysm wall by wrapping it

with a piece of muscle [ 76 ] Walter Dandy was credited in

1942 with the idea of trapping aneurysms to exclude them

from the circulation All of these methods had high failure

rates, morbidity, and mortality Eventually, a few brilliant

and dedicated surgeons came up with the idea that placing a

clip at the base of aneurysm while keeping the parent

cere-bral circulation patent may allow for defi nitive treatment On

March 23, 1937, Walter Dandy placed a V-shaped silver clip

to the neck of an internal carotid artery aneurysm, and since

then this has become the gold standard for treatment of

rup-tured and unruprup-tured aneurysms [ 77 ] Multiple variations

and improvements have been made to the clip by many

sur-geons including Olivecrona, Schwartz, Mayfi eld, McFadden,

Kees, Drake, Heifetz, Sundt, Yasargil, Sugita, Spetzler, and

others [ 78 ]

Prior to 1970, carotid ligation was a common treatment

for ruptured intracranial aneurysms Studies have shown

variable data in regard to rates of rebleeding and treatment

morbidity and mortality In the Cooperative Aneurysm

Randomized Treatment Study [ 79 ], carotid ligation did not

lead to a signifi cant improvement in mortality or rebleeding

in the acute period, compared with bed rest in the intent-to-

treat analysis Only 67 % of those patients randomized to

carotid ligation actually received that therapy, and in that

group there was actually a lower mortality when compared to

the bed rest group, and no rebleeding occurred Long-term

follow-up revealed a benefi t for carotid ligation in reducing

rebleeding at 3 years and mortality at 5 years when

com-pared to bed rest A large retrospective study by Nishioka

[ 80], however, reported a rebleeding rate of 7.8 % after

carotid ligation with other associated complications of

treat-ment Overall, the treatment of ruptured aneurysms with

carotid ligation likely reduces the rate of rebleeding when

compared to bed rest alone, but the rate of complications

associated with treatment and rebleeding likely exceeds

those of surgical clipping

Surgical clipping and endovascular embolization are

pre-ferred over carotid ligation for modern day treatment of

rup-tured cerebral aneurysms Aneurysm location, morphology,

neck size, patient age, and medical comorbidities are all

fac-tors that may make a ruptured aneurysm more likely to be

coiled or surgically clipped There has only been one large

trial comparing surgical and endovascular therapy for

rup-tured cerebral aneurysms The ISAT [ 81 ] trial is a

prospec-tive, randomized study that selected 2,143 patients of 9,559

patients with aneurysmal SAH to be randomized to surgical

clipping or endovascular treatment, on the assumption that it

was agreed that their aneurysm could be treated by either modality There was no signifi cant difference in mortality rates at 1 year, 8.1 % in the endovascular group and 10.1 %

in the surgical group Greater disability rates were seen in the surgically treated group 21.6 % versus the endovascularly treated group 15.6 % This made the overall morbidity and mortality of those treated surgically signifi cantly higher than those treated by endovascular means at 1 year follow-up The rebleeding rate was reported to be 2.9 % for coil embolization and 0.9 % for clipping, and 139 patients who underwent coil-ing required further treatment compared to 31 patients that were clipped The confounding factor in many aneurysmal SAH studies is what makes an aneurysm randomizable? In this study they chose all patients with aneurysms in the ante-rior circulation, in awake, young patients, which is unclear if that can be extrapolated to other groups

Surgical clipping of aneurysms has been considered a highly effective method for aneurysm treatment after SAH with its low recanalization and rehemorrhage rates It has been shown that long-term rebleeding is reduced by either carotid ligation or direct surgical clipping of the aneurysm when compared to hypotension and bed rest [ 2 ], but there is

a higher rehemorrhage rate and complication rate with carotid ligation when compared to direct surgical clipping

In the Cooperative Study [ 82 ], all patients underwent cal treatment for their ruptured aneurysms Of the 453 patients, only nine patients (2 %) suffered rehemorrhage, where four of these patients had multiple aneurysms Sundt [ 83 ] also reported a large study of 644 patients who under-went surgical clipping of ruptured aneurysms, with a 1.2 % rate of rehemorrhage after clipping In a more recent study

surgi-by David [ 84 ] in 1999, 160 aneurysms in 102 patients were treated by surgical clipping and followed for mean of 4.4 years They reported a complete obliteration rate of 91.8 %

on follow-up angiography, with a 0.5 % recurrence rate for completely clipped aneurysms with no rehemorrhages There was a 1.9 % rehemorrhage rate for incompletely clipped aneurysms with a small “dog-ear” residual Incompletely clipped aneurysms with a wide residual neck had a 19 % recurrence and 3.8 % rehemorrhage rate In total, they reported a 2.9 % recurrence rate for all incompletely clipped aneurysms with a total 1.5 % rehemorrhage rate

Wrapping of aneurysms that are deemed unable to be clipped has been described as a treatment modality with an expected higher rehemorrhage rate than those that are clipped

or coiled Small, older clinical studies have reported a smaller rate of rehemorrhage than conservative management [ 85 , 86 ]

A more recent long-term study reported an overall risk of rehemorrhage after aneurysm wrapping or coating to be

33 % [ 87 ] A long-term follow-up study of patients who underwent surgical wrapping of ruptured aneurysms showed

a rehemorrhage rate of 11.7 % at 6 months and 17.8 % at 6 months to 10 years [ 88 ] The rehemorrhage rate is similar to

rates of ruptured aneurysms treated by conservative

manage-ment The current data do not support the use of wrapping or

coating of ruptured cerebral aneurysms

Endovascular Treatment

Endovascular management for treatment of cerebral

aneu-rysms is a relatively young fi eld despite the development of

cerebral angiography by Egas Moniz in 1927 Guido

Guglielmi [ 89] in 1991 fi rst described the technique of

occluding aneurysms by an endovascular approach by using

platinum coils called Guglielmi detachable coils that were

detachable by applying a small current The memory of the

coils allows them to fi ll the aneurysm and the coils induce

thrombosis The aneurysm is packed until it is excluded from

the normal cerebral circulation Technology in this fi eld has

expanded much faster than our ability to study current

modalities As endovascular methods have become more

available, the coil technology, delivery methods, and

assis-tive techniques such as stent-assisted coiling or balloon-

assisted coiling (Fig 24.1d, e ) have become more common

allowing the morbidity to continue to decrease and ability to

coil aneurysms that were initially felt to be uncoilable

There is great variability in the use of endovascular

ther-apy for ruptured cerebral aneurysms Some centers use it

as a fi rst-line treatment and only clip if coiling cannot be

achieved Other centers use endovascular treatment in

criti-cally ill patients or those with signifi cant medical

comor-bidities that would otherwise be poor surgical candidates

Some centers base their treatment modality on the CTA or

angiographic characteristics of the aneurysm Despite the

variability in criteria for use, hospitals where

endovascu-lar techniques are available have been linked to improved

outcomes [ 90 , 91 ]

It is diffi cult to study treatment modalities for SAH,

because it is often hard to separate the complications,

mor-bidity, and mortality of the disease from the treatment When

studying aneurysms, the two most important factors when

evaluating treatment modalities are the rebleeding rate and

recurrence or recanalization rate Sluzewski [ 92 ] reported a

rebleeding rate of 1.4 % in 431 patients who underwent

endovascular coil embolization of ruptured cerebral

aneu-rysms Smaller studies have reported between a 0.9 and

2.9 % annual rate of rehemorrhage after endovascular

embo-lization with increasing aneurysm size being an important

factor for rehemorrhage [ 24 ] Degree of aneurysm occlusion

is also an important factor in risk of rehemorrhage Murayama

[ 87 ] reported on their most recent 665 aneurysms in 558

patients treated by endovascular embolization In small

aneurysms (4–10 mm) with small necks (≤4 mm),

incom-plete coiling occurred in 25.5 % with recurrence in 1.1 % of

completely coiled aneurysms and 21 % of incompletely

coiled aneurysms In small aneurysms with wide necks (>4 mm), incomplete coiling occurred in 59 %, with recur-rence in 7.5 % of completely coiled aneurysms and 29.4 % of incompletely coiled aneurysms In large aneurysms (11–

25 mm), incomplete coiling occurred in 56 %, with rence in 30 % of completely coiled aneurysms and 44 % of incompletely coiled aneurysms Giant aneurysms (>25 mm) had incomplete occlusion in 63 %, with recurrence in 42 %

recur-of completely coiled aneurysms and 60 % in incompletely coiled aneurysms Despite the recurrence rates, most patients with incomplete aneurysm obliteration do not rebleed Aneurysm recurrence is not uncommon after endovascu-lar embolization, and recanalization can occur even in com-pletely treated aneurysms Close follow-up of patients treated

by endovascular means with formal cerebral angiography, CTA, or MRA is extremely important, as additional emboli-zation can be performed with low morbidity in an elective environment Timing for follow-up imaging is not defi ned and can be variable depending upon whether the aneurysm was found after SAH or incidentally, degree of occlusion, size, and location Derdeyn [ 88 ] followed 466 patients with

501 aneurysms for greater than 1 year after coil embolization

of cerebral aneurysms They found recurrence in 33.6 % of patients that occurred at a mean interval of 12.3 months after the initial procedure Frequent and long-term follow-up of aneurysms treated by endovascular means are recommended

to identify recanalization and treat before SAH occurs Catheter cerebral angiography is the recommended modality

of choice for follow-up imaging in previously coiled or clipped aneurysms Although a small risk of permanent com-plications exists with diagnostic angiography, felt to be

<0.1 % [ 24 ], it allows the most precise view of the aneurysm and neck and at the same time allows for retreatment if needed Coil and clip artifacts are often a problem with using CTA and MRA for follow-up studies, although these are noninvasive modalities

No matter what treatment modality is chosen for ruptured cerebral aneurysms, treatment should be done early to pre-vent rebleeding and to have a secured aneurysm prior to the vasospasm window Surgical clipping and endovascular coil-ing are both accepted treatment options for ruptured cerebral aneurysms Surgical wrapping or coating are not supported

by the data and may have similar rehemorrhage rates when compared to conservative management, while placing the patient at risk of the morbidity of a craniotomy after SAH Patient characteristics, medical comorbidities, aneurysm location and morphology, and surgeon experience should all

be taken into account when deciding which modality should

be chosen Currently, it is felt that the rate of incomplete obliteration and recurrence is lower with surgical clipping than with endovascular techniques; however, the morbidity

of surgical clipping and the long-term disability rates are higher than endovascular treatment

Cerebral Vasospasm and SAH

After the aneurysm has been secured by surgical or

endovas-cular means, the risk of rebleeding has generally been

removed; however, the treatment goals need to now be

focused on the prevention and treatment of cerebral

vaso-spasm, delayed cerebral ischemia (DCI), and delayed

isch-emic neurologic defi cits (DINDs) Cerebral vasospasm is a

delayed narrowing of the intracranial arteries from

vasocon-striction leading to a decrease in cerebral blood fl ow, which

may lead to delayed cerebral ischemia (DCI) or delayed

ischemic neurologic defi cits (DINDs) and cerebral

infarc-tion There is a signifi cant amount of variation in the

litera-ture about how cerebral vasospasm is identifi ed, reported,

and defi ned Some authors use vasospasm, DINDs, and DCI

synonymously, which makes interpretation of the literature

and the ability to compare treatment and prevention

modali-ties very diffi cult For the purposes if this chapter, vasospasm

is defi ned as the actual narrowing of intracranial arteries

diagnosed by cerebral angiography, CTA, or elevated

veloci-ties on transcranial dopplers (TCD), with the fact that there

is intra-observer error in interpreting these studies In the

set-ting of SAH, DCI and DINDs are typically secondary to

cerebral vasospasm and the reason they get used

interchange-ably; however, DCI is a clinical change in neurologic status

and may occur with or independently of angiographic

evi-dence of vessel narrowing The opposite may occur as well

where angiographic evidence of cerebral vasospasm occurs

in the absence of clinical decline Delayed cerebral ischemia

may be reversible or may progress to DIND or cerebral

infarction on CT or MRI The terms delayed cerebral

isch-emia (DCI) and delayed ischemic neurologic defi cit (DIND)

are diagnoses of exclusion after all other causes of

neuro-logic decline have been excluded including, seizures,

hydro-cephalus, hyponatremia, infection, iatrogenic from clipping

or coiling, or other metabolic causes Delayed cerebral

isch-emia (DCI) and delayed ischemic neurologic defi cits

(DINDs) will be defi ned as a neurologic decline that cannot

be explained by other means independently of angiographic

or TCD evidence of vasospasm A third outcome measure

commonly used in SAH studies is the presence of cerebral

infarction on CT or MRI imaging of the brain Cerebral

infarction is the irreversible loss of blood fl ow, which was

presumptively secondary to cerebral vasospasm in the

set-ting of SAH There has been a push to use cerebral infarct,

also known as “hypodensity on CT scan” in the literature, as

an independent outcome measure as it has been associated

with death or severe disability at 3 months, and is easily

mea-surable in patients in a comatose state where neurologic

decline may be diffi cult to assess [ 93 ]

