Pharmacologic treatment:(1,4)
Numerous drugs have been investigated for prevention or treatment vasospasm but most are ineffective.
Calcium channel blockers (calcium antagonist) which nimodipine has been more extensively studied are the only drugs that have been shown to consistently reduce the mortality and morbidity from vasospasm in all patients with SAH irrespective of the grades.
Nimodipine, a dehydropyridine calcium antagonist blocks the intracellular influx of extra cellular calcium, preventing arterial smooth muscle contraction. It was initially believed that this agent prevents constriction of vessels; however clinical trial have shown no change in the incidence or severity of angiographic vasospasm.
It is now postulated that improved outcome is related either to decrease in vasospasm in the microvasculature which is not visualized by angiography or to a modification of calcium influx into the damage cells which limited the extent of neural injury.
Interestingly none of these favourable studies with calcium antagonist prophylaxy was able to demonstrate any signifi
signicant change in the incidence or severity of vasospasm.
Nicardipine is another dehydropyridine calcium antagonist in high dose intravenous has been investigated for prevention of vasospasm.
Nicardipine studied in SAH therapy continuous iv infusion for 14 days after SAH has shown to decrease the incidence of vasospasm but compared with placebo,nicardipine has not shown to improve clinical of vasospasm outcome at 3 months.
Nimodipine,60 mg every 4 hours should be used enterally as soon after the ictus as possible ;preferably before 96 hrs.
It is continued for 14 to 21 days
Hypotension is seen in about 5% of patients treated with enteral nimodipine and in 28% to 33% of patients treated iv nicardipine.
Therefore the BP should be monitored carefully;the hypo
tension is typically readily treatable with fluid adminstra
tion.Pulmonary oedema,presumably as manifestation of high output congestive heart failure(CHF) has also been associated with dehydropyridine therapy.
An early clinical trial of tirilazad mesylate,a potent lipid peroxidation inhibitor in Europe,Australia and New Zealand demonstrated that at 6 mg per kg per day,a significant reduction in symptomatic vasospasm occured primarily
primarily in men.However a subsequent trial in North America involving 897 patients failed to demonstrate any improvement over placebo.
A subsequent trial with a higher dose(15mg/kg per day) in women demonstrated a slight improvement in mortality in patients with poor neurologic grade but no difference from the placebo group when all patients were considered.
Approaching from another direction,a clinical trial with a hydroxyl radical scavenger (nicaraven) reported a 35% reduction of the incidence of delayed ischemic deficit.
These result although promising,await confirmation with a larger clinical trial.
In retrospective study,patients taking aspirin before their SAH had reduced risk of delayed ischemic deficit and there
fore the use of aspirin post aneurysm clipping require further study.
HYPERVOLEMIC,HYPERTENSIVE AND HEMODILUTION
(TRIPLE H)(1,2)
The rationale behind induced hypervolemia and hyper
tension is that in SAH the ischemic area of the brain have
impaired autoregulation and thus CBF depends on the
intravascular volume and mean arterial pressure(MAP).
The aims of triple H therapy is to optimize cerebral
perfusion by increasing CBF and improving flow
characteristics by haemodilution.
Hypervolemia is achieved by the administration of some
combination of colloids,crystalloids and blood products.
Colloid may at times be superior to crystalloid solution in
maintaining hypervolemia.
This therapy is most successful if instituted early when the
neurologic deficit are mild and before the onset of
infarction.However prophylactic treatment initiated before aneurysm clipping,is associated with a significant risk of rebleeding(19% in one series).
Other concerns include worsening of cerebra oedema,
increasing ICP,and causing hemorrhage into an infarcted area.Other systemic complications included pulmonary oedema(7% to 17%),myocardial infarction(2%),dilutional hyponatremia(3% t0 35%),and cogulopathy(3%).
To optimized theraphy and minimize the potential cardio
vascular and pulmonary complication,invasive monitors including direct arterial pressure,CVP or preferably a pulmonary artery catheter are essential.
Sufficient iv fluids are infused to increase the CVP to 10 mmHg or the pulmonary artery wedged pressure (PAWP) t0 12 to 20 mmHg.
In recent study where a starling curve was constructed in nine patients with a ruptured aneurysm ,Levy and Giannotta observed the increasing the PAWP from 8 to 14 mmHg correlated with significant increases in left ventricular stroked work index,stroke volume index,and cardiac index.
However further volume expansion to increase PAWP to above 14 mmHg resulted in a decline in the cardiac index.
The initial step is to increase cardiac output and BP with agressive volume expansion.In addition to maintanance fluids of 2-3 litres per day,colloids or packed red cell are used to obtain the following:
-Hematocriet of 30-35%
-PAWP of 8-14 mmHg
-Cardiac Index(CI) of 4,5L/m2/min
-Systemic vascular resistance(SVR) index of 1400-
2000 dyne/sec/cm3.
-SBP of 120 -150 mmHg in unclipped and 160-200
mmHg in clipped aneurysm.
Although iv fluid alone is often effective is at times
insufficient to raise BP or reverse the ischemic symptoms;
vasopressors are then initiated to induce hypertension .
The most widely used vasopressors are dopamine,dobu-
tamine,nor adrenaline or phenylephrine.
If after volume expansion the above parameters cannot be achieved or there are no improvement in neurologic status
inotropes(usually dopamine 2,5-15 mcg/kg/min)are started.
The use of appropriate inotropes/vasopressors is guided by a pulmonary artery catheter.
In some cases nimodipine may have to be withdrawn as it can interfere with attempt to induce hypertension.
Triple H therapy may induce a vagal response,as well as profound diuresis ,requiring administration of large amounts of iv fluids.
