Cerebral Vasospasms Following Subarachnoid Bleeding – Diagnosis, Monitoring and Treatment Options

Authors: J. Adamkov 1;  J. Náhlovský 1;  J. Habalová 1;  A. Krajina 2;  S. Řehák 1;  M. Kanta 1;  T. Česák 1
Authors‘ workplace: LF UK a FN Hradec Králové Neurochirurgická klinika 1;  LF UK a FN Hradec Králové Radiologická klinika 2
Published in: Cesk Slov Neurol N 2014; 77/110(2): 158-167
Category: Review Article

Podpořeno MZ ČR –  RVO (FNHK). Podpořeno programem PRVOUK P37/ 4.


Despite availability of sophisticated surgical procedures, endovascular techniques and new trends in neuro-intensive care, treatment outcomes in patients with subarachnoid bleeding from a ruptured aneurysm are still very unsatisfactory. The first step in patient management, i.e. treating the source of bleeding, is followed by close patient monitoring, taking into account the natural course of the disease. Cerebral vasospasms are among the most severe complications, identified in 40–70% of patients after subarachnoid bleeding. In patients in whom the source of bleeding has been treated, cerebral vasospasms are responsible for the development of delayed cerebral ischemia, the most common cause of high morbidity rates or deaths (15–20%). Effective prevention of such complications is based on detailed clinical observation. Invasive monitoring of cerebral metabolism and intracranial pressure is to be applied in patients with impaired consciousness in order to detect a threatening cerebral ischemia as early as possible. Current knowledge and technology enable more aggressive treatment that concentrates on normalising perfusion in the brain.

Key words:
cerebral vasospasms – subarachnoid haemorrhage – delayed cerebral ischemia

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.


1. Ignarro LJ. Biosynthesis and metabolism of endothelium‑ derived nitric oxide. Annu Rev Pharmacol Toxicol 1990; 30: 535– 560.

2. Pluta RM. Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther 2005; 105(1): 23– 56.

3. Jung CS, Iuliano BA, Harvey‑ White J, Espey MG, Oldfield EH, Pluta RM. Association between cerebrospinal fluid levels of asymmetric dimethyl‑ L‑ arginine, an endogenous inhibitor of endothelial nitric oxide synthase, and cerebral vasospasm inaprimate model of subarachnoid hemorrhage. J Neurosurg 2004; 101(5): 836– 842.

4. Thomas JE, Nemirovsky A, Zelman V, Giannotta SL. Rapid reversal of endothelin‑ 1‑induced cerebral vasoconstriction by intrathecal administration of nitric oxide donors. Neurosurgery 1997; 40(6): 1245– 1249.

5. Chow M, Dumont AS, Kassell NF. Endothelin receptor antagonists and cerebral vasospasm: an update. Neurosurgery 2002; 51(6): 1333– 1341.

6. Juvela S. Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage. J Neurosurg 2000; 92(3): 390– 400.

7. Seifert V, Löffler BM, Zimmermann M, Roux S, Stolke D. Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg 1995; 82(1): 55– 62.

8. Duerrschmidt N, Wippich N, Goettsch W, Broemme HJ, Morawietz H. Endothelin‑1 induces NAD(P)H oxidase in human endothelial cells. Biochem Biophys Res Commun 2000; 269(3): 713– 717.

9. Dumont AS, Dumont RJ, Chow MM, Lin CL, Calisaneller T, Ley KF et al. Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 2003; 53(1): 123– 135.

10. Grisham MB, Granger DN, Lefer DJ. Modulation of leukocyte‑ endothelial interactions by reactive metabolites of oxygen and nitrogen: relevance to ischemic heart disease. Free Radic Biol Med 1998; 25(4– 5): 404– 433.

11. Fassbender K, Hodapp B, Rossol S, Bertsch T, Schmeck J, Schütt S et al. Endothelin‑1 in subarachnoid hemorrhage: An acute‑  phase reactant produced by cerebrospinal fluid leukocytes. Stroke 2000; 31(12): 2971– 2975.

12. Ni W, Gu XY, Song DL, Leng B, Li PL, Mao Y. The relationship between IL‑6 in CSF and occurrence of vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl 2011; 110(1): 203– 208.

