THE INTERNET STROKE CENTER

PRESENTATIONS AND DISCUSSIONS ON STROKE MANAGEMENT

Evidence Based Management of Intracerebral Hemorrhage

Aninda Acharya, M.D.
Director of Neuro-Rehabilitation, Forest Park Hospital
Assistant Professor, St. Louis University

TABLE OF CONTENTS
Introduction

Medical Management of ICH

Hypertension in ICH

Lowering Blood Pressure and Outcome

Rate of Blood Pressure Decline

Hematoma Enlargement

Summary of Hypertension Treatment in Intracerebral Hemorrhage

Treating Mass Eect

Corticosteroids

Glycerol

Mannitol

Summary of Medical Treatment of Mass Eect in ICH

Hemodilution

Summary of Medical Management of ICH

Surgical Treatment of ICH

Open Craniotomy with Evacuation of Supratentorial ICH: Randomized Control Trials

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Open Craniotomy with Evacuation of Supratentorial ICH: Ultra-Early Treatment

11

Open Craniotomy with Evacuation of Supratentorial ICH: Acute Worsening

11

Endoscopic Aspiration for Supratentorial ICH

12

Meta-analysis

12

Summary of Surgical Treatment for Supratentorial ICH

12

Surgical Evacuation of Cerebellar ICH

12

Ventriculostomy

13

Conclusions

14

References

15

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Introduction
Definition
Intracerebral hemorrhage (ICH) results from the rupture of an intracerebral vessel
leading to the development of a hematoma in the substance of the brain.
Significance
In the US ICH represents 10 percent of all strokes (approximately 70,000 new cases each year).
It is twice as common as subarachnoid hemorrhage and carries an equally poor prognosis.
Economic Cost
The estimated the lifetime cost for a new case of ICH to be on average $123,565.
This translates to 8-9 billion dollar cost to society to treat the new cases of ICH each year.

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Medical Management of ICH

Is there any medical therapy which has been proven to benefit patients who suer an ICH?
Does treating hypertension in the acute period improve outcome?
Is there any evidence that medical treatment of mass eect in patients with ICH improves
outcome?

Hypertension in ICH
Hypertension is very common after ICH.
MAP > 140 in 34%
MAP > 120 in 78%
Typically, blood pressure returns to baseline over the course of one week, with the greatest decline
occurring during the first 24 hours.
The Evidence
Does lowering BP in acute period after ICH improve outcome?
Does lowering of BP in acute period decrease changes of hematoma enlargement?

Lowering Blood Pressure and Outcome

Study One
Meyer JS, Bauer RB. Medical treatment of spontaneous intracranial hemorrhage by use of hypotensive
drugs. Neurology. 1962; 12: 36-47.
167 patients with ICH (diagnosed by clinical suspicion, LP, and angiography) were separated into
treated and untreated group.
123 patients treated with hypotensive drug (Reserpine IM)
44 patients untreated
Goal BP not stated, and degree of lowering variable.
Typically Systolic BP brought to range of 160-180 mm Hg.
Outcome: Mortality at 6 weeks.
Results: Overall mortality rate 81%

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# Patients

Mortality

Coma on Admission Coma on Admission

-#
-%

Adequately Treated

40

63%

29/40

73%

Inadequately
Treated

83

82%

65/83

78%

No treatment

44

98%

41/44

93%

Study Two
Dandapani BR, Suzuki S, Kelly RE, et al. Relation between blood pressure and outcome in intracerebral
hemorrhage. Stroke. 1995. 26; 21-24.
Retrospective chart review.
Subjects: 87 patients with hypertensive ICH in thalamus or basal ganglia who had history of HTN.
Analysis: Mortality and severe morbidity in patients with MAP > 125 mm Hg after treatment vs.
MAP < 125 mm Hg after treatment at 6 hours.
Results:
Mortality Rate (30d)

Mortality / Severe Morbidity (30 d)

MAP > 125

43%

60%

MAP < 125

21%

34%

Confounder:

