Monday, February 27, 2012

Cerebral Vasopasm (PART 2)

TREATMENT :


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.

 REFERENCES :
1.Lam M Arthur :Cerebral aneurysm :Anesthetic 
   concidreation;Cottrell E James,Smith S David;Anesthesia 
   and Neurosurgery ;4th edit.Mosby A harcourt Health 
   Sciences Company ,2000:pp 373-6


2.Weir K Bryce:Intracranial Aneurysm and AV Malformation
   Surgical Consideration ;Albin S Maurice;Textbook of 
   Neuroanesthesia with Neurosurgical and Neuroscience 
   Perspective ;The Mc Graw Hill Companies Newyork,StLouis 
   San Franscisco,1997:pp 852-3.


3.Godsiff S Leisha,Matta FBasil:Intensive care management 
   of intracranial hemorrhage ;Matta F Basil,Menon K David
   Turner M John:Textbook of Neuroanesthesia and Critical 
   Care,Greenwich Medical Media Ltd,London
    2000,pp 335-9.


4.Chang W.J.Cherylee,Bleck P Thomas:Neuroscience Inten
   sive Care:StoneJ.D.Sperry J.Richard;The Neuroanesthesia 
   Handbook;Mosby Year Book Inc.USA,1996;pp457-60.

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