13. Ostrowski RP, Colohan AR, Zhang JH. Molecular mechanisms of early brain injury after subarachnoid hemorrhage. Neurol Res 2006; 28(4): 399– 414.

14. Sehba FA, Mostafa G, Knopman J, Friedrich V jr, Bederson JB. Acute alterations in microvascular basal lamina after subarachnoid hemorrhage. J Neurosurg 2004; 101(4): 633– 640.

15. Chou SH, Feske SK, Simmons SL. Elevated peripheral neutrophils and matrix metalloproteinase 9 as bio­markers of functional outcome following subarachnoid hemorrhage. Transl Stroke Res 2011; 2(4): 600– 607.

16. Juul R, Hara H, Gisvold SE, Brubakk AO, Fredriksen TA, Waldemar G et al. Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid hemorrhage. Acta Neurochir 1995; 132(1– 3): 32– 41.

17. Edvinsson L, Ekman R, Jansen I, McCulloch J, Mortensen A, Uddman R. Reduced levels of calcitonin gene‑related peptide‑like immunoreactivity in human brain vessels after subarachnoid haemorrhage. Neurosci Lett 1991; 121(1– 2): 151– 154.

18. Schebesch KM, Brawanski A, Kagerbauer SM, Martin J, Bele S, Herbst A et al. The possible role of neuropeptide Y after spontaneous subarachnoid hemorrhage. Acta Neurochir 2011; 153(8): 1663– 1668.

19. Schebesch KM, Brawanski A, Bele S, Schödel P, Herbst A, Bründl E et al. Neuropeptide Y –  an early bio­marker for cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurol Res 2013; 35(10): 1038– 1043.

20. Lin CL, Hsu YT, Lin TK, Morrow JD, Hsu JC, Hsu YHet al. Increased levels of F2– isoprostanes following aneurysmal subarachnoid hemorrhage in humans. Free Radic Biol Med 2006; 40(8): 1466– 1473.

21. Clark JF, Sharp FR. Bilirubin oxidation products (BOXes) and their role in cerebral vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab 2006; 26(10): 1223– 1233.

22. Qureshi AI, Sung GY, Razumovsky AY, Lane K, Straw RN, Ulatowski JA. Early identification of patiens at risk for symptomatic vasospasm after aneurysmal subarachnoid haemorrhage. Crit Care Med 2000; 28(4): 984– 990.

23. Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KTS. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth 2012; 109(3): 315– 329.

24. Hirashima Y, Nakamura S, Endo S, Kuwayama N,Naruse Y, Takaku A. Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid haemorrhage. Neurochem Res 1997; 22(10): 1249– 1255.

25. Romano JG, Forteza AM, Concha M, Koch S, Heros RC, Morcos JJ et al. Detection of microemboli by transcranial Doppler ultrasonography in aneury­smal subarachnoid hemorrhage. Neurosurgery 2002; 50(5): 1026– 1030.

26. Weir B. Aneurysms affecting the nervous system. Baltimore: Williams & Wilkins 1987: 323– 324.

27. Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ,Wijdicks EF, Muizelaar JP et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid haemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 2010; 41(10): 2391– 2395.

28. Okada Y, Shima T, Nishida M, Yamane K, Hatayama T, Yamanaka C, Yoshida A. Comparison of transcranial Doppler investigation of aneurysma vasospasm with digital subtraction angiographic and clinical findings. Neurosurgery 1999; 45(3): 443– 450.

29. Laumer R, Steinmeier R, Gonner F, Vogtmann T,Priem R, Fahlbusch R. Cerebral hemodynamics in subarachnoid hemorrhage evaluated by transcranial Doppler sonography: Part 1. Reliability of flow velocities in clinical management. Neurosurgery 1993; 33(1): 1– 9.

30. Vora YY, Suarez‑ Almazor M, Steinke DE, Martin ML, Findlay JM. Role of transcranial Doppler monitoring in the dia­gnosis of cerebral vasospasm after subarachnoid hemorrhage. Neurosurgery 1999; 44(6): 1237– 1248.