Treated MAP

MAP < 125

MAP > 125

Initial MAP < 145

39 patients

14 patients

MAP MAP > 145

11 patients

23 patients

Rate of Blood Pressure Decline

Qureshi AI, Bliwise DL, Bliwise NG, et al. Rate of 24-hour blood pressure decline and mortality after
spontaneous intracerebral hemorrhage: A retrospective analysis with a random eects regression
model. Crit Care Med. 1999. 27(3): 480-485.
Design: Retrospective Chart Review
Inclusion Criteria: 105 patients with ICH who had more than 5 blood pressure measurements
over the first 24 hours were included in the analysis.
MAP calculated as a slope ( change mm Hg/hr)

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 Determine eect of MAP Slope decline on mortality and functional outcome adjusted for GCS
and hematoma volume.
Results:
Rate decline patients who died -2.7 +2.1 mm Hg
vs -1.2 + 1.1 mm Hg
Logistic regression analysis showed that the rate of decline of BP in the first 24 hours an
independent predictor of mortality but did not aect functional outcome of survivors.

Hematoma Enlargement
Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral
hemorrhage. Stroke. 1997; 28: 1-5.
103 patients with ICH had CT done within 3 hours of onset. Repeat CT was done at 1 hour and 20
hours after baseline
> 33% growth had occurred in 26% of patients between baseline and 1 hour CT scan
> 33% growth had occurred in 40% of patients by 20 hour CT scan.

> 33% growth

< 33% growth

Systolic BP at onset mm Hg

200 + 34

199 + 38

Diastolic BP at onset, mm Hg

110 + 18

108 + 28

History of HTN

62%

68%

Summary of Hypertension Treatment in Intracerebral Hemorrhage

Prospective

Retrospective

Case Series

Meyer et al. 1962

Results
Lower BP good

Dandapani et al. 1995

Lower BP good

Qureshi et al. 1999

Lower BP bad
Brott T et al 1995

Hematoma enlargement
not associated with
degree of HTN

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Treating Mass Eect

Is there any benefit of medically treating mass eect in ICH?
Corticosteroids
Glycerol
Mannitol

Corticosteroids
Poungvarin N, Bhoopat W, Viriyavejakul A et al. Eects of dexamethasone in primary supratentorial
intracerebral hemorrhage. N Engl J Med. 1987; 316: 1229-1233.
Double Blind, Randomized, Block Design.
93 patients with CT confirmed ICH within 48 hours of the onset were randomized.
Treatment involved Dexamethasone 10 mg 1st day, then 5 mg every 6 hours for 5 days, then 5
mg every 12 hours for 2 days, then 5 mg for one day.
During third interim analysis mortality rates were identical between two groups, but rate of
complications ten times higher in treated group.
Result: No benefit

Glycerol
Yu YL, Kumana CR, Lauder IJ, et al. Treatment of acute cerebral hemorrhage with intravenous glycerol:
a double-blind, placebo controlled, randomized trial. Stroke. 1992; 23: 967-971.
Double-blind, randomized placebo-controlled trial.
Patients with first stroke, with CT confirmed ICH within 24 hours of onset were recruited.
107 received active treatment, 109 given placebo.
Treatment consisted of 400 cc of 10% glycerol in saline over 4 hours on 6 consecutive days.
Outcomes (mortality, improvement in Scandinavian Stroke Study Group scores, Improvement in
Barthal index) measured at 6 months.
Result: No dierence between groups

Mannitol
Santambrogio S, Martinotti R, Sardella F, Porro F, Randazzo A. Is there a real treatment for stroke?
Clinical and statistical comparison of dierent treatments in 300 patients. Stroke. 1978; 9: 130-132.

Improved

Worsened

Control

14/41 (34%)

18/41 (44%)

Mannitol

12/36 (33%)

16/36 (44%)

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Summary of Medical Treatment of Mass Eect in ICH

Corticosteroids = No benefit
Glycerol = No benefit
Mannitol = No proven benefit
There is no evidence from randomized trials that corticosteroid, glycerol, or mannitol improves patient
outcome.

