3. INTERACT 1
• Aimed to determine if early intensive BP lowering is:
– feasible
– safe
– attenuates haematoma expansion
• Sample size (n=400) provided 80% power to detect
17% (≥60% reduction in relative risk) minimum
absolute difference in proportional mean haematoma
growth between randomised groups, assuming 30%
(SD60) mean growth in guideline group.
4. Blood Pressure Management
• Study evaluated a management policy and NOT of
a single agent
• Pragmatic approach to treatment
– Agents used are those available in hospitals
– Agents that are approved for clinical use
– Lower study costs versus packaging and use of placebo
• BP management protocols provided to standardise
therapies across countries
5. INTERACT1 Protocol Scheme
Acute spontaneous ICH
onset < 6 hours
SBP ≥ 150 and ≤ 220 mmHg
No definite indications or contraindications to treatment
Able to be actively managed
Provide informed consent
Repeat CT scans 24 and 72 hrs
Vital signs and BP over 7 days
In-person 28 day and 3 month follow-up
Intensive BP lowering
Target systolic BP 140 mmHg
within 1 hour and for 24+ hrs
Standard BP management
AHA Guideline-based
(treatment if systolic BP >180 mmHg)
R
Standard
best
practice
stroke unit
care
R
6. Measurement of haematoma parameters
• Repeat CTs at 24 and 72 hrs
• DICOM digital CT images sent
to central core lab (Sydney)
• Multi-slice planimetric technique
using MIStar 3.2 software
(Melbourne, Aust)
• Analysed by 2 neurologist
readers blind to clinical, centre,
treatment and time of CT data
8. Patient characteristics
Standard
(n = 201)
Intensive
(n = 203)
Time to randomization,
hr:min median (IQR) 3.4 (2.5-4.5) 3.4 (2.5-4.5)
Age (mean SD), yrs 62 13 63 12
Gender (male) 69% 61%
China 95% 95%
Systolic BP (mean SD) 182 19 180 18
Diastolic BP (mean SD) 105 15 101 14
Heart rate 79 79
NIHSS, median (IQR) 9 (5-16) 9 (5-14)
GCS, median (IQR) 14 (12-15) 14 (13-15)
History of hypertension 74% 74%
Use of antihypertensives 45% 42%
Deep location of hematoma 84% 83%
9. Therapies and management
Standard
(n = 201)
Intensive
(n = 203)
Any blood pressure lowering 74% 98%
Method - bolus 48% 58%
- infusion 66% 73%
Single iv agents 34% 66%
Intubation 9% 7%
Intravenous fluids 98% 98%
Fever treated 39% 36%
Nasogastric feeding 21% 20%
Intravenous mannitol 86% 82%
Neurosurgery intervention 7% 7%
Use of FFP or vitamin K 5% 3%
Use of rFVIIa 3% 6 %
10. INTERACT – Relative increase in haematoma volume for tertiles of
systolic BP, by baseline and achieved levels
Proportionalincrease(%)
150 160 170 180 190 200 210
0
10
20
30
40
50
120 130 140 150 160 170 180
0
50
10
20
30
40
P trend=0.03P trend=0.12
Baseline SBP (mmHg) Achieved SBP (mmHg)
Adjusted for age, sex, haematoma location, baseline haematoma volume, time from onset to CT, and study treatment.
