the pathophysiology and management of hemorrhagic stroke

Continuous Medical Continuous Medical EducationEducation

Department of Neurosurgery, HKL

14 February 2007

EPIDEMIOLOGYEPIDEMIOLOGY

For a patient who presents with the For a patient who presents with the abrupt abrupt onsetonset of a new focal of a new focal neurological deficitneurological deficit : :

5% are seizure, tumour or psychogenic5% are seizure, tumour or psychogenic 95% are vascular95% are vascular

– 15% haemorrhagic15% haemorrhagic ICH, SAH, SDHICH, SAH, SDH

– 85% ischaemic infarct85% ischaemic infarct Unknown, lacunar, cardiogenic embolus, large Unknown, lacunar, cardiogenic embolus, large

artery cerebrovascular lesion, tandem arterial artery cerebrovascular lesion, tandem arterial pathology,pathology, atherosclerotic plaques in the aortic atherosclerotic plaques in the aortic archarch


Incidence 12-15/100,000/yrIncidence 12-15/100,000/yr Intracerebral hemorrhage (ICH) is more than Intracerebral hemorrhage (ICH) is more than

twice as common as subarachnoid twice as common as subarachnoid hemorrhage (SAH)hemorrhage (SAH)

Much more likely to result in death or major Much more likely to result in death or major disability than cerebral infarction or SAH disability than cerebral infarction or SAH

35% to 35% to 50%50% can be expected to die within can be expected to die within the the first monthfirst month after bleeding after bleeding

Only Only 10% of patients are living independently10% of patients are living independently 1 month after the hemorrhage1 month after the hemorrhage

20% are independent at 6 months 20% are independent at 6 months


Risk factorsRisk factors– Advancing Advancing ageage and and hypertension hypertension are the most are the most

important risk factorsimportant risk factors– Age : >after Age : >after 55, doubles55, doubles with each decade with each decade– Gender : more common in Gender : more common in menmen– Ethnic : More common among young and middle-ageEthnic : More common among young and middle-age blacks than whites of similar ages blacks than whites of similar ages

More common in Asians compared to More common in Asians compared to whiteswhites

– Previous CVA increases risk by Previous CVA increases risk by 23:123:1– Alcohol consumptionAlcohol consumption– Drug abuseDrug abuse– Liver dysfunctionLiver dysfunction


Causes of Intracranial HaemorrhageCauses of Intracranial Haemorrhage1.1. Primary ( hypertensive ) intracerebral haemorrhagePrimary ( hypertensive ) intracerebral haemorrhage2.2. Ruptured saccular aneurysmRuptured saccular aneurysm3.3. Ruptured AVMRuptured AVM4.4. Haemorrhagic disorders ( leukaemia, aplastic Haemorrhagic disorders ( leukaemia, aplastic

anaemia, anticoagulant therapy, haemophilia..)anaemia, anticoagulant therapy, haemophilia..)5.5. Haemorrhage into brain tumoursHaemorrhage into brain tumours6.6. Septic embolismSeptic embolism7.7. Haemorrhagic infarctHaemorrhagic infarct8.8. Inflammatory diseases of blood vesselsInflammatory diseases of blood vessels9.9. Amyloidosis Amyloidosis


Locations of haemorrhageLocations of haemorrhage– Putamen, lenticular nucleus, internal capsule, Putamen, lenticular nucleus, internal capsule,

globus pallidus globus pallidus 50%50%– Thalamus Thalamus 15%15%– Pons Pons 10-15%10-15%– Cerebellum Cerebellum 10%10%– Cerebral white matter Cerebral white matter 10%10%– Brain stem Brain stem 6%6%

Common Common arterial feedersarterial feeders of ICH of ICH– Lenticulostriates – putaminalLenticulostriates – putaminal– ThalamoperforatorsThalamoperforators– Paramedian branches ofParamedian branches of the basilar artery the basilar artery

EPIDEMIOLOGYEPIDEMIOLOGY Lobar haemorrhageLobar haemorrhage vs deep haemorrhage vs deep haemorrhage

– Haemorrhage into the occipital, temporal, frontal and Haemorrhage into the occipital, temporal, frontal and parietal lobes as opposed to deep structures – BG, parietal lobes as opposed to deep structures – BG, thalamus, infratentorial structuresthalamus, infratentorial structures

