Arginine vasopressin as a supplementary vasopressor in refractory hypertensive, hypervolemic, hemodilutional therapy in subarachnoid hemorrhage



Hypertensive, hypervolemic, and hemodilutional (HHH) therapy for vasospasm in subarachnoid hemorrhage (SAH) refractory to phenylephrine requires high doses of catecholamines, leading to adverse adrenergic effects. Arginine vasopressin (AVP) has been shown to stabilize advanced shock states while facilitating reduction of catecholamine doses, but its use has never been reported in SAH. In this retrospective study, we investigated the hemodynamic effects and feasibility of supplementary AVP in refractory HHH therapy in SAH.


Hemodynamic response (mean arterial pressure [MAP], heart rate, central venous pressure, cardiac index, systemic vascular resistance index, and end diastolic volume index) to a supplementary AVP infusion (0.01–0.04 IU/minute) was recorded within the first 24 hours in 22 patients. Secondary end points (serum sodium concentration, incidence of vasospasm, and intracranial pressure [ICP]) were compared to controls on HHH therapy with phenylephrine alone.


After initiation of AVP, MAP increased significantly compared to baseline. Phenylephrine doses decreased significantly, whereas other hemodynamic parameters remained stable. Serum sodium concentrations decreased similarly in both groups (−7 mmol/L versus −6±4 mmol/L; p=0.25). No detrimental effects on vasospasm incidence or ICP and cerebral perfusion pressure were noted.


AVP may be considered as an alternative supplementary vasopressor in refractory HHH therapy with phenylephrine in SAH. Although we did not observe any deleterious effect of AVP on cerebral circulation, close observation for development of cerebral vasospasm should be undertaken, until it is clearly demonstrated that AVP has no adverse effects on regional cerebral blood flow and symptomatic cerebral vasospasm. Our limited data suggest that low-dose AVP does not cause brain edema, but further study is merited.

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  1. 1

    Johnston SC, Selvin S, Gress DR. The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 1998;50(5):1413–1418.

    CAS  PubMed  Google Scholar 

  2. 2

    Hop JW, Rinkel GJ, Algra A, van Gijn J. Case-fatality rates and functional outcome after subarachnoid hemorrhage: a systematic review. Stroke 1997;28(3):660–664.

    CAS  PubMed  Google Scholar 

  3. 3

    Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 1985; 16(4):562–572.

    CAS  PubMed  Google Scholar 

  4. 4

    Origitano TC, Wascher TM, Reichman OH, Anderson DE. Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic hemodilution (“triple-H” therapy) after subarachnoid hemorrhage. Neurosurgery 1990;27(5):729–739; discussion 39–0.

    Article  CAS  PubMed  Google Scholar 

  5. 5

    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.

    Article  CAS  PubMed  Google Scholar 

  6. 6

    Mori K, Arai H, Nakajima K, Tajima A, Maeda M. Hemorheological and hemodynamic analysis of hypervolemic hemodilution therapy for cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 1995;26(9):1620–1626.

    CAS  PubMed  Google Scholar 

  7. 7

    Rose JC, Mayer SA. Optimizing blood pressure in neurological emergencies. Neurocrit Care 2004;1(3):287–300.

    Article  PubMed  Google Scholar 

  8. 8

    Dunser MW, Wenzel V, Mayr AJ, Hasibeder WR. Management of vasodilatory shock: defining the role of arginine vasopressin. Drugs 2003;63(3):237–256.

    Article  CAS  PubMed  Google Scholar 

  9. 9

    Landry DW, Levin HR, Gallant EM, et al. Vasopressin pressor hypersensitivity in vasodilatory septic shock. Crit Care Med 1997; 25(8):1279–1282.

    Article  CAS  PubMed  Google Scholar 

  10. 10

    Luckner G, Dunser MW, Jochberger S, et al. Arginine vasopressin in 316 patients with advanced vasodilatory shock. Crit Care Med 2005;33(11):2659–2666.

    Article  CAS  PubMed  Google Scholar 

  11. 11

    Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350(2):105–113.