31. Clyde BL, Resnick DK, Yonas H, Smith HA, Kaufmann AM. The relationship of blood velocity as measured by transcranial Doppler ultrasonography to cerebral blood flow as determined by stable xenon computed topographic studies after aneurysmal subarachnoid hemorrhage. Neurosurgery 1996; 38(5): 896– 905.

32. Lindegaard KF, Nornes H, Bakke SJ et al. Cerebral casospasm after aubarachnoid hemorrhage investigated by means of transcranial Doppler ultrasound. Acta Neurochir Suppl (Wien) 1988; 42: 81– 84.

33. Sloan MA, Alexandrov AV, Tegeler CV, Spencer MP,Caplan LR, Feldmann E et al. Transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004; 62(9): 1468– 1481.

34. Dorsch NW. Therapeutic approaches to vasospasm in subarachnoid hemorrhage. Review. Curr Opin Crit Care 2002; 8(2): 128– 133.

35. Unterberg AW, Sakowitz OW, Sarrafzadeh AS, Benndorf G, Lanksch WR. Role of bedside microdialysis in the dia­gnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 2001; 94(5): 740– 749.

36. van Santbrink H, vd Brink WA, Steyerberg EW, Carmona Suazo JA, Avezaar CJ, Maas AI. Brain tissue oxygen response in severe traumatic brain injury. Acta Neurochir (Wien) 2003; 145(6): 429– 438.

37. Steifel MF, Udoetuk JD, Spiotta AM. Conventional neurocritical care and cerebral oxygenation after traumatic brain injury. J Neurosurg 2006; 105(4): 568– 575.

38. Chen H, Stiefel M, Oddo M, Milby AH, Maloney‑ Wilensky E, Frangos S et al. Detection of cerebral compromise with multimodality monitoring in patients with subarachnoid hemorrhage. Neurosurgery 2011; 69(1): 53– 63.

39. Väth A, Kunze E, Roosen K, Meixensberger J. Therapeutic aspects of brain tissue pO2 monitoring after subarachnoid hemorrhage. Acta Neurochir Suppl 2002; 81: 307– 309.

40. Oddo M, Milby A, Chen, Frangos S, MacMurtrie E, Maloney‑ Wilensky E et al. Hemoglobin concentration and cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. Stroke 2009; 40(4): 1275– 1281.

41. Ďuriš K, Smrčka M, Ševčík P, Gál R, Juráň V, Neuman E et al. Možnosti využití mozkové tkáňové oxymetrie v detekci vazospazmů u pacientů po subarachnoideálním krvácení. Anest Intenziv Med 2009; 20(2): 102– 106.

42. Smrčka M, Neuman E, Ďuriš K, Svoboda T, Duba M. Monitoring PtiO2 a změny frakce kyslíku ve vdechované směsi u pacientů po těžkém subarachnoideálním krvácení. Cesk Slov Neurol N 2010; 73/ 106(6): 694– 700.

43. Ohmae E, Ouchi Y, Oda M, Suzuki T, Nobesawa S,Kanno T et al. Cerebral hemodynamic evaluation by near‑ infared time‑ resolved spectroscopy: correlation with simultaneous positron emission tomography measurements. Neuroimage 2006; 29(3): 697– 705.

44. Habalová J, Kanta M, Ehler E, Náhlovsky J, Bartoš M.Využití regionální mozkové oxymetrie jako neinvazivní metody ke sledování pacientů v neurointenzivní péči. Cesk Slov Neurol N 2010; 73/ 106(3): 285– 293.

45. Vajkoczy P, Horn P, Thome C, Munch E, Schmiedek P. Regional cerebral blood flow monitoring in dia­gnosis of delayed ischemia following aneurysmal subarachnoid hemorrhage. J Neurosurg 2003; 98(6): 1227– 1234.

46. Jaeger M, Soehle M, Schuhmann MU, Winkler D, Meixensberger J. Correlation of continuously monitored regional cerebral blood flow and brain tissue oxygen. Acta Neurochir (Wien) 2005; 147(1): 51– 56.

47. Persson L, Valtysson J, Enblad P, Warme PE, Cesarini K, Lewen A et al. Neurochemical monitoring using intracerebral microdialysis in patients with subarachnoid hemorrhage. J Neurosurg 1996; 84(4): 606– 616.

