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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
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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).
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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.
REFERENCES1. Hop JW, Rinkel GJE, Algra A, et al. Case-fatality
rates and functional outcome after subarachnoid
hemorrhage: a systematic review. Stroke
1997;28:6604.
2. Macrea LM, Tramer MR, Walder B. Spontaneous
subarachnoid hemorrhage and serious
cardiopulmonary dysfunctiona systematic review.
Resuscitation 2005;65:13948.
3. Schuiling WJ, de Weerd AW, Dennesen PJ, et al. The
simplified acute physiology score to predict
outcome in patients with subarachnoid
hemorrhage. Neurosurgery 2005;57:2306.
4. Sarker SJ, Heuschmann PU, Burger I, et al.Predictors of survival after haemorrhagic stroke in
PRACTICE POINTS
l Treating patients with aneurysmal SAH is taking care of critically illpatients. This should be done on an intensive or medium care unit by ateam consisting of neurologists, neurosurgeons, radiologists,neurointensivists, rehabilitation physicians, neuropsychologists and a
dedicated team of nurses, physiotherapists, speech therapists andoccupational therapists.
l In addition to occlusion of the ruptured aneurysm, an important part ofthe management consists of prevention and treatment of medical andneurological complications.
l Antifibrinolytics reduce the risk of rebleeding, even when given for a shorttime, but there is no evidence that this strategy improves overall outcome.
l Oral nimodipine decreases the occurrence of delayed cerebral ischaemiaand improves clinical outcome.
l Treatment of hypertension should probably be avoided unless cardiacfailure develops.
l We aim for normovolaemia, also in cases of hyponatraemia.
l There is no evidence supporting prophylactic use of antiepileptic drugs orthe use of corticosteroids.
l For patients who develop delayed cerebral ischaemia, hypervolaemia andhypertension is often performed but this strategy is based on case reportsand uncontrolled observational series of patients. Balloon angioplasty andintra-arterial administration of vasodilating drugs are experimentaltreatments.
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-
8/2/2019 Prevention and Rx Medical and Neuro Complication of Anurysmal Bleed
13/15
a multi-ethnic population: The South London
Stroke Register (SLSR). J Neurol Neurosurg
Psychiatry 2008;79:2605.
5. Frontera JA, Fernandez A, Schmidt JM, et al. Impact
of nosocomial infectious complications after
subarachnoid hemorrhage. Neurosurgery
2008;62:807.
6. Wijdicks EFM, Vermeulen M, Murray GD, et al. The
effects of treating hypertension followinganeurysmal subarachnoid hemorrhage. Clin Neurol
Neurosurg 1990;92:11117.
7. Hasan D, Vermeulen M, Wijdicks EFM, et al. Effect
of fluid intake and antihypertensive treatment on
cerebral ischemia after subarachnoid hemorrhage.
Stroke 1989;20:151115.
8. Varon J, Marik PE. Clinical review: the management
of hypertensive crises. Crit Care 2003;7:37484.
9. Wijdicks EFM, Vermeulen M, Hijdra A, et al.
Hyponatremia and cerebral infarction in patients
with ruptured intracranial aneurysms: is fluid
restriction harmful? Ann Neurol 1985;17:13740.
10. Oliveira-Filho J, Ezzeddine MA, Segal AZ, et al. Fever
in subarachnoid hemorrhage. Relationship to
vasospasm and outcome. Neurology2001;56:1299304.
11. Siironen J, Juvela S, Varis J, et al. No effect of
enoxaparin on outcome of aneurysmal
subarachnoid hemorrhage: a randomized, double-
blind, placebo-controlled clinical trial. J Neurosurg
2003;99:9539.
12. Amaragiri SV, Lees TA. Elastic compression
stockings for prevention of deep vein thrombosis.
Cochrane Database Syst Rev 2000;CD001484.
13. Black PM, Crowell RM, Abbott WM. External
pneumatic calf compression reduces deep venous
thrombosis in patients with ruptured intracranial
aneurysms. Neurosurgery 1986;18:258.
14. Lacut K, Bressollette L, Le Gal G, et al. Prevention of
venous thrombosis in patients with acute
intracerebral hemorrhage. Neurology2005;65:8659.
15. Lin CL, Dumont AS, Lieu AS, et al. Characterization
of perioperative seizures and epilepsy following
aneurysmal subarachnoid hemorrhage. J Neurosurg
2003;99:97885.
16. Claassen J, Bateman BT, Willey JZ, et al. Generalized
convulsive status epilepticus after nontraumatic
subarachnoid hemorrhage: the nationwide
inpatient sample. Neurosurgery 2007;61:605.
17. Dennis LJ, Claassen J, Hirsch LJ, et al.
Nonconvulsive status epilepticus after
subarachnoid hemorrhage. Neurosurg
2002;51:113644.
