Neurocritical Care

, Volume 4, Issue 1, pp 68–76 | Cite as

“Triple-H” therapy for cerebral vasospasm following subarachnoid hemorrhage

  • Kendall H. Lee
  • Timothy Lukovits
  • Jonathan A. FriedmanEmail author


The combination of induced hypertension, hypervolemia, and hemodilution (triple-H therapy) is often utilized to prevent and treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Although this paradigm has gained widespread acceptance over the past 20 years, the efficacy of triple-H therapy and its precise role in the management of the acute phase of SAH remains uncertain. In addition, triple-H therapy may carry significant medical morbidity, including pulmonary edema, myocardial ischemia, hyponatremia, renal medullary washout, indwelling catheter-related complications, cerebral hemorrhage, and cerebral edema. This review examines the evidence underlying the implementation of triple-H therapy, and makes practical recommendations for the use of this therapy in patients with aneurysmal SAH.

Key Words

Subarchnoid hemorrhage cerebrovascular disease vasospasm aneurysm triple-H therapy 


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  1. 1.
    Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 1985; 16(4):562–572.PubMedGoogle Scholar
  2. 2.
    Kassell NF, Torner JC, Haley EC Jr., Jane JA, Adams HP, Kongable GL. The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1: Overall management results. J Neurosurg 1990;73(1):18–36.PubMedGoogle Scholar
  3. 3.
    Allen GS, Ahn HS, Preziosi TJ, et al. Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 1983;308(11):619–624.PubMedCrossRefGoogle Scholar
  4. 4.
    Heros RC, Zervas NT, Varsos V. Cerebral vasospasm after subarachnoid hemorrhage: an update. Ann Neurol 1983;14(6):599–608.PubMedCrossRefGoogle Scholar
  5. 5.
    Allen GS, Ahn HS, Preziosi TJ, et al. Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 1983;308(11):619–624.PubMedCrossRefGoogle Scholar
  6. 6.
    Kassell NF, Peerless SJ, Durward QJ, Beck DW, Drake CG, Adams HP. Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 1982;11(3):337–343.PubMedCrossRefGoogle Scholar
  7. 7.
    Mayberg MR, Batjer HH, Dacey R, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Circulation 1994; 90(5):2592–2605.PubMedGoogle Scholar
  8. 8.
    Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6(1):1–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Reilly C, Amidei C, Tolentino J, Jahromi BS, Macdonald RL. Clot volume and clearance rate as independent predictors of vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg 2004;101(2):255–261.PubMedGoogle Scholar
  10. 10.
    Friedman JA, Goerss SJ, Meyer FB, et al. Volumetric quantification of fisher Grade 3 aneurysmal subarachnoid hemorrhage: a novel method to predict symptomatic vasospasm on admission computerized tomography scans. J Neurosurg 2002;97(2):401–407.PubMedGoogle Scholar
  11. 11.
    Millikan CH. Cerebral vasospasm and ruptured intracranial aneurysm. Arch Neurol 1975;32(7):433–449.PubMedGoogle Scholar
  12. 12.
    Millikan CH. Cerebral vasospasm associated with subarachnoid hemorrhage due to ruptured intracranial aneurysm. Trans Am Neurol Assoc 1974;99:1–23.PubMedGoogle Scholar
  13. 13.
    Bergvall V, Steiner L, Foster DMC. Early pattern of cerebral circulatory disturbances following subarachnoid haemorrhage. Neuroradiology 1973;5:24–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Ferguson GG, Harper AM, Fitch W. Cerebral Blood flow measurements after spontaneous subarachnoid haemorrhage. Eur Neurol 1972;8:15–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Hellinger FR, Bloor BM, Mc CJ. Total cerebral blood flow and oxygen consumption using the dye-dilution method. A study of occulusive arterial disease and cerebral infarction. J Neurosurg 1962;19:964–970.PubMedGoogle Scholar
  16. 16.
    Morawetz RB, DeGirolami U, Ojemann RG, Marcoux FW, Crowell RM. Cerebral blood flow determined by hydrogen clearance during middle cerebral artery occlusion in unanesthetized monkeys. Stroke 1978;9(2):143–149.PubMedGoogle Scholar
  17. 17.
