Acute Stroke: Melbourne
Edward Jauch, MD MS
1
Advances in the Role of
Emergency Medicine Management
of Cerebrovascular Events
Edward C. Jauch, MD MS FACEP
Assistant Professor
Director of Research
Department of Emergency Medicine
University of Cincinnati College of Medicine
Faculty, Greater Cincinnati / Northern Kentucky Stroke Team
Disclosure
• Industry
BoehringerBoehringer-Ingelheim
Biosite
Johnson & Johnson
Novo Nordisk
Speakers Bureau
Consultant & Site investigator (BRAIN)
Consultant & Site investigator (AbESTT
(AbESTT--II)
Consultant & Site investigator (FAST)
• American Heart Association
ASA and ACLS Stroke Guidelines Committees
Editorial Board, CPR and ECC Guidelines
Various administrative AHA committees
• National Institutes of Health funding (acute trials)
CLEAR, IMSIMS-II/III, SPOTRIAS, THIS, MR RESCUE
Introduction
Neurologic Emergency Management
• Review advances in Emergency Medicine
management of cerebrovascular events
–
–
–
–
Acute ischemic stroke
Intracerebral hemorrhage
Subarachnoid hemorrhage
Transient ischemic attack
• Highlight the role of Emergency Medicine in goal
directed brain resuscitation
Where to Start, Learn from Others
Trauma and AMI
•
•
•
•
•
•
•
•
•
•
Protocol development
Centers of excellence
High public awareness
Rapid access to EMS
Prehospital notification, triage
Prehospital ECG, interventions
Confirmatory tests
Strong collaboration with specialists
Team and protocols in place in ED
“Door to Drug/Groin - 30 Minutes”
Minutes” or
Golden hour of trauma
Intracranial
Hemorrhage
Ischemic
Stroke
Cardiac Arrest
Subarachnoid
Hemorrhage
/ TIA
Trauma
But the Brain is not the Heart
• Brain receives 20% of C.O. yet
represents only 2% TBW
• Highly dependant upon continuous
supply of oxygen and glucose
• Minimal energy reserves
• Compensation strategies limited
Acute Stroke: Melbourne
Edward Jauch, MD MS
2
After the initial insult to the brain:
Brain Ischemic Cascade
A. Nothing can be done and the injury is complete
B. The injury develops over days but can not be
stopped
C. The injury evolves with multiple opportunities for
intervention
Acute Ischemic Stroke
Barriers to Stroke (Neurologic) Treatment
• Slow response
– Poor public education
– EMS onon-board but needs direction
– ED response variable
• Challenging diagnosis
• Lack of
– Physician integration / Neurology
– Hospital commitment
• Treatment issues
– Labor intensive (?)
– Narrow therapeutic windows
– Concern of complications
Areas of Advancement
•
•
•
•
•
•
•
•
•
•
Epidemiology
Public education
EMS education and integration
Medical community education
Prevention
Acute management
Rehabilitation
Public policy & health care systems development
Basic science research and funding
But clearly more data are needed
Rates for Vascular Events
• Age-specific rates for stroke, myocardial infarction and sudden
cardiac death combined, and acute peripheral vascular events
(Rothwell, Lancet, 2005;366:29-36)
Acute Stroke: Melbourne
Edward Jauch, MD MS
3
Contribution of Selected Risk Factors
to Stroke Incidence
TIA – Prediction of Secondary Risk
A sixsix-point ABCD score:
• Age
Risk Factor
RR
Hypertension
Cardiac disease
Atrial fibrillation
Diabetes mellitus
Cigarette smoking
Heavy alcohol use
3.0
2.0
5.0
1.5
1.5
1.0
Prevalence (%)
– 5.0
– 4.0
– 18.0
– 3.0
– 3.0
– 4.0
[>60 years=1]
• Blood pressure
[systolic 140 mm Hg and/or
diastolic 90 mm Hg =1]
25 – 56
10 – 20
1–2
4–8
20 – 40
5 – 30
• Clinical features
[unilateral weakness = 2,
speech disturbance without
weakness = 1,other = 0]
• Duration of symptoms (min)
[60 = 2, 10–
10–59 = 1, 10 = 0]
Adapted from Sacco. In: Gorelick and Alter (eds). Handbook of Neuroepidemiology. New
York: Marcel Dekker, Inc; 1994:87, with data from Feinberg. Curr Opin Neurol. 1996;9:46;
Gorelick. Stroke. 1994;25:222.