18. Claassen J, Hirsch LJ, Frontera JA, et al. Prognosticsignificance of continuous EEG monitoring in
patients with poor-grade subarachnoid
hemorrhage. Neurocrit Care 2006;4:10312.
19. Kull LL, Emerson RG. Continuous EEG
monitoring in the intensive care unit: technical
and staffing considerations. J Clin Neurophysiol
2005;22:10718.
20. Molyneux AJ, Kerr RS, Yu LM, et al. International
subarachnoid aneurysm trial (ISAT) of neurosurgical
clipping versus endovascular coiling in 2143
patients with ruptured intracranial aneurysms: a
randomised comparison of effects on survival,
dependency, seizures, rebleeding, subgroups, and
aneurysm occlusion. Lancet 2005;366:80917.
21. Foy PM, Chadwick DW, Rajgopalan N, et al. Doprophylactic anticonvulsant drugs alter the pattern
of seizures after craniotomy? J Neurol Neurosurg
Psychiatry 1992;55:7537.
22. Feigin VL, Anderson N, Rinkel GJE, et al.
Corticosteroids for aneurysmal subarachnoid
haemorrhage and primary intracerebral
haemorrhage. Cochrane Database Syst Rev
2005;CD004583.
23. Katayama Y, Haraoka J, Hirabayashi H, et al. A
randomized controlled trial of hydrocortisoneagainst hyponatremia in patients with aneurysmal
subarachnoid hemorrhage. Stroke2007;38:23735.
24. Harrigan MR. Cerebral salt wasting syndrome. Crit
Care Clin 2001;17:12538.
25. Suarez JI, Qureshi AI, Parekh PD, et al.
Administration of hypertonic (3%) sodium chloride/
acetate in hyponatremic patients with symptomatic
vasospasm following subarachnoid hemorrhage.
J Neurosurg Anesthesiol 1999;11:17884.
26. Hasan D, Lindsay KW, Wijdicks EF, et al. Effect
of fludrocortisone acetate in patients with
subarachnoid hemorrhage. Stroke
1989;20:115661.
27. Mori T, Katayama Y, Hirayama T. Improved
efficiency of hypervolemic therapy with inhibitionof natriuresis by fludrocortisone in patients with
aneurysmal subarachnoid hemorrhage. J Neurosurg
1999;91:94752.
28. Wartenberg KE, Schmidt JM, Claassen J, et al.
Impact of medical complications on outcome after
subarachnoid hemorrhage. Crit Care Med
2006;34:61723.
29. Dorhout Mees SM, van Dijk GW, Algra A, et al.
Glucose levels and outcome after subarachnoid
hemorrhage. Neurology 2003;61:11323.
30. Bilotta F, Spinelli A, Giovannini F, et al. The effect of
intensive insulin therapy on infection rate,
vasospasm, neurologic outcome, and mortality in
neurointensive care unit after intracranial
aneurysm clipping in patients with acute
subarachnoid hemorrhage: a randomized
prospective pilot trial. J Neurosurg Anesthesiol
2007;19:15660.
31. Dorhout Mees SM, Luitse MJ, van den Bergh WM, et
al. Fever after aneurysmal subarachnoid
hemorrhage: relation with extent of hydrocephalus
and amount of extravasated blood. Stroke
2008;39:21413.
32. Todd MM, Hindman BJ, Clarke WR, et al. Mild
intraoperative hypothermia during surgery for
intracranial aneurysm. N Engl J Med
2005;352:13545.
33. Parr MJ, Finfer SR, Morgan MK. Reversible
cardiogenic shock complicating subarachnoidhaemorrhage. BMJ 1996;313:6813.
34. Schuiling WJ, Dennesen PJ, Rinkel GJE.
Extracerebral organ dysfunction in the acute stage
after aneurysmal subarachnoid hemorrhage.
Neurocrit Care 2005;3:110.
35. Parr MJ, Finfer SR, Morgan MK.
Reversible cardiogenic shock complicating
subarachnoid haemorrhage. BMJ
1996;313:6813.
36. Deehan SC, Grant IS. Haemodynamic changes in
neurogenic pulmonary oedema: effect of
dobutamine. Intensive Care Med 1996;22:6726.
37. Kahn JM, Caldwell EC, Deem S, et al. Acute lung
injury in patients with subarachnoid hemorrhage:
Incidence, risk factors, and outcome. Crit Care Med2006;34:196202.
2Rinkel, Klijn
www.practical-neurology.com
-
8/2/2019 Prevention and Rx Medical and Neuro Complication of Anurysmal Bleed
14/15
38. Muench E, Bauhuf C, Roth H, et al. Effects of positive
end-expiratory pressure on regional cerebral blood
flow, intracranial pressure, and brain tissue
oxygenation. Crit Care Med2005;33:236772.