    Article  CAS  PubMed  Google Scholar 

  12. 12

    Delgado TJ, Arbab MA, Warberg J, Svendgaard NA. The role of vasopressin in acute cerebral vasospasm. Effect on spasm of a vasopressin antagonist or vasopressin antiserum. J Neurosurg 1988; 68(2):266–273.

    Article  PubMed  Google Scholar 

  13. 13

    Trandafir CC, Nishihashi T, Wang A, Murakamis S, Ji X, Kurahashi K. Participation of vasopressin in the development of cerebral vasospasm in a rat model of subarachnoid haemorrhage. Clin Exp Pharmacol Physiol 2004;31(4):261–266.

    Article  CAS  PubMed  Google Scholar 

  14. 14

    Doczi T, Laszlo FA, Szerdahelyi P, Joo F. Involvement of vasopressin in brain edema formation: further evidence obtained from the Brattleboro diabetes insipidus rat with experimental subarachnoid hemorrhage. Neurosurgery 1984;14(4):436–441.

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Bemana I, Nagao S. Treatment of brain edema with a nonpeptide arginine vasopressin V1 receptor antagonist OPC-21268 in rats. Neurosurgery 1999;44(1):148–154; discussion 54–55.

    Article  CAS  PubMed  Google Scholar 

  16. 16

    Kagawa M, Nagao S, Bemana I. Arginine vasopressin receptor antagonists for treatment of vasogenic brain edema: an experimental study. J Neurotrauma 1996;13(5):273–279.

    Article  CAS  PubMed  Google Scholar 

  17. 17

    Suzuki Y, Satoh S, Oyama H, Takayasu M, Shibuya M, Sugita K. Vasopressin mediated vasodilation of cerebral arteries. J Auton Nerv Syst 1994;49 Suppl:S129-S132.

    Article  CAS  PubMed  Google Scholar 

  18. 18

    Katusic ZS, Shepherd JT, Vanhoutte PM. Vasopressin causes endothelium-dependent relaxations of the canine basilar artery. Circ Res 1984;55(5):575–579.

    CAS  PubMed  Google Scholar 

  19. 19

    Onoue H, Nakamura N, Toda N. Endothelium-dependent and-independent responses to vasodilators of isolated dog cerebral arteries. Stroke 1988;19(11):1388–1394.

    CAS  PubMed  Google Scholar 

  20. 20

    Tsugane S, Suzuki Y, Takayasu M, Shibuya M, Sugita K. Effects of vasopressin on regional cerebral blood flow in dogs. J Auton Nerv Syst 1994;49 Suppl:S133-S136.

    Article  CAS  PubMed  Google Scholar 

  21. 21

    Argenziano M, Choudhri AF, Oz MC, Rose EA, Smith CR, Landry DW. A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation 1997;96(9 Suppl):II-286–90.

    CAS  PubMed  Google Scholar 

  22. 22

    Dunser MW, Mayr AJ, Ulmer H, et al. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003;107(18):2313–2319.

    Article  PubMed  CAS  Google Scholar 

  23. 23

    Krismer AC, Wenzel V, Voelckel WG, et al. Employing vasopressin as an adjunct vasopressor in uncontrolled traumatic hemorrhagic shock. Three cases and a brief analysis of the literature. Anaesthesist 2005;54(3):220–224.

    Article  CAS  PubMed  Google Scholar 

  24. 24

    Fisher CM, Kistler JP, Davis JM. Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 1980;6(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  25. 25

    Hunt WE, Hess RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 1968; 28(1):14–20.

    Article  CAS  PubMed  Google Scholar 

  26. 26

    Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1(7905):480–484.

    Article  CAS  PubMed  Google Scholar 

  27. 27

    Yamour BJ, Sridharan MR, Rice JF, Flowers NC. Electrocardiographic changes in cerebrovascular hemorrhage. Am Heart J 1980;99(3):294–300.

    Article  CAS  PubMed  Google Scholar 

  28. 28

    Theodore J, Robin ED. Pathogenesis of neurogenic pulmonary oedema. Lancet 1975;2(7938):749–751.