– More likely associated with More likely associated with structural abnormalitiesstructural abnormalities– More common in patients with high alcohol consumptionMore common in patients with high alcohol consumption– More benign outcomeMore benign outcome– CausesCauses

Extension of deep haemorrhageExtension of deep haemorrhage Cerebral amyloid angiopathyCerebral amyloid angiopathy TraumaTrauma Haemorrhagic transformationHaemorrhagic transformation TumourTumour AVM/aneurysmAVM/aneurysm

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Chronic hypertensionChronic hypertension stimulates the brain's stimulates the brain's blood vessels to make gradual, blood vessels to make gradual, adaptive adaptive changeschanges in an attempt to in an attempt to preserve the blood-preserve the blood-brain barrier brain barrier

One gradual change that may develop is One gradual change that may develop is lipohyalinosislipohyalinosis

Subintimal fibroblast proliferation occurs, Subintimal fibroblast proliferation occurs, with an accumulation of lipid-laden with an accumulation of lipid-laden macrophages and cholesterol deposits; this macrophages and cholesterol deposits; this results in results in hyalinization and lipidosishyalinization and lipidosis of the of the blood vessels blood vessels

This process segmentally affects the This process segmentally affects the smaller smaller penetrating arteriespenetrating arteries (<200 mm in diameter) (<200 mm in diameter)

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

Plasma leakagePlasma leakage from persistently from persistently elevated blood pressures also can elevated blood pressures also can result in result in hyaline degenerationhyaline degeneration of the of the cerebral blood vessels cerebral blood vessels

Arterial sclerosis and fibrinoid necrosisArterial sclerosis and fibrinoid necrosis may occur, as well as focal aneurysmal may occur, as well as focal aneurysmal dilatation (Charcot-Bouchard dilatation (Charcot-Bouchard intracerebral microaneurysm)intracerebral microaneurysm)

HemorrhageHemorrhage may then arise from may then arise from rupture of the Charcot-Bouchard rupture of the Charcot-Bouchard aneurysms aneurysms

ManagementManagement

1.1. CTCT of the head is the imaging procedure of of the head is the imaging procedure of choice in the initial evaluation of suspected choice in the initial evaluation of suspected ICHICH

2.2. Angiography should be considered for all Angiography should be considered for all patients patients without a clear cause of without a clear cause of hemorrhagehemorrhage who are who are surgical candidatessurgical candidates, , particularly young, normotensive patients particularly young, normotensive patients who are clinically stable.who are clinically stable.

3.3. Angiography is Angiography is not requirednot required for older for older hypertensive patients who have a hypertensive patients who have a hemorrhage in the basal ganglia, thalamus, hemorrhage in the basal ganglia, thalamus, cerebellum, or brain stem and in whom CT cerebellum, or brain stem and in whom CT findings do not suggest a structural lesion findings do not suggest a structural lesion

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

(1999 American Heart Association )

4. MRI and MRA are helpful and may obviate 4. MRI and MRA are helpful and may obviate the need for contrast cerebral angiography in the need for contrast cerebral angiography in selected patients. They should also be selected patients. They should also be considered to look for considered to look for cavernous cavernous malformationsmalformations in in normotensive patients with normotensive patients with lobar hemorrhageslobar hemorrhages and and normal angiographicnormal angiographic results who are surgical candidates results who are surgical candidates

Guidelines for the Management of Spontaneous Intracerebral Hemorrhage

(1999 American Heart Association )

ManagementManagement

ManagementManagement - - TreatmentTreatment

MedicalMedical SurgicalSurgical

There is a lack of proven medical or There is a lack of proven medical or surgical treatment for ICHsurgical treatment for ICH

This has lead to great variation among This has lead to great variation among physicians concerning both surgical physicians concerning both surgical and medical treatmentand medical treatment

Well-designed and well-executed Well-designed and well-executed randomized treatment studies of ICH randomized treatment studies of ICH are urgently neededare urgently needed


MedicalMedical Airway and oxygenationAirway and oxygenation Blood pressureBlood pressure ICPICP Fluid managementFluid management Prevention of seizuresPrevention of seizures Body temperatureBody temperature Other issuesOther issues


Airway and oxygenationAirway and oxygenation Although intubation is not required for Although intubation is not required for

all patients, all patients, airway protectionairway protection and and adequate ventilationadequate ventilation are critical are critical

