prevention and rx medical and neuro complication of anurysmal bleed

8/2/2019 Prevention and Rx Medical and Neuro Complication of Anurysmal Bleed

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REVIEWPract Neurol 2009; 9: 195209

Prevention and treatment ofmedical and neurologicalcomplications in patients withaneurysmal subarachnoid

haemorrhageGabriel J E Rinkel, Catharine J M Klijn

Treatment of patients with aneurysmal subarachnoid haemorrhage not onlyinvolves securing the aneurysm by endovascular coiling or surgical clippingbut also prevention and treatment of the medical and neurologicalcomplications of the bleed. These acutely ill patients should be looked after inspecialised centres by a multidisciplinary team that is available 24 h a day,

7 days a week. No medical intervention is known to improve outcome byreducing the risk of rebleeding but oral nimodipine should be standard care toprevent delayed cerebral ischaemia. For patients who develop delayedischaemia, there is no evidence that hypervolaemia, haemodilution,hypertension, balloon angioplasty or intra-arterial vasodilating agentsimprove outcome. Lumbar puncture is a safe and reasonably effective way oftreating those forms of acute hydrocephalus that are not caused byintraventricular obstruction.

Subarachnoid haemorrhage (SAH) from

a ruptured intracranial aneurysm car-ries a gloomy prognosis. Approximately

half of the patients die within a month,

and one in five remain dependent on help in

activities of daily living.1 Poor outcome can be

caused by a poor clinical condition from the

outset, or by one of the many medical and

neurological complications that can occur

during the early clinical course. These acutely

ill patients should therefore be transferred

immediately to a specialised centre where a

multidisciplinary team is available 24 h a day,7 days a week. The team should investigate and

G J E Rinkel, C J M Klijn

Department of Neurology, Rudolf

Magnus Institute of Neuroscience,

University Medical Centre Utrecht,

The Netherlands

Correspondence to:

Professor Gabriel J E Rinkel

Professor of Neurology, Head of

Cerebrovascular Unit, Departments

of Neurology and Neurosurgery,

Room No G03.228, University

Medical Centre Utrecht,

Heidelberglaan 100, 3484 CX

Utrecht, The Netherlands;[email protected]

1Rinkel, Klijn

www.practical-neurology.com


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treat the cause of a poor clinical condition in

patients who are not alert on admission, such

as an intracerebral haematoma, extensive

intraventricular haemorrhage, subdural hae-

matoma, hydrocephalus or cardiopulmonary

complications. Only by exclusion should it be

assumed that the cause of a poor clinicalcondition on admission is global ischaemic

brain damage from reduced or absent cerebral

blood flow as a result of the high pressure after

aneurysmal rupture.

Patients who survive the initial hours after

aneurysmal rupture are at risk of rebleeding,

delayed (also called secondary) cerebral ischae-

mia, hydrocephalus and a variety of systemic

disorders.2, 3 Rebleeding occurs in approxi-

mately 40% within the first month if the

aneurysm is left untreated, and occlusion of theaneurysm is therefore an important goal in

treating patients with aneurysmal SAH.

Occlusion of the aneurysm by neurosurgical

clipping or endovascular coiling is usually done

within the first day after admission although

there is no evidence from clinical trials that

early occlusion results in better outcome than

postponed treatment. But, although occlusion

of the ruptured aneurysm is an important part,it is by no means the only part in the

management. In this review we describe the

prevention and treatment of the medical and

neurological complications after SAH.

INITIAL TREATMENTMonitoringRecommendations for monitoring and gen-

eral management are summarised in table 1.

Patients should be under continuous obser-

vation in an intensive care unit or on amedium care facility of a stroke or neuro-

sciences unit experienced in SAH manage-

ment.4 The staff should have ample experi-

ence in assessing swallowing function to

prevent pneumonia, a frequent complication

after SAH and an independent risk factor for

poor outcome.5 For patients on our medium

care unit, we start monitoring the ECG, level

of consciousness (Glasgow Coma Scale), focal

deficits, temperature and pupils at least every

hour. Depending on the patients condition,

monitoring may be less frequent later during

the clinical course. We insert a urinary

catheter on admission in all patients and

calculate fluid balance every 6 h during the

initial week. In the intensive care unit, blood

pressure is monitored continuously via an

arterial line. Patients in a good clinical

condition in whom the aneurysm has been

secured, may be transferred to a regular care

bed in the stroke or neurosciences unit.