48. Nilsson OG, Brandt L, Ungersted U, Säveland H. Bedside detection of brain ischemia using intracerebral microdialysis:subarachnoid hemorrhage and delayed ischemic deterioration. Neurosurgery 1999; 45(5): 1176– 1185.

49. Skjøth‑ Rasmussen J, Schulz M, Kristensen SR, Bjerre P. Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 2004; 100(1): 8– 15.

50. Schulz MK, Wang LP, Tange M, Bjerre P. Cerebral microdialysis monitoring: determination of normal and ischemic cerebral metabolism in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 2000; 93(5): 808– 814.

51. Hejčl A, Bolcha M, Procházka J, Sameš M. Multimodální monitorování mozku u pacientů s těžkým kraniocerebrálním traumatem a subarachnoidálním krvácením v neurointenzivní péči. Cesk Slov Neurol N 2009; 72/ 105(4): 383– 387.

52. Klimo P jr, Kestle JR, MacDonald JD, Schmidt RH. Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 2004; 100(2): 215– 224.

53. Kinouchi H, Ogasawara K, Shimizu H, Mizoi K, Yoshimoto T. Prevention of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage by intraoperative cisternal fibrinolysis using tissue‑type plasminogen activator combined with continuous cisternal drainage. Neurol Med Chir (Tokyo) 2004; 44(11): 569– 577.

54. Hoh BL, Topcuoglu MA, Singhal AB, Pryor JC, Rabinov JD, Rordorf GA et al. Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery 2004; 55(4): 779– 786.

55. Dumont AS, Crowley RW, Monteith SJ, Ilodigwe D,Kassel NF, Mayer S et al. Endovascular treatment or neurosurgical clipping of ruptured intracranial aneurysms: effect on angiographic vasospasm, delayed ischemic neurological deficit, cerebral infarction, and clinical outcome. Stroke 2010; 41(11): 2519– 2524.

56. Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC et al. Cerebral arterial spasm –  a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 1983; 308(11): 619– 624.

57. Kasuya H, Hideaki O, Mikihiko T, Yoshikazu O, Tomokastu O. Efficacy and safety of nicardipine prolonged‑ release implants for preventing vasospasm in humans. Stroke 2002; 33(4): 1011– 1015.

58. Thomé C, Seiz M, Schubert A, Barth M, Vajkoczy P, Kasuya H et al. Nicardipine pellets for the prevention of cerebral vasospasm. Acta Neurochir Suppl 2011; 110(2): 209– 211.

59. van den Bergh WM, Algra A, van Kooten F, Dirven CM, van Gijn J, Vermeulen M. Magnesium sulfate in aneurysmal subarachnoid haemorrhage: a randomised controlled trial. Stroke 2005; 36(5): 1011– 1015.

60. Akdemir H, Kulakszoğlu E, Tucer B, Menkü A, Postalc L, Günald Ö. Magnesium sulfate therapy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurg Q 2009; 19(1): 35– 39.

61. Tseng MY, Czosnyka M, Richards H, Pickard JD, Kirkpatrick PJ. Effects of acute treatment with pravastatin on cerebral vasospasm, autoregulation, and delayed ischemic deficits after aneurysmal subarachnoid hemorrhage: a phase II randomised placebo‑ controlled trial. Stroke 2005; 36(8): 1627– 1632.

62. Kramer AH, Gurka MJ, Nathan B, Dumont AS, Kassel NF, Bleck TP. Statins use was not associated with less vasospasm or improved outcome after subarachnoid hemorrhage. Neurosurgery 2008; 62(2): 422– 427.

63. Haley EC jr, Kassell NF, Torner JC, Truskowski LL, Germanson TP. A randomised trial of two doses of nicardipin in aneurysmal subarachnoid hemorrhage: A report of the Cooperative Aneurysm Study. J Neurosurg 1994; 80(5): 788– 796.

64. Honma Y, Fujiwara T, Irie K, Ohkawa M, Nagao S. Morphological changes in human cerebral arteries after percutaneous transluminal angioplasty for vasospasm caused by subarachnoid hemorrhage. Neurosurgery 1995; 36(6): 1073– 1080.