Arima et al. J Hypertension 2010; 56:852-858
11. INTERACT: Reduction in absolute hematoma growth over 72
hours according to time from onset to treatment
Reduction
in
Volume
6.5 ml
3.3 ml
0.9 ml
0.6 ml
Intensive
-4.4 ml
0.1 ml
-1.1 ml
-0.2 ml
Guideline
2.1 ml
3.4 ml
-0.2 ml
0.4 ml
Absolute growthTime from onset
to treatment
<2.9h
2.9-3.6h
3.7-4.8h
≥ 4.9h
Favors
intensive
Favors
guideline
Reduction in hematoma growth over 72h (ml)
15 0 -510 5
Time from onset
to treatment Intensive Guideline
Unpublished data
12. Interact: Reduction in relative hematoma growth over 72 hours
according to time from onset to treatment
Reduction
In
volume
21%
15%
7%
4%
Intensive
-10%
16%
-6%
19%
Guideline
10%
31%
1%
22%
Favors
intensive
Relative growth
Favors
guideline
Reduction in hematoma growth over 72h (%)
30 0
P for
trend
0.02
Time from
onset
<2.9h
2.9-3.6h
3.7-4.8h
≥ 4.9h
-1020 10
Time from onset
to treatment
P for
trend
Unpublished data
14. Clinical outcomes (90 days)
Standard
(n = 201)
Intensive
(n = 203)
p
Death or dependency 49 48 0.81
Death 12 10 0.51
Dependency 41 36 0.98
Modified Rankin Score, median 2 2 0.66
NIHSS, median 2 2 0.97
Barthel Index Score, median 95 95 0.77
MMSE, median 28 27 0.97
EuroQoL, EQ5D, median, % 78 75 0.97
15. Conclusion
• INTERACT1 shows consistency of the BP lowering
treatment effect across various different analyses
BP lowering on haematoma growth at 24 and 72
hours
Haematoma rather than perihaematoma oedema
is the principle therapeutic target
Lower BP levels (140-150 mmHg) are likely to
produce greater benefits
Early BP lowering are likely to produce greater
benefits
16. Conclusion (cont.)
• Early rapid BP lowering is:
– clinically feasible
– not associated with excess hazard
– appears to reduce haematoma expansion
• However, some limitations:
– single study, mainly Chinese participants
– potential play of chance
– no effect on clinical outcomes, as in rFVIIa
studies
17. Conclusion (cont.)
Recommendations
1.Until ongoing clinical trials of BP intervention for ICH are completed,
physicians must manage BP on the basis of the present incomplete efficacy
evidence. Current suggested recommendations for target BP in various
situations are listed in Table 6 and may be considered (Class IIb; Level of
Evidence: C). (Unchanged from the previous guideline)
2.In patients presenting with a systolic BP of 150 to 220 mmHg, acute lowering
of systolic BP to 140 mmHg is probably safe (Class IIa; Level of Evidence: B).
(New recommendation)
18. Summary
• INTERACT shows that early intensive BP lowering with
careful monitoring is:
feasible, safe, and attenuates hematoma growth
• As antihypertensive agents are inexpensive and widely
available
widespread adoption of a standard policy could
translate into high absolute benefits
• A large-scale trial powered to evaluate modest but still
worthwhile effects on clinical endpoints is required to
influence clinical practice
21. Method:
INTERACT2 is a clinical study involving 2800 patients with acute ICH recruited from
approximately 140 centres around the world. Not only this is a global study, it is the
largest study that has ever been conducted on ICH.
Eligible participants are allocated to receive either intensive blood pressure lowering
treatment, or the currently recommended (more conservative) blood pressure
management.
Trial Progression:
Participant recruitment for INTERACT2 began in October 2008. Approximately 140
centres from around the world participated in the trial and this includes centres in
Australia, Europe, China, India, Africa, and North and South America. Trial recruitment
was completed on 31st August 2012, with a total of 2839 patients recruited.
WHAT IS INTERACT 2 TRIAL?
22. INTRODUCTION
• Acute intracerebral hemorrhage which is the least treatable
form of stroke ,affects more than 1 million people worldwide
annually with the outcome determined by the volume and
growth of the underlying hematoma.
• Blood pressure often becomes elevated after intracerebral
hemorrhage, frequently reaching very high levels, and is a
predictor of outcome.