Blood pressureBlood pressure is often high in the early hours

to days after SAH, generally considered a

compensatory mechanism to overcome the

increased intracranial pressure and so preserve

cerebral blood flow. Treatment of high blood

pressure after SAH remains controversial

because of the lack of evidence from random-

ised trials. Data from observational studies

suggest that aggressive treatment of blood

pressure may decrease the risk of rebleeding

but at the cost of an increased risk of delayedcerebral ischaemia,6 and that the combined

TABLE 1 Recommendations for monitoring and general management ofpatients with aneurysmal subarachnoid haemorrhage

Monitoringl Intensive observation at least until occlusion of the aneurysml Continuous ECG monitoringl Glasgow Coma Scale, focal neurological deficits, blood pressure and

temperature at least every hour to begin withBlood pressurel Stop any antihypertensive medication that the patient was usingl Do not treat hypertension unless it is extreme. Limits for extreme blood

pressures should be set on an individual basis, taking into account theage of the patient, pre-SAH blood pressures and cardiac history

Fluids and electrolytesl Intravenous line mandatoryl Insert an indwelling urinary catheterl Start with 3 l/day (isotonic saline 0.9%) and adjust infusion for any

additional oral intakel Aim for normovolaemia, also in cases of hyponatraemia, and compensate

for feverl Monitor electrolytes, glucose and white blood cell count at least everyother day

Painl Start with paracetamol (acetaminophen) 500 mg every 34 h; avoid

aspirin, certainly before aneurysm occlusionl For severe pain, use codeine, tramadol (suppository or intravenous) or, as

a last resort, piritramide intramuscularly or intravenouslyPrevention of deep venous thrombosis and pulmonary embolisml Compression stockings and intermittent compression by pneumatic

devices

SAH, subarachnoid haemorrhage.

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strategy of avoiding antihypertensive medica-

tion and increasing fluid intake decreases the

risk of cerebral infarction.7

On admission, we stop any antihyperten-

sive medication that the patients were using,

and we do not treat hypertension unless

blood pressure is extreme. It is not possible togive limits for extreme blood pressures

because extreme differs in different patients

according to their age, previous blood

pressure, cardiac history and other factors.

If blood pressure is lowered, for example by

means of esmolol or labetolol,8 it seems

reasonable to aim for a modest (eg, 25%)

decrease in mean arterial pressure.

Fluid managementFluid management should avoid any reduction

in plasma volume because this may contribute

to the development of delayed cerebral

ischaemia.9 Firm evidence is not available but

aiming at normovolaemia by giving 2.53.5 l/

day of isotonic saline, unless contraindicated by

signs of pulmonary oedema, appears reason-

able. Any diuretics that patients were using are

generally stopped. The amount of intravenous

saline should be reduced if the patient is also

receiving nutritional solution via the enteral

route. In patients with fever, fluid intake should

be gradually increased10

; we add 0.5 l for every1uC temperature increase. An indwelling urin-

ary catheter is almost always needed for

accurate calculation of fluid balance.

AnalgesicsHeadache is usually so severe that codeine

needs to be added to paracetamol (acetamin-

ophen). If pain persists, codeine should be

replaced by a synthetic opiate such as

tramadol. Tramadol should be given by

suppository or intravenously until the aneur-

ysm is occluded, to avoid nausea and

vomiting associated with oral administration.

Patients in whom the headache remains

severe can be treated with opiates.

Salicylates are best avoided because their

antihaemostatic effect is unwanted in

patients who may have to undergo external

ventricular drainage.

Prevention of venousthromboemolism

Because low molecular weight heparinsincrease the risk of intracranial bleeding,11

graduated compression stockings are the

preferred form of prevention of deep venous

thrombosis in patients with SAH, although

admittedly this advice lacks support from a

randomised trial in this specific situation.12

Compression stockings must be individually

fitted to be efficacious and some favourpneumatic devices that apply intermittent

venous compression to the legs.13 In a

randomised trial in patients with intracerebral

haemorrhage, the combination of stockings

and intermittent pneumatic compression

resulted in a lower risk of deep venous

thrombosis than prevention by stockings

alone.14 This combination may be the pre-

ferred strategy because there is no reason to

suppose that their benefit would be any

different in patients with SAH.