65. MacDonald RL, Zhang J, Han H. Angioplasty reduces pharmacologically mediated vasoconstriction in rabbit carotid arteries with and without vasospasm. Stroke 1995; 26(6): 1053– 1060.

66. Newell DW, Elliott JP, Eskridge JM, Aaslid R. Current indications and results of cerebral angioplasty. Acta Neurochir Suppl 2001; 77: 181– 183.

67. Zwienenberg‑ Lee M, Hartman J, Rudisill N, Kennedy LM, Smith K, Eskridge J et al. Effect of prophylactic transluminal balloon angioplasty on cerebral vasospasm and outcome in patients with Fisher grade III subarachnoid hemorrhage: results of a phase II multicenter, randomized, clinical trial. Stroke 2008; 39(6): 1759– 1765.

68. Jestaedt L, Pham M, Bartsch AJ, Kunze E, Roosen K,Solymosi L et al. The impact of balkon angioplasty on the evolution of vasospasm‑related infarction after aneurysmal subarachnoid hemorrhage. Neurosurgery 2008; 62(3): 610– 617.

69. Clyde BL, Firlik AD, Kaufmann AM, Spearman MP, Yonas H. Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report. J Neurosurg 1996; 84(4): 690– 695.

70. Andaluz N, Tomsick TA, Tew JM jr, van Loveren HR,YehHS, Zuccarello M. Indications for endovascular therapy for refraktory vasospasm after aneurysmal subarrachnoid hemorrhage: experience at the University of Cincinnati. Surg Neurol 2002; 58(2): 131– 138.

71. Korenkov AI, Pahnke J, Frei K, Warzok R, Schroeder HW, Frick R et al. Treatment with nimodipine or mannitol reduces programmed cell death and infarct size following focal cerebral ischemia. Neurosurg Rev 2000; 23(3): 145– 150.

72. Biondi A, Ricciardi GK, Puybasset L, Abdennour L, Longo M, Chiras J et al. Intra‑ arterial nimodipine for the treatment of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage: preliminary results. Am J Neuroradiol 2004; 25(6): 1067– 1076.

73. Stuart RM, Helbok R, Kurtz P, Schmidt M, Fernandez L, Lee K et al. High‑dose intra‑ arterial verapamil for the treatment of cerebral vasospasm after subarachnoid hemorrhage: prolonged effects on hemodynamic parameters and brain metabolism. Neurosurgery 2011; 68(2): 337– 345.

74. Fraticelli AT, Cholley BP, Losser BP, Saint Maurice JP,Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 2008; 39(3): 893– 898.

75. Lennihan L, Mayer SA, Fink ME, Beckford A, Paik MC,Zhang H et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage: a randomized controlled trial. Stroke 2000; 31(2): 383– 391.

76. Yamakami I, Isobe K, Yamaura A. Effects of intravascular volume expansion on cerebral blood flow in patients with ruptured cerebral aneurysms. Neurosurgery 1987; 21(3): 303– 309.

77. Solomon RA, Fink ME, Lennihan L. Prophylactic volume expansion therapy for the prevention of delayed cerebral ischemia after early aneurysm surgery. Results of a preliminary trial. Arch Neurol 1988; 45(3): 325– 332.

78. Treggiari MM, Walder B, Suter PM, Romand JA. Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and haemodilution therapy following subarachnoid haemorrhage. J Neurosurg 2003; 98(5): 78– 84.

79. Darby JM, Yonas H, Marks EC, Durham S, Snyder RW, Nemoto EM. Acute cerebral blood flow response to dopamine‑induced hypertension after subarachnoid hemorrhage. J Neurosurg 1994; 80(5): 857– 864.

80. Muizelaar JP, Becker DP. Induced hypertension for the treatment of cerebral ischemia after subarachnoid hemorrhage. Direct effect on cerebral blood flow. Surg Neurol 1986; 25(4): 317– 325.

81. Dankbaar JW, Slooter AJC, Rinkel GJ, Schaaf IC. Effect of different components of triple‑ H therapy on cerebral perfusion in patients with aneurysmal subarachnoid haemorrhage: a systematic review. Crit Care 2010; 14(1): R23.

82. Thomas JE, Rosenwasser RH, Armonda RA, Harrop J, Mitchell W, Galaria I. Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humus. Stroke 1999; 30(7): 1409– 1416.