Cerebral vasospasm accounts for the majority of

morbid-ity and mortalmorbid-ity for patients who survive to undergo

treatment after aneurysmal SAH Angiographic vasospasm

is observed in 30–70 % of patients after SAH and most monly occurs between day 5 and 14, peaking around day 7 after the hemorrhage [ 20 , 21 ] It is estimated that about 50 %

com-of patients with angiographic vasospasm will develop DCI, and about 15–20 % of these patients will develop DINDs, stroke, or death despite aggressive therapy [ 22 , 23 ] Many modalities for the prevention and treatment of cerebral vasospasm, DCI and DINDs have been studied over the years with variable results This will be an evidence-based synopsis for the diagnosis, management, and prevention of cerebral vasospasm

Modalities for Identifying Cerebral Vasospasm

Clinical evaluation of patients with symptomatic vasospasm and DINDs are easy to identify because a measurable defi cit exists; however, a clinical evaluation may not be sensitive enough to detect DCI as some patients may develop asymp-tomatic cerebral infarctions on CT or MRI A prospective study by Schmidt [ 94 ] studied 580 patients with aneurysmal and non-aneurysmal SAH, where CT scans were done as needed for clinical reasons Asymptomatic infarcts were noted on CT scans in 26 (4 %) patients and were noted to be more common in patients in comatose states After data anal-ysis, those with cerebral infarcts were noted to have worse modifi ed Rankin Scores (mRS) at 3 months, which is consis-tently reported in the literature Asymptomatic delayed cere-bral infarction was also noted on CT scan in 4 % of patients

in a retrospective study of 143 aneurysmal SAH patients by Rabinstein [ 95 ] A prospective study by Shimoda [ 96 ] fol-lowed 125 patients with aneurysmal SAH with MRIs imme-diately after securing of the aneurysm, 3 days after SAH, 14 days after SAH, and 30 days after SAH They reported asymptomatic cerebral infarction rates of 23 % This may be due to the sensitivity of MRI for small ischemic events and may actually represent a higher rate of cerebral infarction than we know, as most studies use CT as the imaging modal-ity of choice Clinical exam is accurate for identifying patients with symptomatic vasospasm and DINDs when compared to CT fi ndings; however, asymptomatic cerebral infarctions are still missed, especially in comatose patients where the exam is limited Further imaging modalities such

as TCDs, CTA, or angiography may be more benefi cial for comatose patients Digital subtraction angiography (DSA) remains the gold standard for diagnosis of cerebral vaso-spasm and for which all other modalities are compared

dependent upon multiple factors including consistency of the

individual performing the exam, experience of the individual

performing the exam, vascular anatomy, age, intracranial

pressure (ICP), hematocrit, mean arterial blood pressure

(MAP), and patient anatomical factors allowing for viewing

of the temporal window [ 97 ] Transcranial dopplers have

been shown to have a high specifi city and positive predictive

value (PPV) for diagnosing vasospasm in the middle

cere-bral arteries (MCA) In a meta-analysis by Lysakowski [ 98 ],

TCD fi ndings were compared with angiographic fi ndings to

report sensitivity and specifi city of TCDs for diagnosing

vasospasm Those who were assumed to have vasospasm on

TCDs of the MCAs were found to have vasospasm on

angi-ography with a sensitivity of 67 % and specifi city of 99 %

with a PPV of 97 % and negative predictive value (NPV) of

78 % However, if vasospasm was not predicted on TCDs, it

did not exclude vasospasm diagnosed by angiography They

concluded that TCD of the MCA was not likely to show

vasospasm if the angiography was negative (high specifi

c-ity), and that TCDs may be used to identify patients with

vasospasm (high PPV) All other vessels studied did not have

suffi cient data or evidence to support their use in diagnosing

vasospasm Sloan [ 97] reported that when studying the

MCAs with TCD, certain criteria could reliably predict the

presence or absence of angiographic vasospasm MCA fl ow

velocities of >200 cm/s, a rapid rise in fl ow velocities, and a

higher Lindegaard (vMCA/vICA) ratio (6 ± 0.3) were

reli-ably predictive of angiographic vasospasm An MCA

veloc-ity below 120 cm/s also reliably predicted the absence of

angiographic vasospasm Sviri [ 99] similarly studied the

vertebra-basilar system with TCD and comparing them to

follow-up angiography They found that the velocity ratio

between the basilar artery (BA) and the vertebral artery (VA)

correlated with angiographic vasospasm in the basilar artery

They reported that BA/VA ratio >2 had a 73 % sensitivity

and 80 % specifi city for basilar artery vasospasm A ratio

higher than 2.5 with BA velocity greater than 85 cm/s was

associated with 86 % sensitivity and 97 % specifi city for BA

narrowing of more than 25 % A BA/VA ratio higher than 3.0

with BA velocities higher than 85 cm/s was associated with

92 % sensitivity and 97 % specifi city for BA narrowing of

more than 50 %; however, the NPV and PPV were not

reported The presence of vasospasm based on TCD or

angi-ographic data does not predict DCI or DINDs

Computed Tomographic Angiogram (CTA)

The use of CTA for the diagnosis of vasospasm is quick,

noninvasive, and easily available CTA is also useful for the

quick diagnosis of postoperative bleeding, rehemorrhage,

stroke, hydrocephalus, or retraction edema when evaluating

for causes of neurologic decline Almost all studies

compar-ing CTA to DSA for diagnosis of vasospasm are fairly

con-sistent CTA seems to underestimate the diameter of large

cerebral arteries and overestimate the distal smaller cerebral vessels Surgical clips or coils can lead to artifact and make

it diffi cult to fully evaluate the vessels CTA has a high racy, sensitivity, and specifi city for diagnosing severe vaso-spasm or no vasospasm in larger proximal arteries but loses accuracy in detecting it in distal, smaller vessels when com-pared to DSA [ 100 , 101 ] CTA tended to overestimate the degree of vasospasm when there was a discrepancy The use

accu-of CTA as a screening tool may signifi cantly limit the ber of DSA done to diagnose vasospasm; however, CTA is limited in that it lacks the ability to use intra-arterial methods

no standardization for triple-H therapy for blood pressure parameters or goal hemoglobin levels Egge [ 102 ] random-ized 16 patients to prophylactic triple-H therapy and 16 patients to euvolemic therapy Triple-H therapy was associ-ated with more complications, higher cost, and had no sig-nifi cant difference in vasospasm rates or improvements in TCD velocities when compared to the euvolemic group Lennihan [ 103 ] randomized 82 patients to receive hypervol-emia therapy or euvolemic therapy Cardiac fi lling pressures were noted to be higher with hypervolemic therapy, but with-out any evidence of increased cerebral blood fl ow and sig-nifi cant difference were seen on GOS at 2 weeks, 6 months,

or 1 year between the two groups Complications have been directly attributable to prophylactic triple-H therapy includ-ing pulmonary edema and worsening intracranial edema with hemorrhagic transformation [ 104 , 105 ] Prophylactic hemodilution has not shown to add any benefi t to outcome or vasospasm risk and has the negative effect of decreasing oxygen carrying capacity and cerebral oxygenation The overall benefi t of prophylactic triple-H therapy is not clear and may pose signifi cant physiologic risks including myo-cardial infarction, pulmonary edema, cerebral edema, renal failure, and even potential rupture of additional intracranial

aneurysms Prophylactic triple-H therapy is not

recom-mended; however, hypotension should be avoided

Therapeutic induced hypertension and volume expansion

have been shown in small studies to improve neurologic defi

-cits if started after the onset of symptoms Multiple pressors

have been studied and many MAP and SBP goals have been

suggested Systolic blood pressures of 160–200 mmHg are

commonly quoted for goals, but patient-specifi c factors need

to be taken into account such as baseline cardiac and

pulmo-nary disease The limited data support that induced

hyperten-sion with pressors and volume expanhyperten-sion may improve

neurologic defi cits but may be at the risk of pulmonary

edema, myocardial infarction, and hyponatremia No

ran-domized trials exist evaluating benefi t and risk of induced

hypertension in patients that develop a neurologic defi cit felt

to be secondary to cerebral vasospasm

Calcium Channel Blockers

Calcium channel blockers act by inhibiting the fl ow of

cal-cium into arteriolar smooth muscle, causing vascular

dila-tion, and therefore are felt to reduce vasospasm in the

cerebral vasculature Many calcium channel blockers exist;

however, the four that have been the most studied for

vaso-spasm prevention are nimodipine, nicardipine, nitroprusside,

and verapamil Nimodipine is the most well-studied drug for

vasospasm prophylaxis It has been shown to have a signifi

-cant reduction in the incidence of symptomatic vasospasm for

patients that received oral nimodipine compared to placebo

[ 106 ] The largest randomized clinical trial for nimodipine

[ 107 ] showed signifi cant reductions in the incidence of

cere-bral infarction and poor clinical outcome for patients treated

with oral nimodipine Nicardipine has similar pharmacology

to nimodipine It has been studied and used in many forms

including intravenous (IV), intra-arterial (IA), intrathecal

(IT), and as prolonged-release implants (NPRI) Two

ran-domized controlled trials showed signifi cantly reduced

inci-dence of symptomatic vasospasm when nicardipine was used

compared to placebo [ 108 , 109 ] Nitroprusside is a

medica-tion that is pharmacologically broken down into nitrous oxide

which causes relaxation of vascular smooth muscle leading

to vasodilation It is usually used intrathecally due to its short

half-life in the blood One small prospective non-randomized

case-control trial showed improved TCD velocities, but large

studies are limited on this medication Verapamil is another

calcium channel blocker which specifi cally blocks the L-type

calcium channel It has been studied in the intra-arterial form

in case series with variable results Among the calcium

chan-nel blockers, nimodipine was shown in more randomized

con-trolled trials to signifi cantly reduce symptomatic vasospasm

and improve outcomes A recent meta-analysis on calcium

channel blockers showed an overall reduction in poor

out-come compared to placebo, with the oral route of nimodipine

having the largest reduction in poor clinical outcome [ 110 ]

Magnesium Sulfate

Magnesium sulfate directly acts on and antagonizes voltage- dependent calcium channels, which prevents vascular smooth muscle contraction It has also been shown to have a neuroprotective benefi t which is believed to be from blocking

N -methyl- D -aspartate (NMDA) receptors and inhibiting the

release of glutamate in tissues Magnesium sulfate is monly administered by the intravenous route after SAH Magnesium has been well studied for the prevention of vaso-spasm Randomized controlled trials have shown a statisti-cally signifi cant decrease in symptomatic vasospasm when compared to placebo [ 111 ], a trend toward reduced MCA TCD velocities and improved clinical outcome [ 112 ], a non-signifi cant reduction in DCI and poor clinical outcomes at 3 months [ 113], and a trend toward improved clinical out-comes at 3 months [ 114 ] A meta-analysis [ 115 ] done in

com-2009 reported a statistically signifi cant reduction in poor outcomes including dependency and vegetative state Known complications of magnesium sulfate infusion include hypo-calcemia and hypotension The evidence shows a signifi cant improvement in outcome possibly from its neuroprotective benefi ts and a reduction in symptomatic vasospasm in some studies but in others only shows nonsignifi cant trends toward improved outcome The evidence is inconclusive at this time and large randomized controlled trials are currently being done for magnesium in SAH

Statins

Statins, also known as hydroxymethylglutaryl coenzyme-A reductase inhibitors (HMG-CoA reductase inhibitors) are well-known cholesterol-lowering medications that have been shown to decrease infl ammation, inhibit thrombogenesis, and induce nitric oxide synthase Multiple randomized con-trolled trials (RCT) have been done showing promising results A meta-analysis of three RCT showed a statistically signifi cant reduction in vasospasm incidence and mortality [ 116 ] Tseng [ 117 ] fi rst reported the results of statin use in SAH in 2005 This RCT studied pravastatin versus placebo, which showed a signifi cant reduction in vasospasm inci-dence, DINDs, and mortality A RCT by Lynch [ 118 ] pro-duced similar results using simvastatin versus placebo where the treatment group showed a signifi cant reduction in vaso-spasm Kramer [ 119] published the most recent meta- analysis of six randomized clinical trials showing a signifi cant reduction in DINDs and a trend toward decreased mortality

in those given a statin after aneurysmal SAH No notable side effects have been reported with statin use after SAH except for the known small risks of elevated liver enzymes and muscle breakdown with general statin use