Monitoring and prevention ofseizuresApproximately 10% of patients with SAH

develop epileptic seizures in the first few

weeks,15 and convulsive status epilepticus

occurs in 0.2%.16 In patients who are

comatose, non-convulsive status epilepticus

has been detected in 8% of patients17 but this

might have been an overestimate because an

EEG was only done if non-convulsive status

was suspected. In one retrospective study,

continuous EEG monitoring yielded prognos-

tic information for a poor outcome18 but there

are no data showing that outcome is

improved by continuous EEG monitoring.17

Because prolonged EEG monitoring is expen-

sive, labour intensive, subject to misinterpre-

tation19 and lacks proof of effectiveness, there

are no grounds to use it as part of the routine

monitoring strategy in patients with SAH.

Although intracranial surgery increases the

risk of epileptic seizures,20

a randomised trialof antiepileptic drugs after supratentorial

craniotomy for benign lesions (not only

aneurysms) failed to show benefit in terms

of seizure rate or case fatality.21 Therefore, we

do not advise antiepileptic drugs for prophy-

lactic treatment, only if seizures occur.

CorticosteroidsA Cochrane review last updated in 2005

found one placebo controlled trial on hydro-

cortisone in patients with SAH.22

There was nodifference in clinical outcome between

We do not adviseantiepileptic drugsfor prophylactictreatment, only if

seizures occur

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patients with delayed cerebral ischaemia

treated with hydrocortisone or placebo but

the risk of hyperglycaemia almost doubled.22

A randomised trial published after the

Cochrane review showed that in patients

treated with hydrocortisone, serum sodium

level and plasma osmolarity were controlled

better than in controls but clinical outcome

was no better.23 Based on these studies,

routine hydrocortisone for patients with SAH

is not warranted.

MEDICAL COMPLICATIONSHyponatraemiaHyponatraemia after SAH is caused in most

instances by excessive natriuresis (so-called

cerebral salt wasting)24 which leads to

hypovolaemia and thereby increases the risk

of delayed cerebral ischaemia.

Mild hyponatraemia (sodium 125

134 mmol/l) occurs in about one-third of

patients, most commonly between the second

and tenth day, it is usually well tolerated, self-

limiting and need not be treated. We correct

hyponatraemia in patients with evidence of a

negative fluid balance or excessive natriuresis

with saline (0.9%; sodium concentration

150 mmol/l).

Severe (sodium ,124 mmol/l) sympto-

matic hyponatraemia is rare and requires

treatment with hypertonic saline. Although

rapid correction of hyponatraemia can result

in central pontine myelinolysis if the hypona-traemia is chronic, hypertonic saline appears

safe in patients with hyponatraemia after

SAH.25

Because of its mineralocorticoid effect

(reabsorption of sodium in the distal tubules

of the kidney) fludrocortisone might, in

theory, prevent a negative sodium balance,

hypovolaemia and ischaemic complications.

However, two randomised trials showed that

although this did reduce natriuresis in the

first 6 days after the SAH, there was no effect

on either plasma volume depletion or ischae-mic complications.26, 27

HyperglycaemiaHyperglycaemia develops in one-third of

patients during their clinical course, is

associated with a poor clinical condition on

admission28 and is independently associated

with a poor outcome.29 Whether correction of

hyperglycaemia results in improved outcome

is an unresolved issue.30

FeverDespite treatment with paracetamol to relieve

pain, fever develops in more than half of

patients with SAH,31 more often in those in

poor clinical condition on admission and

those with intraventricular extension of the

haemorrhage,31 and is an independent risk

factor for a poor outcome.28 In approximately

20% of patients, no infection is found and the

fever is attributed to the inflammatory

response to the extravasated blood in thesubarachnoid space. A randomised trial of

Figure 1

An elderly old man was found in the

bathroom by his wife. He was alert and

complained of headache. In the

emergency room he opened his eyes

when spoken to, obeyed commands and

produced single words. His blood

pressure was 100/50 mm Hg and his

pulse was 50/min. Chest x ray on

admission was normal (A). Within hours

he developed shortness of breath and

lapsed into coma. Repeat cheat x ray

showed massive pulmonary oedema (B).

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mild hypothermia during aneurysm surgery

after SAH showed no benefit32 (fanning has

not been studied in SAH).

