Critically evaluate the current approaches to the treatment of cerebral vasospasm following aneurysmal subarachnoid haemorrhage.

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College Answer

Treatment 
b) Triple H therapy-HT, hypervolemia and hemodilution-controversial, not evidence based 
c) Early clipping / coiling 
d) Nimodipine -useful in prophylaxis, 
e) Endoluminal·therapies: Balloon angioplasty and intra-arterial papaverine 

Investigational therapies -proven in animal models, no hard clinical evidence, no RCT 
1) Statins-Early human data 
2) Cisternal tPa 
3) Endothelin antagonists

Discussion

This topic is well developed in the chapter on subarachnoid haemorrhage.

True to the college answer, there is only strong evidence for nimodipine and endovascular vasodilators. Of the "triple-H" therapy, the only evidence-based component is probably hypertension, and even this is being debated.

Judging by the college answer, they did not want a discussion of Class I recommendations from highly regarded advisory bodies. The model answer mentions some wacky "failed therapies" for vasospasm which have subsequently receded into historical background noise.

In summary:

Well-supported therapies

  • Once vasospasm is suspected, DSA (the gold standard investigation) should be performed.
  • On DSA, one can access the vessels involved and inject intra-arterial papaverine or verapimil.
  • Nimodipine is the only preventative pharmacotherapy supported by evidence. The BRANT trial from England has demonstrated a 34% decrease in the risk of SAH-induced stroke.
  • Of the "Triple H" circulating volume expansion strategies, only hypertension persists as a valid treatment - and it is only supported by a consensus of neurosurgeons.

Poorly supported therapies

  • "Triple H therapy" in general- i.e. prophylactic hypertension, haemodilution and hypervolaemia - has little to recommend it. Myburgh was already tearing shreds out of it in 2005.
  • Intrathecal thrombolysis is promising, but not well supported - a 2004 Japanese study found intrathecal urokinase decreased the incidence of vasospasm by almost 50%.
  • Statins - no benefit (STASH trial)
  • Endothelin 1 antagonists (eg. clazosentan) - no strong support, perhaps some subtle benefit (CONSCIOUS-1 trial)
  • Magnesium – no benefit (MASH-2 trial)
  • Tirilazad - a non-glucocorticoid aminosteroid that blocks lipid peroxidation - fiver RCTs; only one showed any benefit, and its efect was lost in the noise accoridng to a Cochrane meta-analysis.
  • Fasudil - a Rho kinase inhibitor that prevents the effects of extracellular calcium on smooth muscle contraction - promising on the basis of 8 RCTs, but still not fully supported by the evidence according to a 2012 meta-analysis.
  • Eicosapentaenoic acid - which also inhibits Rho kinase, like fasudil - promising results of one small study (the EVAS trial); thus far it still falls into the "experimental" category.

References