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Antifibrinolytic therapy in the management of aneurismal subarachnoid hemorrhage revisited. A meta-analysis

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Abstract

Background

To reassess the use of antifibrinolytics (AF) in the management of aneurysmal subarachnoid hemorrhage (SAH) in the setting of present-day treatment strategies.

Method

The authors conducted a systematic review of the literature and a meta-analysis. They reviewed the PubMed database and conducted a manual review of article bibliographies.

Results

Using a pre-specified search strategy, 17 relevant studies involving a total of 2,872 patients with SAH at baseline, from which data of 1,380 patients having received AF, were included in a meta-analysis. Pooled odds ratios of the impact of AF on functional outcomes, rebleeding, and cerebral infarction were calculated. Short-term use of AF (72 h or less) associated with medical prevention of ischemic deficit seems to yield better results on functional outcome than long-term use of AF, especially if not associated with a medical prevention of ischemic deficit. The risk of cerebral infarction is not increased by the short-term use of AF and the risk of rebleeding is decreased independently of the length of AF use.

Conclusions

The use of AF should be reconsidered in the setting of modern-era treatment strategies, as the short-term use associated with medical prevention of ischemic deficit decreases the rate of rebleeding and does not increase the risk of cerebral infarction, thus potentially yielding better protection against poor functional outcome.

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References

  1. Ameen AA, Illingworth R (1981) Anti-fibrinolytic treatment in the preoperative management of subarachnoid hemorrhage caused by ruptured intracranial aneurysm. J Neurol Neurosurg Psy 44:220–226

    Article  CAS  Google Scholar 

  2. Chandra B (1978) Treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm with tranexamic acid: a double-blind clinical trial. Ann Neurol 3:502–504

    Article  PubMed  CAS  Google Scholar 

  3. Chowdhary UM, Carey PC, Hussein MM (1979) Prevention of early recurrence of spontaneous subarachnoid haemorrhage by epsilon-aminocaproic acid. Lancet 1:741–743

    Article  PubMed  CAS  Google Scholar 

  4. Feigin VL, Rinkel GJ, Algra A, Vermeulen M, van Gijn J (1998) Calcium antagonists in patients with aneurysmal subarachnoid hemorrhage: a systematic review. Neurology 50:876–883

    PubMed  CAS  Google Scholar 

  5. Fodstad H, Liliequist B, Schannong M, Thulin CA (1978) Tranexamic acid in the preoperative management of ruptured intracranial aneurysms. Surg Neurol 10:9–15

    PubMed  CAS  Google Scholar 

  6. Fodstad H, Forssell A, Liliequist B, Schannong M (1981) Antifibrinolysis with tranexamic acid in aneurysmal subarachnoid hemorrhage: a consecutive controlled clinical trial. Neurosurgery 8:158–165

    Article  PubMed  CAS  Google Scholar 

  7. Fogelholm R, Hernesniemi J, Vapalahti M (1993) Impact of early surgery on outcome after aneurysmal subarachnoid hemorrhage. A population-based study. Stroke 24:1649–1654

    Article  PubMed  CAS  Google Scholar 

  8. Gelmers HJ (1980) Prevention of recurrence of spontaneous subarachnoid hemorrhage by tranexamic acid. Acta Neurochir 52:45–50

    Article  CAS  Google Scholar 

  9. Gibbs JR, O’Gorman P (1967) Fibrinolysis in subarachnoid hemorrhage. Postgrad Med J 43(506):779–784

    Article  PubMed  CAS  Google Scholar 

  10. Girvin JP (1973) The use of antifibrinolytic agents in the preoperative treatment of ruptured intracranial aneurysms. Trans Am Neurol Assoc 98:150–152

    PubMed  CAS  Google Scholar 

  11. Hijdra A, Vermeulen M, van Gijn J, van Crevel H (1987) Rerupture of intracranial aneurysms: a clinicoanatomic study. J Neurosurg 67:29–33