Cardiopulmonary dysfunctionPulmonary oedema and cardiac dysfunction

may develop within hours of SAH, even inpatients who are admitted in good clinical

condition (fig 1). This becomes evident by a

rapid decline in consciousness associated

with hypoxaemia and hypotension.33

Pulmonary oedema and reversible left ven-

tricular wall motion abnormalities occur in

4% of patients admitted in good clinical

condition,2 and left ventricular dysfunction

was found in 12% of patients who were

found to be at increased risk of delayed

cerebral ischaemia and poor outcome.34

Thecardiopulmonary dysfunction can last for

weeks, but even after prolonged intensive

care treatment good recovery is still possi-

ble.35 If pulmonary oedema and ventricular

dysfunction develop outside an intensive care

unit, patients should be transferred to such a

unit immediately for mechanical ventilation

and treatment with inotropic agents.36

Whether ventilation should be with positive

end expiratory pressure is a matter of

debate.37, 38

NEUROLOGICALCOMPLICATIONSPrevention of rebleedingUp to 15% of patients rebleed in the first few

hours after the initial haemorrhage39 (ie,

during transportation or before the treatment

team is able to occlude the aneurysm). Thus

treatment strategies that can be initiated

early after the haemorrhage to protect

patients until the aneurysm is occluded are

needed.

Antifibrinolytic drugsIn a Cochrane review including nine random-

ised trials in SAH, antifibrinolytic drugs

reduced the risk of rebleeding but did not

influence death from all causes or a poor

outcome.40 A Swedish trial published after the

last update tested a strategy where tranex-

amic acid was given as soon as SAH had been

diagnosed in the local hospital (before the

patients were transported) and continued

until aneurysm occlusion, which was typically

performed within 72 h.41

Again, the overalloutcome did not appreciably improve in

patients treated with tranexamic acid, despite

an impressive reduction in rebleeding. If this

trial is pooled with the nine other trials

included in the Cochrane review, there is still

no effect on overall outcome (fig 2). Further

trials with ultra early short term tranexamic

acid would be worth doing.

Recombinant factor VIIa

Theoretically, recombinant factor VIIa mightprevent rebleeding. But an open label, dose

escalation safety study was suspended when

the 10th patient developed middle cerebral

artery branch occlusion contralateral to the

aneurysm.42 In an uncontrolled series of 18

patients who received an intraoperative dose

during surgical occlusion of a ruptured

Figure 2Forest plot of randomised trials of

antifibrinolytic treatment in patients

with aneurysmal subarachnoid

haemorrhage. We have added the study

of Hillman et al to the studies included

in the Cochrane review.40, 41 Poor

outcome: death, vegetative or severe

disability on the Glasgow Outcome

Scale at 3 months.

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Treatment options for the specific medical management of patients with aneurysmal subarachnoid haemorrhage

Type of treatment Study results and level of evidence Authors practice

Prevention of rebleedingl Antifibrinolytic drugs Cochrane review and one additional trial

failed to show improved clinical outcome,

despite reduction in rebleeding79

Never

Prevention of delayed cerebral ischaemial Nimodipine Cochrane review showed improved clinical

outcome for tablets (not intravenousadministration)47

Nimodipine 6660 mg/day oral

l Magnesium sulphate Cochrane review showed tendency toimproved clinical outcome47

Coordinating randomised trial

l Antithrombotic agents Cochrane review showed tendency toimproved outcome and to moreintracranial bleeding complications50

Never

l Statins Systematic review totalling 153 patientsshowed benefit on vasospasm and case

fatality but not on clinical outcome53

Never; awaiting results of the ongoingrandomised trial

l Lumbar drainage No randomised trials available Not for blood removal; only as treatment forhydrocephalus

l Intracisternal fibrinolysis Two small randomised trials showedbenefit on intermediate outcome measuresbut not on clinical outcome61, 62

Never; organising local trial

Treatment of delayed cerebral ischaemial Hypertension induction No randomised trials performed; only case

reports and observational studies withconflicting results

Performing feasibility study for randomisedtrial. Currently rarely used

l Hypervolaemia No trials, only case reports andobservational studies with conflictingresults.