Patients who exhibit a decreasing level Patients who exhibit a decreasing level of consciousness or signs of of consciousness or signs of brain stem brain stem dysfunctiondysfunction are candidates are candidates

Intubation should be guided by Intubation should be guided by imminent respiratory insufficiency imminent respiratory insufficiency rather than an arbitrary cutoff such as rather than an arbitrary cutoff such as a specific Glasgow Coma Scale (GCS) a specific Glasgow Coma Scale (GCS) score score

“Guidelines for the Management of Spontaneous Intracerebral Hemorrhage”

by the American Heart Association 1999


Indications for intubationIndications for intubation– hypoxiahypoxia (pO2 (pO2 <60<60 mm Hg or PCO2 mm Hg or PCO2 >50>50 mm mm

Hg) Hg) – risk of aspirationrisk of aspiration with or without with or without

impairment of arterial oxygenationimpairment of arterial oxygenation AllAll patients with endotracheal tubes patients with endotracheal tubes

receive receive nasogastric or orogastric tubesnasogastric or orogastric tubes to prevent aspiration and are monitored to prevent aspiration and are monitored for for cuff pressure every 6 hourscuff pressure every 6 hours

Endotracheal tubes with soft cuffs can Endotracheal tubes with soft cuffs can generally be maintained for 2 weeks generally be maintained for 2 weeks




In the presence of prolonged In the presence of prolonged coma or pulmonary coma or pulmonary complications, complications, elective elective tracheostomytracheostomy should be should be performed after 2 weeks performed after 2 weeks

OxygenOxygen should be administered should be administered to to allall patients presenting with a patients presenting with a possible ICH possible ICH




Blood PressureBlood Pressure Optimal level of a patient's blood pressure Optimal level of a patient's blood pressure

should be based on individual factors should be based on individual factors – Chronic Chronic hypertensionhypertension– Raised Raised ICPICP– CauseCause of haemorrhage of haemorrhage

The theoretical rationale for The theoretical rationale for lowering blood lowering blood pressurepressure is to is to decreasedecrease the risk of on going the risk of on going bleedingbleeding from ruptured small arteries and from ruptured small arteries and arterioles arterioles

Conversely, over aggressive treatment of Conversely, over aggressive treatment of blood pressure may blood pressure may decrease cerebral decrease cerebral perfusionperfusion pressure and theoretically pressure and theoretically worsenworsen brain injury brain injury




Blood pressure levels be maintained below a Blood pressure levels be maintained below a mean arterial pressure of 130 mm Hgmean arterial pressure of 130 mm Hg in in persons with a history of hypertension persons with a history of hypertension (level (level of evidence V, grade C recommendation)of evidence V, grade C recommendation)

In patients with elevated ICP who have an ICP In patients with elevated ICP who have an ICP monitor, monitor, cerebral perfusion pressurecerebral perfusion pressure (MAP– (MAP–ICP) should be kept ICP) should be kept >70 mm Hg>70 mm Hg (level of (level of evidence V, grade C recommendation)evidence V, grade C recommendation)

Mean arterial blood pressure Mean arterial blood pressure >110 mm Hg>110 mm Hg should be should be avoidedavoided in the in the immediate immediate postoperative periodpostoperative period

If systolic arterial blood pressure falls below If systolic arterial blood pressure falls below 90 mm Hg, 90 mm Hg, pressors pressors should be givenshould be given



Elevated blood pressureElevated blood pressure Labetalol 5–100 mg/h by intermittent bolus doses of 10–40 mg or continuous drip (2–8 mg/min)

Esmolol 500 µg/kg as a load; maintenance use, 50–200 µg · kg -1 · min-1

Nitroprusside 0.5–10 µg · kg-1 · min-1

Hydralazine 10–20 mg Q 4–6 h

Enalapril 0.625–1.2 mg Q 6 h as needed

1. If 1. If systolicsystolic BP is >230 mm Hg or BP is >230 mm Hg or diastolicdiastolic BP >140 mm Hg on 2 readings 5 minutes apart, institute BP >140 mm Hg on 2 readings 5 minutes apart, institute

nitroprusside.nitroprusside. 2. If 2. If systolicsystolic BP is 180 to 230 mm Hg, BP is 180 to 230 mm Hg, diastolicdiastolic BP 105 to 140 mm Hg, or mean arterial BP 130 mm BP 105 to 140 mm Hg, or mean arterial BP 130 mm Hg on 2 readings 20 minutes apart, institute intravenous labetalol, esmolol, enalapril, or other Hg on 2 readings 20 minutes apart, institute intravenous labetalol, esmolol, enalapril, or other smaller doses of easily titratable intravenous medications such as diltiazem, lisinopril, or verapamil. smaller doses of easily titratable intravenous medications such as diltiazem, lisinopril, or verapamil.