    Morawetz RB, Jones TH, Ojemann RG, Marcoux FW, DeGirolami U, Crowell RM. Regional cerebral blood flow during temporary middle cerebral artery occlusion in waking monkeys. Acta Neurol Scand Suppl 1977;64:114–115.PubMedGoogle Scholar
  18. 18.
    Kosnik Ej, Hunt WE. Postoperative hypertension in the management of patients with intracranial arterial aneurysms. J Neurosurg 1976;45(2):148–154.PubMedGoogle Scholar
  19. 19.
    Awad IA, Carter LP, Spetzler RE, Medina M, Williams FC, Jr. Clinical vasospasm after subarachnoid hemorrhage: response to hypervolemic hemodilution and arterial hypertension. Stroke 1987;18(2):365–372.PubMedGoogle Scholar
  20. 20.
    Friedman JA, Pichelmann MA, Piepgras DG, et al. Pulmonary complications of aneurysmal subarachnoid hemorrhage. Neurosurgery 2003;52(5):1025–1031; discussion 1031–1032.PubMedCrossRefGoogle Scholar
  21. 21.
    Aaslid R. Hemodynamics of cerebrovascular spasm. Acta Neurochir Suppl 1999;72:47–57.PubMedGoogle Scholar
  22. 22.
    Joseph M, Ziadi S, Nates J, Dannenbaum M, Malkoff M. Increases in cardiac output can reverse flow deficits from vasospasm independent of blood pressure: a study using xenon computed tomographic measurement of cerebral blood flow. Neurosurgery 2003;53(5):1044–1051; discussion 1051–1052.PubMedGoogle Scholar
  23. 23.
    Barry KJ, Gogiian MA, Stein BM. Small animal model for investigation of subarachnoid hemorrhage and cerebral vasospasm. Stroke 1979;10(5):538–541.PubMedGoogle Scholar
  24. 24.
    Delgado TJ, Arbab MA, Diemer NH, Svendgaard NA. Subarachnoid hemorrhage in the rat: cerebral blood flow and glucose metabolism during the late phase of cerebral vasospasm. J Cereb Blood Flow Metab 1986;6(5):590–599.PubMedGoogle Scholar
  25. 25.
    Solomon RA, Antunes JL, Chen RY, Bland L, Chien S. Decrease in cerebral blood flow in rats after experimental subarachnoid hemorrhage: a new animal model. Stroke 1985;16(1):58–64.PubMedGoogle Scholar
  26. 26.
    Solomon RA, Lovitz RL, Hegemann MT, Schuessler GB, Young WL, Chien S, Regional cerebral metabolic activity in the rat following experimental subarachnoid hemorrhage. Cereb Blood Flow Metab 1987;7(2):193–198.Google Scholar
  27. 27.
    Chan RC, Durity FA, Thompson GB, Nugent RA, Kendall M. The role of the prostacyclin-thromboxane system in cerebral vasospasm following induced subarachnoid hemorrhage in the rabbit. J Neurosurg 1984;61(6):1120–1128.PubMedGoogle Scholar
  28. 28.
    Kapp J, Mahaley MS, Jr, Odom GL. Cerebral arterial spasm. l. Evaluation of experimental variables affecting the diameteor of the exposued basilar artery. J Neurosurg 1968;29(4):331–338.PubMedGoogle Scholar
  29. 29.
    Kapp J, Mahaley MS, Jr., Odom GL. Cerebral arterial spasm. 3. Partial purification and characterization of a spasmogenic substance in feline platelets. J Neurosurg 1968;29(4):350–356.PubMedGoogle Scholar
  30. 30.
    Kapp J, Mahaley MS, Jr., Odom GL. Cerebral arterial spasm. 2. Experimental evaluation of mechanical and humoral factors in pathogenesis. J Neurosurg 1962;29(4):339–349.Google Scholar
  31. 31.
    Takemae T, Branson PJ, Alksne JF. Antimal proliferation of cerebral arteries after subarachnoid blood injection in pigs. J Neurosurg 1984;61(3):494–500.PubMedGoogle Scholar
  32. 32.
    Lougheed WM, Tom M. A method of introducing blood into the subarachnoid space in the region of the circle of Willis in dogs. Can J Surg 1961;4:329–337.PubMedGoogle Scholar
  33. 33.
    Wilkins RH, Levitt P. Intracranial arterial spasm in the dog. A chronic experimental model. J Neurosurg 1970;33(3):260–269.PubMedGoogle Scholar
  34. 34.