(Rothwell, Lancet, 2005;366:29-36)
General EM Community View
ACEP Survey on tPA Use
ECASS, NINDS ATLANTIS
Pooled Analysis
• 1105 practicing EM Physicians responded to survey
• 40% responded not likely to use tPA
– 65% due to risk of ICH
– 23% due to lack of efficacy
– 12% due to both
• Use of tPA associated with:
– Previous use
– Female gender
• Highest acceptable risk of ICH 4.3%
(Lancet 2004; 363:768–
363:768–74)
(Brown, Ann Emer Med 2005;46:56-60)
18.0%
15.7%
16.0%
14.0%
12.0%
10.8%
10.0%
8.0%
9.1%
8.8%
8.0%
6.4%
6.0%
7.0%
6.4%
5.8%
5.3%
4.5%
4.6%
4.0%
6.3%
5.2%
4.9%
4.0%
3.3%
2.7%
All
All Prosective
Michigan
Indianapolis
Connecticut
Oregon
tPA Survey
OSF
Mercy (Sac)
Calgary
Cleveland 2
Berlin
Cleveland 1
Cologne
STARS
Houston
0.0%
NINDS
2.0%
CASES
Symptomatic Intracerebral Hemorrhage
Overall Safety of tPA in General Practice
(Graham, Stroke 2003; 34:248734:2487-50)
Given 8% of ED visits are for potentially
neurological conditions, what % residency
programs have required neurology rotations:
A.
B.
C.
D.
E.
15%
25%
50%
75%
>90%
Acute Stroke: Melbourne
Edward Jauch, MD MS
4
Neurologic Education in US
Emergency Medicine Residencies
• Survey of all US EM training programs
– 78% response rate
– 12 hours annually of neurologic didactic education
• Required rotations:
– Neurology
17.4%
– Neurosurgery 15.2%
– Both
1%
(~50% ICU based only)
• Neurology / neurosurgery / neuroradiology electives
– Available in 32% programs
– Rarely utilized
Solution: Education
• Foundation for Education and
Research in Neurological
Emergencies
• Fellowship training
–
–
–
One year stroke fellowship
Two year neurocritical care fellowship
Joint AHAAHA-ACEPACEP-SAEMSAEM-EMF
Fellowship
• 2005 Neurocritical Care
– Neurology subspecialty
– Open to emergency medicine
(Stettler, Acad Emer Med 2005; 12:909–911)
Solution: Combine the Strengths
Solution: Collaborative Education
• 2005 1st National Stroke Conference
– Sponsored by:
Canadian Stroke Consortium
Canadian Stroke Network
Canadian Association of Emergency Medicine
Canadian Society of Internal Medicine
– 150 emergency physicians, internists, and stroke
neurologists
• 2005 ILCOR consensus on science
• 2006 Joint ACEP / AAN statement
• 2006 Joint ACEM / SUHA statement
• EM essential element in
recent NIH/NINDS/NHLBI
initiatives:
– Specialized Program of
Translational Research in
Stroke (SPOTRIAS)
– Neurological Emergencies
Trialists Network (NET*2)
– Resuscitation Collaborative
(ROC)
Solution: Organized Stroke Care
25
25
• 21% reduction in early
mortality
• 18% reduction in 12
month mortality
• Decreased length of
hospital stay
• Decreased need for
institutional care
P=0.043
20
20
ortality (%
(%))
MMortality
Solution: Collaborative Research
15
15
P=0.077
10
10
55
21.4
21.4
P=0.017
10.3
10.3
16
16
15.4
15.4
9.6
9.6
6.4
6.4
00
10
10 Days
Days
11 Month
Month
33 Months
Months
Time
Time After
After Initial
Initial Stroke
Stroke
Stroke