Endothelin Receptor Antagonists

Endothelin is a peptide that acts on vascular smooth cle causing long-acting and severe vascular constriction

mus-Clazosentan and bosentan are two different endothelin

recep-tor antagonists (ERA) that have been studied in humans

One of the largest and most recent randomized controlled

studies [ 119 ] assigned 313 patients to receive dose-escalated

clazosentan and compared them to 96 placebo patients

A signifi cant reduction in moderate and severe vasospasm

was noted in the clazosentan group when given at the high

dose compared to placebo, and there was also a reduction

in the development of DIND and DCI Endothelin receptor

antagonists are showing promise in the prevention of

vaso-spasm, and further studies are currently being done

Other Medical Treatments

Many other medical management options for the treatment

and prevention of vasospasm and DINDs have been studied

Most of the following have been studied in smaller studies

with variable results Fasudil is a rho-kinase inhibitor

admin-istered by the intravenous route that has been studied in

Japan In one RCT [ 120 ], it was shown to have a signifi cant

reduction in angiographic and symptomatic vasospasm, low-

density areas on CT, and improved 1-month Glasgow

out-come scores (GOS) when compared to placebo In a second

RCT [ 121 ], it was shown to have a nonsignifi cant reduction

in symptomatic vasospasm when compared to nimodipine

The use of thrombolytics such as urokinase and tissue

plasminogen activator (tPA) have been studied for

intrathe-cal use, with the theory that they will break down

subarach-noid blood products and decrease the irritation of the blood

vessels and prevent vasospasm Only 2 RCT have been done

One large randomized controlled trial [ 122 ] using urokinase

showed a signifi cant reduction in symptomatic vasospasm

and improved GOS at 6 months compared to placebo when

used intrathecally after aneurysm coiling The second study

[ 123 ] used intrathecal tPA after aneurysm clipping and was

noted to have a trend toward reduced vasospasm severity but

was not signifi cant The data on thrombolytic use are

vari-able and cannot be recommended for use based on current

literature

Papaverine is a well-known cerebral and coronary

vasodi-lator Its exerts its mechanism of action by inhibiting cyclic

adenosine monophosphate (cAMP) and cyclic guanosine 3,5

(cGMP) phosphodiesterase activity Papaverine has been

delivered by many mechanisms including intracisternal use,

as a pellet form left at the time of surgery, and intra-arterially

by endovascular means Prophylactic studies using the pellet

delivery system and intracisternal use are small; however,

they did show some improvement in neurologic outcome and

symptomatic vasospasm No randomized controlled trials

have been done to study papaverine in SAH, but non-

randomized case-control studies have been reported Intra-

arterial (IA) papaverine given, not prophylactically, but

instead for the treatment of vasospasm has been reported to

have both improvement in angiographic vasospasm and

clinical symptoms Kassel [ 124] was the fi rst to use IA papaverine as a single agent for vasospasm treatment, with two-thirds of patients showing angiographic improvement and one- third showing clinical improvement

Many other medical therapies have been studied for the prevention and treatment of vasospasm; however, they are small studies Some of these include antifi brinolytics, throm-boxane synthetase inhibitors, low-molecular-weight heparin, and intravenous erythropoietin

Endovascular Interventions

Medical management of vasospasm consists generally of a combination of medications to prevent vasospasm, as indi-cated previously When vasospasm occurs, however, medical options typically only include triple-H therapy, which is associated with many medical complications including heart failure, pulmonary edema, and myocardial infarction Endovascular interventions include intra-arterial administra-tion of vasodilators (Fig 24.2a) or transluminal balloon angioplasty (TBA) (Fig 24.2b )

Transluminal balloon angioplasty is the act of dilating the intracranial arteries with a small balloon This technique has been used both prophylactically prior to vasospasm and as a therapeutic modality after vasospasm develops Angioplasty can be used alone or in combination with IA vasodilators such as papaverine and verapamil Prophylactic TBA was studied in an RCT [ 125 ] where 85 patients with SAH under-went TBA of bilateral A1, M1, P1, basilar, and intradural portion of the dominant vertebral artery within 96 h of hem-orrhage Patients who underwent TBA had a trend toward a reduction in DINDs and also had a signifi cant reduction compared to placebo in those requiring therapeutic angio-plasty The risks of TBA include vessel perforation, hemor-rhage, and death and are higher if TBA is performed distally

in the vessels During this study, prophylactic angioplasty of the A1 and P1 segments was discontinued due to complica-tions Prophylactic balloon angioplasty, despite showing a decrease in the need for therapeutic angioplasty, is not rec-ommended due to the risk of vessel perforation and no sig-nifi cant improvement in overall outcome

Although TBA is not recommended for prophylaxis of vasospasm, it is successful in the treatment of vasospasm when it does develop Vessels that are treated successfully have been shown to reduce the incidence of DCI [ 126 , 127 ] The timing of endovascular intervention after development

of cerebral vasospasm has not been well defi ned Two ies have reported the timing of endovascular intervention, analyzing early versus delayed intervention after the onset of cerebral vasospasm Rosenwasser [ 128 ] retrospectively reviewed 84 patients that underwent balloon angioplasty with or without IA papaverine Fifty-fi ve patients were treated within 2 h of neurologic decline, and 33 patients were treated greater than 2 h after neurologic decline Patients that

stud-were treated within 2 h had a signifi cantly better neurologic

improvement than those that had delayed treatment Bejjani

[ 129] reported similar fi ndings when they retrospectively

studied 21 patients treated within 24 h of neurologic decline

and 10 patients treated greater than 24 h after neurologic

decline They reported a more signifi cant improvement in

those that underwent early treatment compared to those that

had delayed treatment

The use of intra-arterial agents during endovascular

treat-ment of cerebral vasospasm offers direct delivery of

vasodi-lators to the vessels in vasospasm Three medications have

been well studied for intra-arterial delivery for vasospasm,

papaverine, nicardipine, and verapamil There have been many case series using IA papaverine showing successful treatment of cerebral vasospasm with both good clinical and angiographic results Nicardipine in the IA form has been evaluated in retrospective studies to improve angiographic vasospasm and transiently improve neurologic defi cits [ 130 ] Verapamil has been shown in retrospective studies to show improvements in arterial diameter without signifi cant side effects [ 131 , 132 ] Any agent may be chosen for IA therapy, and dose is limited by systemic hemodynamic response Further studies need to be done to determine if any agent is more effi cacious

a

b

Fig 24.2 ( a , b ) Cerebral vasospasm ( a ) Intra-arterial verapamil

treat-ment Left panel , focal vasospasm of M2 branch of the left middle

cere-bral artery ( arrowhead ) Middle panel , microcatheter injection of

verapamil into the affected branch vessel Right panel , immediate

improvement in vessel diameter after intra-arterial verapamil treatment

( arrowhead ) ( b ) Transluminal balloon angioplasty Left panel ,

vaso-spasm of the right middle cerebral artery after clipping of a ruptured

right middle cerebral bifurcation aneurysm Right panel , immediate

improvement in vessel diameter after transluminal balloon angioplasty

of the right middle cerebral artery

Medical Complications of Subarachnoid

Hemorrhage

Medical complications are frequent after SAH and increase

the morbidity and mortality; however, they can be managed

if recognized early The Aneurysm Cooperative Study [ 133 ]

reported the frequency of having at least one life-threatening

medical condition after SAH to be 40 %, with a proportion of

the deaths from a medical complication to be 23 % This rate

is similar to that quoted to the causes of death from the initial

hemorrhage which was 19 %, rehemorrhage which was

22 %, and vasospasm which was 23 % Pulmonary edema

was reported in 23 % of patients, with a 6 % rate of severe

pulmonary edema Renal dysfunction was noted to be 7 % in

the whole group, with 15 % of that group that developed

severe, life-threatening renal dysfunction Pulmonary

com-plications were noted to be the most common non-neurologic

cause of death Thrombocytopenia, hepatic dysfunction, and

hyponatremia are metabolic disturbances that are also

asso-ciated with SAH and need to be routinely monitored

Cardiac and Pulmonary Complications

Cardiac and pulmonary complications have been well

docu-mented after aneurysmal SAH The relationship between

SAH and myocardial injury or dysfunction has been

hypoth-esized to be secondary hypothalamic dysfunction or

hyper-dynamic response to catecholamine release after SAH

Although there has been no specifi c cause identifi ed, there is

clearly an association between the two It has been shown in

clinical studies that there are elevated catecholamine levels

early after SAH [ 134 , 135 ] and that cardiac lesions after

SAH when studied pathologically appear very similar to

those found in catecholamine-induced myocardial necrosis

[ 136 ] It is not felt that cardiac dysfunction is from acute

coronary spasm or disease; however, these must be ruled out

in patients with cardiovascular risk factors

Recognizing cardiac and pulmonary complications early

better allow the team to maximize medication choices for

volume status and induced hypertension if needed Two of

the most commonly studied variables for understanding

car-diac dysfunction after SAH are troponin levels and wall

motion abnormalities (WMA), also known as regional wall

motion abnormalities (RWMA) diagnosed by

echocardiog-raphy A large meta-analysis [ 137 ] including 2,690 patients

from 25 studies, 16/25 studies being prospective, evaluated

cardiac complications after SAH and their effect on

out-come Elevation of troponin I was noted in 34 % of patients

which was associated with cardiac dysfunction Poor

out-come was associated with elevated troponin levels (RR 2.3)

and ST-segment depression (RR 2.4) Factors associated

with mortality included wall motion abnormalities (WMA)

(RR 1.9), elevated troponin (RR 2.0) and brain natriuretic peptide (BNP) levels (RR 11.1), tachycardia (RR 3.9), Q waves (RR 2.9), ST-segment depression (RR 2.1), T-wave abnormalities (RR 1.8), and bradycardia (RR 0.6) Occurrence of DCI was associated with WMAs (RR 2.1); elevated troponin (RR 3.2), CK-MB (RR 2.9), and BNP lev-els (RR 4.5); and ST-segment depression (RR 2.4) There is some variation among these studies of what is considered elevated troponin, which had a range of 0.1–1 ng/ml Diastolic dysfunction has been reported to occur in 71–89 % [ 138 , 139 ] of patients after SAH and has been associated with development of pulmonary edema

Electrocardiogram (ECG) changes are common after SAH and include deep T-wave inversion and QT prolonga-tion A report by the Cooperative Aneurysm Study [ 133 ] reported a frequency of life-threatening cardiac arrhythmias

of 5 %, with other cardiac dysrhythmias occurring in about

30 % of patients Ventricular arrhythmias were more mon if troponin I was elevated [ 140 ] No current randomized controlled trials exist evaluating the use of invasive cardio-vascular monitoring and its effect on morbidity and mortality after SAH At this time, the need for invasive cardiovascular monitoring should be evaluated on a patient-by-patient basis The prophylactic placement of invasive monitoring, exclud-ing arterial lines, is not indicated by the data; however, it may

com-be helpful in preventing cardiopulmonary complications if hyperdynamic or hypertensive therapy is being used Frequent monitoring of electrolytes and correction of meta-bolic disturbances such as magnesium and potassium can help prevent arrhythmias

Wall motion abnormalities (WMA) after SAH are well reported and typically involve left ventricular dysfunction Kothavale and coworkers [ 141 ] prospectively studied 300 patients with aneurysmal SAH with serial echocardiography with a primary outcome of measuring the presence of RWMA Eight hundred and seventeen echocardiograms were analyzed and RWMA were found in 18 % of patients Patients with higher admission Hunt-Hess grades had higher rates of RWMA Patients with Hunt-Hess grades 3–5 had an incidence of 35 % There was also an association between elevated troponin I and RWMA, where 65 % of patients with troponin I levels greater than 1mcg/L had RWMA They also reported prior use of cocaine or amphetamine were indepen-dent predictors of RWMA A study by Sugimoto and cowork-ers [ 142 ] studied the prognostic signifi cance of RWMA on outcome They prospectively enrolled 47 patients after aneu-rysmal SAH and performed early echocardiography and ECG, within 3 days of SAH They recorded the incidences of pathologic ECG changes, global hypokinesia defi ned as a left ventricular ejection fraction (LVEF) <50 %, and RWMA The incidence of pathologic ECG changes was 62 %, LV ejection fraction <50 % was 11 %, and RWMA was 28 % Rate-corrected QT interval, LV ejection fraction <50 %, and

RWMA were all signifi cant predictors of death A specifi c

form of RWMA more commonly being recognized in SAH

is what is termed takotsubo cardiomyopathy This form of

cardiomyopathy is defi ned by left ventricular dysfunction

consisting of akinesia of predominantly the apex and

mid-ventricle with relative sparing of the basal segment, which

gives it a typical appearance on echocardiography

Cardiomyopathy seen in SAH, commonly called neurogenic

stress cardiomyopathy (NSC), is defi ned by hypokinesia of

the basal and midventricular portions with relative sparing of

the apex Most cardiomyopathies induced after SAH are

believed to be secondary to catecholamine release and not

coronary in nature and are felt to be mostly reversible [ 143 ]

