Vasospasm in Subarachnoid Haemorrhage

Reviewed and revised 1 September 2014

OVERVIEW

Definitions

• vasospasm is dynamic narrowing of vessels due to a radiological diagnosis
• delayed neurological deterioration (DND) is clinically detected neurological deterioration after stabilisation that is not due to re-bleeding, may be due to multiple other causes
• delayed cerebral ischaemia (DCI) is any neurological deterioration >1 hour that presumed due to ischemia, and other causes excluded
• aneurysmal subarachnoid haemorrhage (aSAH)

Vasospasm

• vasospasm occurs in up to 70% of aSAH
• 3-15d, most frequently 7-10d, resolves spontaneously at 21d
• DCI is the most important secondary cause of deterioration following SAH (occurs in about 30%)
• early vasospasm occurs in 10%, associated with poor grade but not delayed vasospasm; independent poor prognostic indicator

Oli Flower discusses vasospasm following aneurysmal SAH in this PK SMACC-talk:

SUMMARY

Summary of options for prevention, monitoring and treatment

• prevention: removal of SAH at surgery, nimodipine, maintenance of euvolaemia, avoiding hypotension
• monitoring: clinical, transcranial doppler, 4 vessel angio, CTA/MRI, EEG, SPECT/PET, microdialysis catheters
• treatment: haemodynamic augmentation to reverse neurological deficits, endovascular treatment (balloon angioplasty, papaverine, nicardipine), investigational therapies
• because of the disparity between vasospasm on trans-cranial Doppler, angio and what happens clinically there is disagreement about how aggressively vasospasm should be treated.

RISK FACTORS

Prediction

• best predicted by radiological grade (e.g. Fisher, Classen)
• amount of blood and location
• thick basal cistern blood and blood in lateral ventricles

Other risk factors include:

• poor clinical grade
• prolonged coma after aneurysm rupture
• age <50y
• smoker
• hypertension
• hyperglycemia
• cocaine use
• genetics

No difference between clipping and coiling

PATHOPHYSIOLOGY

• oxyHb contacts intraluminal wall of vessel
• calcium dependent and independent pathways
• free radical mechanisms
• imbalance in vasoactive agents: NO, endothelin, arachidonic acid
• neuronal mechanisms leading to increased vascular tone, endothelial tone and apoptosis

DIAGNOSIS

• serial clinical examination (poor sensitivity if low clinical grade)
• DSA is gold standard (also allows treatment) > CTA and MRA > TCD for large vessels only
• Perfusion imaging may supersede DSA

Experimental methods

• continuous EEG
• brain tissue oxygenation monitoring
• cerebral microdialysis catheters

See Monitoring in Subarachnoid Haemorrhage

MANAGEMENT OPTIONS

Drug Therapy

Nimodipine

• calcium channel antagonist that has is known to have some selectivity for the cerebral circulation
• used in cerebral aneurysm surgery to decrease perioperative vasospasm associated with blood in the cranium and also from perioperative handling/disruption of cerebral blood vessels during clipping (after a rupture of a berry aneurysm)
• high risk time is between 4-10 days after clipping of the aneurysm
• goal = to decrease neurological deficits that develop as a result of distal infarction of brain from site of vasospasm
• should be commenced within 96 hours of subarachnoid haemorrhage
• may be given PO, IV or intra-arterially (at angiography)
• dose: PO 60mg Q4 hourly or IV 0.1-1mcg/kg/min
• continuation of dose for 5-14 days in established vasospasm (IV) or else 3 weeks (PO)
• predicting those patients who will get vasospasm is very difficult so invariably all patients are started on it post-operatively during elective surgery
• has been shown to decrease morbidity surrounding aneurysm surgery but not mortality
• data indicating decrease in morbidity has been documented for patients receiving PO or N/G nimodipine rather than IV – so some centres administer this via N/G tube placement in patient who can not reliably swallow
• useful in prophylaxis
• exact mechanism unknown — no convincing evidence that it affects vasospasm or DCI; only proven treatment for improving aSAH outcomes
• side effects; hypotension, flushing
• some patients do not develop vasospasm but everyone is treated because of uncertainty about those that will and won’t develop this complication

Nicardipine & AT877

• both reduce vasospasm but do not improve outcome

Haemodynamic therapies

• target euvolemia with isotonic crystalloid, avoid hypovolemia
• target hypertension titrated to clinical response
• HHH therapy is not currently recommended

Hypervolaemia

• correct hypovolaemia
• belief that patients need a supraphysiological blood volume and thus preload to help increased perfusion to the vasospastic arteries.
• no good data to support hypervolaemia over euvolaemia
• harm may be produced in patients who are unable to deal with large fluid boluses.

Hypertension

• evidence that works both based on clinical response (reversible neurology with an increase in BP) and published studies
• it is unclear whether hypertension, cardiac output or volume expansion is the best therapy
• the goal MAP should the titrated against clinical response to MAP elevation
• aneurysm must be secured first!

Haemodilution

• the proposed mechanism is that a decreased haematocrit increases laminar flow through the vasospastic vessel by the decrease in blood viscosity
• it is often not specifically targeted as hypervolaemia induces a degree of haemodilution
• no good data to support it use
• only indicated if coexistent polycythemia

Endoluminal Therapy

Early Coiling

• good data that improves mortality but manipulation of vessel though to predispose to vasopasm
• ISAT trial = RCT of neurosurgical clipping vs endovascular coiling – coiling ruptured aneurysms @ 1 year follow up
• not all aneurysms can be coiled

Balloon Angioplasty

• good data that sequential treatment with angioplasty does increase flow through the vasospastic area -> dilation is seen at the time of the angiogram
• ? data on mortality and morbidity
• associated risks are inherent

Papaverine

• macroscopic evidence of dilation seen at the time
• ? data on mortality on morbidity

Investigational Therapies

Studied in animal models, no hard clinical evidence, no RCTs

• Statins – continue statins if patient is already on; phase 3 study in progress (STASH)
• Intra-cisternal thrombolytics such as tPa and urokinase, intrathecal urokinase
• early cisternal washout during operative repair
• Endothelin 1 antagonists
• Magnesium – no benefit in Phase 3 studies (e.g. MASH-II)

References and Links

• CCC — Monitoring in Subarachnoid Haemorrhage