ED Hemorrhagic Stroke Patient Management: What Role for Operative Intervention

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ED Hemorrhagic Stroke Patient ManagementWhat
Role for Operative Intervention Factor VIIa?
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4th EuSEM CongressCrete, GreeceOctober 5-7, 2006
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Edward P. Sloan, MD, MPH FACEP
ProfessorDepartment of Emergency
MedicineUniversity of Illinois College of
MedicineChicago, IL
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Attending PhysicianEmergency
MedicineUniversity of Illinois HospitalOur
Lady of the Resurrection HospitalChicago, IL
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Disclosures

• NovoNordisk, King Pharmaceuticals, UCB Pharma
  Advisory Boards
• Eisai Speakers Bureau
• ACEP Clinical Policies Committee
• ACEP Scientific Review Committee
• Executive Board, Foundation for Education and
  Research in Neurologic Emergencies

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Session Objectives

• Discuss the potential role for operative
  intervention given the results of the STICH
  trial.
• Determine the optimal protocol for treating
  elevated INR in ICH patients and the possible
  role of factor VIIa in this setting.

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Key Clinical Questions

• What is the role of operative intervention in ICH
  patients given the results of the STICH trial?
• What is the optimal management of anti-coagulated
  ICH patients and the potential role of factor
  VIIa?

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ED ICH Patients Key Clinical Concepts
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ICH Key Concepts

• This is a high morbidity mortality Dx

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)
• Hemorrhage volume predicts outcome

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ICH Volume and Outcome

• Broderick 1993 Stroke
• Key Concept Hemorrhage volume and GCS predict
  30 day mortality
• Data 60 cc blood, GCS lt 9, mort 91
• Data 30 cc blood, GCS gt 8, mort 19
• Implications Simple ED observations allow for
  a reasonable outcome assessment

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)
• Hemorrhage volume predicts outcome
• Hemorrhage volume increases over time

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ICH Hemorrhage Growth

• Brott 1997 Stroke
• Key Concept ICH volume is dynamic, changes
  correlate clinically
• Data 26 had 1/3 growth in 1 hour
• Data 1/3 growth drop in NIHSS, GCS
• Implications Efforts directed at stabilizing
  hemorrhage volume may impact patient outcome

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)
• Hemorrhage volume predicts outcome
• Hemorrhage volume increases over time
• Guidelines exist that direct ED acute care

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Evidence-Based ICH Patient Management
Broderick JP et al. Stroke 199930905-15.
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ICH Treatment Guidelines

• ASA Council 1999 Stroke
• Key Concept ICH guidelines exist
• Data Detailed data on disease, epi
• Data BP, ICP Rx recommendations
• Implications The procedures of ICP and BP
  management can be uniformly applied by EM
  physicians

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)
• Hemorrhage volume predicts outcome
• Hemorrhage volume increases over time
• Guidelines exist that direct ED acute care
• Recent data regarding surgery important

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ICH Surgical Concepts

• Remember Only 4 clinical trials!
• Total of 353 patients studied in all
• Remove clot, reduce pressure
• Manage brain trauma and edema
• Minimize trauma (superficial clots best)
• Minimally invasive approaches now used
• 75-100 mortality in surgical ICH trials

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ICH Surgical Indications

• Difficult to specify
• Some general principles
• Cerebellar hemorrhage 3 cm or larger or those
  that cause mass effect, compression
• ICH related to a surgical lesion
• Young patients who deteriorate
• Other indications less clear

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STITCH ICH Surgical Trial

• Mendelow 2005 Lancet
• Key Concept Surgery within 24 hours does not
  affect 6 month outcome
• Data 25 of pts had a good outcome
• Data Surgery did not change this rate
• Implications ED Rx becomes more important,
  given lower likelihood of operative
  neurosurgical intervention

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STITCH ICH Surgical Trial

• Mendelow 2005 Lancet
• 1033 pts, non-US settings
• Data early surgery vs. medical, surgical
• Data Hemorrhage volume 40 cc
• Data 81 had GCS 9-15
• Data Surgical time 30 hrs, 60 hrs
• Data Only 16 had surgery lt 12 hrs

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STITCH ICH Surgical Trial

• Mendelow 2005 Lancet
• Key concept This study may not exactly tell the
  story of practice that includes rapid
  identification of optimal surgical candidates and
  early OR intervention
• May still need to consider operative
  intervention, will need to stabilize patients
  first in the ED

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ICH Key Concepts

• This is a high morbidity and mortality Dx
• Like ischemic stroke (core, penumbra)
• Hemorrhage volume predicts outcome
• Hemorrhage volume increases over time
• Guidelines exist that direct ED acute care
• Recent data regarding surgery important
• Need to treat elevated INR in ICH setting

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Effect of Warfarin on 3 Month ICH Patient Outcome
Rosand J et al. Arch Intern Med 2004164880-884.
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Sixth ACCP Recommendations on Managing Patients
with high INR Values
Chest 2001119(1 Suppl)22S-38S
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6th ACCP INR Recommendations

• Consensus, evidence based
• 2001 Chest
• Key Concept Guidelines exist for managing
  anticoagulated patients with serious or life
  threatening bleeding
• Grade 2C evidence

Chest 2001119(1 Suppl)22S-38S
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Elevated INR Rx Key Concepts