• On the basis of the results of the pilot-phase study, Intensive
Blood Pressure Reduction in Acute Cerebral Hemorrhage
Trial 1 (INTERACT1) a main-phase study, INTERACT2 was
conducted to determine the safety and effectiveness of early
intensive lowering of blood pressure in patients with
intracerebral hemorrhage
23. TRIAL DESIGN
• INTERACT2 was an international, multicenter, prospective,
randomized, open-treatment, blinded end-point trial.
• In brief, the effect of a management strategy was compared :-
. targeting a lower systolic blood pressure within 1 hour, with
the current guideline-recommended strategy which targets a
higher systolic blood pressure in patients who had a systolic
blood pressure between 150 and 220 mm Hg and who did not
have a definite indication for or contraindication to blood-
pressure–lowering treatment that could be commenced
within 6 hours after the onset of spontaneous intracranial
hemorrhage
24. • Reduced number of in-hospital assessments but includes
an assessment of ICU stay and use of renal dialysis
• Repeat 24 hr CT scan to be collected only in 600 patients
(300 Chinese and 300 non-Chinese)
• Option of telephone-based outcome assessments at 28
and 90 days
• Screening logs kept for only 1 month of the year
– sites to be notified of the randomly selected month
in advance.
• Use of an Interactive Voice Randomisation System (IVRS)
in China
INTERACT2: New design features
25. INTERACT2 BP Management
• Evaluation of a management policy and NOT
of a single agent
• Inclusion of BP lowering management
protocols for key available agents
• Pragmatic approach to treatment
• Agents readily available in hospitals
• Agents approved for clinical use
• Lower study costs
26. Study Outline
Acute spontaneous ICH
onset <6 hours
SBP ≥150 and ≤220 mmHg
No definite indications or contraindications to treatment
Able to be actively managed
Provide informed consent
Repeat CT scans 24 hrs in selected patients
Vital signs and BP over 7 days
28 day and 3 month follow-up
IntensiveBP lowering
Target systolic BP 140 mmHg
within 1 hour and for 24+ hrs
Conservative BP management
AHA Guideline-based
(treatment if systolic BP >180 mmHg)
R
Standard
best
practice
stroke unit
care
27. Sample Size
• 2800 patients from 140+ sites
• 90% power for:
– 14% RRR in death/dependency in active vs
control
– 20% RRR in (50%) randomised<4 hours
28. Network
Australia
14 centres
China
49 centres
India
/Pakistan
13 centres
USA
(Rochester)
1 centre
Chile
6 centres
Argentina
6 centres
Brazil
9 centres
Europe
Austria, Finland, France,
Germany, Portugal, Spain,
Switzerland, The Netherlands,
Italy, Poland
64 centres
UK
27 centres
29. Inclusion Criteria
• Age 18 years or above
• Acute spontaneous ICH (history and CT)
• At least two systolic BP 150-220 mmHg,
recorded ≥2 min apart
• Able to be randomly assigned BP lowering
therapy within 6 hours of stroke onset
• Able to receive active (‘intensive’) care in a
monitored facility
30. Exclusion Criteria
• Known definite contraindication to intensive
BP lowering
• Known definite indication to intensive BP
lowering
• ICH secondary to a structural abnormality
• Ischemic stroke in last 30 days
• High likelihood of death within 24 hours (GCS
3-5)
31. Exclusion Criteria (cont.)
• Known advanced dementia or significant pre-
stroke disability
• Concomitant medical illness
• Planned early surgical intervention
• Participation in other trial
• Unlikely to adhere to treatment or follow-up
32. Eligibility
To be eligible for INTERACT2:
• All inclusion criteria questions must be
answered “YES”
• All exclusion criteria questions must be
answered as “NO”
33. Randomisation system
Patients are stratified according to: time since stroke onset (0-4
vs. 4-6 hours), site and country of recruitment
Randomised to either
Intensive BP lowering
treatment
Control; current
guideline based
management of BP
34. RANDOMIZATION
• Investigators entered baseline data into a database
associated with a secure Web-based randomization
system.