    Echlin FA. Spasm of basilar and vertebral arteries caused by experimental subarachnoid hemorrhage. J Neurosurg 1965; 23(1):1–11.PubMedGoogle Scholar
  35. 35.
    Megyesi JF, Vollrath B, Cook DA, Findlay JM. In vivo animal models of cerebral vasospasm: a review. Neurosurgery 2000;46(2) 448–460; discussion 460–461.PubMedCrossRefGoogle Scholar
  36. 36.
    Fukuroda T, Nishikibe M, Ohta Y, et al. Analysis of responses to endothelins in isolated porcine blood vessels by using a novel endothelin antagonist, BQ-153. Life Sci 1992;50(15): PL107–112.PubMedCrossRefGoogle Scholar
  37. 37.
    Takahashi S, Kassell NF, Toshima M, Dougherty DA, Foley PL, Lee KS. Effect of U88999E on experimental cerebral vasospasm in rabbits. Neurosurgery 1993;32(2):281–288 discussion 288.PubMedCrossRefGoogle Scholar
  38. 38.
    White RP. Responses of isolated cerebral arteries to vasoactive agents. Neurosurg Clin N Am 1990;1(2):401–415.PubMedGoogle Scholar
  39. 39.
    Weir B, Macdonald RL, Stoodley M. Etiology of cerebral vasospasm. Acta Neurochir Suppl 1999;72:27–46.PubMedGoogle Scholar
  40. 40.
    Macdonald RL, Weir BK. A review of hemoglobin and the pathogenesis of cerebral vasospasm. Stroke 1991;22(8):971–982.PubMedGoogle Scholar
  41. 41.
    Macodnald RL. Pathophysiology and molecular genetics of vasospasm. Acta Neurochir Suppl 2001;77:7–11.Google Scholar
  42. 42.
    Osaka K. Prolonged vasospasm produced by the breakdown products of erythrocytes. J Neurosurg 1977;47(3):403–411.PubMedGoogle Scholar
  43. 43.
    Dora E, Feher E, Farago M, Horvath I, Szabo C. Mechanism of hemoglobin-induced spasm in the isolated middle cerebral artery of the cat. Adv Exp Med Biol 1989;248:533–542.PubMedGoogle Scholar
  44. 44.
    Mayberg MR, Okada T, Bark DH. The role of hemoglobin in arterial narrowing after subarachnoid hemorrhage. J Neurosurg 1990;72(4):634–640.PubMedGoogle Scholar
  45. 45.
    Fuwa I, Mayberg M, Gadjusek C, Harada T, Luo Z. Enhanced secretion of endothelin by endothelial cells in response to hemoglobin. Neurol Med Chir (Tokyo) 1993:33(11):739–743.CrossRefGoogle Scholar
  46. 46.
    Rubanyi M. Endothelium-derived relaxing and contracting factors. J Cell Biochem 1991;46(1):27–36.PubMedCrossRefGoogle Scholar
  47. 47.
    Misra HP, Fridovich I. The generation of superoxide radical during the autoxidation of hemoglobin. J Biol Chem 1972;247(21):6960–6962.PubMedGoogle Scholar
  48. 48.
    Mayberg MR. Cerebral vasospasm. Neurosurgery Clinics of North America 1998;9:615–627.PubMedGoogle Scholar
  49. 49.
    Seifert V, Stolke D, Reale E. Ultrastructural changes of the basilar artery following experimental subarachnoid haemorrhage. A morphological study on the pathogenesis of delayed cerebral vasospasm. Acta Neurochir (Wien) 1989;100(3–4):164–171.CrossRefGoogle Scholar
  50. 50.
    Mayberg MR, Okada T, Bark DH. The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage. J Neurosurg 1990;72(4):626–633.PubMedGoogle Scholar
  51. 51.
    Corsten L, Raja A, Guppy K, et al. Contemporary management of subarachnoid hemorrhage and vasospasm: The UIC experience. Surg Neurol 2001;56(3):140–148; discussion 148–150.PubMedCrossRefGoogle Scholar
  52. 52.
    Pasqualin A. Epidemiology and pathophysiology of cerebral vasospasm following subarachnoid hemorrhage. J Neurosurg Sci 1998;42(1 Suppl 1):15–21.PubMedGoogle Scholar
  53. 53.
