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Three Part Question

[In patients with confirmed SAH] are [antifibrinolytics better than placebo] at [reducing rebleeding, improving survival or improving morbidity]

Clinical Scenario

A 24 year old man presents to the emergency department following a sudden headache and collapse. He is GCS 14 on arrival with no localising signs. CT scan demonstrates a sub arachnoid haemorrhage. In a previous hospital you were advised to give tranexamic acid to prevent rebleeding. You suggest this to the neurosurgical SpR on call who thinks you are talking rubbish and strongly advises against it.
You wonder if he is an evidence-based neurosurgeon....or whether he is behind the times?

Search Strategy

Medline 1966-12/04 using the OVID interface.
The Cochrane Library Issue 4, 2004.
Medline: {exp Subarachnoid Hemorrhage/ or subarachnoid haemorrhage.mp. or exp Aneurysm, Ruptured/ or SAH.mp} AND {exp Antifibrinolytic Agents/ or antifibrinolytics.mp or exp Tranexamic Acid/ or tranexamic acid.mp or exp Aminocaproic Acids/ or aminocaproic acid.mp or exp 6-Aminocaproic Acid/ or epsilon aminocaproic acid.mp or epsilon amino-caproic acid.mp or antifibrinolytic$.mp}
Cochrane: subarachnoid hemorrhage [all fields] OR subarachnoid haemorrhage [all fields]

Search Outcome

267 references found including one recent Cochrane review. No papers after the publication of the cochrane review were found.
The summary of the cochrane review is presented here.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Roos YBWEM et al, 2003 Netherlands	9 trials involving 1399 patients included. Papers sourced through electronic and hand searching methods. RCTs of IV or oral agents included. Only confimed SAH patients.	Systematic review and Meta analysis.	Poor outcome (defined as death, vegative state or severe disability)	Non significant. OR of 1.12 (CI 0.88-1.43) for poor outcome with treatment	This is a well researched review. The studies match the clinical problem well. Of 21 trials found only 9 satisfied the quality filter of the authors which suggests some rigour in the approach used). One of the review authors' own study was included in the review.
			Rebleeding at end of follow up	Less with treatment OR=0.55 (CI 0.42-0.71)
			Risk of cerebral ischaemia	Worse with treatment OR=1.39 (CI 1.07-1.82)
			Risk of death	Non significant. OR=0.99 (CI 0.79-1.24)
			Rate of hydrocephalus	Non significant. OR=1.14 (CI 0.86-1.51)

Comment(s)

A well constructed review article answers the question. Although there appears to be a reduction in the rate of rebleeding this is not matched by an improvement in patient outcome. The authors of this review postulate that the increase in cerebral ischaemia seen in most of the trials may account for this. From a clinical perspective there appears to be little to be gained from the administration of antithrombolytics in confirmed SAH

Clinical Bottom Line

Antithrombolytics are not indicated in the emergency management of sub-arachnoid haemorrhage.

Level of Evidence

Level 1 - Recent well-done systematic review was considered or a study of high quality is available.

References

1. Roos, YBWEM; Rinkel, GJE; Vermeulen, M; Algra, A; van Gijn, J. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.