Neurocritical Care

, Volume 16, Issue 3, pp 354–362 | Cite as

Milrinone and Homeostasis to Treat Cerebral Vasospasm Associated with Subarachnoid Hemorrhage: The Montreal Neurological Hospital Protocol

  • Marcelo Lannes
  • Jeanne Teitelbaum
  • Maria del Pilar Cortés
  • Mauro Cardoso
  • Mark Angle
Original Article



For the treatment of cerebral vasospasm, current therapies have focused on increasing blood flow through blood pressure augmentation, hypervolemia, the use of intra-arterial vasodilators, and angioplasty of proximal cerebral vessels. Through a large case series, we present our experience of treating cerebral vasospasm with a protocol based on maintenance of homeostasis (correction of electrolyte and glucose disturbances, prevention and treatment of hyperthermia, replacement of fluid losses), and the use of intravenous milrinone to improve microcirculation (the Montreal Neurological Hospital protocol). Our objective is to describe the use milrinone in our practice and the neurological outcomes associated with this approach.


Large case series based on the review of all patients diagnosed with delayed ischemic neurologic deficits after aneurysmal subarachnoid hemorrhage between April 1999 and April 2006.


88 patients were followed for a mean time of 44.6 months. An intravenous milrinone infusion was used for a mean of 9.8 days without any significant side effects. No medical complications associated with this protocol were observed. There were five deaths; of the surviving patients, 48.9 % were able to go back to their previous baseline and 75 % had a good functional outcome (modified Rankin scale ≤2).


A protocol using intravenous milrinone, and the maintenance of homeostasis is simple to use and requires less intensive monitoring and resources than the standard triple H therapy. Despite the obvious limitations of this study’s design, we believe that it would be now appropriate to proceed with formal prospective studies of this protocol.


Subarachnoid hemorrhage Cerebral vasospasm Milrinone lactate Phosphodiesterase inhibitors Cerebrovascular circulation Treatment outcome 



The study was partially supported by internal departmental funds from the Department of Anesthesia of the Montreal Neurological Hospital.