Stroke Unit
Unit General
General Medical
Medical Ward
Ward
(Ronning, Stroke 1998; 29:58-62)
(Jorgensen, Stroke 1994)
Acute Stroke: Melbourne
Edward Jauch, MD MS
5
Solution: Stroke Unit
• Distinct facility staffed by physicians,
nurses, and rehabilitation personnel
or mobile stroke service with similar
components
• Monitoring capabilities providing close
observation for neurological
worsening or other complications
• Regular communication and
coordinated care
• Neurologist or stroke specialist
involvement improves outcome
(van der Walt, Med J Aust 2005 Feb 21;182(4):160-3)
Adams HP, Stroke 2003;34:1056-1083)
(Goldstein, Neurology 2003;61:792–796)
• Patient care areas
–
–
–
–
Acute stroke teams
Written care protocols
EMS participation
Emergency Department
participation
– Stroke unit*
– Neurosurgical services**
• Support services
–
–
–
–
–
Organizational support
Stroke center director
Neuroimaging
Laboratory
Outcome & quality
measures
– CME
As of 11/05 186 JCAHO Approved PSC, ~920 pending
(Brain Attack Coalition, JAMA 2000)
It is Not Just About tPA
Putting It All Into Context
Stroke Systems
• “A stroke system should coordinate and promote patient access
to the full range of activities and services associated with stroke
stroke
prevention, treatment, and rehabilitation, including the following
following
key components:”
components:”
–
–
–
–
Primordial and primary prevention
Community education
Regional integration of emergency medical services
Acute stroke treatment, including the hyperacute and emergency
department phases
– Subacute stroke treatment and secondary prevention
– Rehabilitation
– Continuous quality improvement (CQI) activities
(Schwamm etal, Circulation. 2005;111:1078-1091)
Solution: Provide Neurologic Expertise
• On site
• Phone consultation
• North East Melbourne Stroke Incidence Study
• Of 306,631 people, there were 645 incident strokes
• Extrapolated number saved from death or dependency for
every 1,000 cases:
– 46 (95% CI 17–69) with stroke unit management
– 6 (95% CI 1–11) by using aspirin
– 11 (95% CI 5–17) by using tPA at 3 hrs
– 10 (95% CI 3–16) by using tPA at 6 hrs
• “Although tPA is the most potent intervention, management
in stroke units has the greatest population benefit and
should be a priority”
(Stroke Unit Collaborative, 2002 Cochrane Review)
(Gilligan, Cerebrovasc Dis 2005;20:239–244)
Greater Cincinnati / Northern
Kentucky Stroke Team History
• Conceived in 1978 and formed in 1982 as a
collaboration between the Departments of
Neurology and Emergency Medicine
– Kansas City
• Telemedicine
–
–
–
–
–
Primary Stroke Centers
Reno NV
Bavaria & Swabia
Massachusetts
UC – San Diego
UT - Houston
• Original goal was to “Maximize stroke patient
outcome by delivering evidencedevidenced-based
effective, efficient and safe stroke care
throughout prepre-hospital and acute
hospitalization to all stroke patients in the
TriTri-state region.”
region.”