• The data were checked to confirm the eligibility of the
patient, and several key clinical variables were
recorded before the system assigned a participant to
intensive or guideline-recommended management of
blood pressure with the use of a minimization
algorithm to ensure that the groups were balanced
with respect to country, hospital, and time (≤4 hours
vs. >4 hours) since the onset of the
intracerebralhemorrhage
35. Protocol scheme
from INTERACT1 (Lancet Neurol 2008) and (Int J Stroke 2010)
Acute spontaneous ICH confirmed by CT/MRI
Definite time of onset within 6 hours
Systolic BP 150 to 220 mmHg
No indication/contraindication to treatment
In-hospital vital signs, NIHSS, GCS and BP over 7 days
Intensive BP lowering
SBP <140 mmHg
Standard BP management
Guidelines SBP <180 mmHg)
R
35
Independent 90 day outcome with
modified Rankin scale (mRS)
N=2800 gives 90% power for
7% absolute (14% relative)
decrease (50% standard vs
43% intensive) in outcome
36. Patient Flow – 2839 patients recruited
October 2008 to August 2012
1382 (98.5%) for primary outcome 1412 (98.3%) for primary outcome
2839 Randomised
28,829 Total estimated screened
3 no consent
1 missing baseline data
2 lost to follow-up
3 withdrew consent
12 alive without mRS data
Reasons for exclusion (n=3572)
39% Outside time window
16% Judged unlikely to benefit
11% BP outside criteria
8% Planned early surgery
5% Refused
21% Other reasons
6411 Screening logs completed
1403 Intensive BP lowering 1436 Standard BP lowering
5 no consent
1 missing baseline data
5 lost to follow-up
4 withdrew consent
9 alive without mRS data
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52. Systolic BP time trends
1 hour - Δ14 mmHg (P<0.0001)
6 hour - Δ14 mmHg (P<0.0001)
Systolic BP control
Median (iqr) time to treatment, hr - intensive 4 (3-5), standard 5 (3-7)
Intensive group to target (<140mmHg)
462 (33%) at 1 hour
731 (53%) at 6 hours
MeanSystolicBloodPressure(mmHg)
0
110
120
130
140
150
160
170
180
190
200
R 15 30 45 60 6 12 18 24 2 3 4 5 6 7
Standard
Intensive
////
Minutes Hours Days / Time
164
153
150
139
am pm am pm am pm am pm am pm am pm
P<0.0001
beyond 15mins
Target level
52
54. Management - Baseline to Day 7
Variable
Intensive
(N=1399)
Standard
(N=1430)
Intubation 7% 7%
ICU admission 39% 38%
DVT prophylaxis 22% 22%
Intravenous mannitol 62% 61%
Surgery 6% 6%
evacuation/decompression 3% 3%
ventricular drain 3% 3%
*all non-significant
54
55. Primary clinical outcome
Death or major disability (mRS 3-6) at 90 days
12.0 12.0
40.0
43.6
0
10
20
30
40
50
60
Intensive Standard
Major
Disability
(3-5)
Death (6)
%
(N=1399) (N=1430)
52.0%
55.6%
Odds ratio 0.87 (95%CI 0.75 to 1.01) P=0.06
55
Among survivors
Odds Ratio 0.85
(95%CI 0.73-0.99)
P=0.05
56. Key secondary outcome
Ordinal shift in mRS scores (0-6)
Odds ratio 0.87 (95%CI 0.77 to 1.00); P=0.04
56
18.0% 18.8% 16.6% 19.0%
12.0%8.0%
0 1 2 3 4 5 6
Intensive
Standard
Major disability DeathDisability but independent
18.7% 15.9% 18.1% 6.0%21.1%8.1% 12.0%
