evidence based management of intracerebral hemorrhage
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THE INTERNET STROKE CENTERPRESENTATIONS AND DISCUSSIONS ON STROKE MANAGEMENT
Evidence Based Management of Intracerebral Hemorrhage
Aninda Acharya, M.D.Director of Neuro-Rehabilitation, Forest Park HospitalAssistant Professor, St. Louis University
TABLE OF CONTENTS
Introduction 3
Medical Management of ICH 4
Hypertension in ICH 4
Lowering Blood Pressure and Outcome 4
Rate of Blood Pressure Decline 5
Hematoma Enlargement 6
Summary of Hypertension Treatment in Intracerebral Hemorrhage 6
Treating Mass Effect 7
Corticosteroids 7
Glycerol 7
Mannitol 7
Summary of Medical Treatment of Mass Effect in ICH 8
Hemodilution 8
Summary of Medical Management of ICH 8
Surgical Treatment of ICH 9
Open Craniotomy with Evacuation of Supratentorial ICH: Randomized Control Trials 9
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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
De!nitionIntracerebral hemorrhage (ICH) results from the rupture of an intracerebral vessel leading to the development of a hematoma in the substance of the brain.
Signi!canceIn 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 CostThe 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 bene"t patients who suffer an ICH?
Does treating hypertension in the acute period improve outcome?
Is there any evidence that medical treatment of mass effect 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 "rst 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 OutcomeStudy OneMeyer 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 TwoDandapani 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 MAPTreated MAP MAP < 125 MAP > 125Initial MAP < 145 39 patients 14 patientsMAP MAP > 145 11 patients 23 patients
Rate of Blood Pressure DeclineQureshi 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 effects 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 "rst 24 hours were included in the analysis.
MAP calculated as a slope ( change mm Hg/hr)
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Determine effect 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 "rst 24 hours an independent predictor of mortality but did not affect functional outcome of survivors.
Hematoma EnlargementBrott 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 + 38Diastolic BP at onset, mm Hg 110 + 18 108 + 28History of HTN 62% 68%
Summary of Hypertension Treatment in Intracerebral Hemorrhage
Prospective Retrospective Case Series ResultsMeyer et al. 1962 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 EffectIs there any bene"t of medically treating mass effect in ICH?
Corticosteroids
Glycerol
Mannitol
CorticosteroidsPoungvarin N, Bhoopat W, Viriyavejakul A et al. Effects of dexamethasone in primary supratentorial intracerebral hemorrhage. N Engl J Med. 1987; 316: 1229-1233.
Double Blind, Randomized, Block Design.
93 patients with CT con"rmed 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 bene"t
GlycerolYu 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 "rst stroke, with CT con"rmed 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 difference between groups
MannitolSantambrogio S, Martinotti R, Sardella F, Porro F, Randazzo A. Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients. Stroke. 1978; 9: 130-132.
Improved WorsenedControl 14/41 (34%) 18/41 (44%)Mannitol 12/36 (33%) 16/36 (44%)
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Summary of Medical Treatment of Mass Effect in ICH
Corticosteroids = No bene"t
Glycerol = No bene"t
Mannitol = No proven bene"t
There is no evidence from randomized trials that corticosteroid, glycerol, or mannitol improves patient outcome.
HemodilutionItalian 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(Rankin 3-6)
32/83 (38%) 27/81 (33%)
Independent(Rankin 1-2)
26/83 (32%) 29/81 (37%)
Conclusion: No bene"t
Summary of Medical Management of ICHNo 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 bene"t patients?
Does ventriculostomy for hydrocephalus improve patient outcome?
Open Craniotomy with Evacuation of Supratentorial ICH:Randomized Control TrialsStudy OneMcKissock 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 speci"ed.
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 TwoJuvela 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 con"rmed 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 ThreeBatjer 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 con"rmed 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 FourMorgenstern 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 con"rmed 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 TreatmentMorgenstern 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 HM6 monthmortality
36 18 29
6 monthmedian BI
75 65 55
Open Craniotomy with Evacuation of Supratentorial ICH:Acute WorseningRabinstein 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 re$exes died.
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Endoscopic Aspiration for Supratentorial ICHAuer 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 con"rmed 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 monthsResults:
Surgical MedicalMortality 42% 70%
Poor Outcome 58% 74%
Odds Ratio of Death and Dependency:0.46 (0.20-1.04) surgery better
Meta-analysisFernandes 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 effect of surgery after a supratentorial spontaneous ICH.
Meta-analysis of the randomized controlled trials of the effect of surgery after a supratentorial spontaneous ICH to exclude the trial of McKissock et al.
Meta-analysis of the randomized controlled trials of the effect 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 ICHSeveral randomized trials with low power have failed to demonstrate bene"t associated with surgical evacuation of supratentorial ICH.
Surgical Evacuation of Cerebellar ICH
No evidence from randomized trials of bene"ts of surgical evacuation in ICH.
Evidence mostly in the form of case series.
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StudyKobayaski 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
VentriculostomyAdams 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 bene"t of surgery in patients with ICH.
There is currently few RCT which have adequately evaluated the potential bene"t of medical and surgical intervention for ICH.
The I-STITCH trial should provide valuable insight into the efficacy of craniotomy and surgical evacuation of intracerebral hematoma.
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ReferencesMeyer 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 effects 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. Effects 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 different 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.
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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.
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