SCIENCE OF MEDICINE

STROKE
MICRO
SERIES Hemorrhagic Stroke:
Intracerebral Hemorrhage
by Marilyn M. Rymer, MD

Both headache and Abstract Intracerebral hemorrhage

diminished level Intracerebral hemorrhage accounts for 10-15% of all strokes
of conscious are (ICH) is a devastating event, and carries very high morbidity and
uncommon in acute carrying a very high morbidity mortality rates that have not changed
and mortality rate. Hypertension over the last 30 years. At one year,
ischemic strokes;
and age-related amyloid mortality ranges from 51% to 65%
they are common in
angiopathy are the strongest risk depending on the location of the
hemorrhagic strokes. factors for ICH, but smoking, hemorrhage.1 Half of the deaths
anticoagulation with warfarin, occur in the first two days. At six
excessive alcohol intake and months, only 20% of patients are
cocaine also increase risk. This, expected to be independent.2 The
the fourth in a Missouri Medicine incidence of hemorrhage increases
series on stroke summarizes the exponentially with age and is higher
clinical and imaging aspects of in men than in women.
making the diagnosis of ICH.
Current medical and surgical Clinical Presentation
therapies are discussed as well and Pathogenesis
as predictors of outcome and Sudden onset of focal
recommendations for secondary neurological deficit which progresses
prevention. over minutes to hours is the major
presenting feature of ICH. The
Introduction nature of the deficits reflects the
Intracranial hemorrhage includes location of the initial bleeding
epidural hematoma, subdural and subsequent edema. Seizures,
hematoma, subarachnoid hemorrhage vomiting, headache, and diminished
(SAH), intraventricular hemorrhage level of consciousness are common
(IVH), hemorrhagic transformation associated symptoms. Both headache
of ischemic stroke (HT), venous and diminished level of conscious are
hemorrhage from cortical vein or uncommon in acute ischemic strokes.
sinus thrombosis and intracerebral The majority of patients with
hemorrhage. The primary focus primary ICH develop measureable
Marilyn M. Rymer, MD, is a Professor of
of this, the fourth in a Missouri lesion expansion over the initial few
Medicine at the University of Missouri - Medicine six part series on Stroke, hours. The degree of hematoma
Kansas City School of Medicine and practices is intracerebral hemorrhage (ICH)
at the Saint Luke’s Brain and Stroke growth is an independent
Institute. MSMA member since 1981, she is which, for the purposes of this determinant of mortality and
the lead author and collaborator of Missouri discussion, will include intraventricular functional outcome. The mass
Medicine’s Micro-Series on Stroke. This hemorrhage (IVH). Part 5 will deal
article is fourth in a series of six. effect of the primary bleeding may
Contact: mrymer@saint-lukes.org with subarachnoid hemorrhage (SAH). cause lesions to migrate and dissect
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through less-dense white matter and into the ventricles subcortical locations. Lesions in the peripheral brain
resulting in increased intracranial pressure. A hematoma parenchyma (lobar hemorrhages; see Figure 2) are usually
incites local edema and neuronal damage in the adjacent attributed to amyloid angiopathy in the elderly, but may
brain parenchyma which typically lasts from 5 days to also be due to hypertension. Hemorrhages may dissect
2 weeks, with the largest increase in edema occurring from the brain parenchyma into the adjacent ventricular
in the first 72 hours.3 Thrombin within the hematoma space or they may be isolated to the intraventricular space
plays a central role in promoting perihematomal edema. (see Figure 3), both carrying a poor prognosis.6
Hemoglobin and its products, heme and iron, are potent CT with contrast and CT angiography (CTA) may
mitochondrial toxins leading to cell death. identify associated aneurysms, tumors and underlying
AVMs, although MR scanning is more sensitive for AVMs,
Diagnosis and Assessment especially cavernomas. MRI is a reasonable alternative
The early risk of neurological deterioration and to CT scanning but is usually not as practical in most
cardiopulmonary instability in ICH is high, making hospitals.
urgent diagnosis and management critical. The history Digital subtraction angiography (DSA) is the gold
must be taken quickly. It is important to know whether standard for identification of aneurysms and AVMs. Most
there is any history of trauma, hypertension, excessive cases compatible with either hypertensive or amyloid
use of alcohol, any use of drugs either by prescription angiopathy etiologies will not require angiography. A
or recreation that could play a role such as cocaine, search for a secondary cause is recommended when:
warfarin, aspirin, clopidogrel, or any hematologic UÊ Age <45 years
disorder. UÊ No history or presence of hypertension
The first priority in the physical examination is to UÊ Unusual location i.e. temporal lobe
assess vital signs and determine if intubation is required UÊ Increased edema on initial CT scan
for safety during imaging. It is important to determine UÊ Multiple hemorrhages present
if acute myocardial injury is a risk in patients with UÊ Irregular shape of the hemorrhage
severely elevated blood pressure (BP).After the patient
is medically stabilized, the next step is to obtain stat labs Treatment of ICH
to include protime/INR, PTT, CBC with platelet count, Primary Therapy
D-dimer, fibrinogen, electrolytes, BUN/creatinine, There are no evidence-based primary therapies that
glucose, liver functions and type and screen to blood improve outcomes for acute ICH. Clinical trials have
bank and then get the patient to an imaging study as fast shown that early treatment with recombinant Factor VIIa
as possible. prevents early ICH expansion, but clinical outcomes were
not changed.7
Imaging
CT head scanning has clarified the natural history of Medical Management
ICH and is the major test in use to differentiate between Blood Pressure
acute ICH, SAH, and ischemic stroke. It is an extremely General medical management includes attention
sensitive test to detect both ICH and SAH and to identify to airway, oxygenation, hydration, glucose <180,
the size and location of the hemorrhage. Hematoma temperature at 37.5 degrees C, early nutrition and
expansion, highly associated with clinical deterioration mobilization, and prophylaxis for deep vein thrombosis.
and poor outcomes, is evident in nearly 40% of cases The head of the bed should be up 30 degrees and the
within the first 3 hours after onset of symptoms is also patient should be monitored in an ICU setting.
well-documented with CT scanning.4,5 An approximate The target blood pressure should be individualized
volume of the hemorrhage can be determined by depending on factors including history of hypertension,
multiplying the maximum length (cm) times the intracranial pressure, age, presumed cause of the
maximum width (cm) times the number of transverse CT hemorrhage and interval since onset. In several
scan cuts (height in cm) and dividing by 2. retrospective studies, elevated systolic blood pressure
The most common site for hypertensive ICH is greater than 160 mm HG on admission was associated
the putamen (see Figure 1) but it may occur in other with growth of the hematoma but this has not been