    Rabinstein AA, Friedman JA, Nichols DA, et al. Predictors of outcome after endovascular treatment of cerebral vasospasm. AJNR Am J Neuroradiol 2004;25(10):1778–1782.PubMedGoogle Scholar
  54. 54.
    Minhas PS, Menon DK, Smielewski P, et al. Positron emission tomographic cerebral perfusion disturbances and transcranial Doppler findings among patients with neurological deterioration after subarachnoid hemorrhage. Neurosurgery 2003;52(5):1017–1022; discussion 1022–1024.PubMedCrossRefGoogle Scholar
  55. 55.
    Macdonald RL, Rosengart A, Huo D, Karrison T. Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage. J Neurosurg 2003;99(4):644–652.PubMedGoogle Scholar
  56. 56.
    Adams HP, Jr, Kassell NF, Torner JC, Haley EC, Jr. Predicting cerebral ischemia after aneurysmal subarachnoid hemorrhage influences of clinical condition, CT results, and antifibrionolytic therapy. A report of the Cooperative Aneurysm Study. Neurology 1987;37(10):1586–1591.PubMedGoogle Scholar
  57. 57.
    Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6:1–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Hijdra A, Brouwers PJAM, Vermeulen M, van Gijn J. Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 1990;21:1156–1161.PubMedGoogle Scholar
  59. 59.
    Claassen J, Bernadini GL, Kreiter K, Bates J, Du YE, Copeland D, Connolly ES, Mayer SA. Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage. Stroke 2001;32:2012–2020.PubMedCrossRefGoogle Scholar
  60. 60.
    Rinkel GL, Wijdicks EF, Vermeulen M, Hasan D, Brouwers PJ, van Gijn J. The clinical course of perimesencephalic nonaneurysmal subarachnoid hemorrhage. Ann Neurol 1991;29(5):463–468.PubMedCrossRefGoogle Scholar
  61. 61.
    Rinkel GJ, Wijdicks EF, Vermeulen M, et al. Nonaneurysmal perimesencephalic subarachnoid hemorhage: Ct and MR patterns that differ from aneurysmal rupture. AJNR Am J Neuroradiol 1991;12(5):829–834.PubMedGoogle Scholar
  62. 62.
    Sloan MA, Alexandrov AV, Tegeler CH, et al. Assessment: transcranial Doppler ultrasonography: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2004;62(9):1468–1481.PubMedGoogle Scholar
  63. 63.
    Venkatesh B, Shen Q, Lipman J. Continuous measurement of cerebral blood flow velocity using transcranial Doppler reveals significant moment-to-moment variability of data in healthy volunteers and in patients with subarachnoid Hemorrhage. Crit Care Med 2002;30(3):563–569.PubMedCrossRefGoogle Scholar
  64. 64.
    Manno EM, Gress DR, Schwamm LH, Diringer MN, Ogilvy CS. Effects of induced hypertension on transcranial Doppler ultrasound velocities of patients after subarachnoid hemorrhage. Stroke 1998;29(2):422–428.PubMedGoogle Scholar
  65. 65.
    Giller CA, Purdy P, Giller A, Batjer HH, Kopitnik T. Elevated transcranial Doppler ultrasound velocities following therapeutic arterial dilation. Stroke 1995;26(1):123–127.PubMedGoogle Scholar
  66. 66.
    Sviri GE, Lewis DH, Correa R, Britz GW, Douville CM, Newell DW. Basilar artery vasospasm and delayed posterior circulation ischemia after aneurysmal subarachnoid hemorrhage. Stroke 2004;35(8):1867–1872.PubMedCrossRefGoogle Scholar
  67. 67.
    Sloan MA., Burch CM, Wozniak MA, et al. Transcranial Doppler detection of vertebrobasilar vasospasm following subarachnoid hemorrhage. Stroke 1994;25(11):2187–2197.PubMedGoogle Scholar
  68. 68.
    Lysakowski C, Walder B, Costanza MC, Tramer MR. Transcranial Doppler versus angiography in patients with vasospasm due to a ruptured cerebral aneurysm: A systematic review. Stroke 2001;32(10):2292–228.PubMedCrossRefGoogle Scholar
  69. 69.