The original descriptions and studies of takotsubo

cardiomy-opathy excluded patients with traumatic brain injury and

SAH and were not well understood in patients with

neuro-logic diseases Lee and colleagues [ 144 ] reported the largest

study of takotsubo cardiomyopathy in SAH patients They

retrospectively reviewed all patients with SAH admitted to

the Mayo Clinic Neurological Intensive Care Unit between

1990 and 2005 and found 24 patients that had SAH-induced

reversible cardiac dysfunction, and of those, eight met

echo-cardiographic criteria for takotsubo cardiomyopathy All

eight patients were women with a mean age of 55.5 Seven

patients presented with Hunt-Hess grade III or IV Four

patients underwent coil embolization and four underwent

surgical clipping The mean initial ejection fraction (EF) was

38 %, and the mean EF at recovery was 55 % Six of the eight

patients developed cerebral vasospasm, but only 3 developed

cerebral infarction Takotsubo cardiomyopathy is a rare form

of cardiomyopathy after SAH and is more common in

post-menopausal women; is associated with pulmonary edema,

prolonged intubation, and vasospasm; but is a reversible

form of cardiomyopathy similar to the other neurogenic

stress cardiomyopathies

Pulmonary complications are common after SAH and are

the leading non-neurologic cause of morbidity and mortality

after aneurysmal SAH In retrospective trials it is diffi cult to

assess the cause of the pulmonary edema, but it has been

documented in the literature to be around 27 % In one study

[ 145 ] this was defi ned by a pulmonary arterial O 2 (PaO 2 ) to

fraction of inspired O 2 (FiO 2 ) ratio (PaO 2 /FiO 2 ) of <300

A second study [ 146 ] used evidence of bilateral pulmonary

infi ltrates on chest x-ray and found similar incidence of

pul-monary edema Hypervolemia therapy has not shown to have

a signifi cant benefi t on neurologic outcome and is associated

with medical complications including pulmonary edema

Kim and colleagues [ 147 ] retrospectively reviewed

prospec-tively collected data on 453 patients after SAH They were

divided into two groups: group 1 were those that were treated

with hypervolemic and hypertensive therapy, and group 2

were those that were treated with euvolemic therapy The

rate of pulmonary edema decreased from 14 to 6 % between

groups 1 and 2, respectively, and mortality had also decreased from 34 to 29 % between groups 1 and 2, respectively Patients with pulmonary edema and or cardiac dysfunction may benefi t from invasive cardiovascular monitoring to aim for a euvolemic goal to decrease left ventricular dysfunction from volume loading and appropriate balance volume status

to improve pulmonary edema

Anemia and Transfusion

Blood transfusion has always been a controversial topic among physicians treating medical and surgical patients The risk of blood transfusion includes minor and severe transfu-sion reactions, and the risk of HIV and hepatitis transmis-sion Recent data have suggested that patients can tolerate lower hemoglobin levels than we previously thought, and that there may be adverse outcomes associated with blood transfusions Marik [ 148 ] reviewed forty-fi ve studies that reported the independent effect of red blood cell transfusion (RBCT) on patient outcomes In forty-two of the 45 studies, the risks of RBCT outweighed the benefi ts, the risk was neu-tral in two studies, and the benefi ts outweighed the risks in a subgroup of one study which included elderly patients with acute myocardial infarction and a hematocrit (HCT) less than 30 % Seventeen of the 18 studies that studied death as

a primary outcome showed that BRCT was an independent predictor of death All twenty-two studies that evaluated the association of RBCT and infection showed that RBCT was

an independent predictor of infection There was also signifi cant association between RBCT and development of multi-system organ failure and acute respiratory distress syndrome (ARDS)

There has also been great debate on what levels of globin are thresholds for transfusion The Transfusion Requirements in Critical Care Trial (TRICC) [ 149 ] studied two thresholds for transfusion termed “liberal,” defi ned as hemoglobin (Hgb) of 10 g/dl versus “restricted,” defi ned as Hgb of 7 g/dl in 883 ICU patients The overall 30-day mor-tality was similar between the two groups, except for those who were younger and less ill where mortality was less in the restrictive RBCT group Few studies have evaluated RBCT and its effect on patients with brain injury The best study we have for brain injury patients is a subgroup of the TRICC trial who sustained severe closed traumatic brain injury (TBI) [ 150 ] Twenty-nine patients were randomized to the restrictive (Hgb 7 g/dl) group, and 38 were randomized to the liberal (Hgb 10 g/dl) group There were no signifi cant differ-ences between the two groups in overall mortality, multisys-tem organ failure, length of ICU, or length of hospital stay It

hemo-is diffi cult to extrapolate these data to SAH patients who commonly have cardiac dysfunction and may benefi t from a liberal Hgb level The goal in SAH is to maintain normal

circulating volume with adequate tissue oxygen delivery It

is a complex relationship between the understanding of

ade-quate tissue oxygenation, volume status, current cardiac and

pulmonary dysfunction, and primary medical conditions

Animal studies [ 151 ] have shown that a Hgb <10 g/dl is

asso-ciated with brain hypoxia, and correction with RBCT may

improve brain tissue oxygenation, especially in a brain after

SAH where normal compensatory cerebrovascular response

may be damaged Preventing hypoxia should be a goal of

SAH patient management, as there are limited studies of how

RBCT affects patients after SAH Observational studies

show that RBCT can cause medical complications as noted

earlier, and there are no consistent data that RBCT improves

brain tissue oxygenation As in many of the RBCT trials, it is

often diffi cult to assess whether RBCT is in fact associated

directly with mortality or that those requiring transfusions

with persistently low Hgb (7 g/dl) are more critically ill and

at baseline have a higher mortality and that transfusion is

needed because of that Anemia is a risk factor for poor

out-come after SAH, but it is not clear whether this is an

inde-pendent risk factor or a measure of the severity of disease At

this time there are no randomized controlled trials or large

studies to suggest a threshold hemoglobin level for which

SAH patients should be transfused, and each patient should

be treated on an individual basis

Hyponatremia

Hyponatremia is the most common electrolyte abnormality

in patients after SAH It is commonly defi ned as a serum

sodium <135 mmol/l and has been reported to occur in about

30–50 % of aneurysmal SAH patients [ 152 , 153 ]

Hyponatremia in SAH are often attributed to one of two

dif-ferent mechanisms called cerebral salt wasting (CSW) and

syndrome of inappropriate antidiuretic hormone secretion

(SIADH) Each of these processes is pathophysiologically

different but appears similarly in lab values Both are

associ-ated with low serum sodium and abnormally elevassoci-ated urine

sodium The mechanism behind CSW is felt to be caused by

sympathetic discharge after SAH which stimulates the

release of natriuretic peptides causing sodium loss in the

urine This sodium loss causes an osmotic gradient across

the tubules, which pulls water with it into the urine, causing

an excess of urine output This excessive urine output causes

overall systemic hypovolemic hyponatremia SIADH is

caused by an inappropriate excretion of antidiuretic

hor-mone, causing water reabsorption in the kidney leading to

euvolemic or slightly hypervolemic hyponatremia The

abil-ity to measure intravascular volume with central venous lines

and strict ins and outs is imperative in diagnosis but also

treatment

Recognition and management of hyponatremia is tant because hyponatremia can cause worsening cerebral edema by causing a gradient for water to move into the cere-bral space, increasing intracranial pressure and exacerbating neurologic defi cits Hyponatremia by itself is associated with seizures especially at levels <125 mmol/l and in a patient with intracranial pathology places them at increased risk and lowering the threshold for seizures Hyponatremia has not been associated with worse neurologic outcome

Treatment strategies aim at raising the sodium slowly, due to the risk of central pontine myelinolysis and aim for normonatremia (135–145 mmol/l) Common treat-ment options include mineral corticoids and hypertonic saline Fludrocortisone is a mineralocorticoid often used

in the treatment of hyponatremia associated with SAH Mineralocorticoids act on the renal tubules to form channels that reabsorb sodium from the kidneys, while causing excre-tion of potassium Fludrocortisone has the advantage over hydrocortisone of not signifi cantly altering serum glucose levels There does not appear to be any signifi cant increase

in pulmonary edema or congestive heart failure with fl cortisone use [ 154 ] Hypertonic saline, commonly in the 3 % concentration, is another treatment option for hyponatremia

udro-It can be given as boluses or run as a continuous infusion Continuous infusions are more commonly given unless sei-zures occur or acute cerebral edema is present, in which case boluses may be more effective, followed by a continu-ous infusion to maintain normonatremia Even though the common treatment for isolated SIADH is volume restriction,

in the setting of SAH and vasospasm, this can be ous and place the patient at risk for DCI and vasospasm and

danger-is not recommended [ 155 ] Sodium should be corrected by the hypertonic saline route, and fl udrocortisone may also be used Only observational studies exist for the use of hyper-tonic saline and fl udrocortisone for hyponatremia in SAH, which both show safety of their use but no defi nitive dose or duration of treatment can be suggested based on the litera-ture at this time

Conclusions

Aneurysmal subarachnoid hemorrhage is a multifactorial disease process that requires a treatment team of neuro-surgeons and neurointensivists to maximize each patient’s outcome This chapter encompasses the best literature available at the time of publication to manage the intrica-cies of aneurysmal subarachnoid hemorrhage There is a vast amount of literature available; however, many uncer-tainties exist in the literature, and current studies are being done to better optimize our treatment of these patients At the University of Florida, we have developed treatment practices for the management of aneurysmal SAH patients

as outlined in Table 24.5

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Table 24.5 Management practice for aneurysmal SAH patients at the

University of Florida

Treatment protocol

Admission to neurosurgical ICU

CT angiogram of head and neck with perfusion

Radial arterial line

Strict systolic BP goals <140 mmHg (until aneurysm secured)

Loaded with fosphenytoin and continued for 3 days unless seizures

occur or intraparenchymal hemorrhage

Ventriculostomy placement if hydrocephalus on CT scan or GCS 13

or less

Aminocaproic acid IV infusion for 12–24 h until aneurysm secured a

Nimodipine 60 mg PO every 4 h for 14–21 days

Zocor 40 mg PO daily a

Magnesium sulfate infusion for 14 days (renally dosed) a

Daily transcranial dopplers

Hunt-Hess grades 1–3 undergo coiling or clipping within 24 h

Hunt-Hess grades 4–5 undergo ventriculostomy, if improvement

undergoes treatment

Once aneurysm secured, systolic blood pressure range

100–180 mmHg

No prophylactic HHH therapy

If neurologic decline, CT angiogram with perfusion obtained

If vasospasm present on CT angiogram pt taken to angio suite

a Optional

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A.J Layon et al (eds.), Textbook of Neurointensive Care,

DOI 10.1007/978-1-4471-5226-2_25, © Springer-Verlag London 2013

Abstract

The treatment of primary intracranial hemorrhage (ICH) is one of the most diffi cult problems facing neurologists, neu-rosurgeons, and neurointensivists today, and with an inci-dence of 10–30 cases per 100,000, it represents a major medical problem In spite of marked advances in medical technology, the outcomes for patients suffering from a spon-taneous ICH remain bleak with mortality rates reaching

62 % within the fi rst year of onset The diffi culty in treating these patients has resulted in substantial research efforts into establishing an appropriate management scheme for ICH The purpose of this chapter is to consolidate this infor-mation and provide the clinician with evidence-based, up-to-date treatment guidelines for primary ICH The reader will be led through a discussion of the most current epide-miologic data, use of diagnostic imaging, medical man-agement, and role of surgical intervention While a signifi cant number of questions exist regarding treatment strategies, following each section is a synopsis of the cur-rent literature with treatment recommendations

Keywords

Primary intracranial hemorrhage • Hemorrhagic stroke • Hypertension • Cerebral amyloid angiopathy • Cerebellar hemorrhage • STICH

Introduction

Intracerebral hemorrhage (ICH) is the end result of a number

of pathophysiologic processes where blood is extravasated into the brain parenchyma [ 1 ] These processes are divided

Department of Neurological Surgery ,

Washington University in St Louis ,

660 S Euclid , 8057 , St Louis , MO 63110 , USA

e-mail: washingtonc@wudosis.wustl.edu

A N Hassan , MD

Department of Neurology/Neurocritical Care ,

Washington University School of Medicine ,

660 S Euclid Ave , 8111 , St Louis , MI 63110 , USA

Computed Tomographic Angiography (CTA) 569

Magnetic Resonance Imaging (MRI) 570

Digital Subtraction Angiography (DSA) 570

Recommendations 571

Medical Management 571

Prevention of Hematoma Expansion and Rebleeding 571

Maintaining Cerebral Perfusion: Blood Pressure Management 571

Treatment of Cerebral Edema 571

Seizures 572

General Care 572

Surgical Management 572

Supratentorial Hemorrhage 572 Cerebellar Hemorrhage 573 Intraventricular Hemorrhage and Hydrocephalus 574 Recommendations 574