7.6%
57. Standard (0-2 vs 3-6)
Crude
Adjusted*
Other (0-1 vs 2-6)
Crude
Adjusted*
Other shift analysis
0
1
2
3
versus 4+5+6
Crude
Adjusted*
Intensive
719 (52.0)
978 (70.8)
112 (8.1)
292 (21.1)
259 (18.7)
220 (15.9)
499 (36.1)
Standard
785 (55.6)
1051 (74.4)
107 (7.6)
254 (18.0)
266 (18.8)
234 (16.6)
551 (39.0)
Odds ratio (95%CI)
0.87 (0.75 to 1.01)
0.87 (0.74 to 1.04)
0.83 (0.70 to 0.98)
0.85 (0.70 to 1.03)
0.87 (0.76 to 0.99)
0.88 (0.76 to 1.02)
P value
0.06
0.12
0.03
0.09
0.04
0.08
0.5 1.0 2.0
Odds ratio
(95% CI)
Intensive
Better
Standard
Better
Number of events (%)
Sensitivity analysis – crude and adjusted measures of
primary endpoint and with different mRS cut-points
57
*adjusted for prognostic variables: age, NIHSS score, time
from ICH to randomisation, haematoma volume and
location, and intraventricular haemorrhage
58. 58
Age
<65 years
≥65 years
Region
Chinese
Others
Time to randomisation
<4 hours
≥4 hours
Baseline systolic BP
<180 mmHg
≥180 mmHg
History of hypertension
Yes
No
Baseline NIHSS score
<15
≥15
Baseline haematoma volume
<15 ml
≥15 ml
Baseline haematoma location
Deep
Others
Total
Intensive
340 (43.3)
379 (63.6)
431 (45.8)
288 (65.5)
435 (54.3)
284 (48.9)
372 (50.0)
347 (54.4)
524 (52.5)
194 (50.7)
393 (39.8)
324 (82.9)
285 (39.3)
383 (69.1)
568 (53.1)
100 (47.6)
719 (52.0)
Standard
352 (46.7)
433 (65.7)
480 (49.6)
305 (68.7)
465 (56.7)
320 (54.1)
400 (53.8)
385 (57.6)
555 (54.3)
228 (58.9)
440 (44.3)
341 (83.4)
309 (42.0)
416 (73.4)
614 (56.9)
111 (49.8)
785 (55.6)
Odds Ratio (95%CI)
0.87 (0.71 to 1.06)
0.91 (0.72 to 1.15)
0.86 (0.72 to 1.03)
0.86 (0.65 to 1.14)
0.91 (0.75 to 1.10)
0.81 (0.65 to 1.02)
0.86 (0.70 to 1.05)
0.88 (0.70 to 1.09)
0.93 (0.78 to 1.11)
0.72 (0.54 to 0.95)
0.83 (0.70 to 0.99)
0.96 (0.67 to 1.40)
0.90 (0.73 to 1.10)
0.81 (0.63 to 1.05)
0.86 (0.73 to 1.02)
0.92 (0.63 to 1.34)
0.87 (0.75 to 1.01)
P homog
0.76
0.97
0.48
0.90
0.12
0.48
0.57
0.76
0.5 1.0 2.0
Odds Ratio (95%CI)
Intensive
Better
Guideline
Better
Number of events (%)
Pre-specified subgroups
and primary endpoint
59. Health-related quality of life
EuroQol EQ-5D domains ‘any problems’ versus ‘no problems’
64
47
61
40
34
67
52
66
45
38
0
10
20
30
40
50
60
70
80
Intensive Standard
P=0.02
P=0.006
P=0.05
% with problems
P=0.13
P=0.01
59
Health utility - 0.6 intensive vs 0.55 standard groups; P=0.002
60. Other secondary clinical outcomes
Parameter
Intensive
(N=1399)
Standard
(N=1430) P
Hospital stay, median (IQR) days 20 (12-35) 19 (11-33) 0.43
Institutional care at 90 days 9% 9% 0.80
Poor outcome at 28 days 66% 68% 0.22
60
Neurological deterioration
in first 24 hours
(≥4 NIHSS or ≥2 GCS)
66% 68% 0.22
61. Safety - cause-specific mortality, n(%)
Cause of Death
Intensive
(N=1394)
Standard
(N=1421) P
Direct effects of primary ICH event 103 (7.4) 111 (7.8) 0.67
Cardiovascular disease 14 (1.0) 15 (1.1) 0.90
ICH 0 (0.0) 2 (0.1)
Ischaemic/undifferentiated stroke 1 (0.1) 1 (0.1)
Acute MI/coronary event/other 3 (0.2) 1 (0.1)