500 ml of colloid solution intravenously incases with clinical diagnosis of delayed cerebralischaemia, in addition to standard infusion

l Transluminal angioplasty Only observational, non-controlled caseseries

Never

Acute hydrocephalusl Lumbar puncture Only observational, non-controlled case

seriesWithin the initial 24 h after the SAH wepostpone treatment unless the patient is in orlapses into a coma. If treatment is indicatedwe start with one or more lumbar punctures,unless the third or fourth ventricles areentirely blocked by intraventricular blood.Only in these patients and in patients whererepeated lumbar punctures are not effectivein restoring consciousness do we ask for an

external ventricular drain

l External ventricular drainage Only for risk of rebleeding retrospectivecontrolled series. For clinical outcome nocontrolled series

Other medical treatmentsl Antiepileptic drugs No evidence for seizure reduction or

improved outcome from prophylactictreatment; observational study suggestsworse outcome after prophylactic treatment

Only after documented seizure unrelated to(re)bleeding

l Corticosteroids Two small randomised trials found nobeneficial effect on clinical outcome;but an increased risk of hyperglycaemia22, 23

Not standard; sometimes in case of spaceoccupying oedema around intracerebralhaematoma

l Low molecular weightheparin/heparinoids

One randomised trial showed no effect onoverall outcome but increased risk ofintracranial bleeding complications11

Often prescribed in addition to stockingsdespite lack of evidence

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aneurysm, no episodes of rebleeding occurred

but one patient developed deep venous

thrombosis and seven an upper extremity

venous thrombosis in association with per-

ipherally inserted central catheter lines.43 At

the moment, there is no evidence to support

the use of recombinant factor VIIa outsidestudy protocols in patients with SAH.

Prevention of delayed cerebralischaemiaCerebral ischaemia or infarction after SAH is

not usually confined to the territory of a

single cerebral artery or one of its branches.44

Vasospasm is often implicated as the cause

for two reasons:

N firstly, its peak frequency from day 5 to

14 coincides with that of delayed cerebralischaemia;

N secondly, vasospasm is often generalisedwhich is in keeping with the multifocal or

diffuse nature of the clinical manifesta-tions of the ischaemic lesions found onbrain CT and at autopsy.

However, one-third of patients with vaso-

spasm do not develop brain infarction, and

one-third of the patients with delayed

infarction do not have vasospasm.45 It is likelythat microthrombosis also plays a role in the

development of delayed cerebral ischaemia

after SAH.46 The lack of progress in prevention

and treatment of delayed ischaemia may in

part be explained by the focus on strategies

that decrease the risk of vasospasm whereas

the goal of treatment should be preventing

delayed ischaemia. Interventions other than

adequate fluid intake and avoiding anti-

hypertensive drugs are discussed below.

Calcium antagonistsA Cochrane review, including 16 trials with

3361 patients, found death or dependency

Figure 3

Forest plot of the randomised trials ofcalcium antagonists in patients with

aneurysmal subarachnoid

haemorrhage.47 Poor outcome: death or

dependency. Cochrane review.

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was reduced in patients treated with calcium

antagonists with a number-needed-to-treat

of 19 (95% confidence interval (CI) 1 to 51).47

Results were statistically robust for oral

nimodipine only, not for other calcium

antagonists or intravenous nimodipine (fig 3).

Currently, treatment with nimodipine (60 mgorally every 4 h for 3 weeks) is regarded as

standard in patients with aneurysmal SAH. If

the patient is unable to swallow, the

nimodipine tablets should be crushed and

washed down a nasogastric tube with normal

saline. There is no evidence to support the

more expensive intravenous administration of

nimodipine47 or nicardipine.48

Magnesium sulphateMagnesium is a readily available, inexpensive,

neuroprotective agent with a well-established

clinical profile. Three randomised trials have

studied intravenous magnesium sulphate in

addition to nimodipine. In the pooled analysis,

the relative risk reduction from added

magnesium was 0.75 (95% CI 0.57 to 1.00)

for a poor outcome and 0.66 (95% CI 0.45 to

0.96) for clinical signs of delayed cerebral

ischaemia (fig 4).47 A phase III trial is currently

underway with poor outcome as the primary

outcome measurement.49

Aspirin and other antithromboticagentsSeveral studies have found that platelets are

activated from day 3 after subarachnoid

haemorrhage, and that microthrombi play a

role in the processes leading to delayed

ischaemia.46 In a Cochrane review of the

seven trials on antiplatelet agents totalling

1385 patients, there was a reduction in poor

outcome (relative risk (RR) 0.79, 95% CI 0.62

to 1.01) and delayed cerebral ischaemia (RR

0.79, 95% CI 0.56 to 1.22) and more

intracranial haemorrhagic complications (RR

1.36, 95% CI 0.59 to 3.12) but none of these

differences were statistically significant.50

Therefore, routine treatment with antiplatelet

agents is not recommended.