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SCIENCE OF MEDICINE

demonstrated in prospective studies of ICH growth. The

ASA Guidelines suggest the following approach for elevated
blood pressure in spontaneous ICH:
UÊ If SBP >200, aggressive reduction of blood pressure
using continuous intravenous infusion with frequent BP
monitoring every 5 minutes
UÊ If SBP >180 and evidence for elevated ICP, then monitor
ICP and lower blood pressure using intermittent or
continuous intravenous medications to keep cerebral
perfusion pressure >60-80 mm Hg
UÊ If SBP >160 and no evidence for elevated ICP then
consider a modest reduction of blood pressure to 150/90
using intermittent or continuous intravenous medications.
Figure 1
Check BP every 15 minutes.
Putamenal hypertensive hemorrhage.
Typical location for hemorrhage secondary Preferred agents are beta blockers (labetalol, esmolol),
to hypertension. ACE inhibitor (enalapril), calcium channel blocker
(nicardipine) or hydralazine.8
Whether more aggressive control of blood pressure
could decrease hematoma expansion without compromising
perfusion of the surrounding brain is unknown. Ongoing
studies (ATACH and INTERACT) may provide more guidance
on acute BP management.

Intracranial Pressure (ICP)

Cerebral perfusion pressure should be >70mm
Hg. Initial treatment should use the simple measures of
elevating the head of bed to 30 degrees combined with pain
management and sedation. Mass effect causing significant
elevation of ICP with a risk of herniation may be managed
emergently with osmotic agents (mannitol, hypertonic saline)
Figure 2
Lobar hemorrhage likely related to amyloid or hyperventilation, but none of these therapies has been
angiopathyv. formally studied in clinical trials.