(Wiborg, Stroke. 2003; 34:2951-2957)
(Schwamm, Acad Emer Med 2004; 11:1193–1197)
(Judy Spilker)
Acute Stroke: Melbourne
Edward Jauch, MD MS
6
GC/NK Stroke Team Elements
•
•
•
•
•
•
•
•
Acute treatment physicians
Nurse coordinators
Neurosurgeons and neuroradiologists
Clinical fellows in neurology, emergency medicine,
neurocritical care
Rehabilitation medicine physicians
Biostatistics / Grant support staff
Basic science researchers
EMS personnel
Stroke System: Spoke and Hub
Ontario Stroke Net
Local Hospital
District Stroke Unit
•Neurologist
•CT Scanner
Regional Stroke
Centre
•Neurosurgeon
•MRI
•Angiography
GC/NK Stroke Team
Commando Model
• MultiMulti-Disciplinary team
–
–
–
–
–
–
3 Emergency physicians
6 Vascular neurologists
3 NeuroNeuro-interventionalists
2 Neurosurgeons
1 Neurointensivist
Hordes of nurses
• 15 Local hospitals
– 1 University
– 3 Teaching
– 11 Community
• 10 Rural hospitals
t-PA treatments within 3 hours – 110 patients/yr
t-PA treatments within 2 hours – 30 patients/yr
30 intra-arterial tPA treats per year
Governmental Support
• Epidemiology
– Coverdale Registry
• Phase IV registry
– SITSSITS-ISTR / MOST
• Governmental Support
– JCAHO certification
– 2005 DRG 559 “Acute Ischemic Stroke with Use of
Thrombolytic Agent”
Agent” with base rate $11,578 up from
$4,000 to $6,000
– STOP Stroke Act
NINDS Symposium Recommendations
• Development: Protocol and pathway development
• DoorDoor-toto-MD:
10 minutes
• Detection:
• DoorDoor-toto-Stroke
Team notification:
15 minutes
• DoorDoor-toto-CT scan:
25 minutes
• DoorDoor-toto-Drug:
60 minutes
Early recognition
• Dispatch:
Early EMS activation
• Delivery:
Transport & management
• Door:
ED triage
• Data:
ED evaluation & management
• Decision:
Neurology input, therapy selection
• Drug:
Thrombolytic & future agents
• Disposition:
Admission or transfer
(80% compliance)
• DoorDoor-toto-Admission
3 hours
(NINDS Stroke Symposium 2003)
Acute Stroke: Melbourne
Edward Jauch, MD MS
7
Development: Stroke Team
Emergency Medicine ≠ Janus (ianua
(ianua))
The Roman god of gates and doors
• Systems and
personnel in place
• Stroke Team well
known to all!
• Treatment oriented
ER Lobby Triage
• Team follows the 3
A’s
– Affable
– Available
– Able
844-7687
Data: Rapid ED Evaluation and the
Paradigm of Stroke Diagnosis
Data: Collection and Preparation
•
•
•
•
•
•
•
General Stroke Management
• Cardiac monitor
– Observe for ischemic changes or atrial fibrillation
• Intravenous fluids
– Avoid D5W and excessive fluid administration
– IV normal saline at 50 cc / hr unless otherwise required
• NPO
– Aspiration risk, avoid PO until swallowing assessed
• Temperature
– Avoid hyperthermia, PO/PR acetaminophen prn
• Blood pressure
– Function of fibrinolytic eligibility
Check glucose & labs
Two large IV lines
Oxygen as needed
Cardiac monitor
Continuous pulsepulse-ox
Stat nonnon-contrast CT scan
Begin general management
•
•
•
•
Activate “Stroke Team”
Team”
Confirm onset
Perform neuro exam
Get “real”
real” rtrt-PA
– Prepare to mix
– Have pharmacy alerted
• Discuss with patient and
family potential treatments
Goal Directed Therapy for
Cerebral Resuscitation - AIS
Homeostasis in Acute Stroke
• Glucose control
– Tighter early control
• Temperature control
– Normothermia at a minimum
– Hypothermia?
• Optimal oxygenation
– MRI infarct volumes reduced with
hyperoxia
Glucose Mediated Proinflammatory
and Procoagulant Effects
• Optimal BP management
(Singhal Stroke. 2005;36:797-802)
Acute Stroke: Melbourne
Edward Jauch, MD MS
8
Physical Exam Challenges
CT Scanning and Interpretation
• Neuro-imaging
• Heterogeneity of stroke
presentations
–
–
–
–
24 / 7 availability & priority acquisition
CT staff on stroke pager
Open lines of communication