Atropine (1 mg im every 3 to 4 hrs ) may be given to maintain the heart rate between 80 and 120 beats/min,and aquous vasopressin(pitressin)( 5 units im) may be adminis
tered to maintain the urine output at less than 200 ml/hr.
The BP is treated to a level necessary to reverse the signs and symptoms of vasospasm or to a maximum of 160 to 200 mmHg systolic,in patients whose aneurysm has been clipped
If the aneurysm has not been clipped then SBP is increased to only 120 to 150 mmHg.
The elevated BP must be maintained until the vasospasm resolves which usually in 3 to 7 days.
Response to therapy can now be monitored non invasively using the TCD,improvement in vasospasm is associated with a decrease in flow velocity.
PET has been performed in patients not responding to triple H therapy,to diagnose any hypoperfused area which are not infarcted,which will benefit from an improvement in blood flow. CBF values <20 ml/100g/min,have been found in the affected hemispheres of patients with symptomatic vaso
spasm and values<12 ml/100g/min have been associated with irreversible changes.
The BP is manipulated using inotropes to see wether there is any increment in blood flow to these hypoperfused areas.
Hemodilution the last component of triple H therapy is based on the correlation of hematocriet and whole blood viscosity.As the Hematocriet and viscosity decrease,the cerebrovascular resistance corresponding decreases and CBF increases and the oxygen carrying capacity is decrease.
Experimental study that suggested that hematocriet of 33%
provides an optimal balance between viscosity and oxygen carrying capacity and this has been applied clinically.
Phlebotomy or blood transfusion are performed to maintain a hematocriet 33%.
Non Pharmacologic treatment:
Reduction of ICP:(1)
In patient has elevated ICP ,cerebral perfusion may be
improved by lowering the ICP.
Improvement in neurologic status with this treatment
alone has been reported.
Interventional neuroradiology:
Percutaneous angioplasty (PTA):(2,4)
If the patient is in imminent danger from severe diffuse vasospasm refractory to triple H therapy ,these spastic arterial segment may be forcibly dilated by means of small low pressure balloon placed through intra arterial catheter.
In expert hands this associated with the permanent rever
sal of vasospasm and clinical improvement in one half to two thirs of patients but there is a risk that the vessels may rupture and dissect with this technique so the procedure should be restricted to experienced interventional neuro
radiologis.
Intra arterial papaverine:(2)
The proximal segment of the anterior cerebral arteries,and
distal middle cerebral arteries are not amenable to balloon
dilatory because of size or angle of take off.
The instillation over several hours of high concentration
of intra arterial papaverine has been associated with rever
sal of vasospasm in some cases.
Papaverine ,a phosphodiesterase inhibitor causes the accu
mulation of cycle adenyl monophosphate within smooth
muscle leading to vasodilatation.
There has been tendency for spasm to recur and the
infusion may have to be repeated but it is sometimes
associated with clinical improvement.
However,papaverine can precipitate systemic hypotension
and intracranial hypertension so measures to support BP
and control ICP must be immediately available.
Prophylaxis:(2,3)
Early surgery permits the mechanical removal of fresh
blood clot by suction and irrigation.
As blood in the subarachnoid space precipitate cereb-
ral vasospasm,it has been postulated that drugs which
dissolve this blood clot may reduce the incidence of
cerebral vasospasm and improve outcome.
Once the offending aneurysm has been secured by a clip
it is possible to place tissue plasminogen activator within
the subarachnoid space,either at the time of surgery or
subsequently through catheters to faciltate the early
fibrinolysis the clot ,thus reducing the amount of decaying
blood pressing against the arteries.
This appear to be effective way of preventing vasospasm.
However,a recent trial using tissue plasminogen activator
showed a reduction in angiographic vasospasm but no
improvement in symptomatic cerebral vasospasm or
neurologic deterioration.
These fibrinolytic agents have a potential to cause
bleeding by dissolving normal clot,so only patients at high
risk of developing vasospasm should be choosen for this
type of prophylaxis.
Summary
One of the most devastating complications of SAH is
cerebral vasospasm.
which can cause delayed focal or diffuse ischaemic
neurologic deficits.
The frequency of occurence as determined by angiography
is estimated to be 40% to 60%,however clinically significant
and symptomatic vasospasm occurs at lower frequency (20% to 30%).
Blood in the subarachnoid space precipitate cerebral vaso
spasm,the component in the blood implicated in pathoge
nesis of vasospasm is currently thought to be oxyhemoglo
bine.
Progressive impairment in level of conciousness or increase
in focal neurologic deficit occuring more than four days
after bleeding episode should raise the suspicion of cereb
ral vasospasm.
There is general belief that early surgery and the removal
of blood reduced the risk of developing cerebral vasospasm
Numerous drugs have been investigated for prevention or
treatment of vasospasm but most are ineffective.
Calcium channel blockers of which nimodipine has been
more extensively studied are the only drugs that have been
shown to consistently reduce the incidence of poor
outcome by 40% to 70%.
Triple H therapy aims to increase cerebral perfusion by
increasing CBF and improving flow characteristic by
haemodilution.
To optimize therapy and minimize the potential
cardiovascular and pulmonary complications,invasive
monitors including direct arterial blood pressure,CVP or
preferably a pulmonary artery catheter are essential.
If there is no improvement after volume expansion ,the use
of inotrope(dopamine,dobutamine and phenylephrine ) are
started.
If the patient is imminent danger from severe diffuse
vasospasm or refractory to triple H therapy then PTA can
be alternatif treatment.
When cerebral arteries are not amenable to balloon
dilatory because of size or angle of take off,intra arterial
papverine can be choosen.
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Perspective ;The Mc Graw Hill Companies Newyork,StLouis
San Franscisco,1997:pp 852-3.
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Turner M John:Textbook of Neuroanesthesia and Critical
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