References 574

into either primary or secondary ICH (Table 25.1 ) Primary

ICH refers to hemorrhage resulting from hypertension or

cerebral amyloid angiopathy (CAA) [ 1 ] The focus here will

be the diagnosis and management of primary ICH While

many of the principles presented can be applied to the

treat-ment of secondary ICH, we direct the reader to the chapters

regarding aneurysmal subarachnoid hemorrhage (Chap 24 ),

vascular malformations (Chap 26 ), and CNS neoplasia

(Chap 34 ) for details specifi c to these pathologies

The treatment of ICH is one of the most diffi cult problems

facing neurologists, neurosurgeons, and neurointensivists

today In spite of marked advances in medical technology, the

outcomes for patients suffering from a spontaneous ICH remain

bleak with mortality rates reaching 62 % within the fi rst year of

onset [ 2 ] The diffi culty in treating these patients has resulted in

substantial research efforts into establishing an appropriate

management scheme for ICH The purpose of this chapter is to

consolidate this information and provide the clinician with

evidence-based, up-to-date treatment guidelines for ICH

Epidemiology

Worldwide, stroke is a major medical problem affecting over

15 million people each year [ 3 ] and accounting for 5.5

mil-lion deaths annually [ 1 ] In the United States, it is the third

leading cause of death [ 4 ], and fi scal costs related to stroke

are thought to be in excess of $50 billion annually [ 1 ]

Incidence

Nontraumatic ICH makes up 10–15 % of reported strokes, with

primary ICH making up 78–88 % of these cases [ 2 3 5 ] The

incidence of ICH varies greatly with regard to the population

being studied There are a number of factors attributable to an

increase incidence in ICH (i.e., age, race, genetic

predisposi-tion, and hypertension), but in general rates are considered to

be in the range of 10–30 cases per 100,000 [ 6 9 ] Interestingly,

in spite of signifi cant efforts from the medical community to

address known risk factors for ICH, the incidence has not

appreciably decreased over the past 30 years [ 10 ]

Risk Factors

While the overall incidence of ICH has remained stable over years, many studies show that a number of factors greatly increase an individual’s chance of suffering an ICH [ 2 ] Non- modifi able risk factors include age, ethnicity, genetic factors, and cerebral amyloid angiopathy; major modifi able risk factors include hypertension and excessive alcohol consumption [ 11 ]

Age

Perhaps the single most important risk factor related to an increase rate of ICH is advancing age [ 6 9 10 ] Sacco and colleagues found the incidence ranged from 1.8 per 100,000

in 0-to-44-year-olds compared to 308.8 per 100,000 in patients over 85 years of age [ 9 ] Similar results were noted

by van Asch and colleagues in their meta-analysis strating an exponential progression in ICH incidence related

demon-to age (Fig 25.1 ) [ 10 ] They found for patients 0–44 years of age, the incidence was 1.9 compared to 196.0 per 100,000 in patients over 85 years of age Ariesen and colleagues calcu-lated a relative risk with each 10-year increase in age of 1.97 (95 % CI, 1.79–2.16) [ 11 ]

Race/Ethnicity

There is a disparate representation of stroke in African- Americans, who are affected at a rate of almost 2–1 com-pared to Caucasians [ 7 , 8 , 12 , 13 ] The reported incidence for this high-risk population varies from 37 to 50 per 100,000 [ 7 , 8 , 12 – 14 ] Much of this burden is carried by middle-aged

Table 25.1 Causes of spontaneous intracranial hemorrhage

45–54 55–64 65–74 75–84 ≥85

≤44

Years Incidence of ICH as a function of age

increasing age (Graph extrapolated from data by van Asch et al [ 10 ])

(35–54 years old) African-Americans, with relative risks for

hemorrhage as high as 9.8 when compared to an aged

matched Caucasian population [ 7] The etiology of this

increased risk has not been fully defi ned; however,

hyperten-sion is likely to play a role, as this condition is an established

strong risk factor for ICH and is overrepresented in the

African-American community [ 7 ] Underlying genetic

fac-tors may also play a role

Japanese heritage is another patient population that has an

increased predilection for ICH [ 15 – 17 ] Their incidence of

ICH is 43–50 per 100,000, which is comparable to the

African-American community [ 15 – 17 ]

Hypertension

Hypertension is the single most important modifi able risk

factor and the most common cause of primary ICH [ 18 ]

Approximately 50 % of ICHs are due to hypertension, and

15 % of patients with chronic hypertension die from

ICH [ 18 ] The presence of hypertension leads to a marked

increase in ICH risk with an odds ratio (OR) ranging from

2.5 to 5.5 [ 19 – 21 ] A component of this risk is attributable to

the degree of hypertension, as Stage 1 vs Stage 3

hyperten-sion is associated with relative risks of 1.6 and 7.3,

respec-tively [ 13 ] Importantly, normalization of hypertension with

treatment substantially lowers this increased risk of ICH;

however, even previously hypertensive patients carry some

hemorrhagic risk (OR of 1.4 vs normotensive patients) [ 20 ]

Finally, hypertension has a well-established specifi city for

ICH type, with the OR for a nonlobar ICH being 4.2 as

com-pared to 1.0 for lobar ICH [ 21 ]

The pathophysiology of hypertension-related ICH stems

largely from the deleterious effects of persistent elevated

blood pressure on penetrating arteries and arterioles [ 18 , 22 ]

This chronic exposure to elevated pressure causes a

progres-sive hyalinosis and sclerosis of these arteries, resulting in

weakening of the vessel walls [ 22 ] and in some patients

for-mation of Charcot-Bouchard microaneurysms [ 18 ] The

combination of high blood pressure, weakened vessel walls,

development of microaneurysms, and low resistance of brain

parenchyma leads to a scenario vulnerable to rupture [ 22 ]

Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) has been implicated in

a number of neurological conditions, especially lobar ICH

[ 23 ] It is responsible for 5–10 % of all primary ICHs [ 23 ]

and is the primary cause of recurrent lobar hemorrhages

[ 24 ] CAA is characterized by deposition of amyloid-β

pep-tide (Aβ) into the wall and adventitia of capillaries,

arteri-oles, and small arteries of the cerebral cortex [ 6 ] Advancing

age is the strongest risk factor for its development [ 23 ], with

approximately 30 % of persons over the age of 60 and more than 50 % of persons over the age of 90 being affected [ 25 , 26] CAA is also commonly seen in patients with Alzheimer’s disease, with at least 80 % of such patients hav-ing histologic evidence of CAA [ 6 ] Aβ deposition into cere-bral vessels causes severe vascular dysfunction, smooth muscle cell loss, vessel wall weakening, and in many patients blood extravasation into the brain parenchyma [ 6 ]

Genetics are also a risk factor for CAA and CAA-related ICH Specifi cally, certain apolipoprotein E (APOE) polymor-phisms have been linked to the presence and severity of CAA and the incidence of CAA-related ICH Specifi cally, carriers

of the ε2 and ε4 alleles of APOE have been shown to be at increased risk of lobar ICH, having an OR of 2.30 compared

to carriers of the more common ε3 allele [ 21 ] The nisms underlying this increased risk, however, differ, as the ε4 allele has been primarily associated with an increased risk

mecha-of CAA formation [ 27 , 28 ], while the ε2 allele has been marily linked to heightened vessel wall fragility [ 29 , 30 ]

Antithrombotic Medications

ICH related to the use of antithrombotic medications (i.e., warfarin, aspirin, clopidogrel, etc.) is not considered a primary ICH; however, it is a special entity that deserves dis-cussion as ~10 % of patients are receiving warfarin, and

~25 % are receiving aspirin at the time of hemorrhage [ 31 ] Hart and coworkers reviewed the incidences of ICH in elderly patients taking aspirin, aspirin + clopidogrel, warfa-rin, or warfarin + aspirin In the patients taking no antithrom-botic medications, they noted an ICH incidence of 0.15 % per year In contrast, patients taking aspirin had a rate of 0.2–0.3 % per year, patients taking aspirin + clopidogrel had

a rate of 0.3–0.4 % per year, patients taking warfarin only had a rate of 0.3–1.0 % per year, and patients taking warfa-rin + aspirin had a rate of 0.5–1.0 % per year [ 31 ] Importantly, the risk related to warfarin therapy is directly related to the degree of anticoagulation, with patients having an INR >4.0 having the greatest risk [ 31 ]

Clinical Presentation

Patients presenting with primary ICH have varied cal symptoms based primarily on the size and location of the hemorrhage One of the most common symptoms is head-ache, which occurs in 34–58 % of ICH patients [ 2 6 ] This symptom is particularly common in patients with hemor-rhages occurring in the cerebellum [ 6 ] Seizures are a less frequent symptom, occurring in 10–11 % of ICH patients [ 6 ] This symptom is more common in lobar hemorrhages and generally refl ects extension of the ICH into the cerebral cortex In patients having a large ICH resulting in elevated

neurologi-intracranial pressure, decreased level of consciousness is very

common [ 2 ] This symptom is likely secondary to pressure on

the thalamic and brainstem reticular activating systems [ 32 ]

Focal neurological defi cits are related to the specifi c

loca-tion of the ICH, which is typically divided into deep cerebral,

lobar, brainstem, and cerebellum Deep cerebral is the most

common location of primary ICH, with incidences ranging

from 36 to 69 % [ 7 ] These patients typically present with

a combination of symptoms including hemiparesis,

hemi-sensory defi cit, gaze paresis, and/or decreased level of

con-sciousness [ 2 , 6 ] Lobar is the second most common location

of primary ICH, with incidences ranging from 15 to 52 %

[ 7 ] These patients present with neurological defi cits related

to the specifi c lobe involved and its laterality Patients with

a frontal ICH often present with headache, limb

hemipare-sis, and gaze deviation [ 2 , 6 , 32 ] Patients with a dominant

temporal ICH usually present with aphasia and/or

hemianop-sia [ 2 6 32 ] Patients with an occipital ICH show evidence

of a homonymous visual fi eld defi cit [ 2 , 6 , 32 ] Brainstem

and cerebellum are less common locations of primary ICH,

with incidences of 4–9 and 7–11 %, respectively [ 7 ] Patients

with a brainstem or cerebellar ICH usually present with a

combination of neurological defi cits including cranial nerve

defi cits, dysarthria, ataxia, and/or decreased level of

con-sciousness [ 2 6 32 ]

Morbidity and Mortality

ICH is a devastating and potentially deadly event in the life

of a patient The mortality rate can be as high a 62 % at 1

year [ 2 ] Sacco and coworkers [ 9 ] in a prospective analysis

of a large cohort of patients with ICH reported 7-day, 30-day,

and 1-year mortality rates of 35, 50, and 59 %, respectively

These rates were dependent upon a number of factors

includ-ing patient age, hemorrhage location, and comorbid

condi-tions [ 9 ] They also reported a 24 % survival rate at 10 years

Other factors associated with prognosis include Glasgow

Coma Scale at presentation, ICH volume, and presence of

intraventricular hemorrhage [ 33 ] One factor associated with

improved mortality rates after ICH is the treatment in a

spe-cialized neurologic/neurosurgical intensive care unit [ 34 ]

In survivors, ICH is associated with substantial morbidity

For example, in the International Surgical Trial in

Intracerebral Haemorrhage (STICH), only 27 % of patients

randomized to conservative therapy had favorable functional outcomes in long-term follow-up [ 35 ] In the meta-analysis

by van Asch and coworkers [ 10 ], only 12–39 % of ICH patients were living independently at last follow-up

ICH can be divided into fi ve temporal stages (Table 25.2 ): hyperacute (<12 h), acute (12–48 h), early subacute (2–7 days), late subacute (8 days to 1 month), and chronic (>1 month) [ 37 , 38 ] Hyperacute hemorrhage is a liquid composed of oxygenated hemoglobin As the hemorrhage matures, it converts to a clot form consisting of blood cells,

platelets, and serum Over the course of acute and early

sub-acute phases the oxygenated hemoglobin becomes gradually

deoxygenated and is eventually converted to

methemoglo-bin The late subacute phase is identifi ed as lysis of red

blood cells that releases methemoglobin into the

surround-ing tissue The chronic phase is the result of macrophages

and glial cells migrating into the region of hemorrhage Methemoglobin is phagocytized and converted into hemo-siderin and ferritin [ 37 , 38 ] Since these phases are related to the actual physical components of the hemorrhage, there is a correlation to changes found on neuroimaging

Computed Tomography (CT)

Non-contrast CT is considered the gold standard (sensitivity approaching 100 %) for the detection of intracranial hemor-rhage [ 6 , 36 ] Because of characteristics such as speed, avail-ability, and relatively low cost, it is often recommended as the fi rst-line imaging study [ 6 33 , 36 ]

CT fi ndings in patients with ICH are determined by the density of the hemorrhage that directly affects the attenua-tion of X-rays [ 37 , 38 ] Hence, as a hemorrhage transitions