Other vascular disease 2 (0.1) 2 (0.1)
Other cardiac disease 8 (0.6) 9 (0.6)
Non-cardiovascular disease 50 (3.6) 45 (3.2) 0.54
Renal failure 2 (0.1) 2 (0.1)
Respiratory infections 17 (1.2) 12 (0.8)
Sepsis (includes other infections) 6 (0.4) 4 (0.3)
Non-vascular medical 25 (1.8) 27 (1.9)
61
62. Safety - non-fatal serious adverse events (SAEs), n(%)
Serious Adverse Event
Intensive
(N=1399)
Standard
(N=1430) P
Direct effects of primary ICH event 47 (3.4) 55 (3.8) 0.49
Cardiovascular disease 37 (2.6) 41 (2.9) 0.72
ICH 4 (0.3) 4 (0.3)
Ischaemic/undifferentiated stroke 8 (0.6) 8 (0.6)
Acute MI/coronary event/other 5 (0.4) 5 (0.3)
Other vascular disease 13 (0.9) 14 (1.0)
Other cardiac disease 9 (0.6) 12 (0.8)
Non-cardiovascular disease 160 (11.4) 152 (10.6) 0.49
Renal failure 5 (0.4) 7 (0.5)
Severe hypotension 7 (0.5) 8 (0.6) 0.83
Respiratory infections 48 (3.4) 53 (3.7)
Sepsis (includes other infections) 21 (1.5) 20 (1.4)
Non-vascular medical /injury 132 (9.4) 125 (8.7)
62
63. • Early intensive BP lowering treatment is:
safe - no increase in death or harms
effective – borderline significant effect on the primary
endpoint
secondary analyses - improved recovery of physical
functioning and health-related quality of life in
survivors
• Consistent direction of effect in sensitivity analyses
• No heterogeneity of the treatment effect across different
patient and disease characteristics
Major findings of INTERACT2
63
64. • Treatment effect smaller (4%) than expected 7%
absolute, but:
active-comparison study on background therapies, some
with BP lowering properties (i.e. mannitol)
equates to NNT 25 (greater than aspirin and near late use
of rtPA in ischaemic stroke)
• No clear time-dependent relationship of treatment
potential mechanisms beyond haematoma growth
benefits of BP control may take several hours to manifest
INTERACT2 - issues
64
65. • Moreover, there was no evidence of a
significant effect modification according to a
history or no history of hypertension — a
finding that is relevant because it has been
postulated that patients with hypertension
have an upward shift in cerebral
autoregulation and possibly an increased risk
of cerebral ischemia related to intensive
lowering of blood pressure
66. • INTERACT2 resolves longstanding uncertainty over the
management of elevated BP in acute ICH
• Provides evidence regarding safety and efficacy in a
broad range of patients with ICH
• Defines for the first time a medical therapy for the
management of acute ICH
• As BP lowering treatment is low cost, simple to
implement, and widely applicable, the treatment
should become standard of care to patients with ICH in
hospitals all over the world
Conclusions
66
67. • BP lowering in acute ICH is safe, so ……
Go early
Go intensive (target systolic BP 140 mmHg)
Go sustained (≥24 hours)
• in most patients
• improves chances of better recovery in
survivors
Take home message
67
69. OUTILNE
• Implications for clinical
practice guidelines
– Statistical significance
