Effect of intrathecal milrinone injection via lumbar catheter on delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

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OBJECTIVE

Delayed cerebral ischemia (DCI) is an important complication after aneurysmal subarachnoid hemorrhage (aSAH). Although intrathecal milrinone injection via lumbar catheter to prevent DCI has been previously reported to be safe and feasible, its effectiveness remains unknown. The goal of this study was to evaluate whether intrathecal milrinone injection treatment after aSAH significantly reduced the incidence of DCI.

METHODS

The prospectively maintained aSAH database was used to identify patients treated between January 2010 and December 2015. The cohort included 274 patients, with group assignment based on treatment with intrathecal milrinone injection or not. A propensity score model was generated for each patient group, incorporating relevant patient variables.

RESULTS

After propensity score matching, 99 patients treated with intrathecal milrinone injection and 99 without treatment were matched on the basis of similarities in their demographic and clinical characteristics. There were significantly fewer DCI events (4% vs 14%, p = 0.024) in patients treated with intrathecal milrinone injection compared with those treated without it. However, there were no significant differences between the 2 groups with respect to their 90-day functional outcomes (46% vs 36%, p = 0.31). The likelihood of chronic secondary hydrocephalus, meningitis, and congestive heart failure as complications of intrathecal milrinone injection therapy was also similar between the groups.

CONCLUSIONS

In propensity score–matched groups, the intrathecal administration of milrinone via lumbar catheter showed significant reduction of DCI following aSAH, without an associated increase in complications.

ABBREVIATIONS ACA = anterior cerebral artery; aSAH = aneurysmal subarachnoid hemorrhage; DCI = delayed cerebral ischemia; DIND = delayed ischemic neurological deficit; IQR = interquartile range; mRS = modified Rankin Scale; WFNS = World Federation of Neurosurgical Societies.
Article Information

Contributor Notes

Correspondence Masaomi Koyanagi, Department of Neurosurgery, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki City, Okayama 710-0052, Japan. email: koyanagm@gmail.com.INCLUDE WHEN CITING Published online March 3, 2017; DOI: 10.3171/2016.10.JNS162227.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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References
  • 1

    Arakawa YKikuta KHojo MGoto YIshii AYamagata S: Milrinone for the treatment of cerebral vasospasm after subarachnoid hemorrhage: report of seven cases. Neurosurgery 48:7237302001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Arakawa YKikuta KHojo MGoto YYamagata SNozaki K: Milrinone reduces cerebral vasospasm after subarachnoid hemorrhage of WFNS grade IV or V. Neurol Med Chir (Tokyo) 44:3934012004

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Austin PC: Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 28:308331072009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Austin PC: An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res 46:3994242011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Austin PC: Optimal caliper widths for propensity-score matching when estimating differences in means and differences in proportions in observational studies. Pharm Stat 10:1501612011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Brown RJKumar ADhar RSampson TRDiringer MN: The relationship between delayed infarcts and angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery 72:7027082013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Connolly ES JrRabinstein AACarhuapoma JRDerdeyn CPDion JHigashida RT: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:171117372012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Crowley RWMedel RDumont ASIlodigwe DKassell NFMayer SA: Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke 42:9199232011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Dankbaar JWRijsdijk Mvan der Schaaf ICVelthuis BKWermer MJHRinkel GJE: Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neuroradiology 51:8138192009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Dhar RDiringer MN: The burden of the systemic inflammatory response predicts vasospasm and outcome after subarachnoid hemorrhage. Neurocrit Care 8:4044122008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Dreier JP: The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease. Nat Med 17:4394472011

  • 12

    Feigin VLRinkel GJAlgra AVermeulen Mvan Gijn J: Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review. Neurology 50:8768831998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Ferguson SMacdonald RL: Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery 60:6586672007

  • 14

    Fraticelli ATCholley BPLosser MRSaint Maurice JPPayen D: Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 39:8938982008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Hijdra ABrouwers PJVermeulen Mvan Gijn J: Grading the amount of blood on computed tomograms after subarachnoid hemorrhage. Stroke 21:115611611990

  • 16

    Klimo P JrKestle JRMacDonald JDSchmidt RH: Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 100:2152242004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Liu GJWang ZJWang YFXu LLWang XLLiu Y: 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 Clin Pharmacol 68:1311392012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Lo BWYFukuda HNishimura YMacdonald RLFarrokhyar FThabane L: Pathophysiologic mechanisms of brain-body associations in ruptured brain aneurysms: a systematic review. Surg Neurol Int 6:1362015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    McDougall CGSpetzler RFZabramski JMPartovi SHills NKNakaji P: The Barrow Ruptured Aneurysm Trial. J Neurosurg 116:1351442012

  • 20

    Nishiguchi MOno SIseda KManabe HHishikawa TDate 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 66:1581642010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Sadamasa NYoshida KNarumi OChin MYamagata S: Milrinone via lumbar subarachnoid catheter for vasospasm after aneurysmal subarachnoid hemorrhage. Neurocrit Care 21:4704752014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Sayama CMLiu JKCouldwell WT: Update on endovascular therapies for cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurosurg Focus 21:3E122006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Schmidt JMWartenberg KEFernandez AClaassen JRincon FOstapkovich ND: Frequency and clinical impact of asymptomatic cerebral infarction due to vasospasm after subarachnoid hemorrhage. J Neurosurg 109:105210592008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Velat GJKimball MMMocco JDHoh BL: Vasospasm after aneurysmal subarachnoid hemorrhage: review of randomized controlled trials and meta-analyses in the literature. World Neurosurg 76:4464542011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Vergouwen MDIAlgra ARinkel GJE: Endothelin receptor antagonists for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. Stroke 43:267126762012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Vergouwen MDIVermeulen MCoert BAStroes ESGRoos YBWEM: Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia. J Cereb Blood Flow Metab 28:176117702008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Vergouwen MDIVermeulen Mvan Gijn JRinkel GJEWijdicks EFMuizelaar JP: Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke 41:239123952010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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