Priority interpretation with treatment
considerations
– An issue for EMS triage
• Many MD’
MD’s poorly trained in
neurologic examinations
• Assessment scales viewed
as cumbersome
• CT in acute stroke
• No common language
between physicians
– 31% with EIC in NINDS (not a/w ICH)
• MRI
– Sensitive (DWI) and can detect ICH (GRE)
(Patel, JAMA 2001:286;2830-2830)
(Nedeltchev, Stroke 2003:34:1230-1234)
Solution: Improved Neuroimaging
TCD
Solution: Biomarkers of Stroke
• Unlike myocardial infarction,
no single biomarker is
sufficiently robust
Xenon CT
CTA
• An integrated panel of
biomarkers targeting different
components of the ischemic
cascade would provide better
diagnostic accuracy
MRA
10
Elevation from Control
MRI DW MRI
8
CRP
NSE,
S100
6
4
2
0
1
2
3
4
5
6
Time From Onset
Potential Marker Targets
•
Glial markers
– S100
– Glial fibrillary acidic protein
•
MMPMMP-9
VCAM
ILIL-6
Intracellular adhesion molecule, ICAM
Tumor necrosis factor
Neuronal cell adhesion molecule
ILIL-1 receptor antagonist
ILIL-1
ILIL-8
Monocyte chemoattractant proteinprotein-1
Vascular endothelial growth factor
Markers of cellular injury and myelin
breakdown
– Creatinine phosphokinase,
brain band
– Tissue factor
– Myelin basic protein
– Proteolipid protein
– Malendialdehyde
Inflammatory mediators
–
–
–
–
–
–
–
–
–
–
–
•
•
Potential Stroke Applications
•
Markers of apoptosis, growth
factors, etc
–
–
–
–
–
Brain natriuretic peptide
Caspase 3
CalbindinCalbindin-D
Heat shock protein 60
Cytochrome C
Markers of thrombosis
– vWF
– ThrombinThrombin-antithrombin III
– D-Dimer
(Lynch, Stroke 2004)
•
•
•
•
•
•
•
•
Assist in triage of patients to appropriate centers
Assist in the diagnosis of disease
Guiding treatment decisions and patient selection
Measuring treatment efficacy
Identifying patients at risk for complications
Providing prognosis
Selection of patients for intensified prevention
Development of new treatment strategies
7
Acute Stroke: Melbourne
Edward Jauch, MD MS
9
Biomarker Panel Model for Stroke
• Patients with potential stroke enrolled within 6o
from symptom onset at two centers
• Initial univariate analysis using: BNP, CaspaseCaspase-3,
CRP, DD-dimer MMPMMP-9, and S100β
S100β
• Multivariate analysis created a model with: CRP,
D-dimer, S100β
S100β using trichotomized output for
diagnosis within 3 hours
– Derivation PPV / NPV 100%
– Validation PPV / NPV 72%
100% 66 pts
90% 54 pts
Stroke Predictors vs Mimics
p< 0.0001
CaspaseCaspase-3
p= 0.0001
D-Dimer
p= 0.006
RAGE
Chimerin
p= 0.011
Secretagogin
p= 0.041
p= 0.046
MMPMMP-9
0
1
2
(Lynch and Jauch, 2005 ISC New Orleans )
BRAIN Study
Overall Accuracy <24h: 91%
Overall Accuracy <6h: 80.5%
3
4
5
6
Multimarker Approach (MMX)
• Design:
– Industry sponsored (Biosite
(Biosite))
– Multicenter prospective study of patients presenting with
possible stroke
• Mathematical model incorporating:
BNP, DD-dimer,
dimer, MMPMMP-9, and S100
10
• Sites:
Two thresholds based on clinical setting:
– 16 U.S, 4 European
5.9
• Subjects:
5
AgeAge-Matched Normals 839
Stroke Mimics
239
TIA
115
Ischemic Stroke
189
Intracranial Hemorrhage 119
1.3
Optimal specificity (rule in)
Optimal sensitivity (screening)
0
Stroke vs. Mimic: Test Performance
MMX vs. Diagnosis
7.0
6.0
Median MMX
OR
(Montaner,
Montaner, 2005 European Stroke Conference,
Conference, Bologna)
Bologna)
Time
Sensitivity Ischemic
Stroke
(MMX <1.3)
Sensitivity
ICH
(MMX <1.3)
Sensitivity
All
(MMX <1.3)
(MMX >5.9)
0-6
88%
(15/17)
86%
(6/7)
88%
(21/24)
90.2%
(37/41)
6-12
93.4%
(199/213)
90.7%
(49/54)
92.9%
(248/267)
91.7%
(133/145)
1212-24
92.4%
(145/157)
96.7%
(57/59)
93.5%
(202/216)
89%
(100/112)
5.0
4.0
3.0
2.0
1.0
0.0
AgeMatched
Normals
Mimic
TIA
Ischemic
Stroke
Diagnosis
Intracranial
Hemorrhage
Specificity
Acute Stroke: Melbourne