Heparin is usually given during and shortly

after coiling because there is a 5% risk of

cerebral infarction caused by thromboembo-lism.51 Many neurointerventionalists also pre-

scribe aspirin in the initial weeks to months

after coiling but without any evidence

supporting this strategy (which may of course

increase the risk of bleeding). Interestingly, in

the International Subarachnoid Aneurysm

Trial (ISAT) the relative risk of a poor outcome

of coiling versus clipping was similar in

institutions that did or did not have a policy

of routine aspirin post coiling.52

StatinsStatins have anti-inflammatory, immuno-

modulatory, antithrombotic and vascular

effects. In a systematic review of three

randomised trials, totalling 158 patients, they

reduced the primary outcome measure of

radiologically confirmed vasospasm as well as

case fatality.53 There are no data on overall

outcome from randomised trials but a large

trial is currently underway in the UK (STASH;

ClinicalTrials.gov Identifier NCT00731627).

Other drugs

N In a systematic review of five randomisedtrials in a total of 3797 patients, tirilazaddid not influence the risk of a pooroutcome or cerebral infarction.54

N The endothelinA/B receptor antagonistTAK-044 was not effective in a multi-centre phase II trial in 420 patients.55

N Another endothelin antagonist, clazosen-tan, which selectively antagonises theendothelin A receptor antagonist, didreduce vasospasm in two phase II

Figure 4

Forest plot of the randomised trials of

magnesium sulphate in addition to

nimodipine compared with nimodipine

alone in patients with aneurysmal

subarachnoid haemorrhage.47

Pooroutcome: death or dependency.

Cochrane review.

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trials56, 57 but did not improve clinicaloutcome.

N For a third endothelinA/B receptor antago-nist, bosentan, only data from a dosefinding and safety study have beenpublished.58

N

One randomised trial of erythropoietinshowed no effect on clinical outcome,after early termination of the trial, whenonly 73 patients had been included.59

Cisternal drainage andintracisternal fibrinolysisBoth of these strategies have been tested on

the assumption that extravasated blood

induces vasospasm and that vasospasm

increases the risk of delayed cerebral ischae-

mia. But the evidence of benefit is not at allsatisfactory. Patients treated with lumbar

drainage of CSF had less cerebral infarction

and more of them returned home than

patients with no lumbar drainage in a non-

randomised comparison.60 A meta-analysis of

intracisternal fibrinolysis included nine trials

but only one was randomised.61 Pooled results

demonstrated benefit but the implications for

practice are limited by the predominance of

non-randomised studies.

A more recent but open, randomised,

controlled trial, not yet included in the

meta-analysis, tested fibrinolysis in 110

patients treated with endovascular coiling.62

Urokinase was administered into the cisterna

magna through a microcatheter inserted via a

lumbar puncture. There was a statistically

significant improvement in the primary out-

come of clinical vasospasm, and a borderline

significant reduction in the secondary out-

come measure of poor outcome. Larger

studies with overall clinical outcome as the

primary outcome measure are needed beforethis promising treatment can be implemented

in clinical practice.

Treatment of delayed cerebralischaemiaThe lack of a reliable diagnostic tool for

delayed cerebral ischaemia is probably one of

the reasons why so many physicians rely on

transcranial Doppler or angiographic studies

to rule in or out the presence of vasospasm,

and why treatment strategies have beenaimed at reversing vasospasm. However, as

the negative and positive predictive values of

vasospasm for cerebral ischaemia are moder-

ate at best, vasospasm is not a reliable proxy

for delayed cerebral ischaemia.

Induced hypertension and volumeexpansionSince the 1970s, induced hypertension has

been used to combat ischaemic deficits in

patients with SAH. Later, hypertension has

often been combined with hypervolaemia,

and sometimes also with haemodilution (so-

called triple H therapy). But, 35 years after

the first published observation of reversing

clinical deficits by induced hypertension,

there are still no randomised trials on triple

H therapy, or any of its components, and yet

many physicians use this treatment. Triple Htherapy is not benign; there are risks of

cerebral oedema, haemorrhagic transforma-

tion in areas of infarction,63 reversible leu-

cencephalopathy,64 myocardial infarction and

congestive heart failure. For these reasons, we

do not routinely induce hypertension in

patients deteriorating from delayed cerebral

ischaemia.

