Skip to main content
Log in

Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage

  • Original Article
  • Published:
Neurocritical Care Aims and scope Submit manuscript

Abstract

Background

The incidence of cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) is reduced by oral nimodipine but acute effects of the drug may include a significant decrease in mean arterial blood pressure (MAP). A dose reduction or discontinuation of the drug is recommended if recurrent MAP drops occur. The aim of our study was to evaluate the frequency and clinical significance of nimodipine dose modifications in patients suffering from aSAH.

Methods

270 patients were included in our retrospective analysis of consecutively collected data of patients suffering from aSAH. The local treatment protocol was in accordance to national and international guidelines. Nimodipine was intended to be applied orally with a dosage of 60 mg every 4 h.

Results

Only 43.6 % of patients eligible for vasospasm prophylaxis with nimodipine received the full daily dose of 60 mg every 4 h. In 28.6 %, the dose had to be reduced by 50 % due to a significant reduction in blood pressure after administration and/or high dose of catecholamines. In 27.7 % of patients, oral administration of the drug was discontinued for the same reason. Dose reduction and discontinuation occurred with a significantly higher frequency in patients in poor clinical condition. Application of the full nimodipine dosage decreased the risk of unfavorable clinical outcome in multivariate analysis (OR 0.895, p = 0.029).

Conclusions

Our results show that dose reduction or discontinuation of nimodipine due to changes in MAP occur frequently in clinical routine and may be associated with unfavorable clinical outcome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Linn FH, Rinkel GJ, Algra A, van Gijn J. Incidence of subarachnoid hemorrhage: role of region, year, and rate of computed tomography: a meta-analysis. Stroke. 1996;27:625–9.

    Article  CAS  PubMed  Google Scholar 

  2. Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010;41:e519–36.

    Article  PubMed  Google Scholar 

  3. Scott RB, Eccles F, Molyneux AJ, Kerr RS, Rothwell PM, Carpenter K. Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT). Stroke. 2010;41:1743–7.

    Article  PubMed  Google Scholar 

  4. Kassell NF, Haley EC Jr, Apperson-Hansen C, Alves WM. Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg. 1996;84:221–8.

    Article  CAS  PubMed  Google Scholar 

  5. Etminan N, Vergouwen MD, Ilodigwe D, Macdonald RL. Effect of pharmaceutical treatment on vasospasm, delayed cerebral ischemia, and clinical outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Cerebral Blood Flow Metab. 2011;31:1443–51.

    Article  CAS  Google Scholar 

  6. Frontera JA, Ahmed W, Zach V, et al. Acute ischaemia after subarachnoid haemorrhage, relationship with early brain injury and impact on outcome: a prospective quantitative MRI study. J Neurol Neurosurg Psychiatry. 2015;86:71–8.

    Article  PubMed  Google Scholar 

  7. Crowley RW, Medel R, Dumont AS, et al. Angiographic vasospasm is strongly correlated with cerebral infarction after subarachnoid hemorrhage. Stroke. 2011;42:919–23.

    Article  PubMed  Google Scholar 

  8. Rabinstein AA, Friedman JA, Nichols DA, et al. Predictors of outcome after endovascular treatment of cerebral vasospasm. AJNR Am J Neuroradiol. 2004;25:1778–82.

    PubMed  Google Scholar 

  9. Vergouwen MD, Vermeulen M, Roos YB. Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: is angiographic vasospasm an epiphenomenon? Stroke. 2009;40:e39.

    Article  PubMed  Google Scholar 

  10. Ostergaard L, Aamand R, Karabegovic S, et al. The role of the microcirculation in delayed cerebral ischemia and chronic degenerative changes after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2013;33:1825–37.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Woitzik J, Dreier JP, Hecht N, et al. Delayed cerebral ischemia and spreading depolarization in absence of angiographic vasospasm after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2012;32:203–12.

    Article  PubMed  Google Scholar 

  12. Wilson DA, Nakaji P, Abla AA, et al. A simple and quantitative method to predict symptomatic vasospasm after subarachnoid hemorrhage based on computed tomography: beyond the Fisher scale. Neurosurgery. 2012;71:869–75.

    Article  PubMed  Google Scholar 

  13. Abla AA, Wilson DA, Williamson RW, et al. The relationship between ruptured aneurysm location, subarachnoid hemorrhage clot thickness, and incidence of radiographic or symptomatic vasospasm in patients enrolled in a prospective randomized controlled trial. J Neurosurg. 2014;120:391–7.

    Article  PubMed  Google Scholar 

  14. Jang YG, Ilodigwe D, Macdonald RL. Metaanalysis of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2009;10:141–7.

    Article  CAS  PubMed  Google Scholar 

  15. Macdonald RL, Kassell NF, Mayer S, et al. Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial. Stroke. 2008;39:3015–21.

    Article  CAS  PubMed  Google Scholar 

  16. Wang X, Li YM, Li WQ, Huang CG, Lu YC, Hou LJ. Effect of clazosentan in patients with aneurysmal subarachnoid hemorrhage: a meta-analysis of randomized controlled trials. PLoS One. 2012;7:e47778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Barker FG 2nd, Ogilvy CS. Efficacy of prophylactic nimodipine for delayed ischemic deficit after subarachnoid hemorrhage: a metaanalysis. J Neurosurg. 1996;84:405–14.