Hyperacute (<12 h) Hyperdense Isointense Hyperintense Hypointense Acute (12–48 h) Hyperdense Isointense Hypointense Hypointense Early subacute (2–7 days) Hyperdense Hyperintense Hypointense Hypointense Late subacute (8–30 days) Isodense Hyperintense Hyperintense Hypointense Chronic (>30 days) Hypodense Hypointense Hypointense Hypointense

Table 25.2 Appearance of ICH

on CT and MRI

from acute to chronic the relative density compared to brain

parenchyma changes from hyperdense to hypodense [ 37 , 38 ]

(Table 25.2 ) Therefore, CT is able to give an immediate

esti-mate regarding the age of the ICH

Another important fi nding assessed by CT is ICH volume,

which is a strong predictor of morbidity and mortality in ICH

patients Broderick and colleagues [ 39 ] reported that patients

with ICH volumes greater than 60 cm 3 had a 30 day mortality

of 91 % as compared to patients with ICH volumes less than

30 cm 3 who had a 30 day mortality of 19 % A similar

asso-ciation between ICH volume and patient morbidity was

found A clinically useful method for rapidly calculating

ICH volume is defi ned in the following equation: ICH

vol-ume = ( A × B × C )/2; where A is the largest cross sectional

diameter of the ICH, B is the diameter perpendicular to A ,

and C equals the number of CT slices showing hemorrhage

multiplied by the slice thickness [ 40 , 41 ]

A factor also found to be related to poor outcomes, which

is readily assessed by CT, is hematoma growth Davis and

colleagues [ 42 ] in a pooled meta-analysis found that for each

10 % increase in ICH volume the hazard ratio for death

increased by 5 % A similar fi nding was noted for patient

morbidity, as each 10 % increase in ICH volume was

associ-ated with a 16 % increase in modifi ed Rankin scale

Computed Tomographic Angiography (CTA)

Computed tomographic angiography (CTA) is a contrasted CT

in which image acquisition is timed to correspond to the late arterial/late venous phase of cerebral perfusion [ 6 43 ] Similar

to non-contrast CT, CTA is rapid, accessible, and relatively inexpensive when compared to magnetic resonance imaging and digital subtraction angiography [ 6] CTA provides an assessment of the cerebral vasculature useful in detecting under-lying etiologies of ICH such as aneurysms and arteriovenous malformations [ 6 ] A number of studies have shown CTA to be 93–98 % sensitive in detecting cerebral aneurysms [ 44 , 45 ] CTA can also be useful in identifying ICH patients that are

at high risk for hematoma expansion [ 43 , 46 ] Wada and leagues [ 43 ] defi ned the “spot sign,” a fi nding on CTA which

col-is a 1–2 mm focus of enhancement within the hematoma ume (Fig 25.2a, b) In their prospective evaluation of 39 patients with spontaneous ICH, they found 33 % demonstrated this so-called spot sign on CTA This fi nding was signifi cantly associated with a high likelihood of hematoma progression Beyond hematoma expansion, the presence of a spot sign has been shown to be an independent predictor of in-hospital mor-tality (OR of 2.5; 95 % CI 1.3–4.7) and poor outcome (modi-

vol-fi ed Rankin score ≥4) (OR of 2.4; 95 % CI 1.1–4.9) [ 47 ]

Fig 25.2 ( a ) Non-contrasted HCT demonstrating a large basal ganglia

ICH with intraventricular extension Size and ventricular involvement

are both independent predictors of worsening outcome ( b ) The “spot

sign” ( arrow ), a 1–2 mm focus of enhancement within the hemorrhage

volume found on CTA, is associated with hemorrhage enlargement Abbreviations: HCT head computed tomography, ICH intracranial

hemorrhage, CTA computed tomographic angiography

Magnetic Resonance Imaging (MRI)

MRI is considered the most sensitive imaging modality in

detecting ICH [ 37] In a prospective evaluation of 200

patients comparing CT to MRI, Kidwell and coworkers [ 48 ]

found these imaging modalities to be equivalent in detecting

acute hemorrhage, but that MRI was signifi cantly more

sen-sitive in detecting chronic hemorrhage In addition to its

increased sensitivity for later phases of ICH, MRI provides

greater detail as compared to CT in regard to the age of

ICH [ 38 ] Specifi cally , the signal detected by MRI is based

on the paramagnetic characteristics of the tissue, the

mag-netic fi eld strength, and pulse sequence used [ 6 , 37 , 38 ], and

therefore, pulse sequence, such as T1, T2, and T2*, and

FLAIR all provide unique information about the age of the

identifi ed ICH (see Table 25.2 for more details)

An additional MRI fi nding of particular interest in patients

with primary ICH is cerebral microhemorrhage This fi nding is

defi ned as a hyperintensity that is most prominent on T2* and

gradient-echo MRI sequences (Fig 25.3 ) [ 6 ] They have been

histopathologically associated with hemosiderin deposition

and evidence of angiopathy-related microhemorrhage [ 49 ]

This association between primary ICH and microhemorrhages

was used by Knudsen and coworkers [ 50 ] to defi ne the Boston criteria (Table 25.3 ) The method was developed to assist clini-cians in diagnosing CAA in patients without the necessity of histopathology For verifi cation, they prospectively followed

39 patients with primary ICH with age ≥55 Of these 13 were categorized as “probable CAA” based on the presence of mul-tiple microhemorrhages on CT and/or MRI All 13 (100 %) patients were found to have histopathologically proven CAA

on biopsy From the remaining 26 patients with possible CAA,

16 (62 %) were pathologically diagnosed with CAA [ 50 ] These results suggest that CAA may be diagnosed with a degree of certainty based on the combination of clinical details and imaging characteristics

Digital Subtraction Angiography (DSA)

DSA is considered the gold standard for evaluating the bral vasculature [ 51 ] Zhu and coworkers [ 51 ] in a prospec-tive evaluation of 206 patients with spontaneous ICH attempted to identify factors indicating which patients should undergo DSA in their work-up for ICH etiology They found that in young patients (age <45 years) without history of hypertension, the DSA yield was 48 % in basal ganglia and cerebellar ICH and 65 % in lobar ICH From this they rec-ommend that all patients with spontaneous ICH should be considered for DSA except hypertensive patients who are over 45 years of age and have a prototypic hypertensive ICH

on neuroimaging (i.e., ICH based in the basal ganglia, bellum, or brainstem)

In attempts to minimize the unnecessary use of DSA, comparisons to CTA and MRI/MRA have been made In a prospective direct comparison of CTA vs the gold standard DSA in 109 ICH patients, Wong and coworkers found that CTA had a sensitivity, specifi city, positive predictive value, and negative predictive value of 100, 99, 97, and 100 %,

Fig 25.3 The T2* sequence from the magnetic resonance imaging of

a patient with histopathologically proven CAA Note the multiple areas

of hypo-intensity within the bilateral frontal and temporal lobes, which

represent multi-focal microhemorrhages

Table 25.3 Boston criteria for diagnosis of CAA ICH

Defi nitive CAA: (requires postmortem examination) Lobar ICH

Histopathologically proven severe, diffuse CAA with vasculopathy

No other ICH etiology Probable CAA with supporting pathology: (requires pathologic specimen) Lobar ICH

Histopathologically proven CAA in specimen

No other ICH etiology Probable CAA:

Multiple lobar ICHs Age ≥55 years

No other ICH etiology Possible CAA:

Single lobar ICH Age ≥55 years

respectively They concluded that CTA compares favorably

to DSA in the work-up of ICH patients suspected of having

an underlying vascular etiology In a separate study

compar-ing the utility of MRI/MRA vs the gold standard DSA in

151 ICH patients, this same group found that MRI/MRA had

a sensitivity, specifi city, positive predictive value, and

nega-tive predicnega-tive value of 98, 100, 98, and 100 %, respecnega-tively

However, MRI/MRA was found to be more sensitive in

detecting angiographically occult lesions such as cavernous

malformations, microhemorrhages, and neoplasms They

concluded that MRI/MRA may be a more appropriate

screening tool for ICH patients suspected of having an

under-lying structural etiology

Recommendations

Initial evaluation of patients with acute neurological defi cits

should include neuroimaging either via CT or MRI If an

MRI is obtained, blood-sensitive sequences such as T2*,

gradient echo, or susceptibility weighted imaging should be

included [ 33 , 36 ] In cases where the clinical and imaging

characteristics are not consistent with a prototypical

hypertensive ICH, further analysis with CTA, MRI/MRA,

and/or DSA is indicated [ 33 , 36 ] CTA is especially useful in

identifying patients who are at an increased risk for

hemor-rhage progression [ 36 ] MRI/MRA is the technique of choice

for identifying angiographically occult lesions DSA is the

gold standard for identifying and characterizing underlying

vascular etiologies

Medical Management

Patients with ICH are at high risk for early deterioration and

should initially be cared for in an intensive care setting [ 34 , 52 ]

(Table 25.4 )

Prevention of Hematoma Expansion

and Rebleeding

Even in the absence of coagulopathy, ICH is prone to expand

and/or recur, usually in the fi rst 12–24 h All anticoagulants

and antiplatelet agents should be stopped Normal coagulation

should be restored with vitamin K and fresh frozen plasma

[ 53 – 55 ] (Table 25.5 ) Patients with a severe coagulation factor defi ciency or severe thrombocytopenia should receive appro-priate factor replacement or platelets Recombinant factor VIIa or prothrombin complex concentrate may be considered

to reverse anticoagulation in those at risk of volume overload

or lung injury, but they have not been shown to improve comes compared with fresh frozen plasma and may carry a greater risk of thromboembolic events [ 56 , 57 ]

Maintaining Cerebral Perfusion:

Blood Pressure Management

High blood pressure (BP) was thought to contribute to ing; however, there is no convincing evidence that lowering

rebleed-BP improves outcome [ 58 – 60 ] A higher BP may be necessary

to provide adequate blood fl ow to the brain while ICP is vated, particularly in chronically hypertensive patients with impaired autoregulation [ 61]; aggressive BP management may cause hypoperfusion Even in normotensive patients, ICH may lead to transient hypertension resolving spontaneously over a few days A modest (~15 %) reduction in BP does not seem to worsen neurological outcome [ 60 ] However, ongoing damage to other organs (heart or kidneys) is a compelling indi-cation to treat elevated BP If mean arterial pressure is above 130–140 mmHg or end-organ damage is present, short-acting agents are used to gently lower BP Nitrates are avoided due to the risk of cerebral vasodilatation with worsening edema Addressing pain may also help control elevated BP (Fig 25.4 )

Treatment of Cerebral Edema

Cerebral edema in ICH can occur as a result of the direct effects of hematoma volume and edema, as well as hydro-cephalus due to intraventricular hemorrhage (IVH) or ven-tricular compression In patients with a decreased level of consciousness (GCS ≤8), clinical evidence of cerebral her-niation, or those with signifi cant IVH or hydrocephalus, ICP monitoring with a ventricular or parenchymal catheter should

Indications for surgical intervention

hemorrhage Discontinue all antiplatelet and anticoagulant medications Reverse anticoagulation or correct coagulopathy:

Vitamin K 10 mg IV or enterally daily for 3 days Fresh frozen plasma 15–20 ml/kg

Platelet and coagulation factor replacement as needed for thrombocytopenia and coagulation factor defi ciency, respectively Consider prothrombin complex concentrate or recombinant factor VIIa for coagulopathic patients needing an urgent surgical procedure

or those at risk for volume overload Follow coagulation panel frequently, keep corrected for 24–48 h

Seizures

The primary neuronal damage and blood products increase

sei-zure risk after ICH Seisei-zures occur in 5–15 % of these patients,

usually in the fi rst few days of hospitalization [ 63 ] Prophylactic

anticonvulsant therapy is not indicated in ICH [ 64 , 65 ], but in

patients with depressed mental status out of proportion to the

degree of brain injury, continuous electroencephalography

(EEG) should be considered Patients with clinical seizures and

patients with mental status changes and electrographic seizures

should be treated with anticonvulsant therapy

General Care

Patients with ICH, like all critically ill patients, are at risk

for numerous complications including myocardial

infarc-tions, heart failure with pulmonary edema, deep vein

thrombosis (DVT), aspiration pneumonia, urinary tract

infections, pressure ulcers, and orthopedic complications

(contractures, etc.) Sequential compression devices in

addition to elastic stockings should be used from

admis-sion, and subcutaneous low-molecular-weight heparin or

unfractionated heparin for DVT prophylaxis can be started

after 48 h if there is no evidence of hematoma expansion

[ 66 – 68] Spontaneous lobar ICH in particular carries a

relatively high risk of recurrence; thus, avoidance of

long-term anticoagulation for nonvalvular atrial fi brillation in

these patients is recommended [ 52 ] In the presence of a

clear indication for anticoagulation (e.g., mechanical heart

valve) or antiplatelet therapy (e.g., coronary artery stents),

it is reasonable to restart anticoagulation in nonlobar ICH

in 2–4 weeks and antiplatelet therapy in all ICH 1–2 weeks after documentation of cessation of bleeding