    Article  PubMed  CAS  Google Scholar 

  12. Hillman J, von Essen C, Leszniewski W et al (1988) Significance of “ultra-early” rebleeding in subarachnoid hemorrhage. J Neurosurg 68:901–907

    Article  PubMed  CAS  Google Scholar 

  13. Hillman J, Fridriksson S, Nilsson O, Yu Z, Saveland H, Jakobsson KE (2002) Immediate administration of tranexamic acid and reduced incidence of early rebleeding after aneurysmal subarachnoid hemorrhage: a prospective randomized study. J Neurosurg 97:771–778

    Article  PubMed  CAS  Google Scholar 

  14. Kassell NF, Peerless SJ, Durward QJ, Beck DW, Drake CG, Adams HP (1982) Treatment of ischemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 11:337–343

    Article  PubMed  CAS  Google Scholar 

  15. Kassell NF, Torner JC, Jane JA et al (1990) The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results. J Neurosurg 73:37–47

    Article  PubMed  CAS  Google Scholar 

  16. Kaste M, Ramsay M (1979) Tranexamic acid in subarachnoid hemorrhage. A double-blind study. Stroke 10:519–522

    Article  PubMed  CAS  Google Scholar 

  17. Leipzig TJ, Redelman K, Horner TG (1997) Reducing the risk of rebleeding before early aneurysm surgery: a possible role for antifibrinolytic therapy. J Neurosurg 86:220–225

    Article  PubMed  CAS  Google Scholar 

  18. Locksley HB (1966) Natural history of subarachnoid hemorrhage, intracranial aneurysms and arteriovenous malformations. J Neurosurg 25:321–368

    Article  PubMed  CAS  Google Scholar 

  19. Maurice-Williams RS (1978) Prolonged antifibrinolysis: an effective nonsurgical treatment for ruptured intracranial aneurysms? Br Med J 1:945–947

    Article  PubMed  CAS  Google Scholar 

  20. Milhorat TH, Krautheim M (1986) Results of early and delayed operations for ruptured intracranial aneurysms in two series of 100 consecutive patients. Surg Neurol 26:123–128

    Article  PubMed  CAS  Google Scholar 

  21. Ohkuma H, Tsurutani H, Suzuki S (2001) Incidence and significance of early aneurysmal rebleeding before neurosurgical or neurological management. Stroke 32:1176–1180

    Article  PubMed  CAS  Google Scholar 

  22. Okamoto S, Hijikata-Okunomiya A, Wanaka K, Okada Y, Okamoto U (1997) Enzyme controlling medicines: introduction. Semin Thromb Hemost 23:493–501

    Article  PubMed  CAS  Google Scholar 

  23. Owen CA Jr, Bowie EJW (1979) Surgical hemostasis. J Neurosurg 51:137–146

    Article  PubMed  CAS  Google Scholar 

  24. Pradilla G, Chaichana KL, Hoang S, Huang J, Tamargo RJ (2010) Inflammation and cerebral vasospasm after subarachnoid hemorrhage. Neurosurg Clin N Am 21:365–379

    Article  PubMed  Google Scholar 

  25. 25-Review Manager (RevMan) [Computer program]. Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008

  26. Roos YB, for the STAR-study group (2000) Antifibrinolytic treatment in aneurysmal subarachnoid haemorrhage: a randomized placebo-controlled trial. Neurology 54:77–82

    Google Scholar 

  27. 27-Roos YB, Rinkel GJE, Vermeulen M, Algra A, van Gijn J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2003, Issue 2. Art. No.: CD001245. doi:10.1002/14651858.CD001245

  28. Sengupta RP, So SC, Villarejo Ortega FJ (1976) Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. J Neurosurg 44:479–484

