Neurocritical Care

, Volume 21, Issue 3, pp 470–475 | Cite as

Milrinone Via Lumbar Subarachnoid Catheter for Vasospasm After Aneurysmal Subarachnoid Hemorrhage

  • Nobutake SadamasaEmail author
  • Kazumichi Yoshida
  • Osamu Narumi
  • Masaki Chin
  • Sen Yamagata
Original Article



Delayed ischemic neurological deficit (DIND) due to symptomatic vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to elucidate the safety and feasibility of intrathecal milrinone infusion via lumber subarachnoid catheter for prevention of DIND after aSAH.


We diagnosed 425 consecutive patients with aSAH who received clipping or coil embolization within 48 h after arrival. Patients with the evidence of vasospasm on CT angiography (CTA) received the milrinone therapy via lumbar subarachnoid catheter. DIND, delayed cerebral infarction (DCI), and modified Rankin scale at 3 months after SAH were used for the assessment of outcome.


Of 425 patients, 170 patients (40.0 %) with CTA-proven vasospasm received the milrinone therapy. DIND was observed in 68 patients (16.0 %), DCI in 30 patients (7.1 %), and the overall mortality was 7.2 %. In patients with WFNS grade IV and V aSAH, 26 out of 145 patients (17.9 %) were presented with DIND, 12 (8.3 %) with DCI, and the mortality was 16.0 %. No major complication related to the milrinone injection was observed.


Intrathecal milrinone injection via lumbar catheter was safe and feasible, and further randomized prospective studies are needed to confirm the effectiveness of this regimen in the patients with SAH.


Intracranial aneurysm Milrinone Subarachnoid hemorrhage Vasospasm Treatment Intrathecal injection 




Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Sadamasa N, Yoshida K, Narumi O, Chin M, Yamagata S. Prediction of mortality by hematological parameters on admission in patients with subarachnoid hemorrhage. Neurol Med Chir (Tokyo). 2011;51:745–8.CrossRefGoogle Scholar
  2. 2.
    Wolf S, Martin H, Landscheidt JF, Rodiek SO, Schürer L, Lumenta CB. Continuous selective intraarterial infusion of nimodipine for therapy of refractory cerebral vasospasm. Neurocrit Care. 2010;12:346–51.PubMedCrossRefGoogle Scholar
  3. 3.
    Liu JK, Couldwell WT. Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2005;2:124–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Kassell NF, Helm G, Simmons N, et al. Treatment of cerebral vasospasm with intra-arterial papaverine. J Neurosurg. 1992;77:848–52.PubMedCrossRefGoogle Scholar
  5. 5.
    Kimball MM, Velat GJ, Hoh BL. Participants in the international multi-disciplinary consensus conference on the critical care management of subarachnoid hemorrhage. Critical care guidelines on the endovascular management of cerebral vasospasm. Neurocrit Care. 2011;15:336–41.PubMedCrossRefGoogle Scholar
  6. 6.
    Santillan A, Knopman J, Zink W, Patsalides A, Gobin YP. Transluminal balloon angioplasty for symptomatic distal vasospasm refractory to medical therapy in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2011;69:95–101.PubMedCrossRefGoogle Scholar
  7. 7.
    Shirao S, Yoneda H, Kunitsugu I, et al. Preoperative prediction of outcome in 283 poor-grade patients with subarachnoid hemorrhage: a project of the Chugoku-Shikoku Division of the Japan Neurosurgical Society. Cerebrovasc Dis. 2010;30:105–13.PubMedCrossRefGoogle Scholar
  8. 8.
    Khajavi K, Ayzman I, Shearer D, et al. Prevention of chronic cerebral vasospasm in dogs with milrinone. Neurosurgery. 1997;40:354–62.PubMedCrossRefGoogle Scholar
  9. 9.
    Nishibuchi 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.CrossRefGoogle Scholar
  10. 10.
    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.PubMedGoogle Scholar
  11. 11.
    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
  12. 12.
    Goto Y, Yamagata S. Differences in outcome in patients with poor grade subarachnoid hemorrhage (WFNS grade IV and V): according to the perioperative management against vasospasm. No Shinkei Geka. 2004;32:579–84.PubMedGoogle Scholar
  13. 13.
    Omar MA, Mohd Haspani MS. The risk factors of external ventricular drainage-related infection at hospital Kuala Lumpur: an observational study. Malays J Med Sci. 2010;17:48–54.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Arakawa Y, Kikuta K, Hojo M, et al. Milrinone reduces cerebral vasospasm after subarachnoid hemorrhage of WFNS grade IV or V. Neurol Med Chir (Tokyo). 2004;44:393–400.CrossRefGoogle Scholar
  15. 15.
    Shirao S, Yoneda H, Ishihara H, Kajiwara K, Suzuki M; Survey Study Members of Japan Neurosurgical Society. A proposed definition of symptomatic vasospasm based on treatment of cerebral vasospasm after subarachnoid hemorrhage in Japan: consensus 2009, a project of the 25 Spasm Symposium. Surg Neurol Int. 2011;2:74.Google Scholar
  16. 16.
    Bracard S, Lebedinsky A, Anxionnat R, et al. Endovascular treatment of Hunt and Hess grade IV and V aneurysm. Am J Neuroradiol. 2002;23:953–7.PubMedGoogle Scholar
  17. 17.
    Taylor CJ, Robertson F, Brealey D, et al. Outcome in poor grade subarachnoid hemorrhage patients treated with acute endovascular coiling of aneurysms and aggressive intensive care. Neurocrit Care. 2011;14:341–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Weir RU, Marcellus ML, Do HM, Steinberg GK, Marks MP. Aneurysmal subarachnoid hemorrhage in patients with Hunt and Hess grade 4 or 5: treatment using the Guglielmi detachable coil system. Am J Neuroradiol. 2003;24:585–90.PubMedGoogle Scholar
  19. 19.
    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
  20. 20.
    Nozaki K. Intraarterial infusion therapy for cerebral vasospasm: promising but preliminary. World Neurosurg. 2012;78:223–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Lannes M, Teitelbaum J, del Pilar Cortés M, Cardoso M, Angle M. Milrinone and homeostasis to treat cerebral vasospasm associated with subarachnoid hemorrhage: the Montreal Neurological Hospital protocol. Neurocrit Care. 2012;16:354–62.Google Scholar
  22. 22.
    Taki W, Sakai N, Suzuki H; PRESAT Group. Determinants of poor outcome after aneurysmal subarachnoid hemorrhage when both clipping and coiling are available: Prospective Registry of Subarachnoid Aneurysms Treatment (PRESAT) in Japan. World Neurosurg. 2011;76:437–45.Google Scholar
  23. 23.
    Molyneux A, Kerr R, Stratton I, International Subarachnoid Aneurysm Trial (ISAT) Collaborative Group, et al. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet. 2002;360:1267–74.PubMedCrossRefGoogle Scholar
  24. 24.
    Nieuwkamp DJ, Vaartjes I, Algra A, Bots ML, Rinkel GJ. Age- and gender-specific time trend in risk of death of patients admitted with aneurysmal subarachnoid hemorrhage in the Netherlands. Int J Stroke. 2013;8 Suppl A100:90–4.Google Scholar
  25. 25.
    Treggiari MM; Participants in the International Multi-disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Hemodynamic management of subarachnoid hemorrhage. Neurocrit Care. 2011;15:329–35.Google Scholar
  26. 26.
    Al-Tamimi YZ, Bhargava D, Feltbower RG, et al. Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS). Stroke. 2012;43:677–82.PubMedCrossRefGoogle Scholar
  27. 27.
    Liu GJ, Wang ZJ, Wang YF, et al. Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage. Eur J of Clin Pharmacol. 2012;68:131–9.CrossRefGoogle Scholar
  28. 28.
    Sadamasa N, Yoshida K, Narumi O, et al. Trends in mortality rates for subarachnoid hemorrhage, from 1999 through 2008: single center experience. No Shinkei Geka. 2010;38:811–5.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nobutake Sadamasa
    • 1
    Email author
  • Kazumichi Yoshida
    • 1
  • Osamu Narumi
    • 1
  • Masaki Chin
    • 1
  • Sen Yamagata
    • 1
  1. 1.Department of NeurosurgeryKurashiki Central HospitalKurashiki CityJapan

Personalised recommendations