3. If 3. If systolicsystolic BP is <180 mm Hg and BP is <180 mm Hg and diastolicdiastolic BP <105 mm Hg, defer antihypertensive therapy. BP <105 mm Hg, defer antihypertensive therapy. Choice of medication depends on other medical contraindications (eg, avoid labetalol in patients with Choice of medication depends on other medical contraindications (eg, avoid labetalol in patients with asthma). asthma).

4. If ICP monitoring is available, cerebral perfusion pressure should be kept at >70 mm Hg. 4. If ICP monitoring is available, cerebral perfusion pressure should be kept at >70 mm Hg.

Low blood pressureLow blood pressure Volume replenishment is the first line of approach. Isotonic saline or colloids can be used and Volume replenishment is the first line of approach. Isotonic saline or colloids can be used and monitored with central venous pressure or pulmonary artery wedge pressure. If hypotension persists monitored with central venous pressure or pulmonary artery wedge pressure. If hypotension persists after correction of volume deficit, continuous infusions of pressors should be considered, particularly after correction of volume deficit, continuous infusions of pressors should be considered, particularly for low systolic blood pressure such as <90 mm Hg. for low systolic blood pressure such as <90 mm Hg.

Phenylephrine 2–10 µg · kg-1 · min-1

Dopamine 2–20 µg · kg-1 · min-1

Norepinephrine Titrate from 0.05–0.2 µg · kg-1 · min-1


ICPICP ICP may be managed through head position, ICP may be managed through head position,

osmotherapy, controlled hyperventilation, osmotherapy, controlled hyperventilation, and barbiturate comaand barbiturate coma

Elevated ICP is defined as intracranial Elevated ICP is defined as intracranial pressure pressure 20 mm Hg for >5 minutes20 mm Hg for >5 minutes

A therapeutic goal for all treatment of A therapeutic goal for all treatment of elevated ICP is elevated ICP is ICP <20 mm HgICP <20 mm Hg and cerebral and cerebral perfusion pressure perfusion pressure (CPP) >70 mm Hg(CPP) >70 mm Hg

Patients with suspected elevated ICP and Patients with suspected elevated ICP and deteriorating level of consciousness are deteriorating level of consciousness are candidates for invasive ICP monitoring candidates for invasive ICP monitoring




In general, ICP monitors should be placed in In general, ICP monitors should be placed in (but not limited to) patients with a GCS score (but not limited to) patients with a GCS score of <9 and all patients whose condition is of <9 and all patients whose condition is thought to be deteriorating due to elevated thought to be deteriorating due to elevated ICP ICP (level of evidence V, grade C (level of evidence V, grade C recommendation)recommendation)

Ventricular drainsVentricular drains should be used in patients should be used in patients with or at risk for hydrocephalus with or at risk for hydrocephalus

Because of infectious complications, external Because of infectious complications, external drainage devices must be drainage devices must be checked regularlychecked regularly, , and duration of and duration of placement ideally should not placement ideally should not exceed 7 daysexceed 7 days (level of evidence V, grade C (level of evidence V, grade C recommendation)recommendation)




Use of Use of anti-infectious prophylaxisanti-infectious prophylaxis is is recommended (level of evidence V, grade C recommended (level of evidence V, grade C recommendation) recommendation)

The beneficial effect of sustained The beneficial effect of sustained hyperventilation on ICP is unresolved hyperventilation on ICP is unresolved

When hyperventilation is deemed no longer When hyperventilation is deemed no longer necessary, necessary, gradual normalization of serum gradual normalization of serum PCO2PCO2 should occur over a 24- to 48-hour should occur over a 24- to 48-hour period period