Edward Jauch, MD MS
10
Other Neurologic Conditions
Ongoing Studies Utilizing Markers
Neurologic Emergencies
• Trauma
• Prevention / Epidemiology
– REGARDS
– Major TBI
– Concussions
– Child abuse
• Acute treatment studies
–
–
–
–
–
ONO 2506 Stroke Trial
CLEAR Trial
IMS II, IMS III
ENOS
FAST (Novo 7)
Others
• Infectious diseases
– Prion, JCD
– Meningitis
• Degenerative diseases
– Alzheimer’
Alzheimer’s
– Parkinson’
Parkinson’s
• Neurovascular
– ICH, SAH, TIA
– Global ischemia
• Status Epilepticus
Decision:
EP, Neurology, Radiology
Drug:
tPA, Mechanical, Other
Disposition: Stroke Unit, ICU, Transfer
• Inflammatory diseases
– Multiple sclerosis
• Perioperative
Current Treatment Decisions
• No thrombolytics
– Nothing
– Aspirin
• Death / nonfatal strokes reduced 11%
– Heparin
Drug of Satan
• Intravenous rtrt-PA
– Risk stratify although all subgroups
benefited from thrombolytics in NINDS
• Other investigational treatment
– IntraIntra-arterial thrombolysis
– Low dose IV rtrt-PA followed by IA rtrt-PA
– Embolectomy (MERCI)
The Future of Stroke Treatment
•
•
•
•
•
•
•
•
•
•
•
Increased public and medical community education
Regional stroke systems
Tiered “Stroke Centers”
Centers”
New diagnostic tools
Neuroimaging, markers
Optimization of physiologic parameters
New thrombolytics
ProUK,
ProUK, TNK, rPA,
rPA, ANCROD
Combination agents
Antiplatelets, neuroprotectives
IntraIA, stents, angioplasty
Intra-arterial approaches
Global cerebral protection
Hypothermia, HBO
Surgical
Hemicraniectomy, cell transplant
Other forms of stroke
Novo 7, vasospasm treatments, surgery
Rehabilitation
• Primary and secondary prevention!
Solution: New Medical Treatments
•
Thrombolytics
TNK, rPA,
rPA, desmotoplase,
desmotoplase,
prourokinase
•
GP IIb/IIIa agents
•
Antithrombotic agents
•
Neuroprotective agents
Abciximab, eptifibatide
Argatroban
•
Other (Albumin, ancrod)
ancrod)
•
Aggressive management
Glucose, temperature and BP control
Acute Stroke: Melbourne
Edward Jauch, MD MS
11
New IntraIntra-arterial Strategies
Endovascular and Surgical Procedures
– Aneurysms
• Coiling
• Glue (AVM’
(AVM’s)
• Embolization
• Aneurysm clipping
– Hemorrhage
• Stereotactic aspiration
– Stroke
• Hemicraniectomy
• Intracranial stenting
• Carotid stenting
• Carotid endarterectomy
Other Developing Strategies
PostPost-Treatment Care
Hyperbaric Oxygen
Therapy
EMS Intervention
Hypothermia
FAST-Mag
Intracerebral Hemorrhage
Early Stroke Care
• Begin Acute Stroke Pathway
• ICU admission now
– 24 hrs for tPA
– Q 15’
15’ X 6 hours, Q 1ox18 hours
• Facilitate medical or surgical measures to
improve outcome after stroke
– Optimize blood pressure, glucose, temp
• Begin to prevent subacute complications
• Plan for longlong-term therapies to prevent
recurrent stroke
• Start efforts to restore neurological function
19 yo with ephedra induced ICH
(Adams Stroke. 2003;34:1056-1083)
Acute Stroke: Melbourne
Edward Jauch, MD MS
12
Goal Directed Therapy for
Cerebral Resuscitation - ICH
Emergent Evaluation
• Immediate stabilization (ABC’
(ABC’s)
• Baseline labs
• Glucose control
– Tighter control with better outcomes
– CBC, coags,
coags, electrolytes
• Temperature control
• Neuroimaging
– CT remains gold standard
• Identify ICH and complications (hydrocephalus, herniation)
– MRI / MRA
• Evaluate for structural abnormalities (AVM, aneurysms)
– Angiography
• Identify vascular issues preoperatively in occult ICH
ICH Prognosis
– Normothermia at a minimum
• Coagulation homeostasis
– Vit K (10mg) / FFP (15ml/kg)
– Every 30’
30’ delay decreases odds of
normalization within 24 hrs
http://www.stopstroke.org
• Fluid management
• Optimal BP management
(Steiner Stroke 2006;37:256-262)
Goldstein Stroke 2006;37;151-155)
General Medical Management
• ICH volume ~ ABC/2