Hemodilution
Italian Acute Stroke Study Group. Heamodilution in acute stroke: results of the Italian haemodilution
trial. Lancet 1988; Feb 13: 1 (8581): 318-321.
164 patients with ICH within 12 hours of onset, and Hct > 35% were randomized to either
hemodilution or control.
83 patients treated
81 patients control
Therapy: 350 cc blood removed, and 350 cc dextran 40 in 0.9 saline infused
Hemodilution

Control

Dead

25/83 (30%)

25/81(30%)

Dependent

32/83 (38%)

27/81 (33%)

26/83 (32%)

29/81 (37%)

(Rankin 3-6)
Independent
(Rankin 1-2)

Conclusion: No benefit

Summary of Medical Management of ICH

No acute medical treatments has been proven to improve patient outcome after ICH in a randomized
trial.

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Surgical Treatment of ICH

Does open craniotomy with evacuation of supratentorial ICH improve patient outcome?
Does endoscopic aspiration for supratentorial ICH improve patient outcome?
Does surgical evacuation of cerebellar ICH benefit patients?
Does ventriculostomy for hydrocephalus improve patient outcome?

Open Craniotomy with Evacuation of Supratentorial ICH:

Randomized Control Trials
Study One
McKissock W, Richardson A, Taylor J. Primary intracerebral hemorrhage: A controlled trial of surgical
and conservative treatment in 180 unselected cases. Lancet. 1961; 2: 221-226.
Inclusion Criteria: Patients with clinical history, physical signs, CSF, and angiography supporting
the diagnosis of supratentorial ICH were randomized to either conservative management or
surgery. No time limit specified.
91 patients randomized to conservative management
89 patients randomized to surgery.
Treatment was craniotomy and evacuation of the hematoma.
Outcome was mortality and disability at 6 months.
Results:
Surgery

Medical

Mortality

65%

51%

Bad Outcome

80%

66%

Odds Ratio of Death and Dependency:

(95% CI) 2.00 (1.04-3.86) medical better
Study Two
Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous intracerebral hemorrhage: a
prospective randomized trial of surgical and conservative treatment. J. Neurosurg. 1989; 70: 755-758.
Inclusion Criteria: Patient with CT confirmed supratentorial ICH who were admitted within 24
hours of the onset. Patient were either unconscious or had severe hemiparesis. Surgery within 48
hours.
26 in conservative management
26 in surgical group
Treatment: Craniotomy with evacuation of hematoma
Outcome: Death or disability (Glasgow Outcome Scale) at 6 months and 12 months.

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Results:
Surgery

Medical

Mortality

46%

38%

Bad Outcome

98%

81%

Odds Ratio of Death and Dependency:

4.39 (0.81-23.65) medical better
Study Three
Batjer HH, Reisch JS, Allen BC, et al. Failure of surgery to improve outcome in hypertensive putaminal
hemorrhage: a prospective randomized trial. Arch Neurol. 1990; 47: 1103-1106.
Inclusion Criteria: 21 patients with CT confirmed putaminal ICH > 3 cm and with hypertensive
history who had altered consciousness or limb weakness.
9 patients in best medical management
4 patients with medical management and ICP monitoring
8 patients with surgical evacuation
Treatment: Craniotomy with evacuation of hematoma
Outcome: Mortality and functional outcome at 3 and 6 months.
Results:
Surgery

Medical

Mortality

78%

67%

Bad Outcome

78%

83%

Odds Ratio of Death and Dependency:

0.86 (0.10-7.64) surgery better
Study Four
Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for intracerebral hemorrhage
(STICH): a single-center, randomized clinical trial. Neurology. 1998; 51: 1359-1363.
Inclusion Criteria: Patients with CT confirmed supratentorial (lobar or extending out o thalamus)
ICH > 9 cc, GCS 5-15 within 12 hours of onset
15 patients in surgical group
16 patients in medical group
Treatment: Craniotomy with evacuation of hematoma
Outcome: Mortality or disability at 1 month and 6 month.