39. Ohkuma H, Tsurutani H, Suzuki S. Incidence and
significance of early aneurysmal rebleeding before
neurosurgical or neurological management. Stroke
2001;32:117680.
40. Roos YBWEM, Rinkel GJE, Vermeulen M, et al.Antifibrinolytic therapy for aneurysmal
subarachnoid haemorrhage. Cochrane Database
Syst Rev 2003;CD001245.
41. Hillman J, Fridriksson S, Nilsson O, et al. Immediate
administration of tranexamic acid and reduced
incidence of early rebleeding after aneurysmal
subarachnoid hemorrhage: a prospective
randomized study. J Neurosurg 2002;97:7718.
42. Pickard JD, Kirkpatrick PJ, Melsen T, et al.
Potential role of NovoSeven in the prevention of
rebleeding following aneurysmal subarachnoid
haemorrhage. Blood Coagul Fibrinolysis
2000;11(Suppl 1):S11720.
43. Nussbaum ES, Janjua TM, Defillo A, et al.
Perioperative use of recombinant factor VII toprevent intraoperative aneurysm rupture in high
risk patients: a preliminary safety evaluation.
Neurocrit Care 2009;10:5560.
44. Rabinstein AA, Weigand S, Atkinson JL, et al.
Patterns of cerebral infarction in aneurysmal
subarachnoid hemorrhage. Stroke 2005;36:9927.
45. Rabinstein AA, Friedman JA, Weigand SD, et al.
Predictors of cerebral infarction in aneurysmal
subarachnoid hemorrhage. Stroke2004;35:18626.
46. Vergouwen MD, Vermeulen M, Coert BA, et al.
Microthrombosis after aneurysmal subarachnoid
hemorrhage: an additional explanation for delayed
cerebral ischemia. J Cereb Blood Flow Metab
2008;28:176170.
47. Dorhout Mees SM, Rinkel GJE, Feigin V, et al.
Calcium antagonists for aneurysmal subarachnoid
haemorrhage. Cochrane Database Syst Rev
2007;CD000277.
48. Kronvall E, Undren P, Romner B, et al. Nimodipine
in aneurysmal subarachnoid hemorrhage: a
randomized study of intravenous or peroral
administration. J Neurosurg 2009;110:5863.
49. Dorhout Mees SM. Magnesium in aneurysmal
subarachnoid hemorrhage (MASH II) phase III
clinical trial MASH-II study group. Int J Stroke
2008;3:635.
50. Dorhout Mees SM, van den Bergh WM, Algra A, et
al. Antiplatelet therapy for aneurysmal
subarachnoid haemorrhage. Cochrane DatabaseSyst Rev 2007;CD006184.
51. Qureshi AI, Luft AR, Sharma M, et al. Prevention
and treatment of thromboembolic and ischemic
complications associated with endovascular
procedures: Part IIClinical aspects and
recommendations. Neurosurg 2000;46:136076.
52. van den Bergh WM, Kerr RS, Algra A, et al. The
effect of antiplatelet therapy for endovascular
coiling in aneurysmal subarachnoid hemorrhage.
Stroke 2009 April 23 (Epub ahead of print).
53. Sillberg VA, Wells GA, Perry JJ. Do statins improve
outcomes and reduce the incidence of vasospasm
after aneurysmal subarachnoid hemorrhage. A
meta-analysis. Stroke 2008;39:26226.
54. Jang YG, Ilodigwe D, Macdonald RL. Metaanalysisof tirilazad mesylate in patients with aneurysmal
subarachnoid hemorrhage. Neurocrit Care
2009;10:1417.
55. Shaw MD, Vermeulen M, Murray GD, et al. Efficacy
and safety of the endothelin, receptor antagonist
TAK-044 in treating subarachnoid hemorrhage: a
report by the Steering Committee on behalf of the
UK/Netherlands/Eire TAK-044 Subarachnoid
Haemorrhage Study Group. J Neurosurg
2000;93:9927.56. Vajkoczy P, Meyer B, Weidauer S, et al. Clazosentan
(AXV-034343), a selective endothelin A receptor
antagonist, in the prevention of cerebral vasospasm
following severe aneurysmal subarachnoid
hemorrhage: results of a randomized, double-blind,
placebo-controlled, multicenter phase IIa study.
J Neurosurg 2005;103:917.
57. Macdonald RL, Kassell NF, Mayer S, et al.
Clazosentan to overcome neurological ischemia
and infarction occurring after subarachnoid
hemorrhage (CONSCIOUS-1). Randomized, double-
blind, placebo-controlled phase 2 dose-finding trial.
Stroke 2008;39:301521.
58. Nogueira RG, Bodock MJ, Koroshetz WJ, et al. High-
dose bosentan in the prevention and treatment ofsubarachnoid hemorrhage-induced cerebral
vasospasm: an open-label feasibility study.