Transluminal angioplasty andvasodilating drugsIn an overview of the studies on transluminal

angioplasty and vasodilating drugs, sustained

improvement was claimed in more than half

of the cases but the series were uncontrolled

and there must be publication bias.65 In one of

these studies, cerebral infarction occurred less

often in the territories of arteries that had

been treated than in arteries that had been

left alone.66 In another uncontrolled series of

patients treated with transluminal angio-

plasty, papaverine injection or both, overallclinical outcome was poor despite successful

arterial dilatation.67 Balloon angioplasty

causes vessel rupture in approximately 1%

of the procedures and other complications

such as hyperperfusion injury in 4%.65In view

of the risks, high cost and lack of controlled

trials, transluminal angioplasty and intra-

arterial infusion of drugs through super-

selective catheterisation should still be

regarded as experimental. A randomised pilot

trial comparing the effects on clinical out-come of angioplasty versus standard therapy

The negative andpositive predictivevalues ofvasospasm for

cerebral ischaemiaare moderate atbest

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is currently underway in the UK (VERITAS;

ISRCTN18815770)

Treatment of acutehydrocephalusWe define acute hydrocephalus as hydro-

cephalus occurring within the initial 2 daysafter the haemorrhage. The typical presenta-

tion is that of an alert patient who becomes

increasingly drowsy or even comatose a few

hours after SAH. In patients who were alone

at the time of the haemorrhage, the initial

clinical course may of course be unknown,

and consciousness can also be impaired from

the onset. In such patients, ocular signs

(small, non-reactive pupils with otherwise

intact brainstem reflexes) may help to

corroborate the diagnosis but normal findings

do not exclude acute hydrocephalus. If there

are no clues from the history and neurological

examination, a CT brain scan is the only way

to detect hydrocephalus. Acute hydrocepha-

lus may be caused by obstruction of the CSF

flow in the tentorial hiatus by extensive

haemorrhage in the perimesencephalic cis-

terns, or in the ventricles by frank intraven-

tricular haemorrhage.

Wait and see

A policy of wait and see for 24 h is justified inpatients with dilated ventricles on the

admission CT scan who are alert because

only about one-third of them will become

symptomatic in the next few days.68

Postponing any intervention for a day can

also be rewarding even if the level of

consciousness decreases within the initial

hours after onset to a moderate extent

because spontaneous improvement within

this period occurs in approximately half of

patients.68 We intervene in patients with a

decreased level of consciousness to eye

opening only on painful stimuli, no longer

obeying simple commands and speaking only

single or a few words (Glasgow Coma Score

equal or less than E2M5V3)

Lumbar punctureLumbar puncture is an often neglected option

for acute hydrocephalus in patients with SAH

(fig 5) who have neither an intracerebral

haematoma nor complete filling of the third

or fourth ventricles with blood. In a prospec-tive but uncontrolled study of such patients,

one- third fully recovered after one or several

lumbar punctures.69 There are no data

supporting the notion of an increased risk

of rebleeding after lumbar puncture or

drainage but the controlled studies that have

been done are too small to exclude a small

risk.70, 71

Our experience is that in patientswith hydrocephalus occurring later during the

clinical course, lumbar puncture may provide

temporary improvement but in the end does

not necessarily obviate the need for contin-

uous lumbar or ventricular drainage.

External ventricular drainageExternal ventricular drainage is in many

centres the most common method of treating

acute hydrocephalus and usually leads to

rapid improvement.72

However, in a studyfrom the Mayo clinics on complications of

ventricular catheters in general (not restricted

to patients with SAH), 12% of catheters were

misplaced, a ventriculostomy related haemor-

rhage occurred in 7% and drain related

infections were identified in 3% of patients.73

In recent reviews of the literature, similar

haemorrhage rates and even higher drain

infection rates (520%) were found.74, 75

Because drain related ventriculitis is so

frequent and often leads or contributes to

poor outcome,74 several strategies have beendeveloped to decrease this problem.

N In a controlled study, regular exchange ofthe intraventricular catheter did not help.76

N Some advocate rigid antiseptic techni-ques and prophylactic antibiotics.77

N Implementation of a protocol for inser-tion and handling the drain in theintensive care unit with strict surveillanceand adhering to the protocol may behelpful.78

Rebleeding is another concern after inser-

tion of an external drain although not all

studies agree.72 A recent controlled study did

not find an increased rebleeding risk after

correction for several risk factors for rebleed-

ing. It has been suggested that maintenance

of intracranial pressure above 1520 mm Hg

will minimise the risk of rebleeding.72 Given

the uncertainty of the risk of rebleeding after

inserting a ventricular drain it seems prudent

to aim for prompt aneurysm occlusion after

insertion of a drain if the aneurysm has notalready been secured.