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Results:
Surgery

Medical

Mortality

24%

18%

Bad Outcome

50%

69%

Odds Ratio of Death and Dependency:

0.46 (0.11 to 1.86) surgery better

Open Craniotomy with Evacuation of Supratentorial ICH:

Ultra-Early Treatment
Morgenstern LB, Demchuk AM, Kim DH, et al. Rebleeding leads to poor outcome in ultra-early
craniotomy for intracerebral hemorrhage. Neurology 2001; 56(10): 1294-1299.
Adult patients within 4 hours of onset of spontaneous supratentorial intracerebral hemorrhage.
Comparison made to medical and surgical group treated within 12 hour time window.
11 patients treated surgically within 4 hours
12 patients treated surgically within 12 hours
12 patients treated medically within 12 hours
Outcome: Mortality and functional outcome at 6 months
Study stopped because of safety concerns
Rebleeding rate 4 HS 40%, 12 HS 12%.
Outcome

4 HS

12 HS

12 HM

6 month

36

18

29

75

65

55

mortality
6 month
median BI

Open Craniotomy with Evacuation of Supratentorial ICH:

Acute Worsening
Rabinstein AA, Atkinson JL, Wijdicks EF. Emergency craniotomy in patients worsening due to
expanding cerebral hematoma: to what purpose? Neurology. 2002; 58(9): 1325-1326.
Reviewed 26 cases of spontaneous ICH with acute worsening who had surgery for clot
evactuion.
56% died, 22% remained severely disabled, 22% regained independence.
All patients with loss of brainstem reflexes died.

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Endoscopic Aspiration for Supratentorial ICH

Auer LM, Deinsberger W, Neiderkorn K, et al. Endoscopic surgery versus medial treatment for
spontaneous intracerebral hematoma: a randomized study. J Neurosurg. 1989; 70: 530-535.
Inclusion Criteria: Patients with CT confirmed supratentiorial ICH > 10 cc and < 48 hours from
time of onset with altered level of consciousness.
50 patients surgical group
50 patients medical group
Treatment: Endoscopic aspiration of clot
Outcome: Mortality and disability at 6 months
Results:

Surgical

Medical

Mortality

42%

70%

Poor Outcome

58%

74%

Odds Ratio of Death and Dependency:

0.46 (0.20-1.04) surgery better

Meta-analysis
Fernandes HM, Gregson B, Siddique S, et al. Surgery in intracerebral hemorrhage: the uncertainty
continues. Stroke. 2000; 31: 2511-2516.
Meta-analysis of all 7 randomized controlled trials of the eect of surgery after a supratentorial
spontaneous ICH.
Meta-analysis of the randomized controlled trials of the eect of surgery after a supratentorial
spontaneous ICH to exclude the trial of McKissock et al.
Meta-analysis of the randomized controlled trials of the eect of surgery after a supratentorial
spontaneous ICH to exclude the trials of McKissock et al and Chen et al.

Summary of Surgical Treatment for Supratentorial ICH

Several randomized trials with low power have failed to demonstrate benefit associated with surgical
evacuation of supratentorial ICH.

Surgical Evacuation of Cerebellar ICH

No evidence from randomized trials of benefits of surgical evacuation in ICH.
Evidence mostly in the form of case series.

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Study
Kobayaski S, Miyata A, Serizawa T, et al. Treatment of cerebellar hemorrhagesurgical or conservative.
Stroke. 1990; 21(8) Suppl: I-62.
Design: Non-randomized Prospective
Patients: 75 patients with cerebellar hemorrhage were studied.
45 treated medically
30 treated with decompressive surgery.
Patients with GCS < 13, and hematoma > 40 mm
Good outcome occurred 58% with surgery while only 18% with conservative medical therapy

Ventriculostomy
Adams RE, Diringer MN. Response to external ventricular drainage in spontaneous intracerebral
hemorrhage with hydrocephalus. Neurology. 1998; 50: 519-523.
Method: Retrospective chart review.
Inclusion: 24 patients with spontaneous supratentoral ICH who were treated with external
ventricular drainage were included.
Treatment: Ventriculostomy catheter. Best medical care.
Results 16/22 patients died in hospital. 17/20 patients died at 3 months. 2 were lost to follow-up
External ventricular drains did not improve hydrocephalus, and changes in ventricular volume
did not correlate with changes in level of alertness.

