Episode 17 Part 2: Stroke, Dabigatran and Intracranial Hemorrhage

In the 2nd part of this episode on Stroke, Dabigitran & Intracranial Hemorrhage Dr. Walter Himmel & Dr. Dan Selchen tell us everything the ED doc needs to know about the oral direct thrombin inhibitor Dabigatran and how to reverse a Dabigatran ICH. The ED treatment of stroke is reviewed including best medications and a simple way to remember BP goals. They review the management of ICH including BP goals, indications for neurosurgery, the role of recombinant Factor Vlla, and how best to reverse Warfarin-associated and platelet-associated ICH.

Dr. Himmel & Dr. Selchen answer questions such as: When should we use heparin in the setting of stroke? Is Dabigatran any better than Warfarin in preventing stroke in patients with Atrial Fibrillation? What is only medication worth trying in the setting of a Dabigatran-associated ICH? How does the ED management of spontaneous ICH differ to that of ischemic stroke? Which ICHs are more likely to benefit from neurosurgical intervention? Is there a role for Recombinant Factor Vlla for the treatment of ICH? What is the best way to reverse a Warfarin-associated ICH? An ASA-associated ICH? and many more……

Written Summary and blog post by Lucas Chartier, edited by Anton Helman September 2011

Dabigatran

  • Oral direct thrombin inhibitor reaching peak concentration in 2hrs and no monitoring required, but no way of ensuring compliance (i.e. no monitoring strategy as aPTT increase is not linear nor reliable), contraindicated in renal failure (because 80% renaly excreted) and no antidote to reverse its effects (in the setting of half-life of 12-14hrs)
  • At least as good as warfarin in preventing stroke in atrial fibrillation in RCTs, with lower rate ICH, but slightly higher rate of GI bleeding (Dabigatran vs Warfarin in Patients with Atrial Fibrillation. NEJM 2009;361:1139-1151)
  • Patients already taking Warfarin with excellent INR control have little to gain by switching to Dabigatran. Where Dabigatran has an advantage is in the patient whose INR is poorly controlled within the 2-3 INR range.
  • Dabigatran Reversal: In the setting of life-threatening bleed, the only method to mitigate the effects of dabigatran is hemodialysis – cryoprecipitate may be of help as well as activated charcoal in acute overdose

For an update and in-depth discussion on new anticoagulants including Dabigitran, Rivaroxiban & Abixaban see Episode 37

 

Intracranial hemorrhage (ICH)

  • Mortality of ICH 3x higher than ischemic stroke which is attributed to the mass effect of the bleed, leading to increased ICP, as opposed to ischemic stroke mortality associated with complications of stroke such as aspiration and sepsis.
  • 40% of patients with ICH have significant hematoma expansion in the first few hours after ICH and so the ED doc needs to do everything they can to minimize this hematoma expansion early on.
  • Supportive care: similar to ischemic stroke (see above), except –
    • have low threshold for early intubation as many patients deteriorate early on
    • if BP >180/105 (MAP >130) lower the pressure to 160/90 (MAP 110) and avoid hypotension
    • Elevate head of bed 30 degrees and keep neck in midline to prevent internal jugular veins compression and worsened increased ICP
    • For raised ICP consider using mannitol for clinical deterioration and gentle hyperventilation with PCO2 down to 35mmHg only as a bridge to definitive treatment in the O.R. with neurosurgery
    • No seizure prophylaxis required as per recent AHA guidelines

     

  • Indications for neurosurgical intervention: no clear data on this topic, but some possible indications include:
    • Ventricular drains for posterior fossa bleeds
    • Superficial bleeds within 1cm of cortical surface showed a trend toward improved outcome in the STICH trial with neurosurgical intervention compared to medical management alone (Early surgery versus initial conservative treatment in patients with spontaneous supratentorial inctracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomized trial. Lancet. 2005; 365(9457):387-97)
    • Neurosurgery may be beneficial in lobar bleeds associated with cocaine, AVMs or amyloid

     

  • Recombinant Factor VIIa for treatment of ICH has been shown to significantly decrease hematoma size in RCT but has never shown an outcome benefit.
    • Current Canadian Study looking at patients with a ‘spot sign’ on CT Angiogram (which is an indicator of high likelihood of hematoma expansion) who may be a subset of patients that do derive an outcome benefit

     

  • Warfarin-associated ICH Reversal: replace the missing clotting factors and ensure they stay up by giving Vitamin K 10mg IV (1mg per minute) and Prothrombin Complex Concentrates (PCCs) – Octaplex in Canada (fast onset in minutes and small volume of infusion – dose is 1,000u if INR 4 or body weight >90kg) or fresh frozen plasma (which takes hours to thaw and to reverse INR plus requires large volumes, and therefore less optimal compared with PCCs)
  • Antiplatelet-associated ICH: consider giving a pool of platelets in the setting of ASA, but less likely to be useful for Clopidogrel

emcases-update Update 2016: The PATCH trial suggests that platelets do not benefit patients with anti-platelet associated ICH. Abstract

emcases-update Review of the PATCH trial at EM Literature of Note

 

For more on stroke on EM Cases:
Episode 17 Part 1: Emergency Stroke Controversies
Ep 104 Emergency Management of Intracerebral Hemorrhage – The Golden Hour
Journal Jam 10 Thrombolysis & Endovascular Therapy for Stroke Part 1
Journal Jam 10 Part 2 Endovascular Therapy for Stroke

 

Dr. Himmel, Dr. Helman and Dr. Selchen have no conflicts of interest to declare.

 

Key References

Mendelow AD, Gregson BA, Fernandes HM, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365(9457):387-97.

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51.

Brody DL, Aiyagari V, Shackleford AM, Diringer MN. Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage.Neurocrit Care. 2005; 2: 263–267.

Lin Y, Callum J. Emergency reversal of warfarin anticoagulation. CMAJ. 2010;182(18):2004.

 

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About the Author:

Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.

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