Lumbar puncture isan often neglectedoption for acutehydrocephalus in

patients with SAH

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Figure 5

CT scans of an elderly woman with

sudden headache. On admission she

was alert but disoriented. CT scan

showed subarachnoid blood and

enlarged third and lateral ventricles (A,

B). Within hours she lapsed into a

coma. A repeat CT showed furtherenlargement of the ventricles (C, D). A

lumbar puncture was performed and

she regained consciousness within an

hour. A repeat CT scan the following

day showed marked improvement of

the hydrocephalus (E, F).

2Rinkel, Klijn



12/15

THE GENERAL APPROACH TOPATIENTS WITH COMPLICATIONSHalf of patients with SAH lose consciousness

at the time of haemorrhage but many

improve in the first few hours to days.

Therefore, it important to realise that in the

initial days after the haemorrhage a complica-

tion may not manifest itself by clinical

deterioration but rather by lack of improvement

in the neurological condition; for example, a

patient who is expected to recover from the

initial ischaemia but does not improve because

of developing acute hydrocephalus. If a patient

is not in perfect clinical condition one shouldask oneself repeatedly why notwhat factors

may be contributing to this?

If deterioration occurs, the speed of onset

is an important feature in assessing the type

of complication. In patients who suddenly

become comatose, rebleeding is the first

diagnosis to think of, especially before the

aneurysm has been occluded. But even in

patients with treated aneurysms, rebleeding

can occur during the hospital stay, although

obviously less frequently. After aneurysmocclusion other causes such as pulmonary

embolism and cardiac arrhythmia or failure

should be high on the differential diagnosis.

In patients with a gradual decline in

consciousness the list of possible causes is

much longer. Our general approach is to start

by checking blood pressure, pulse rate, blood

oxygen content, fluid balance and tempera-ture. Unless there are signs of cardiac failure

or pulmonary oedema, we add 500 ml of

gelofuscin before ordering ancillary investiga-

tions. If a decrease in blood pressure is related

in time to nimodipine administration, we

halve the next dose. A decreased oxygen

content may be the result of pulmonary

oedema, pulmonary embolism or, if accom-

panied by fever, pneumonia.

The most common infections are of the

urinary tract and lungs and, if there is

extraventricular drainage, ventriculitis, but

phlebitis should not be forgotten as a possible

cause of fever. It is not uncommon however

to find no obvious cause for fever.

If clinical examination reveals no clue for

the cause of the deterioration, we order a CT

brain scan to rule hydrocephalus in or out.

Blood tests should include electrolytes (espe-

cially sodium), glucose and infection para-

meters.

ACKNOWLEDGEMENTSRustam Al-Shahi Salman reviewed this article.

Competing interests: We are neurologistsinvolved in the management of patients withaneurysmal and non-aneurysmal subarachnoidhaemorrhage, and we are coordinating a trial onmagnesium sulphate in patients with subarachnoidhaemorrhage. We are paid by the UniversityMedical Centre Utrecht, The Netherlands. We havehad research grants from The Netherlands Heart

foundation, the Hersenstichting Nederland and TheNetherlands Organisation of Scientific ResearchNetherlands Organisation for Health Care.

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31st Clinical Neurology Course, 2830 September 2009, University of Edinburgh,

Edinburgh, UK

Speakers will include: Dr Rustam Al-Shahi Salman, Dr Kailash Bhatia, Professor Siddharthan Chandran,

Dr Jeremy Chataway, Dr Brendan Davies, Dr Mark Edwards, Dr Gareth Evans, Dr Marria Farrugia, Dr

Tom Hughes, Dr John Paul Leach, Professor Keith Muir, Dr Richard Petty, Dr Hugh Rickards, Professor

Neil Scolding, Dr Graham Venables, Professor Hugh Willison, Professor Adam Zeman

Topics will include: Movement disorders, multiple sclerosis, the Periphery, a CPC, What to do with

difficult epilepsy, difficult headache, difficult myasthenia, and a session on stroke. The course is

aimed at neurologists in training, but others are very welcome.

Course fee - 200; Course fee and all meals - 350; Accommodation - 170.

Further details and application forms can be downloaded from: http://www.dcn.ed.ac.uk/pages/

training.asp or contact Mrs Judi Clarke: Tel 0131 537 2082.

2Rinkel, Klijn

prevention and rx medical and neuro complication of anurysmal bleed

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