Figure 3 Figure 4
Intraventricular hemorrhage, usually related Cerebellar hemorrhage. This is the one potential neurosurgical
to hypertension. emergency.
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Seizures surgical candidates are patients with an initial Glasgow

In the first two weeks after ICH 5-10% of patients Coma Scale (GCS) <14 and hematomas >40 mL while
will have a clinically manifest seizure, reflecting cortical those with higher GCS and smaller lesions are likely to
involvement. In addition, with continuous EEG have a good outcome with conservative, non-surgical
monitoring, 30% of patients will demonstrate electrical management.10
seizure activity without clinically evident seizures. The The largest trial looking at surgical intervention for
clinical significance of this is unclear. Anticonvulsant supratentorial ICH is the STITCH Trial.11 Patients were
therapy is indicated for clinical seizures and could be randomized to surgery or medical therapy. Mortality
considered in those cases where there is electrical seizure and favorable outcomes were equal in the two groups.
activity and the patient is not waking up as expected. The Surgery does not appear to be helpful in most cases and
appropriate duration of anticonvulsant treatment is not is probably harmful in those presenting in coma. The
established. subset of patients who may benefit from early evacuation
of the clot are those who have lobar hemorrhages within
Warfarin Related ICH 1cm of the surface of the brain and milder clinical deficits
Warfarin accounts for a substantial proportion of cases (GCS>9). Craniotomy in this group was associated with
of ICH presenting to general hospitals. Among patients 29% relative benefit in functional outcome when compared
with supratentorial ICH admitted to Massachusetts General to medical management. The STITCH II Trial is currently
Hospital over a seven year period, 23.4% were taking randomizing patients with lobar hemorrhages to early open
warfarin.9 surgery versus conservative management.
The risk factors are age, hypertension, intensity of Minimally invasive surgery involves stereotactic
anticoagulation,and poor balance. placement of a cannula into the center of the clot with
The goal of treatment is to rapidly reverse the subsequent dosing of tPA through the cannula to dissolve
coagulation defect to minimize hematoma growth. The the clot from the inside out. The ongoing MISTIE Trial is
following options are available: testing this technique in supratentorial ICH and the CLEAR
Vitamin K1 can be administered intravenously at 10-25 Trial is testing the same procedure for intraventricular
mg to correct the INR, but it will take several hours to hemorrhage. Early results indicate significant decrease in
reach a normalized INR.. clot size. Whether this will translate to improved clinical
Fresh frozen plasma (FFP) at 15-20 mL/kg can be outcomes remains to be seen.
used to correct the INR faster. It has the disadvantage of
requiring the infusion of large volumes that can lead to Predictors of Outcomes
volume overload. There is also the potential for allergic The volume of the ICH and the clinical grade on the
reaction and infection. Often Vitamin K will be started Glasgow Coma Scale on admission are the most powerful
immediately and FFP added when it is available. predictors of 30-day mortality.12 Hemispheric lesions
Prothrombin complex concentrate is gaining >30 cc have a high mortality rate. Patients with GCS
popularity because it requires smaller volumes and corrects <9 and hematoma >60 cc have a 90% mortality rate.8
the coagulopathy quickly. There is the risk of inducing Intraventricular involvement with associated hydrocephalus
thromboembolic events. There is no risk of infection. predicts a mortality rate of 43% at 30 days.13,14 Brainstem
Recombinant Factor VIIa has the potential to hemorrhages, even when small, carry a poor prognosis. Age
normalize the INR very quickly, but it has not been over 80 years also carries a higher risk of mortality.
tested in this setting. The short half-life of 2.6 hours
might require repeated injections, and there is a risk of Recovery and Secondary Prevention
thromboembolic complications. Early mobilization and involvement of the neuro-
rehabilitation team is essential to maximizing recovery.
Surgical Management People with severe ICH have the potential to do better than
The single mandated indication for neurosurgical those with severe ischemic stroke.
decompression is cerebellar hemorrhage (see Figure 4) There is a 2.1-3% risk of recurrent ICH per patient
causing decreased level of consciousness, hydrocephalus year. Lobar hemorrhages have a higher risk of recurrence
or brainstem compression. Early craniotomy prior to that is likely related to underlying amyloid angiopathy.
significant brainstem compression is critical. The best Other factors increasing the risk of recurrence are older
108:1 Missouri Medicine | January/February 2011 | 53
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4. Brott T, Broderick J, Kothari R, et al. Early Hemorrhage Growth in Patients