Surgical Management

With mortality rates for ICH patients being as high as

62 % [ 3 ], there has been tremendous effort toward ing whether surgical intervention in this patient population improves outcome Herein, we present a brief review of the clinical trials that have addressed this question and provide the reader with the most current recommendations provided

determin-by the American Heart Association Stroke Council [ 36 ] and the European Stroke Initiative [ 33 ]

Supratentorial Hemorrhage

One of the fi rst attempts in identifying the role of surgery in primary supratentorial ICH was provided by McKissock and colleagues [ 69 ] in their randomized controlled trial compar-ing surgical intervention via open craniotomy to conserva-tive management in 180 patients with spontaneous ICH They found no benefi t of surgery in regard to mortality or morbidity They did fi nd increasing age and decreased level

of consciousness on admission to be strong predictors of mortality Of note, ICH diagnosis in this study was based on DSA, as this study was completed in the pre-CT era

In 1989, Auer and colleagues [ 70 ] published their results from a randomized clinical trial evaluating endoscopic sur-gery (rather than open craniotomy) vs medical treatment in

100 patients with primary supratentorial ICH They found that those treated with this minimally invasive surgery had a signifi cant improvement in survival and functional outcome

At 1 week, the mortality was 14 % in the surgical group vs

28 % in the medical group At 6 months, the difference in mortality between surgery and medical groups was even greater (42 % vs 70 %, respectively) They also found that the improved outcome was limited to patients who were less than 60 years of age, who had ICH volumes less than 50 cm 3 , and who had admission neurologic status of alert or somno-lent (vs comatose) They also found that the improvement related to surgical intervention was only signifi cant in patients with subcortical ICH, while patients with basal ganglia ICH had no apparent benefi t related to surgical intervention The encouraging fi ndings for surgery in the Auer and col-leagues study were soon followed by the discouraging fi nd-ings of Juvela and colleagues [ 71 ] who found no benefi t of surgery via open craniotomy in a prospective randomized trial of 52 patients with primary supratentorial ICH They reported a mortality rate of 46 % for surgery vs 38 % for

Risk of end -organ damage? EKG

changes, elevated troponins,

proteinuria, high creatinine, heart

failure/pulmonary edema, aneurismal

dissection, etc.

No treatment

EVD external ventricular drain ICP intracranial pressure

Lower BP cautiously, only

as needed to decrease

end-organ damage, prevent

abrupt drops Avoid

nitrates

Fig 25.4 Blood pressure management algorithm after intracerebral

hemorrhage

conservative therapy They did fi nd that the length of survival

was improved with surgery in the semicomatose or

stupor-ous patients, but found no overall improvement in quality of

life Similar results were reported by Batjer and colleagues

[ 72 ] in their small prospective randomized trial comparing

best medical management vs best medical management with

intracranial pressure monitoring vs surgery via open

crani-otomy for patients with primary supratentorial ICH

In an attempt to build on the favorable results reported by

Auer and colleagues [ 70 ] who utilized a minimally invasive

approach for ICH evacuation, several groups have examined

other minimally invasive surgical approaches Teernstra and

colleagues [ 73] evaluated the utility of stereotactic

aspira-tion + urokinase infusion as a means for treating primary

supra-tentorial ICH In their randomized clinical trial of 70 patients,

they found that surgery resulted in a decrease in ICH volume,

but that this hematoma reduction was not associated with a

sig-nifi cant improvement in patient outcome In contrast, Hosseini

and coworkers [ 74 ] randomized 37 primary supratentorial ICH

patients to surgical management via stereotactic aspiration

without urokinase infusion vs conservative therapy and found

that surgery led to a signifi cant improvement in mortality (15 %

vs 53 %) and morbidity (Karnofsky’s score of 51 vs 25)

Hattori and colleagues [ 75 ] also evaluated the potential of

min-imally invasive surgery for hematoma evacuation In their trial,

242 patients with primary supratentorial ICH were randomized

to stereotactic aspiration without urokinase infusion vs

medi-cal therapy They reported a nonsignifi cant trend toward

decreased mortality and morbidity in surgical patients

In an effort to defi nitively answer the question whether

surgical intervention carries clinical benefi t in patients with

primary supratentorial ICH, Mendelow and colleagues

orga-nized STICH – a multicentered randomized controlled trial

examining surgical intervention (primarily open craniotomy)

vs best medical therapy [ 35 ] Over an 8-year period, 1,033

patients were randomized to either early surgery vs initial

conservative treatment They reported unfavorable outcomes

in 74 % of surgical patients vs 76 % of conservatively

man-aged patients In subgroup analysis, however, an 8 % absolute

benefi t for surgery in patients with ICH within 1 cm of the

cortical surface was found They also noted that surgery was

harmful in patients presenting with Glasgow Coma Scale ≤8,

where the relative risk for a poor outcome was raised by 8 %

The main conclusion from this very large, well-conducted

randomized controlled trial was that surgery provides no

defi nitive benefi t for primary ICH; however, a suggestion that

surgical intervention may be benefi cial in patients with ICH

within <1 cm of the cortical surface was noted

Recently, Prasad and colleagues [ 76 ] published a meta-

analysis of ten randomized controlled trials that met

pre-defi ned inclusion and exclusion criteria and addressed the

question of surgery vs medical therapy for patients with

supratentorial primary ICH A total of 2,059 patients were

included in their analysis Their results indicated that surgery provided an overall benefi t to this patient population, as the risk of death or dependence was signifi cantly lower in the surgical vs medical patients (OR of 0.71; 95 % CI 0.58–0.88) Specifi cally, surgery provided a 26 % relative reduction in being dead and 29 % reduction in being dead or dependent as compared to medical therapy They also found a suggestion (though this did not reach statistical signifi cance) that mini-mally invasive surgery (stereotactic or endoscopic tech-niques) produced better outcomes when compared to open craniotomy (OR of 0.66 vs 0.82, respectively) Importantly, the authors acknowledged that the benefi t of surgery was not consistent across all studies, and, therefore, results from their analysis were not considered robust

man-Da Pian and coworkers [ 77 ] retrospectively evaluated 205 rior fossa hemorrhages and found a 38 % mortality in patients with cerebellar hemorrhage, which was primarily determined

poste-by hemorrhage size and level of patient consciousness at sentation They suggested that surgery should be limited to patients with fourth ventricular involvement and hydroceph-alus Koziarski and coworkers [ 80 ] retrospectively reviewed

pre-11 cases of cerebellar hemorrhage and found that when hematomas were large (>3 cm), surgical intervention was required Similar fi ndings were noted by Kobayashi and col-leagues [ 79 ] who retrospectively reviewed 101 consecutive patients with cerebellar ICH They proposed a treatment strategy where surgery was performed for patients with hem-orrhage size ≥4 cm and/or Glasgow Coma Scale ≤13 In patients who presented in moribund condition, no intensive therapy was recommended Kirollos and colleagues [ 78 ] proposed a management scheme based on a grading scale for fourth ventricular compression along with Glasgow Coma Scale and prospectively applied this protocol to a consecu-tive series of 50 patients with cerebellar hemorrhage Three grades of fourth ventricular compression were defi ned: Grade I, normal size and location; Grade II, partially com-pressed and shifted; and Grade III, completely obliterated They recommended the following: expectant management for Grade I and II patients with a Glasgow Come Scale ≥13; CSF diversion for Grade I and II patients with hydrocephalus and a Glasgow Coma Scale <13; surgery for Grade II patients without hydrocephalus and a Glasgow Coma Scale <13; and surgery for all Grade III patients With this scheme, good outcome (Glasgow Outcome Scale ≥4 at 3 months) for Grade

I, II, and III patients was 100, 58, and 17 %, respectively

Overall mortality was 40 % at 3 months Interestingly, 60 %

of Grade I and II patients had hematomas ≥3 cm and did not

require surgical evacuation

Intraventricular Hemorrhage

and Hydrocephalus

Intraventricular hemorrhage (IVH) is a frequent occurrence

in spontaneous ICH patients, occurring in approximately

19–45 % of cases [ 82 – 84 ]; and its presence in ICH patients

has great impact on patient outcome Mortality in ICH

patients without IVH is 8.5–28.6 % in ICH patients, while

mortality in ICH patients with IVH is 29–79 % [ 82 ] Not

only is the presence of IVH associated with worse patient

outcome, but a dosage effect in which increasing volumes of

intraventricular blood are associated with progressively

worse patient outcome has also been noted [ 85 ] In addition,

the presence of hydrocephalus in ICH patients has been

iden-tifi ed as independent risk factor for mortality [ 86 ]

The standard treatment for IVH with associated

hydro-cephalus is placement of an external ventricular drain (EVD);

however, whether this treatment leads to improved patient

outcomes has not been proven In a retrospective study of 40

IVH patients with hydrocephalus, Coplin and colleagues [ 87 ]

noted that the mean initial intracranial pressure was only

16 mmHg and only 15 % of patients had an initial pressure

>20 mmHg Similarly, Ziai and colleagues [ 88 ] prospectively

followed 11 IVH patients with hydrocephalus who were

treated with an EVD and found that only one had increased

intracranial pressure In retrospective studies by Diringer and

colleagues [ 86 ] and Adams and colleagues [ 89 ], placement of

an EVD in IVH patients with hydrocephalus was not found to

improve overall patient mortality, despite controlling

intra-cranial pressure (<20 mmHg) in 91 % of patients

In addition to EVD placement, other therapies for IVH

have been considered Use of intraventricular thrombolytics,

for example, has been examined as a means for improving

patient outcome [ 83 ] The fi rst report presenting a human

case where tissue plasminogen activator was injected into the

ventricle of a patient with IVH was presented by Findlay and

coworkers [ 90 ] They reported a marked decrease in IVH

volume and resultant reduction in intracranial pressure

Since this report, a number of small case series have been

published suggesting that intraventricular thrombolysis may

be a viable treatment strategy [ 91 – 93 ] There has been one

reported prospective, randomized, double-blinded,

con-trolled trial by Naff and colleagues [ 94 ] In their pilot study

they presented the results of 12 patients (7 treatment, 5

pla-cebo) who underwent ventriculostomy for IVH and infusion

with urokinase vs placebo In serial imaging, they found the

half-life of the blood products based on imaging was

4.69 days for the urokinase group vs 8.48 days in the cebo group The preliminary results from an ongoing study CLEAR-IVH were presented by Morgan and coworkers [ 84 ] For patients receiving intraventricular recombinant tis-sue plasminogen activator, they found the adverse event pro-

pla-fi le to be satisfactory for continuation of the study

In an effort to consolidate the data regarding the treatment

of IVH, there have been a number of reviews [ 91 – 93 ] Nieuwkamp and coworkers [ 92 ] in their meta-analysis of 18 publications found the mortality rates for conservative manage-ment, EVD, and EVD plus thrombolysis were 78, 58, and 6 % respectively For these groups the poor outcome rates were 90,

89, and 34 % From this they felt that EVD plus thrombolysis

is a reasonable management strategy but acknowledged that future randomized studies must be initiated A similar review was attempted by LaPointe and Haines [ 91 ] However , they felt that secondary to fl aws in study design and biased control groups, the data were anecdotal and no defi nitive conclusion could be drawn Most recently, a review by Staykov and coworkers [ 93 ] found mortality rates related to conservative management, EVD, and EVD plus thrombolysis were 71, 53, and 16 % They also found rates of poor outcomes to be 86, 70, and 45 % From their fi ndings, they feel that the data support-ing the use of EVD plus thrombolysis are increasing, and this will likely be the treatment of choice for a select population of patients with IVH

Recommendations

The usefulness of surgical intervention for ICH is unclear It

is reasonable to consider hematoma evacuation for those with superfi cial lobar clots (<1 cm from the cortical surface) and

>30 ml in size [ 33 , 36 ] Cerebellar hemorrhage showing signs

of brainstem compression, hydrocephalus, and/or clinical deterioration should undergo rapid surgical evacuation [ 36 ] Treatment with EVD only is not recommended [ 36 ]

Treatment of hydrocephalus with EVD and/or lumbar drain (for nonobstructive hydrocephalus) are considered rea-sonable [ 33 , 36 ] Patients who have a Glasgow Coma Scale

of ≤8 and show evidence of herniation may be considered for intracranial pressure monitoring or EVD in setting of hydrocephalus The use of intraventricular thrombolysis can

be considered; however, at this time its use and effectiveness

is still considered investigational [ 33 , 36 ]

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A.J Layon et al (eds.), Textbook of Neurointensive Care,

DOI 10.1007/978-1-4471-5226-2_26, © Springer-Verlag London 2013

Abstract

Cerebral arteriovenous malformations (AVMs) are plex lesions that require specialized, multidisciplinary treatment Patients may be encountered in the intensive care unit either following intracranial hemorrhage from AVM rupture or following elective surgical resection of

com-an unruptured AVM This chapter reviews all aspects of clinical management of AVMs including initial assess-ment and critical care, perioperative considerations, and the available neurosurgical interventions utilized for defi nitive AVM treatment