  1. 1.
    Bederson JB, Connolly ES, Batjer HH, 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. Stroke. 2009;40:994–1025.PubMedCrossRefGoogle Scholar
  2. 2.
    Kassell NF, Peerless SJ, Durward QJ, Beck DW, Drake CG, Adams HP. Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced hypertension. Neurosurgery. 1982;11:337–43.PubMedCrossRefGoogle Scholar
  3. 3.
    Rinkel GJ, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2004:CD000483.Google Scholar
  4. 4.
    Treggiari MM, Walder B, Suter PM, Romand JA. Systematic review of the prevention of delayed ischemic neurological deficits with hypertension, hypervolemia, and hemodilution therapy following subarachnoid hemorrhage. J Neurosurg. 2003;98:978–84.PubMedCrossRefGoogle Scholar
  5. 5.
    Dorsch NWC. Therapeutic approaches to vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2002;8:128–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Lynch JR, Wang H, McGirt MJ, et al. Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke. 2005;36:2024–6.PubMedCrossRefGoogle Scholar
  7. 7.
    Parra A, Kreiter KT, Williams S, et al. Effect of prior statin use on functional outcome and delayed vasospasm after acute aneurysmal subarachnoid hemorrhage: a matched controlled cohort study. Neurosurgery. 2005;56:476–84. (discussion 476–84).PubMedCrossRefGoogle Scholar
  8. 8.
    Ma L, Liu WG, Zhang JM, Chen G, Fan J, Sheng HS. Magnesium sulphate in the management of patients with aneurysmal subarachnoid haemorrhage: a meta-analysis of prospective controlled trials. Brain Inj. 2010;24:730–5.PubMedCrossRefGoogle Scholar
  9. 9.
    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 randomized placebo-controlled trial. Stroke. 2005;36:1627–32.PubMedCrossRefGoogle Scholar
  10. 10.
    Westermaier T, Stetter C, Vince GH, et al. Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, placebo-controlled, clinical study. Crit Care Med. 2010;38:1284–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Wong GK, Poon WS, Chan MT, et al. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial. Stroke. 2010;41:921–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Wong GK, Chan MT, Gin T, Poon WS. Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: current status. Acta Neurochir Suppl. 2011;110:169–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Zhang S, Wang L, Liu M, Wu B. Tirilazad for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2010:CD006778.Google Scholar
  14. 14.
    Nishiguchi M, Ono S, Iseda K, Manabe H, Hishikawa T, Date I. Effect of vasodilation by milrinone, a phosphodiesterase III inhibitor, on vasospastic arteries after a subarachnoid hemorrhage in vitro and in vivo: effectiveness of cisternal injection of milrinone. Neurosurgery. 2010;66:158–64. discussion 164.PubMedCrossRefGoogle Scholar
  15. 15.
    Khajavi K, Ayzman I, Shearer D, et al. Prevention of chronic cerebral vasospasm in dogs with milrinone. Neurosurgery. 1997;40:354–62. (discussion 362–3).PubMedCrossRefGoogle Scholar
  16. 16.
    Arakawa Y, Kikuta K, Hojo M, Goto Y, Ishii A, Yamagata S. Milrinone for the treatment of cerebral vasospasm after subarachnoid hemorrhage: report of seven cases. Neurosurgery. 2001;48:723–8. (discussion 728–30).PubMedGoogle Scholar
  17. 17.
    Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008;39:893–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Lao A, Sharma VK, Katz ML, Alexandrov AV. Diagnostic criteria for transcranial doppler ultrasound. In: McGahan JP, Goldberg BB, eds. Diagnostic ultrasound: logical approach. 2nd ed. New York: Informa Healthcare; 2008. p. 552–554.Google Scholar
  19. 19.
    Kruyt ND, Biessels GJ, de Haan RJ, et al. Hyperglycemia and clinical outcome in aneurysmal subarachnoid hemorrhage: a meta-analysis. Stroke. 2009;40:e424–e30.PubMedCrossRefGoogle Scholar
  20. 20.
    Wartenberg KE, Schmidt JM, Claassen J, et al. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med. 2006;34:617–23.PubMedCrossRefGoogle Scholar
  21. 21.
    Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354:387–96.PubMedCrossRefGoogle Scholar
  22. 22.
    Tavernier B, Decamps F, Vega E, Poidevin P, Verdin M, Riegel B. Systemic treatments of the vasospasm. Ann Fr Anesth Reanim. 2007;26:980–4.PubMedCrossRefGoogle Scholar
  23. 23.
    Diringer MN. Management of aneurysmal subarachnoid hemorrhage. Crit Care Med. 2009;37:432–40.PubMedCrossRefGoogle Scholar
  24. 24.
    Lee KH, Lukovits T, Friedman JA. “Triple-H” therapy for cerebral vasospasm following subarachnoid hemorrhage. Neurocrit Care. 2006;4:68–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Rhoney DH, McAllen K, Liu-DeRyke X. Current and future treatment considerations in the management of aneurysmal subarachnoid hemorrhage. J Pharm Pract. 2010;23:408–24.PubMedCrossRefGoogle Scholar
  26. 26.
    Wijdicks EFM. The clinical practice of critical care neurology. Oxford: Oxford University Press; 2003.Google Scholar
  27. 27.
    Dankbaar JW, Slooter AJ, 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:R23.PubMedCrossRefGoogle Scholar
  28. 28.
    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;31:383–91.PubMedCrossRefGoogle Scholar
  29. 29.
    Egge A, Waterloo K, Sjøholm H, Solberg T, Ingebrigtsen T, Romner B. Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: a clinical, prospective, randomized, controlled study. Neurosurgery. 2001;49:593–605. (discussion 605–6).PubMedGoogle Scholar
  30. 30.
    Al-Tamimi YZ, Orsi NM, Quinn AC, Homer-Vanniasinkam S, Ross SA. A review of delayed ischemic neurologic deficit following aneurysmal subarachnoid hemorrhage: historical overview, current treatment, and pathophysiology. World Neurosurg. 2010;73:654–67.PubMedCrossRefGoogle Scholar
  31. 31.
    Janjua N, Mayer SA. Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003;9:113–9.PubMedCrossRefGoogle Scholar
  32. 32.
    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;78:423–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Meyer R, Deem S, David Yanez N, Souter M, Lam A, Treggiari MM. Current practices of triple-H prophylaxis and therapy in patients with subarachnoid hemorrhage. Neurocrit Care. 2011;14:24–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Vroom MB, Pfaffendorf M, van Wezel HB, van Zwieten PA. Effect of phosphodiesterase inhibitors on human arteries in vitro. Br J Anaesth. 1996;76:122–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Hayashida N, Tomoeda H, Oda T, et al. Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass. Ann Thorac Surg. 1999;68:1661–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Chwajol M, Starke RM, Kim GH, Mayer SA, Connolly ES. Antifibrinolytic therapy to prevent early rebleeding after subarachnoid hemorrhage. Neurocrit Care. 2008;8:418–26.PubMedCrossRefGoogle Scholar
  37. 37.
    Lovelock CE, Rinkel GJ, Rothwell PM. Time trends in outcome of subarachnoid hemorrhage: population-based study and systematic review. Neurology. 2010;74:1494–501.PubMedCrossRefGoogle Scholar
  38. 38.
    Romero CM, Morales D, Reccius A, et al. Milrinone as a rescue therapy for symptomatic refractory cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2009;11:165–71.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Marcelo Lannes
    • 1
  • Jeanne Teitelbaum
    • 2
  • Maria del Pilar Cortés
    • 3
  • Mauro Cardoso
    • 2
  • Mark Angle
    • 1
  1. 1.Department of Anesthesia, Faculty of Medicine McGill UniversityMontreal Neurological HospitalMontrealCanada
  2. 2.Department of Neurology, Faculty of Medicine McGill UniversityMontreal Neurological HospitalMontrealCanada
  3. 3.Department of Radiology, Faculty of Medicine McGill UniversityMontreal Neurological HospitalMontrealCanada

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