• ABC’
ABC’s
• Blood pressure control
• ICP management (goal ICP < 20 mm Hg & CPP > 70 mm Hg)
• Worse prognosis
– Volume > 60 cm3 and GCS < 9
• 91% dead at 30 days
– Patients with volume >30 cm3 1 / 71
independent at 30 days
– Intraventricular extension, age
– Hyperventilation
– Osmotherapy
– No role for glycerol, corticosteroids, hemodilution
• Other
– Prevention of hyperthermia
– Fluid management (CVP at 55-12 mm Hg)
• Better
– Volume < 30 cm3 and GCS 9 or higher
• 19% dead at 30 days
(Broderick, Stroke 1997)
Surgical Evacuation
• Modifications for age, comorbidities, size, severity, location
• Seizure control
• Find somebody to take the patient
Surgical Evacuation
• No difference in:
• Largest surgical trial (1033 patients, 27 countries, 8 years)
• Surgery within 96 hours from onset vs medical management
• Outcome
– Primary
– Secondary
Favorable outcome at 6 months
Mortality
(Mendelow, A. Lancet, 2005;365:387-397)
– Favorable outcome
(26% vs. 24%, OR 2.3)
– Mortality
(36% vs 37%, OR 1.2)
– Mean total 6 month cost
(£18452 vs £20513)
• Unanswered questions
– Timing, location, methods
Mortality curves
(Mendelow, A. Lancet, 2005;365:387-397)
Acute Stroke: Melbourne
Edward Jauch, MD MS
13
Hemostatic Therapy
Factor rVIIa Treatment
35
35
• Few late studies (mostly in SAH*)
P=0.07
30
30
ICH Volume
Volume (ml)
(ml)
ICH
– Aminocaproic acid
– Tranexamic acid*
• UltraUltra-early studies
– rFVIIa
• Pilot (n=48)
• F7ICHF7ICH-1371 (n=399)
– Within 3 hrs onset
P=0.05
P=0.02
25
25
Baseline
Baseline
24
24 hour
hour
%
% Increase
Increase
20
20
15
15
10
10
55
• Phase III (n=675) ongoing
00
Placebo
Placebo
40
40 ug/kg
ug/kg
Factor rVIIa Treatment
80
80 ug/kg
ug/kg
160
160 ug/kg
ug/kg
Treatment
Treatment Group
Group
(Mayer, Stroke 2005;36:74-79)
(Mayer, NEJM 2005;352:777-785)
Potential Future Tools in ICH
• Medical therapies
• rFVIIa limits ICH growth,
reduces mortality, and
improves functional
outcomes
–
–
–
–
–
• A small increase in the
frequency of
thromboembolic adverse
events occurs with
treatment
Optimizing blood pressure (ATACH)
Tight glycemic control (THIS)
Early anticoagulation reversal
Neuroprotectives (CHANT, FastFast-MAG, hypothermia)
UltraUltra-early hemostatic therapy (rFVIIa)
• Surgery
– Surgical patient selection and new approaches
• Stereotactic evacuation with tPA (MISTIE)
• Intraventricular evacuation with fibrinolysis (ITT, DITCH)
(2% vs 7%, p=0.12)
(Mayer NEJM 2005;352:777-785)
Subarachnoid Hemorrhage
Subarachnoid Hemorrhage
Diagnosis and Prognosis
• Improved bilirubin/xanthochromia
detection as a better diagnostic tool
• Serum S100β
S100β levels correlated with early
neurologic deficit and outcome:
< 20 ng/ml favorable outcome
> 100 ng/ml severely disabled or died
• BOXes potent vasoconstrictor and present
(Morgan, J Neurosurg 2004;101:1026-9)
in CSF in vasospam
(Pyne, J Cereb Blood Flow Metab 2005)
(Persson, Acta Neuro 1988)
(Weisman, Acta Neurochir 1997)
Acute Stroke: Melbourne
Edward Jauch, MD MS
14
Goal Directed Therapy for
Cerebral Resuscitation - SAH
• Glucose control
– Tighter control with better outcomes
• Temperature control
– Normothermia at a minimum
– Hypothermia local / global
SAH Treatment
• Endovascular strategies increasingly
effective with better longlong-term outcomes
• Concentrating care at specialized high
volume centers may improve outcomes
• Keys to future advances
–
–
–
–
• Inflammation control
– NO pathways
• Optimal BP management
Earlier diagnosis
Initiation of homeostasis
Initiation of modulators of inflammation
Emergent referral for definitive correction
(Frontera Stroke 2006 37:199-203)
(Provencio Semin Neurology 2005; 25:435-444)
In the future, which physician will
have the greatest opportunity to alter
outcome in acute brain injury:
A.