    Article  PubMed  Google Scholar 

  18. Pickard JD, Murray GD, Illingworth R, et al. Effect of oral nimodipine on cerebral infarction and outcome after subarachnoid haemorrhage: British aneurysm nimodipine trial. BMJ. 1989;298:636–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. van Gijn J, Kerr RS, Rinkel GJ. Subarachnoid haemorrhage. Lancet. 2007;369:306–18.

    Article  PubMed  Google Scholar 

  20. Roos YB, Levi M, Carroll TA, Beenen LF, Vermeulen M. Nimodipine increases fibrinolytic activity in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2001;32:1860–2.

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012;43:1711–37.

    Article  PubMed  Google Scholar 

  23. Steiner T, Juvela S, Unterberg A, et al. European Stroke Organization guidelines for the management of intracranial aneurysms and subarachnoid haemorrhage. Cerebrovasc Dis. 2013;35:93–112.

    Article  PubMed  Google Scholar 

  24. Choi HA, Ko SB, Chen H, et al. Acute effects of nimodipine on cerebral vasculature and brain metabolism in high grade subarachnoid hemorrhage patients. Neurocrit Care. 2012;16:363–7.

    Article  CAS  PubMed  Google Scholar 

  25. Diringer MN, Bleck TP, Claude Hemphill J 3rd, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocrit Care. 2011;15:211–40.

    Article  PubMed  Google Scholar 

  26. Frontera JA, Fernandez A, Schmidt JM, et al. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009;40:1963–8.

    Article  PubMed  Google Scholar 

  27. Weidauer S, Lanfermann H, Raabe A, Zanella F, Seifert V, Beck J. Impairment of cerebral perfusion and infarct patterns attributable to vasospasm after aneurysmal subarachnoid hemorrhage: a prospective MRI and DSA study. Stroke. 2007;38:1831–6.

    Article  PubMed  Google Scholar 

  28. Burch CM, Wozniak MA, Sloan MA, et al. Detection of intracranial internal carotid artery and middle cerebral artery vasospasm following subarachnoid hemorrhage. J Neuroimaging. 1996;6:8–15.

    Article  CAS  PubMed  Google Scholar 

  29. Lindegaard KF, Nornes H, Bakke SJ, Sorteberg W, Nakstad P. Cerebral vasospasm after subarachnoid haemorrhage investigated by means of transcranial Doppler ultrasound. Acta Neurochir Suppl. 1988;42:81–4.

    CAS  PubMed  Google Scholar 

  30. Vergouwen MD, Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid H. Vasospasm versus delayed cerebral ischemia as an outcome event in clinical trials and observational studies. Neurocritical care 2011;15:308–11.

  31. Etminan N, Vergouwen MD, Macdonald RL. Angiographic vasospasm versus cerebral infarction as outcome measures after aneurysmal subarachnoid hemorrhage. Acta Neurochir Supp. 2013;115:33–40.

    Google Scholar 

  32. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19:604–7.

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. Porchet F, Chiolero R, de Tribolet N. Hypotensive effect of nimodipine during treatment for aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien). 1995;137:62–9.

    Article  CAS  Google Scholar 

  36. Soppi V, Kokki H, Koivisto T, et al. Early-phase pharmacokinetics of enteral and parenteral nimodipine in patients with acute subarachnoid haemorrhage—a pilot study. Eur J Clin Pharmacol. 2007;63:355–61.

    Article  CAS  PubMed  Google Scholar 

  37. Fergusen S, Macdonald RL. Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2007;60:658–67 discussion 67.

    Article  PubMed  Google Scholar 

  38. Shen J, Pan JW, Fan ZX, Xiong XX, Zhan RY. Dissociation of vasospasm-related morbidity and outcomes in patients with aneurysmal subarachnoid hemorrhage treated with clazosentan: a meta-analysis of randomized controlled trials. J Neurosurg. 2013;119:180–9.

    Article  PubMed  Google Scholar 

  39. Kobayashi T, Mori Y. Ca2+ channel antagonists and neuroprotection from cerebral ischemia. Eur J Pharmacol. 1998;363:1–15.

    Article  CAS  PubMed  Google Scholar 

  40. Pisani A, Calabresi P, Tozzi A, D’Angelo V, Bernardi G. L-type Ca2+ channel blockers attenuate electrical changes and Ca2+ rise induced by oxygen/glucose deprivation in cortical neurons. Stroke. 1998;29:196–201 discussion 2.

    Article  CAS  PubMed  Google Scholar 

  41. Duzenli S, Bakuridze K, Gepdiremen A. The effects of ruthenium red, dantrolene and nimodipine, alone or in combination, in NMDA induced neurotoxicity of cerebellar granular cell culture of rats. Toxicol In Vitro. 2005;19:589–94.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are grateful to Norbert Baro for assistance and data management.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nora Sandow.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sandow, N., Diesing, D., Sarrafzadeh, A. et al. Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care 25, 29–39 (2016). https://doi.org/10.1007/s12028-015-0230-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12028-015-0230-x

Keywords

Navigation