• Implications for
clinicians at bedside
– Clinical significance
– Systems of care
• Implications for future
UCLA Stroke Center
73. INTERACT 2: A Near Win Trial
Trial Intervention OR P
primary
P
ordinal
INTERACT 2 BP↓ for ICH 0.87 (0.75-1.01) 0.06 0.04
UCLA Stroke Center
74. Stroke and Near Win Trials
Trial Intervention OR P
primary
P
ordinal
INTERACT 2 BP↓ for ICH 0.87 (0.75-1.01) 0.06 0.04
IST 3 TPA to 6 hours 1.13 (0.95-1.35) 0.18 0.001
SPS3 BP Arm BP↓ prevent
recurrent stroke
0.81 (0.64-1.03) 0.08
UCLA Stroke Center
84. Benefit Over All Health State
Transitions
• Benefit per Thousand:
81
• NNT: 12.3
UCLA Stroke Center
85. Benefit in INTERACT 2 vs Other
Acute Stroke Interventions
Intervention Net Benefit per Thousand
TPA under 3h 290
IA Pro-UK 208
Coiling in SAH 169
TPA 3-4.5h 136
BP lowering for ICH 81
Clinician worthwhile 50
Socioeconomic model worthwhile 20
UCLA Stroke Center
--Samsa et al, Am Heart J 1998;136:703-13
--Saver, Stroke 2007;38:3055-3062
--Saver et al, Stroke 2009;40:2433-7
86. Door to BP Control in Community
Practice in ICH
• 100 patients, 32 Emergency
Departments
• At ED arrival
– NIHSS 18
– Time from LKW 63 mins
– Mean BP 176/94
• 54% received BP therapy in ED
• Among the 48 patients with SBP ≥
180
– Control (<180) never achieved in
19%
– Median door to control 118 mins
– Door to control ≤ 90m in 31%
UCLA Stroke Center
--Sanossian et al, Ann Emerg Med 2012;60: S56
87. Other Treatment Recommendations
for ICH
• ICU monitoring
• Antipyretics in febrile patients
• Early mobilization
• ICP management
– Head of bed, analgesia, sedation
– Osmotic diuretics, CSF drainage,
hyperventilation
• Maintain serum glucose < 185
• Seizures
– Prophylactic antiepileptics for
lobar ICH
– Antiepileptics for clinical seizures
– Antiepileoptics for electrographic
seizures
• DVT prophylaxis
– Intermittent compression on
arrival
– SQ LMWH or UH after 3-4d
• For DVT, consider vena cava filter
• Reversal of coagulopathies
– Protamine for heparin
– Vitamin K, PCC, rF7 for warfarin
• Surgery
– Definite for select cerebellar
– Consider for lobar
– Consider minimally invasive for
deep
UCLA Stroke Center
--Morgenstern et al, Stroke 2010
88. ICH Critical Pathway
Identify Signs of Possible Stroke
Critical EMS Assessments & Actions
Immediate General Assessment/Stabilization
Immediate Neurologic Assessment
(stroke team or designee)
Does CT scan show
hemorrhage?
No Hemorrhage Hemorrhage
Possible
ischemic stroke
Consult neurologist or neurosurgeon
If not available, consider transfer
BP Management
ICP Management
Seizure Prevention and
Management
Fluid Management
Body Temperature
Management
Surgical Treatment of ICH
Cerebellar hemorrhage >3 cm with
neurologic deterioration or brain
stem compression and/or
hydrocephalus
Consider in lobar clots <1 cm of
surface
AHA Adult Stroke Guidelines. Circulation. 2005;112(suppl 24):IV-111-IV-120; Broderick J,
et al. Stroke. 2007;38:2001-2023; Qureshi AI, et al. N Engl J Med. 2001;344:1450-1460.
