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

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Abstract

Introduction

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.

Methods

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.

Results

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).

Conclusion

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.

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References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  3. Rinkel GJ, Feigin VL, Algra A, van Gijn J. Circulatory volume expansion therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2004:CD000483.

  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.

    Article  PubMed  Google Scholar 

  5. Dorsch NWC. Therapeutic approaches to vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2002;8:128–33.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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).

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

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

  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.

    Article  PubMed  Google Scholar 

  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).

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  21. Suarez JI, Tarr RW, Selman WR. Aneurysmal subarachnoid hemorrhage. N Engl J Med. 2006;354:387–96.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  23. Diringer MN. Management of aneurysmal subarachnoid hemorrhage. Crit Care Med. 2009;37:432–40.

    Article  PubMed  Google Scholar 

  24. Lee KH, Lukovits T, Friedman JA. “Triple-H” therapy for cerebral vasospasm following subarachnoid hemorrhage. Neurocrit Care. 2006;4:68–76.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  26. Wijdicks EFM. The clinical practice of critical care neurology. Oxford: Oxford University Press; 2003.

    Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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).

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  31. Janjua N, Mayer SA. Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003;9:113–9.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Anesthesia, Faculty of Medicine McGill University, Montreal Neurological Hospital, Room 548, 3801 University Street, Montreal, QC, H3A 2B4, Canada

    Marcelo Lannes & Mark Angle

  2. Department of Neurology, Faculty of Medicine McGill University, Montreal Neurological Hospital, Montreal, QC, Canada

    Jeanne Teitelbaum & Mauro Cardoso

  3. Department of Radiology, Faculty of Medicine McGill University, Montreal Neurological Hospital, Montreal, QC, Canada

    Maria del Pilar Cortés

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  1. Marcelo Lannes
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Correspondence to Marcelo Lannes.

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Lannes, M., Teitelbaum, J., del Pilar Cortés, M. et al. Milrinone and Homeostasis to Treat Cerebral Vasospasm Associated with Subarachnoid Hemorrhage: The Montreal Neurological Hospital Protocol. Neurocrit Care 16, 354–362 (2012). https://doi.org/10.1007/s12028-012-9701-5

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