age, anticoagulation, and the APOE genotype which is with Intracerebral Hemorrhage. Stroke. 1997; 28(1): 1-5.
associated with amyloid deposition. 5. Hill MD, Silver FL, Austin PC, et al. Rate of Stroke Recurrence in Patients
The major factor in preventing recurrence is blood with Primary Intracerebral Hemorrhage. Stroke. 2003; 31(1): 123-127.
6. Arakawa S, Saku Y, Ibayashi S, et al. Blood Pressure Control and
pressure control. The odds ratio for recurrent ICH with Recurrence of Hypertensive Brain Hemorrhage. Stroke. 1998: 29:1806-9.
untreated hypertension in one study was 3.5 but only 7. Mayer S, Brun NC, Begtrup K, et al. Recombinant Activated Factor VII
for Acute Intracerebral Hemorrahge. New England J.Med.Feb 24, 2005; 352(8):
1.4 for treated hypertension suggesting that treatment of 777-785.
hypertension can prevent ICH.15 Smoking, heavy alcohol use 8. Broderick J, Connolly S, Feldmann E, et al. Guidelines for the Management
of Spontaneous Intracerebral Hemorrhage in Adults: 2007 Update: A Guideline
and cocaine are also associated with increased rates of ICH from the American Stroke Association Stroke Council. Stroke. 2007;38:2001-23.
so these should be addressed with cessation strategies. 9. Rosand J, Eckman MH, Knudsen KA, et al. The Effect of Warfarin and
Intensity of Anticoagulation on Outcome of Intracerebral Hemorrhage. Archives
The issue of anticoagulation in patients who have of Int Med April 26, 2004;164(8): 880-884.
had an ICH and also have atrial fibrillation or another 10. Kobayashi S, Sato A, Kageyama Y, et al. Treatment of Hypertensive
condition where warfarin is indicated is a difficult one. Cerebellar Hemorrhage—Surgical or Conservative Management. Neurosurgery
1994;32:246-50.
Anticoagulated patients have a higher likelihood of 11. Mendelow AD, Gregson BA, Fernandes HM, et al. Early Surgery versus
recurrent ICH when the prior location of the hemorrhage Initial Conservative Treatment in Patients with Spontaneous Supratentorial
Intracerebral Hemorrahge in the International Surgical Trial in Intracerebral
was lobar rather than subcortical. Overall, there is a Hemorrhage (STICH): A Randomized Trial. Lancet Jan 29, 2005;365(9457):
relatively strong contraindication to using warfarin in people 387-397.
who have had an ICH. There is weaker evidence against the 12. Broderick J, Brott T, Duldner JE, et al. Volume of Intracerebral
Hemorrhage: A Powerful and Easy to Use Predictor of 30-day Mortality. Stroke
use of antiplatelet therapy. This issue should be addressed 1993; 24(7):987-993.
on a case by case basis. 13. Tuhrim S, Horowitz D, Sacher M, et al. Validation and Comparison of
Models Predicting Survival Following Intracerebral Hemorrhage. Critical Care
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Unrecognized Predictor of Poor Outcomes from Supratentorial Intracerebral
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Risk of Intracerebral Hemorrhage. Stroke. 2005; 36 (5): 934-937. 15. Woo D, Haverbusch M, Sekar P, et al. Effect of Untreated Hypertension on
2. Counsell C, Boonyakamkul S, Dennis M, et al. Primary Intracerebral Hemorrhagic Stroke. Stroke 2004; 35(7): 1703 1708.
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