Neurocrit Care 2007;7:194202.
59. Springborg JB, Moller C, Gideon P, et al.
Erythropoietin in patients with aneurysmal
subarachnoid haemorrhage: a double blind
randomised clinical trial. Acta Neurochir (Wien)
2007;149:1089101.
60. Klimo P Jr, Kestle JR, MacDonald JD, et al. Marked
reduction of cerebral vasospasm with lumbar
drainage of cerebrospinal fluid after subarachnoid
hemorrhage. J Neurosurg 2004;100:21524.
61. Amin-Hanjani S, Ogilvy CS, Barker FG. Does
intracisternal thrombolysis prevent vasospasm
after aneurysmal subarachnoid hemorrhage? A
meta-analysis. Neurosurgery 2004;54:32634.
62. Hamada JI, Kai Y, Morioka M, et al. Effect on
cerebral vasospasm of coil embolization followed
by microcatheter intrathecal urokinase infusion
into the cisterna magna. A prospective randomized
study. Stroke 2003;34:254954.
63. Amin-Hanjani S, Schwartz RB, Sathi S, et al.
Hypertensive encephalopathy as a complication of
hyperdynamic therapy for vasospasm: report of
two cases. Neurosurgery 1999;44:111316.
64. Wartenberg KE, Parra A. CT and CT-perfusion
findings of reversible leukoencephalopathy during
triple-H therapy for symptomatic subarachnoid
hemorrhage-related vasospasm. J Neuroimaging2006;16:1705.
65. Hoh BL, Aghi M, Pryor JC, et al. Heparin-induced
thrombocytopenia type II in subarachnoid
hemorrhage patients: incidence and complications.
Neurosurgery 2005;57:2438.
66. Jestaedt L, Pham M, Bartsch AJ, et al. The impact of
balloon angioplasty on the evolution of
vasospasm-related infarction after aneurysmal
subarachnoid hemorrhage. Neurosurgery
2008;62:61017.
67. Rabinstein AA, Friedman JA, Nichols DA, et al.
Predictors of outcome after endovascular
treatment of cerebral vasospasm. AJNR
Am J Neuroradiol 2004;25:177882.
68. Hasan D, Vermeulen M, Wijdicks EFM, et al.Management problems in acute hydrocephalus
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8/2/2019 Prevention and Rx Medical and Neuro Complication of Anurysmal Bleed
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after subarachnoid hemorrhage. Stroke
1989;20:74753.
69. Hasan D, Lindsay KW, Vermeulen M. Treatment of
acute hydrocephalus after subarachnoid
hemorrhage with lumbar puncture. Stroke
1991;22:1904.
70. Ruijs AC, Dirven CM, Algra A, et al. The risk of
rebleeding after external lumbar drainage in
patients with untreated ruptured cerebralaneurysms. Acta Neurochir (Wien)
2005;147:115762.
71. Hellingman CA, Beijer I, van Dijk GW, et al. Risk of
rebleeding after treatment of acute hydrocephalus
in patients with aneurysmal subarachnoid
hemorrhage. Stroke 2007;38:969.
72. Fountas KN, Kapsalaki EZ, Machinis T, et al. Review
of the literature regarding the relationship of
rebleeding and external ventricular drainage in
patients with subarachnoid hemorrhage of
aneurysmal origin. Neurosurg Rev 2006;29:1418.
73. Saladino A, White JB, Wijdicks EF, et al.
Malplacement of ventricular catheters by
neurosurgeons: a single institution experience.
Neurocrit Care 2009;10:24852.
74. Beer R, Lackner P, Pfausler B, et al.
Nosocomial ventriculitis and meningitis in
neurocritical care patients. J Neurol
2008;255:161724.
75. Binz DD, Toussaint LG III, Friedman JA.
Hemorrhagic complications of ventriculostomy
placement: a meta-analysis. Neurocrit Care
2009;10:2536.
76. Wong GK, Poon WS, Wai S, et al. Failure of regularexternal ventricular drain exchange to reduce
cerebrospinal fluid infection: result of a randomised
controlled trial. J Neurol Neurosurg Psychiatry
2002;73:75961.
77. Choksey MS, Malik IA. Zero tolerance to shunt
infections: can it be achieved? J Neurol Neurosurg
Psychiatry 2004;75:8791.
78. Korinek AM, Reina M, Boch AL, et al.
Prevention of external ventricular drainrelated
ventriculitis. Acta Neurochir (Wien)
2005;147:3945.
79. Roos YBWEM, Rinkel GJE, Vermeulen M, et al.
Antifibrinolytic therapy for aneurysmal
subarachnoid haemorrhage. Cochrane Database
Syst Rev 2000;CD001245.
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