Keywords

Arteriovenous malformation • Radiosurgery • zation • Vascular malformation • Spetzler-Martin Grade

Defi nition

Arteriovenous malformations (AVMs) are a complex tangle

of abnormal arteries and veins, with an anatomic absence of the normal capillary bed This absence of a capillary bed can lead to high-fl ow shunting through various fi stulas [ 1 ] Cerebral AVMs, though relatively rare, are complex entities

to diagnose and treat

Epidemiology and Natural History

It is unclear when the time of onset of cerebral AVMs are, but certain features, such as their presentation in younger patients, including infants, and their abnormal architecture, suggest that at least some are due to a developmental derangement [ 1 2 ] Other evidence of early incidence is the fact that in the presence of an AVM, there are clear rear-rangements of neuronal networks, such as the translocation

of eloquent areas, a phenomenon seldom encountered in the face of acute intracranial hemorrhages [ 3 ] This may also

Brigham and Women’s Hospital, Harvard Medical School ,

75 Francis Street , Boston , MA 02115 , USA

e-mail: mabd-el-barr@partners.org

S F Oliveria , MD, PhD • B L Hoh , MD, FACS, FAHA, FAANS (*)

Department of Neurological Surgery ,

University of Florida College of Medicine ,

Vanderbilt University Medical Center ,

1161 21st Ave S, RM T4224 MCN , Nashville , TN 37232 , USA

e-mail: j.mocco@vanderbilt.edu

Contents

Defi nition 579

Epidemiology and Natural History 579

Critical Care Management 580

Treatment Modalities for AVM Management 585

Intraoperative and Postoperative Care 587

References 587

explain the lower rates of hemorrhages in AVMs compared

to other intracranial vascular abnormalities [ 4 ] A point of

evidence against an embryonic disturbance is that, whereas

there are numerous reports of in utero diagnosis of other

vas-cular abnormalities, the number of AVMs diagnosed in utero

are limited to single-digit case reports [ 5 6 ]

Genetic predisposition to cerebral AVMs has been diffi

-cult to prove, with only a few candidate genes having been

identifi ed to this point [ 7 , 8 ] There are a number of germline

mutations that have been found to be particularly important

in the pathogenesis of AVMs Some of these candidate

pro-teins include transforming growth factor-beta (TGF-β),

vas-cular endothelial growth factor (VEGF), and the angiopoietin

receptor Tie-2 [ 4 9 12 ]

The prevalence of AVMs has been diffi cult to pinpoint,

with ranges from 5 to 600 per 100,000 persons [ 13 , 14 ]

A retrospective analysis of symptomatic AVMs yielded a

rate of 1.1 per 100,000 [ 15 ], though this fi gure may be falsely

elevated due to the concurrent existence of other vascular

malformations A prospective, population-based survey

yielded an incidence of 1.34 per 100,000 person-years, with

approximately one-half presenting with a fi rst-ever

hemor-rhage (0.51 per 100,000 person-years) [ 16 ]

Much of what is known about the natural history of

cere-bral AVMs is based on a cohort study of 262 symptomatic

unoperated patients that presented to a central referral center

in Finland [ 17 ] In that study, 40 % of the patients were

excluded because they received a treatment upfront, but, for

the remaining 160 patients, the incidence of hemorrhage

averaged approximately 4 % per year A recent update to this

data set revealed a somewhat similar risk of hemorrhage

(2.4 % per year), but this risk was higher in the fi rst 5 years

after diagnosis [ 18 ] Multivariate analyses revealed that

pre-vious rupture, large AVMs (>50 mm nidus size), and

infraten-torial and deep locations were independent risk factors to

higher hemorrhage rates [ 18 ] Other studies have reported

that small AVM size and exclusive deep venous drainage and

AVM-related aneurysms are also risk factors associated with

higher rates of AMV hemorrhage [ 19 , 20 ]

Critical Care Management

Acute Evaluation

The most common clinical presentation of cerebral AVMs is

hemorrhage (70 %), seizures (25 %), and 5 % of patients will

present with headaches and other various vague neurologic

complaints [ 17 , 18 ]

Because hemorrhage is the most common presentation,

the hallmark characteristics of hemorrhage must be

recog-nized readily by the medical team These include the sudden

onset of headache, focal neurologic symptoms, and changes

in the level of consciousness

As with all acute presentations, the ABCs of intensive care must be secured This refers to the airway, breathing or blood pressure, and circulation or coagulation It is estimated that approximately 30 % of all patients with intracerebral hemorrhage will need to be mechanically ventilated [ 21 ] It has been suggested that any patient with a Glasgow Coma Scale (GCS) of eight or below should be intubated [ 22 ] Importantly, a complete arterial blood gas (ABG) should

be drawn, as making sure that the patient is well oxygenated

is not enough, since hypercapnia can worsen intracranial hypertension (discussed later in this chapter)

Blood pressure should be controlled to a limited extent, until the etiology of the focal neurological defi cit or decrease

of consciousness is elucidated As many of these patients will present with signs and symptoms of a hemorrhagic stroke, recent guidelines suggest that lowering the blood pressure to systolic pressures close to 140 mmHg may be benefi cial [ 23 , 24 ] As for coagulation, it is important to eval-uate if the patient is on anticoagulation medications It is estimated that approximately 15 % of patients with ICH are

on oral anticoagulation (OAC) therapy [ 25 ] If it is found that the patient is on anticoagulation, reversal of this anticoagula-tion is recommended [ 26 ] The traditional agents for this have been vitamin K and fresh frozen plasma (FFP) Vitamin

K, even given intravenously, takes many hours to have an effect [ 27 , 28 ] FFP, as a transfused blood product, carries the extra risk of allergic transfusion reactions and requires increased volumes to be effective

Two classes of drugs that have recently gained some prominence in the treatment of anticoagulation are pro-thrombin complex concentrates (PCCs) and recombinant factor VIIa (fFVIIa) PCCs are used to treat factor IX defi -ciency primarily but can also reverse defi ciencies of factors

II, VII, and X There is also some interest in using them to counteract warfarin [ 26 ] There is some evidence to suggest that use of these PCCs may decreased the amount of FFP needed to correct abnormal INRs, though clinical outcomes appear to be the same, with perhaps some decrease in adverse effects due to decreased volume overload to patients [ 26 ] rFVIIa, which is licensed to be used by hemophilia patients

or those with decreased factor VII or high titers of inhibitors, had originally garnered much attention as a potential potent reversal agent for OAC-associated ICH, but further studies revealed that it does not generate thrombin as effectively as PCCs [ 29] A phase 2 trial of rFVIIa showed promising results in terms of limiting hematoma expansion and clinical outcomes, but the phase III failed to reproduce these results and resulted in greater thromboembolic events in the rFVIIa treatment group [ 30 ]

Intracranial pressure (ICP) and cerebral perfusion sures (CPP) are also important parameters that are distinct to this patient population CPP is defi ned as the mean arterial pressure minus intracranial pressure (CPP = MAP – ICP) Elevated ICP is usually defi ned as greater than 20 mmHg for

pres-greater than 5 min, and the goal of CPP is to be pres-greater than

60–70 mmHg To measure intracranial pressure, a fi beroptic

ICP wire or an external ventricular drain (EVD) should be

placed Trauma guidelines suggest the insertion of such a

device in patients with a GCS of eight or below and

abnor-mal head CT and in the case of a patient with an acute

neu-rological defi cit and possible AVM (discussion of

radiographic signs follows later in this chapter); this should

also be done in the case of a patient without a robust

neuro-logical examination that can be followed An EVD also

allows for drainage of cerebrospinal fl uid (CSF), which can

also be helpful in lowering ICPs

Lowering intracranial pressure can be accomplished both

by decreasing the volume demands of the various

intracra-nial constituents or by sedation, which acts to decrease brain

tissue metabolism The Kellie-Monro hypothesis states that

the cranial compartment is incompressible and the volume of

the intracranial contents is fi xed Thus, any increase in any

of the three main constituents of cranial contents—namely,

brain tissue, CSF, and blood—must be accompanied by a

decrease in one of the others [ 31 ] It is because of this

princi-ple that CSF drainage with the use of an EVD is helpful in the

setting of hemorrhage from an AVM Similarly, brain tissue

volume can be decreased by the administration of mannitol

or hypertonic saline Mannitol, which is an osmotic diuretic,

works by two mechanisms The fi rst mechanism is that, when

it is given as bolus, it increases oxygen delivery by increasing

blood volume The second mechanism is that, by being an

osmotic agent, it draws water out of neurons [ 32 ] In the

trau-matic brain injury literature, it has been shown to decrease

mortality compared to barbiturates [ 33 ] However, mannitol

does have some adverse effects, namely nephrotoxicity and

causing patients to become hypovolemic [ 32 ] Hypertonic

saline, on the other hand, works by the same mechanism of

making an osmotic potential across neurons but does not have

the same negative effects A recent meta-analysis comparing

the two agents suggested that hypertonic saline does seem to

be more effi cacious in lowering ICP, though the number of

patients (112) was relatively small [ 34 ]

Another mechanism used to decrease ICP is causing

vasoconstriction through hypocarbia This can be

accom-plished by mild hyperventilation with a goal of PaCO 2 of

25–30 mmHg Severe hypocarbia should be avoided as it can

cause decreased cerebral blood fl ow This therapy is effective

when used intermittingly, but chronic hyperventilation may

cause rebound increased ICP when normocapnea is achieved

[ 35 ] Therefore, it is strongly recommended not to pursue

prolonged hypocarbia and to use this method of ICP control

only for brief periods

Increased ICP can also be lowered using sedation, which

by decreasing agitation, decreases brain tissue metabolic

demands If normal agents (propofol, benzodiazepines such

as versed and opioid agonists such as fentanyl) are unable to

control ICPs, an induced barbiturate coma with continuous

electroencephalogram (EEG) can be considered This is ally done until burst suppression is achieved [ 22 ] The last resort for increased ICPs is decompressive craniectomy or craniotomy, discussed elsewhere (Chaps 27 and 35 ) Many

usu-of the techniques usu-of ICP management are borrowed from the traumatic brain injury (TBI) literature, and, in the author’s institute, a detailed algorithm is followed in the cases of severe TBI (GCS ≤8) (Fig 26.1 )

As stated earlier, approximately one-third of patients with cerebral AVMs will present with seizures [ 36 ] A retrospec-tive analysis of 424 patients that presented with cerebral AVMs showed that male sex, age less than 65, AVM size of greater than 3 cm, and location in the temporal lobe were signifi cantly associated with seizures being the presenting symptom [ 37 ] In the acute setting, it is important to initiate antiepileptic prophylaxis in patients presenting with hemor-rhage, as this has been shown to increase risk of future sei-zures [ 37] For those patients that present with seizures, antiepileptic therapy is warranted

Important in the management of patients with AVMs are the systemic complications of neurological insult Subendocardial ischemia, which has been shown to be in proportion to the neurological insult, may result in a myriad

of symptoms from benign elevations in cardiac enzymes to life-threatening arrhythmias and pulmonary edema [ 38 , 39 ]

It is important to note preexisting cardiac conditions of these ill patients and monitor their progress

Another organ system at risk in these situations is the monary system Patients with neurological compromise are

pul-at higher risk for pul-atelectasis, aspirpul-ation, and pulmonary embolism [ 22] Oftentimes, patients with neurological decline with AVMs require pulmonary catheter to keep track

of their central venous pressures (CVPs) to avoid pulmonary hypertension, a consequence of hypervolemia for patients undergoing “triple H” therapy for vasospasm, an infrequent but very real potential complication of SAH from an AVM or feeding artery aneurysm associated with an AVM (see Chap

24 on SAH)

Electrolyte abnormalities must also be monitored in patients with AVMs The most common abnormality is hyponatremia [ 40 ] There has been a lack of a consensus on the diagnosis and management of hyponatremia in neurosur-gical patients The two most common reasons for hyponatre-mia, after exclusion of diuretic use, is cerebral salt wasting (CSW) and the syndrome of inappropriate antidiuretic hor-mone (SIADH) It is important to distinguish between these two etiologies, as the treatment for each is completely differ-ent and has signifi cant consequence to the patient The most important laboratory value to differentiate between the two diagnoses is the patient’s volume status Greatly simplifi ed, patients that are hypovolemic are most likely to have CSW, while those patients with euvolemia or hypervolemia are more likely to harbor SIADH SIADH is treated with water and volume restriction, while CSW is treated with replacing

Fig 26.1 Algorithm for management of patient’s decreased Glasgow Coma Scale (GCS ≤8) Although this algorithm is used for patients with

traumatic brain injury (TBI), many of the same methods are used in critically ill patients harboring AVMs or other vascular abnormalities