    Article  PubMed  CAS  Google Scholar 

  29. Shucart WA, Hussain SK, Cooper PR (1980) Epsilon-aminocaproic acid and recurrent subarachnoid hemorrhage: a clinical trial. J Neurosurg 53:28–31

    Article  PubMed  CAS  Google Scholar 

  30. Starke RM, Kim GH, Fernandez A (2008) Impact of a protocol for acute antifibrinolytic therapy on aneurysm rebleeding after subarachnoid hemorrhage. Stroke 39:2617–2621

    Article  PubMed  CAS  Google Scholar 

  31. Tovi D, Nilsson IM, Thulin CA (1973) Fibrinolytic activity of the cerebrospinal fluid after subarachnoid hemorrhage. Acta Neurol Scand 49:1–9

    Article  PubMed  CAS  Google Scholar 

  32. Tsementzis SA, Hitchcock ER, Meyer CH (1990) Benefits and risks of antifibrinolytic therapy in the management of ruptured intracranial aneurysms. A double-blind placebo-controlled study. Acta Neurochir 102:1–10

    Article  CAS  Google Scholar 

  33. Van Rossum J, Wintzen AR, Endtz LJ, Schoen JHR, de Jonge H (1977) Effect of tranexamic acid on rebleeding after subarachnoid hemorrhage: a double-blind controlled clinical trial. Ann Neurol 2:238–242

    Article  PubMed  Google Scholar 

  34. Vermeulen M, Lindsay KW, Murray GD et al (1984) Antifibrinolytic treatment in subarachnoid hemorrhage. N Eng J Med 311:432–437

    Article  CAS  Google Scholar 

  35. Whitfield PC, Moss H, O’Hare D et al (1996) An audit of aneurysmal subarachnoid haemorrhage: earlier resuscitation and surgery reduces inpatient stay and deaths from rebleeding. J Neurol Neurosurg Psy 60:301–306

    Article  CAS  Google Scholar 

  36. Yusuf S, Peto R, Lewis J, Collins R, Sleight P (1985) Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 27(5):335–371

    Article  PubMed  CAS  Google Scholar 

  37. Zacharia BE, Hickman ZL, Grobelny BT, DeRosa P, Kotchetkov I, Ducruet AF, Sander Connolly S Jr (2010) Epidemiology of aneurysmal subarachnoid hemorrhage. Neurosurg Clin N Am 21:221–233, Review

    Article  PubMed  Google Scholar 

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Acknowledgements

We would like to express our gratitude to Dr Andrew F. Ducruet from Columbia University, NY, USA, for his prompt response to our questions.

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Correspondence to Thomas Gaberel.

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Comment

The authors’ meta-analysis shows a decrease in rehemorrhage rates without any clear increase in stroke risk using short-term (<3 days) antifibrinolytic therapy (AF). The meta-analysis shows a trend towards fewer poor outcomes with short-term use of AF. In the older literature, patients were often actively dehydrated as part of the SAH management principles of the time, since hyponatremia was thought to be due to SIADH. Following the redescription of cerebral salt wasting and the description of hyperdynamic therapy in the early 1980s, patients were then hydrated following SAH, and this may well contribute to reduction in ischemic events over time. The current meta-analysis includes two recent papers not considered in the 2003 Cochrane Review: Hillman in 2002 and Starke in 2008. These two papers contain 753 patients and represent the most up-to-date treatment of subarachnoid hemorrhage. In the authors’ analysis, the results of short-term AF treatment and medical prevention of vasospasm described in these articles compare favorably to prior literature.

Patrick J. Connolly

Christopher M. Loftus

Philadelphia, Pennsylvania, USA

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Gaberel, T., Magheru, C., Emery, E. et al. Antifibrinolytic therapy in the management of aneurismal subarachnoid hemorrhage revisited. A meta-analysis. Acta Neurochir 154, 1–9 (2012). https://doi.org/10.1007/s00701-011-1179-y

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  • DOI: https://doi.org/10.1007/s00701-011-1179-y

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