83. Agrawal A, Patir R, Kato Y, Chopra S, Sano H, Kanno T. Role of intraventricular sodium nitroprusside in vasospasm secondary to aneurysmal subarachnoid haemorrhage: a 5‑year prospective study with review of the literature. Minim Invasive Neurosurg 2009; 52(1): 5– 8.

84. Fathi AR, Pluta RM, Bakhtian KD, Qi M, Lonser RR. Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates. J Neurosurg 2011; 115(6): 1213– 1220.

85. Oldfield EH, Loomba JJ, Monteith SJ, Crowley RW, Medel R, Gress DR. Safety and pharmacokinetics of sodium nitrite in patients with subarachnoid hemorrhage: a Phase IIA study. Clinical article. J Neurosurg 2013; 119(3): 634– 641.

86. Shaw M, Vermeulen M, Murray GD, Pickard JD, Bell BA, Teasdale GM. Efficacy and safety of the endothelin, receptor antagonist TAK‑ 044 in treating subarachnoid hemorrhage: a report by the Steering Committee on behalf of the UK/ Netherlands/ Eire TAK‑ 044 Subarachnoid Haemorrhage Study Group. J Neurosurg 2000; 93(6): 992– 997.

87. Macdonald RL, Kassell NF, Mayer S. Clazosentan after subarachnoid hemorrhage (CONSCIOUS‑ 1): randomized, to overcome neurological ischemia and infarction occurring double‑blind, placebo‑ controlled phase 2 dose‑finding trial. Stroke 2008; 39(11): 3015– 3021.

88. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A et al. Clazosentan, an endothelin receptor antagonist, in patients with aneurysma subarachnoid haemorrhage undergoing surgical clipping: a randomised, double‑blind, placebo‑ controlled phase 3 trial (CONSCIOUS‑ 2). Lancet Neurol 2011; 10(7): 618– 625.

89. Macdonald RL, Higashida RT, Keller E, Mayer SA, Molyneux A, Raabe A et al. Randomized trial of clazosentan in patients with aneurysmal subarachnoid hemorrhage undergoing endovascular coiling. Stroke 2012; 43(7): 1463– 1469.

90. Vergouwen MD, Algra A, Rinkel GJ. Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta‑analysis update. Stroke 2012; 43(10): 2671– 2676.

91. Yanamoto H, Kikuchi H, Sato M, Shimizu Y, Yoneda S, Okamoto S. Therapeutic trial of cerebral vasospasm with the serine protease inhibitor, FUT‑ 175, administered in the acute stage after subarachnoid hemorrhage. Neurosurgery 1992; 30(3): 358– 363.

92. Chyatte D, Fode NC, Nichols DA, Sundt TM jr. Preliminary report: effects of high dose methylprednisolone on delayed cerebral ischemia in patients at high risk for vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 1987; 21(2): 157– 160.

93. Zhang S, Wang L, Liu M, Wu B. Tirilazad for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev 2010; 2: CD006778.

94. Schubert GA, Poli S, Schilling L, Heiland S, Thomé C.Hypothermia reduces cytotoxic edema and metabolic alterations during the acute phase of massive SAH: a diffusion weighted imaging and spectroscopy study in rats. J Neurotrauma 2008; 25(7): 841– 852.

95. Wang ZP, Chen HS, Wang FX. Influence of plasma and cerebrospinal fluid levels of ednothelin‑1 and NO in reducing cerebral vasospasm after subarachnoid hemorrhage during treatment with mild hypothermia, in a dog model. Cell Biochem Biophys 2011; 61(1): 137– 143.

96. Kawamura S, Suzuki A, Hadeishi H, Yasui N, Hatazawa J. Cerebral blood flow and oxygen metabolism during mild hypothermia in patients with subarachnoid haemorrhage. Acta Neurochir 2000; 142(10): 1117– 1121.

97. Seule MA, Muroi C, Mink S, Yonekawa Y, Keller E.Therapeutic hypothermia in patients with aneurysmal subarachnoid hemorrhage, refractory intracranial hypertension, or cerebral vasospasm. Neurosurgery 2009; 64(1): 86– 92.

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