• Measure INR
• Establish the extent of INR elevation
  (lt 5, 5-9, gt9) and presence of bleeding
• Determine if an immediate neurosurgical
  intervention is needed
• Administer Vitamin K IV
• Order Coagulation Factor Replacement

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Elevated INR Rx ACCP Info
Derived from Chest 2001119(1 Suppl)22S-38S,
courtesy of Wjasow C, McNamara R. J Emerg Med
200324(2)169-72.
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Elevated INR Therapy The Procedure
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Elevated INR Rx Procedure

• Vitamin K 10 mg by slow IV infusion

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Elevated INR Rx Procedure

• Vitamin K 10 mg by slow IV infusion
• Fresh frozen plasma (5-8 ml/kg, 1-2 units,
  250-500 cc total)

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Elevated INR Rx Procedure

• Vitamin K 10 mg by slow IV infusion
• Fresh frozen plasma (5-8 ml/kg, 1-2 units,
  250-500 cc total)
• OR
• Prothrombin Complex Conc at 25-50 IU/kg
• Dose based on Factor IX units
• Alternatively, 500 IU initially followed by
  second administration of 500 IU according to the
  INR value measured just after the first
  administration

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Elevated INR Rx Procedure

• Vitamin K 10 mg subq or IVP
• Fresh frozen plasma (5-8 ml/kg)
• 1-2 units, 250-500 cc total
• OR
• Prothrombin Complex Concentrate 25-50 IU/kg
• OR
• Recombinant Factor VIIa (40-60 µgr/kg)
• Usually 3-4 mg total

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Recombinant Factor VIIa

• Rapid onset of action
• Almost immediate
• Clinically apparent hemostasis in 10 minutes
• Short half life (2.3 hours)
• Relatively high acquisition cost
• 2,500-3,500 for 3-4 gm dose

Park p et al. Neurosurgery 20035334-39. Sorensen
B et al. Blood Coagulation and Fibrinolysis
200314469-477. Novoseven package insert.
Princeton, NJ Novo Nordisk Pharmaceuticals, Inc
2003.
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FVIIa in Warfarin-Related ICH

• Freeman 2004 Mayo Clin Proc
• Key Concept Warfarin-related ICH can be
  treated successfully with rec FVIIa
• Data 62 micrograms/kg Factor VIIa
• Data INR decreased from 2.7 to 1.1
• Implications This therapy used today as an
  adjunct to blood therapies in ICH patients whose
  bleed is INR-related

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FVIIa in Warfarin-Related ICH

• Freeman 2004 Mayo Clin Proc
• Data 12-28 growth by 24 hours
• Data INR normalized within 2 hours
• Implications May facilitate craniotomy for
  patients who are surgical candidates

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FVIIa Safety in ICH

• Mayer 2005 Stroke
• Key Concept FVIIa is safe when given within 3
  hours of presentation
• Data 36 patients, 6 doses tested
• Data No safety issues preclude phase III
• Implications Larger study is justified, given
  data on hemorrhage volume growth and outcome

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FVIIa Safety in ICH

• Mayer 2005 Stroke
• Key Concept Careful with thromboembolic events
  
• Data 2 Significant AEs
• Data DVT at 72 hours, Angina at 29 days
• Implications Careful pt selection may allow for
  minimal complications to occur

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FVIIa Safety, Efficacy in ICH

• Mayer 2005 NEJM
• Key Concept FVIIa is safe when given within 3
  hours of presentation
• Data 399 pts, 3 doses, ICH growth, 90-day
• Data Less ICH growth, improved outcome
• Data Thromboembolic events noted
• Implications Larger study is critical in order
  to establish clear benefit, safety

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FVIIa Safety, Efficacy in ICH

• Mayer 2005 NEJM
• Key Concept Optimal patient population
• Data GCS 14, NIHSS 12-15
• Data 24 cc hemorrhage volume
• Data 180 minutes to treatment
• Implications Good population for surgical Rx,
  fits with ED paradigm of stabilization
• Role in larger population of ICH pts?

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FVIIa Safety, Efficacy in ICH

• Mayer 2005 NEJM
• Key Concept Good outcome, limited AEs
• Data 47 vs. 31 favorable outcome
• Data NIHSS 6 vs. 12
• Data 7 cardiac ischemia, 9 CVAs, 1 AMI
• Implications May represent a favorable
  risk/benefit profile

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FVIIa in ICH Commentary

• Brown 2005 NEJM
• Key Concept Editorial provides perspective on
  Mayer study
• Data How should data be interpreted?
• Data What can be learned from study?
• Implications What are the implications of this
  study? What do we do now?

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FVIIa in ICH Commentary

• Brown 2005 NEJM
• Key Concept Many unknowns persist
• Data BP and ICH management unclear
• Data Surgical Rx indications variable
• Implications Use it for good surgical
  candidate, related to elevated INR, in pt not
  at high risk for thromboembolic event

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Conclusions

• ICH is a bad disease
• Literature defines pathology and acute treatment
  options
• Surgical intervention enhances outcome
• Reversal of elevated INR a critical skill
• Await the confirmatory study of FVIIa in ICH
  patients

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Recommendations

• Learn about the disease state
• Aggressively define extent of ICH
• Know how to manage ICH patients
• Know what the guidelines suggest
• Look for the upcoming trial results
• Continue to explore best approaches

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Questions?
www.FERNE.org edsloan_at_uic.edu 312 413 7490
ferne_eusem_2006_sloan_ich_100706_finalcd 11/12/20
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