Supplementary Table 2: Meta-analyses of subarachnoid haemorrhage trials
Reference
Treatment
Number
of trials
Total
number of
patients
Results
Feigin et al.
(2005)4
Dorhout-Mees
et al. (2007)3
Corticosteroids
3
256
Antiplatelet drugs (aspirin,
ticlopidine, dipyridamole,
OKY-046)
7
1,385
Too few patients treated with hydrocortisone or fludrocortisone to draw any definitive
conclusions
No effect of antiplatelet drugs on poor outcome, secondary brain ischaemia or
intracranial hemorrhage, ticlopidine significantly reduced poor outcome
Dorhout-Mees
et al. (2007)2
Calcium channel
antagonists (magnesium,
nimodipine, nicardipine,
AT877)
16
3,361
Included three studies of magnesium, overall calcium channel antagonists reduced
poor outcome, oral nimodipine alone also improved outcome, whereas other calcium
channel antagonists or intravenous nimodipine did not. Overall analysis also showed
that they reduced secondary ischaemia
Dankbaar et
al. (2010)1
Haemodynamic therapy
11
ND
Haemodilution did not improve cerebral blood flow, one uncontrolled study found that
hypervolaemia increased cerebral blood flow and some studies of hypertension or a
combination of haemodilution, hypervolaemia and haemodilution increased cerebral
blood flow, but overall there was no good evidence from controlled studies for a
positive effect of haemodynamic manouevres on cerebral blood flow, let alone clinical
outcome
Vergouwen et
al. (2010)10
Zhang et al.
(2010)11
Kramer et al.
(2011)7
3-hydroxy-3-methylglutarylcoenzyme A
Tirilazad
4
190
5
3,821
Fibrinolytics (urokinase,
recombinant tissue
plasminogen activator)
5
465
No signficant effect on transcranial Doppler flow velocities, delayed cerebral
ischaemia, poor outcome or mortality
No effect of tirilazad on death or poor outcome, although the drug was associated with
less delayed cerebral ischaemia
Fibrinolytic drugs significantly reduced poor outcome, delayed neurological deficits,
angiographic vasospasm and hydrocephalus
Liu et al.
(2011)8
Liu et al.
(2011)9
Guo et al.
(2012)6
Fasudil
8
843
Nimodipine
8
1,514
Endothelin receptor
antagonists
4
2,024
Golan et al.
(2013)5
Magnesium
13
2,401
Abbreviation: ND, not determined.
Fasudil significantly reduced angiographic vasospasm, symptomatic vasospasm and
cerebral infarction and improved clinical outcome
Nimodipine improved outcome and reduced mortality, symptomatic vasospasm,
delayed neurological deficit and cerebral infarction
Endothelin receptor antagonists reduced angiographic vasospasm and delayed
ischaemic neurological deficits but had no effect on unfavourable outcome or death
Magnesium reduced delayed cerebral ischaemia but did not improve neurological
outcome or decrease cerebral infarction, radiographic vasospasm or mortality
1. Dankbaar, J. W., Slooter, A. J., Rinkel, G. J. & van der Schaaf, I. C. Effect of different components of triple-H therapy on cerebral perfusion in patients with
aneurysmal subarachnoid haemorrhage: a systematic review. Crit Care 14, R23 (2010)
2. Dorhout Mees, S. M., et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane. Database. Syst. Rev. CD000277 (2007)
3. Dorhout Mees, S. M., van den Bergh, W. M., Algra, A. & Rinkel, G. J. Antiplatelet therapy for aneurysmal subarachnoid haemorrhage. Cochrane.
Database. Syst. Rev. CD006184 (2007)
4. Feigin, V. L., et al. Corticosteroids for aneurysmal subarachnoid haemorrhage and primary intracerebral haemorrhage. Cochrane. Database. Syst. Rev.
CD004583 (2005)
5. Golan, E., Vasquez, D. N., Ferguson, N. D., Adhikari, N. K. & Scales, D. C. Prophylactic magnesium for improving neurologic outcome after aneurysmal
subarachnoid hemorrhage: systematic review and meta-analysis. J. Crit Care 28, 173-181 (2013)
6. Guo, J., Shi, Z., Yang, K., Tian, J. H. & Jiang, L. Endothelin receptor antagonists for subarachnoid hemorrhage. Cochrane. Database. Syst. Rev. 9, CD008354
(2012)
7. Kramer, A. H. & Fletcher, J. J. Locally-administered intrathecal thrombolytics following aneurysmal subarachnoid hemorrhage: a systematic review and
meta-analysis. Neurocrit. Care 14, 489-499 (2011)
8. Liu, G. J., et al. Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with
subarachnoid hemorrhage. Eur. J. Clin. Pharmacol. (2011)
9. Liu, X. & Rinkel, G. J. Aneurysmal and clinical characteristics as risk factors for intracerebral haematoma from aneurysmal rupture. J. Neurol. 258, 862865 (2011)
10. Vergouwen, M. D., de Haan, R. J., Vermeulen, M. & Roos, Y. B. Effect of statin treatment on vasospasm, delayed cerebral ischemia, and functional
outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. 41, e47-e52 (2010)
11. Zhang, S., Wang, L., Liu, M. & Wu, B. Tirilazad for aneurysmal subarachnoid haemorrhage. Cochrane. Database. Syst. Rev. 2, CD006778 (2010)