    Rabinstein AA, Friedman JA, Weigand SD, et al. Predictors of cerebral infarction in aneurysmal subarachnoid hemorrhage. Stroke 2004;35(8):1862–1866.PubMedCrossRefGoogle Scholar
  70. 70.
    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):1237–1247; discussion 1247–1248.PubMedCrossRefGoogle Scholar
  71. 71.
    Mascia L., Fedorko L., terBrugge K, et al. The accuracy of transcranial Doppler to detect vasospasm in patients with aneurysmal subarachnoid hemorrhage. Intensive Care Med 2003;29(7):1088–1094.PubMedCrossRefGoogle Scholar
  72. 72.
    Grosset DG, Straiton J, McDonald I, Bullock R. Angiographic and Doppler diagnosis of cerebral artery vasospasm following subarachnoid haemorrhage. Br J Neurosurg 1993;7(3):291–298.PubMedCrossRefGoogle Scholar
  73. 73.
    Grosset DG, Squire IB, Georgiadis D, Lees KR. Repeatability testing for transcranial Doppler sonography. Clin Sci (Lond) 1993; 85(6):761–762.Google Scholar
  74. 74.
    Anderson GB, Ashforth R, Steinke DE, findlay JM. CT angiography for the detection of cerebral vasospasm in patients with acute subarachnoid hemorrhage. AJNR Am J Neuroadiol 2000;21(6):1011–1015.Google Scholar
  75. 75.
    Otawara Y, Ogasawara K, Ogawa A, Sasaki M, Takahashi K. Evaluation of vasospasm after subarachnoid hemorrhage by use of multislice computed tomographic angiography. Neurosurgery 2002;51(4):939–942; discussion 942–943.PubMedCrossRefGoogle Scholar
  76. 76.
    Solomon RA, Fink ME, Lennihan L. Early aneurysm surgery and prophylactic hypervolemic hypertensive therapy for the treatment of aneurysmal subarachnoid hemorrhage. Neurosurgery 1988;23(6):699–704.PubMedCrossRefGoogle Scholar
  77. 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.PubMedGoogle Scholar
  78. 78.
    Lennihan L, Mayer SA, Fink ME, et al. Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorhage: a randomized controlled trial. Stroke 2000;31(2):383–391.PubMedGoogle Scholar
  79. 79.
    Mayer SA, Solomon RA, Fink ME, et al. Effect of 5% albumin solution of sodium balance and blood volume after subarachnoid hemorrhage. Neurosurgery 1998;42(4):759–767; discussion 767–768.PubMedCrossRefGoogle Scholar
  80. 80.
    Rabinstein AA, Pichelmann MA, Friedman JA, et al. Symptomatic vasoapasm and outcomes following aneurosymal subarachnoid hemorrhage: a comparison between surgical repair and endovascular coil occlusion. J Neurosurg 2003;98(2):319–325.PubMedGoogle Scholar
  81. 81.
    Hoh BL, Carter BS, Ogilvy CS. Risk of hemorrhage from unsecured, unruptured anuerysms during and after hypertensive hypervolemic therapy. Neurosurgery 2002;50(6):1207–1211: discussion 1211–1212.PubMedCrossRefGoogle Scholar
  82. 82.
    Badjatia N, Topcuoglu MA, Pryor JC, et al. Preliminary experience with intra-arterial nicardipine as a treatment for cerebral vasospasm. AJNR Am J Neuroradiol 2004;25(5):819–826.PubMedGoogle Scholar
  83. 83.
    Shimoda M, Oda S, Tsugane R, Sato O. Intracranial complications of hypervolemic therapy in patients with a delayed ischemic deficit attributed to vasospasm. J Neurosurg 1993;78(3):423–429.PubMedCrossRefGoogle Scholar
  84. 84.
    Rosenwasser RH, Jallo JI, Getch CC, Liebman KE. Complications of Swan-Ganz catheterization for hemodynamic monitoring in patients with subarachnoid hemorrhage. Neurosurgery 1995;37(5):872–875; discussion 875–876.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Kendall H. Lee
    • 1
  • Timothy Lukovits
    • 2
  • Jonathan A. Friedman
    • 1
    Email author
  1. 1.Section of NeurosurgeryDartmouth Hitchcock Medical CenterLebanon
  2. 2.Department of NeurologyDartmouth Hitchcock Medical CenterLebanon

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