NINDS
Time Goals
Monitor Blood Glucose
and Treat (if needed)
Begin ICH Pathway
Admit to stroke unit (if available) or ICU
Monitor BP and treat (if indicated)
Monitor neurologic status
(emergent CT if deterioration)
Monitor blood glucose & treat (if needed)
Supportive therapy
Treat comorbidities
89. Time is Brain for Hemorrhagic Stroke
UCLA Stroke Center
--Arima et al, Stroke 2012;43:2236-
8
90. Dynamics of Hyperacute Hematoma Growth
0-120 Minutes: Not Well Delineated
--Kazui et al, Stroke 1996;27:1783-1787
91. Intracerebral Hemorrhage and the
Golden Hour
• Narrow therapeutic time
window
• Early intervention critical
• Prehospital personnel
– 35-70% of stroke patients
arrive by ambulance
– Unique position: first
medical professional to
come in contact with stroke
patient
UCLA Stroke
Center
92. 0
5
10
15
20
25
30
35
40
45
-15 -5 0 20 30 40 60 100 160 200 360
Time in minutes from onset of symptoms
VolumeofHematomainmL
Rupture of
blood vessel
Onset of
Symptoms
Activation
of EMS
EMS
Arrival
EMS Arrival
in ED
Initial ED
Evaluation
CT scan
obtained
CT scan
evaluated
Hospital
Treatment
initiated
Final Hematoma
Volume Established
Sanossian, FAST-BP Trial
93. 0
5
10
15
20
25
30
35
40
45
-15 -5 0 20 30 40 60 100 160 200 360
Time in minutes from onset of symptoms
VolumeofHematomainmL
Rupture of
blood vessel
Onset of
Symptoms
Activation
of EMS
EMS
Arrival
EMS Arrival
in ED
Initial ED
Evaluation
CT scan
obtained
CT scan
evaluated
Hospital
Treatment
initiated
Final Hematoma
Volume Established
Field
Treatment
Initiated
Goal: Control
Hematoma expansion
Earlier in Course
Sanossian, FAST-BP Trial
94. 0
5
10
15
20
25
30
35
40
45
-15 -5 0 20 30 40 60 100 160 200 360
--All hypertensive pts
--All severely hypertensive
pts
Time in minutes from onset of symptoms
VolumeofHematomainmL
Rupture of
blood vessel
Onset of
Symptoms
Activation
of EMS
EMS
Arrival
EMS Arrival
in ED
Initial ED
Evaluation
CT scan
obtained
CT scan
evaluated
Hospital
Treatment
initiated
Final Hematoma
Volume Established
Field
Treatment
Initiated
Goal: Control
Hematoma expansion
Earlier in Course
Sanossian, FAST-BP Trial
95. Onset to Treatment Times in Recent
Trials Enrolling ICH Patients
Trial Setting Intervention Onset to Treatment
INTERACT 1 Hospital Target SBP ≤ 140 4h 00m
ATACH 1 Hospital Nicardipine 4h 17m
INTERACT 2 Hospital Target SBP ≤ 140 4h 00m
RIGHT Prehospital Glyceryl trinitrate 55m
PIL-FAST Prehospital Lisinopril 1h 17m
FAST-MAG Prehospital Magnesium 47m
UCLA Stroke Center
96. Preserve / Treat / Cure
Condition EMS ED OR/Cath Lab
Acute ischemic
stroke
Neuroprotection TPA Endovascular
recanalization
Acute
intracerebral
hemorrhage
BP lowering Hemostatic agent Minimally invasive
hem evacuation
UCLA Stroke Center
97. Preserve / Treat / Cure
Condition EMS ED OR/Cath Lab
Acute ischemic
stroke
Neuroprotection TPA Endovascular
recanalization
Acute
intracerebral
hemorrhage
BP lowering Hemostatic agent Minimally invasive
hem evacuation
UCLA Stroke Center