B.
C.
D.
E.
Emergency physician
Neurologist
Neurosurgeon
Physical medicine and rehabilitation
All the above
(Cross, I 2003;99:810–817)
(ISAT Lancet 2002;360:1267–74)
Conclusion
• It is a great time to be an Emergency Medicine
physician
• It will be the EM physician who will play a key role in
cerebrovascular resuscitation
• Maximizing our potential will require
–
–
–
–
Increased education
Subspecialty support
Institutional commitment
Collaborative research
Community Education: TLL Temple
Foundation Stroke Project
• Aggressive multilevel stroke education
program in rural Texas led to:
– Decreased time to arrival (in both groups)
(Median 8.4 to 3.7 hours)
– Increased treatment in eligible patients
(14% to 52% vs. 7% to 6%)
– Increased rtrt-PA utilization overall
(1.4% to 5.8% vs 0.5 to 0.55% in control community)
(Morgenstern, Stroke 2002 Jan;33(1):160-6)
Acute Stroke: Melbourne
Edward Jauch, MD MS
15
Stroke System: Rural Systems
Washoe Health System
•
•
•
•
•
•
Rural Nevada System
25 hospitals, one team
Teleradiology available
Telemedicine at 3
9% treatment rate
20% transferred to hub
for ICU care
Recurrent Stroke and TIA after TIA
JCAHO Standardized Stroke Measures
1. Deep vein thrombosis (DVT) prophylaxis
2. Atrial fibrillation anticoagulation therapy
3. Tissue plasminogen activator (t(t-PA) considered
4. Antithrombotic medication within 48 hours
5. Lipid profile during hospitalization
6. Screen for dysphagia
7. Stroke education
8. Smoking cessation
9. Discharge on antithrombotics
10.Plan
10.Plan for rehabilitation
Histogram of TIA Values
(Johnston Neurology 2003;60:280-285)
rtrt-PA 3 Hour MetaMeta-Analysis
Biomarkers and the Neurovascular Unit
PREDICT NEUROLOGICAL OUTCOME
(parenchyma information)
PREDICT HEMORRHAGIC COMPLICATIONS
(BBB information)
PREDICT RECANALIZATION, REPERFUSION AND
REOCCLUSION
(vessel information)
(Saver, BMJ 2002; 324:727324:727-729)
(Lo, Broderick and Moskowitz. Stroke 2004)
Acute Stroke: Melbourne
Edward Jauch, MD MS
16
Areas of Advancement
• Acute management
–
–
–
–
–
–
Development of pathways, protocols
Stroke teams, units
Improved diagnosis
Improved general management
Review of tPA data
Additional methods of recanalizaton
More than Just Proteins for Diagnosis
• Proteomics, genomics, and
genetics will aid in diagnosis and
treatment selection
• Genes are quickly and uniquely
regulated in setting on neuronal
injury
• Apo E modulates response to rtPA
(ApoE2 OR 6.4 of favorable
outcome with rtPA)
rtPA)
(Tang, Ann Neuro 2001)
(Broderick, Ann Neuro 2001)
(Clark, Front Biocsci 2002)