    Article  CAS  PubMed  Google Scholar 

  29. 29

    Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004;32(9):1928–1948.

    Article  PubMed  Google Scholar 

  30. 30

    Jiminez E. Shock. In: Civetta JM, Taylor RW; Kirby RR., eds. Critical Care, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 1997:359–387.b

    Google Scholar 

  31. 31

    Hayashi M, Sasaki S, Tsuganezawa H, et al. Expression and distribution of aquaporin of collecting duct are regulated by vasopressin V2 receptor in rat kidney. J Clin Invest 1994;94(5):1778–1783.

    Article  CAS  PubMed  Google Scholar 

  32. 32

    Sayama T, Inamura T, Matsushima T, Inoha S, Inoue T, Fukui M. High incidence of hyponatremia in patients with ruptured anterior communicating artery aneurysms. Neurol Res 2000;22(2):151–155.

    CAS  PubMed  Google Scholar 

  33. 33

    Isotani E, Suzuki R, Tomita K, et al. Alterations in plasma concentrations of natriuretic peptides and antidiuretic hormone after subarachnoid hemorrhage. Stroke 1994;25(11): 2198–2203.

    CAS  PubMed  Google Scholar 

  34. 34

    Holmes CL, Walley KR, Chittock DR, Lehman T, Russell JA. The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 2001;27(8): 1416–1421.

    Article  CAS  PubMed  Google Scholar 

  35. 35

    Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002;96(3):576–582.

    Article  CAS  PubMed  Google Scholar 

  36. 36

    Tsuneyoshi I, Yamada H, Kakihana Y, Nakamura M, Nakano Y, Boyle WA III. Hemodynamic and metabolic effects of low-dose vasopressin infusions in vasodilatory septic shock. Crit Care Med 2001;29(3):487–493.

    Article  CAS  PubMed  Google Scholar 

  37. 37

    Malay MB, Ashton RC Jr, Landry DW, Townsend RN. Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 1999;47(4):699–703; discussion 703–705.

    Article  CAS  PubMed  Google Scholar 

  38. 38

    Suzuki Y, Satoh S, Kimura M, et al. Effects of vasopressin and oxytocin on canine cerebral circulation in vivo. J Neurosurg 1992;77(3):424–431.

    Article  CAS  PubMed  Google Scholar 

  39. 39

    Yeh CC, Wu CT, Lu CH, Yang CP, Wong CS. Early use of smalldose vasopressin for unstable hemodynamcis in an acute brain injury patient refractory to catecholamine treatment a case report. Anesth Analg 2003;97(2):577–579, TOC.

    Article  PubMed  Google Scholar 

  40. 40

    Bradley PG, Allen EK, Menon DK. Terlipressin for cerebral perfusion pressure support in a patient with septic shock. Anaesthesia 2004;59(6):619–620.

    Article  CAS  PubMed  Google Scholar 

  41. 41

    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.

    Article  CAS  PubMed  Google Scholar 

  42. 42

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

    CAS  PubMed  Google Scholar 

  43. 43

    Minciotti P, Ceravolo MG, Provinciali L. Inter-examiner variability of transcranial Doppler procedure and reports: a multicenter survey. Italian Transcranial Doppler Group. Ital J Neurol Sci 1997;18(1):21–30.

    Article  CAS  PubMed  Google Scholar 

  44. 44

    Egge A, Waterloo K, Sjoholm H, Solberg T, Ingebrigtsen T, Romner B. Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study. Neurosurgery 2001; 49(3):593–605; discussion 605–606.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Susanne Muehlschlegel.

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Muehlschlegel, S., Dunser, M.W., Gabrielli, A. et al. Arginine vasopressin as a supplementary vasopressor in refractory hypertensive, hypervolemic, hemodilutional therapy in subarachnoid hemorrhage. Neurocrit Care 6, 3–10 (2007).

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Key Words

  • Arginine vasopressin
  • brain injury
  • subarachnoid hemorrhage
  • hyponatremia
  • cerebral vasospasm
  • HHH therapy