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Conclusions
There is no medical treatment which has been proven by a randomized trial to improve patient
outcome after ICH.
No randomized trial has demonstrated benefit of surgery in patients with ICH.
There is currently few RCT which have adequately evaluated the potential benefit of medical and
surgical intervention for ICH.
The I-STITCH trial should provide valuable insight into the ecacy of craniotomy and surgical
evacuation of intracerebral hematoma.

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14

References
Meyer JS, Bauer RB. Medical treatment of spontaneous intracranial hemorrhage by use of hypotensive
drugs. Neurology. 1962; 12: 36-47.
Dandapani BR, Suzuki S, Kelly RE, et al. Relation between blood pressure and outcome in intracerebral
hemorrhage. Stroke. 1995. 26; 21-24.
Qureshi AI, Bliwise DL, Bliwise NG, et al. Rate of 24-hour blood pressure decline and mortality after
spontaneous intracerebral hemorrhage: A retrospective analysis with a random eects regression
model. Crit Care Med. 1999. 27(3): 480-485.
Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral
hemorrhage. Stroke. 1997; 28: 1-5.
Poungvarin N, Bhoopat W, Viriyavejakul A et al. Eects of dexamethasone in primary supratentorial
intracerebral hemorrhage. N Engl J Med. 1987; 316: 1229-1233.
Yu YL, Kumana CR, Lauder IJ, et al. Treatment of acute cerebral hemorrhage with intravenous glycerol:
a double-blind, placebo controlled, randomized trial. Stroke. 1992; 23: 967-971.
Santambrogio S, Martinotti R, Sardella F, Porro F, Randazzo A. Is there a real treatment for stroke?
Clinical and statistical comparison of dierent treatments in 300 patients. Stroke. 1978; 9: 130-132.
Italian Acute Stroke Study Group. Heamodilution in acute stroke: results of the Italian haemodilution
trial. Lancet 1988; Feb 13: 1 (8581): 318-321.
McKissock W, Richardson A, Taylor J. Primary intracerebral hemorrhage: A controlled trial of surgical
and conservative treatment in 180 unselected cases. Lancet. 1961; 2: 221-226.
Juvela S, Heiskanen O, Poranen A, et al. The treatment of spontaneous intracerebral hemorrhage: a
prospective randomized trial of surgical and conservative treatment. J. Neurosurg. 1989; 70: 755-758.
Batjer HH, Reisch JS, Allen BC, et al. Failure of surgery to improve outcome in hypertensive putaminal
hemorrhage: a prospective randomized trial. Arch Neurol. 1990; 47: 1103-1106.
Morgenstern LB, Frankowski RF, Shedden P, et al. Surgical treatment for intracerebral hemorrhage
(STICH): a single-center, randomized clinical trial. Neurology. 1998; 51: 1359-1363.
Zuccarello M, Brott T, Derex L, et al. Early surgical treatment for supratentorial intracerebral
hemorrhage: a randomized feasibility study. Stroke. 1999; 30: 1833-1839.

www.strokecenter.org

15

Morgenstern LB, Demchuk AM, Kim DH, et al. Rebleeding leads to poor outcome in ultra-early
craniotomy for intracerebral hemorrhage. Neurology 2001; 56(10): 1294-1299.
Rabinstein AA, Atkinson JL, Wijdicks EF. Emergency craniotomy in patients worsening due to
expanding cerebral hematoma: to what purpose? Neurology. 2002; 58(9): 1325-1326.
Auer LM, Deinsberger W, Neiderkorn K, et al. Endoscopic surgery versus medial treatment for
spontaneous intracerebral hematoma: a randomized study. J Neurosurg. 1989; 70: 530-535.
Fernandes HM, Gregson B, Siddique S, et al. Surgery in intracerebral hemorrhage: the uncertainty
continues. Stroke. 2000; 31: 2511-2516.
Kobayaski S, Miyata A, Serizawa T, et al. Treatment of cerebellar hemorrhagesurgical or conservative.
Stroke. 1990; 21(8) Suppl: I-62.
Adams RE, Diringer MN. Response to external ventricular drainage in spontaneous intracerebral
hemorrhage with hydrocephalus. Neurology. 1998; 50: 519-523.

www.strokecenter.org

16