In general, if hyperventilation is instituted for In general, if hyperventilation is instituted for elevated ICP, PCO2 should be maintained elevated ICP, PCO2 should be maintained between between 30 and 35 mm30 and 35 mm Hg until ICP is Hg until ICP is controlledcontrolled

Emergency ICP Emergency ICP therapytherapy

– Comatose patient with clinical signs Comatose patient with clinical signs of brainstem herniationof brainstem herniation Head up 30 degreeHead up 30 degree Mannitol 20% 1-1.5gm/kgMannitol 20% 1-1.5gm/kg Hyperventilation Pco2 30-35 mmHgHyperventilation Pco2 30-35 mmHg

– ““Buy time” before a definitive Buy time” before a definitive neurosurgical procedureneurosurgical procedure

Management of ICPManagement of ICP

OsmotherapyOsmotherapy– The first medical line of defense is osmotherapy. The first medical line of defense is osmotherapy.

However, it However, it should not be used prophylacticallyshould not be used prophylactically. . – Mannitol 20% (Mannitol 20% (0.25–0.5 g/kg every 4 h0.25–0.5 g/kg every 4 h) is reserved ) is reserved

for patients with for patients with type B ICP wavestype B ICP waves, progressively , progressively increasing ICP values, or clinical deterioration increasing ICP values, or clinical deterioration associated with mass effect (level of evidence V, associated with mass effect (level of evidence V, grade C recommendation). grade C recommendation).

– Due to its rebound phenomenon, mannitol is Due to its rebound phenomenon, mannitol is recommended for only 5 d. recommended for only 5 d.

– To maintain an osmotic gradient, furosemide (10 To maintain an osmotic gradient, furosemide (10 mg Q 2–8 h) may be administered simultaneously mg Q 2–8 h) may be administered simultaneously with osmotherapy. with osmotherapy.

– Serum osmolality should be measured twice daily Serum osmolality should be measured twice daily in patients receiving osmotherapy and targeted to in patients receiving osmotherapy and targeted to 310 mOsm/L.310 mOsm/L.

ManagementManagement of ICPof ICP

No steroidsNo steroids– Corticosteroids in ICH are generally Corticosteroids in ICH are generally

avoided because multiple potential avoided because multiple potential side effects must be considered and side effects must be considered and clinical studies have not shown clinical studies have not shown benefit (level of evidence II, grade B benefit (level of evidence II, grade B recommendation).recommendation).


HyperventilationHyperventilation– Hypocarbia causes cerebral vasoconstriction. Hypocarbia causes cerebral vasoconstriction. – Reduction of cerebral blood flow is almost Reduction of cerebral blood flow is almost

immediate, although peak ICP reduction may immediate, although peak ICP reduction may take up to 30 minutes after pCO2 is changed. take up to 30 minutes after pCO2 is changed.

– Reduction of pCO2 to 35–30 mm Hg, best Reduction of pCO2 to 35–30 mm Hg, best achieved by raising ventilation rate at achieved by raising ventilation rate at constant tidal volume (12–14 mL/kg), lowers constant tidal volume (12–14 mL/kg), lowers ICP 25% to 30% in most patients (levels of ICP 25% to 30% in most patients (levels of evidence III through V, grade C evidence III through V, grade C recommendation). recommendation).

– Failure of elevated ICP to respond to Failure of elevated ICP to respond to hyperventilation indicates a poor prognosis.hyperventilation indicates a poor prognosis.


Muscle relaxantsMuscle relaxants– Neuromuscular paralysis in combination with Neuromuscular paralysis in combination with

adequate sedation can reduce elevated ICP by adequate sedation can reduce elevated ICP by preventing increases in intrathoracic and venous preventing increases in intrathoracic and venous pressure associated with coughing, straining, pressure associated with coughing, straining, suctioning, or "bucking" the ventilator (levels of suctioning, or "bucking" the ventilator (levels of evidence III through V, grade C recommendation). evidence III through V, grade C recommendation).

– Nondepolarizing agents, such as vecuronium or Nondepolarizing agents, such as vecuronium or pancuronium, with only minor histamine liberation pancuronium, with only minor histamine liberation and ganglion-blocking effects, are preferred in this and ganglion-blocking effects, are preferred in this situation (levels of evidence III through V, grade C situation (levels of evidence III through V, grade C recommendation). recommendation).

– Patients with critically elevated ICP should be Patients with critically elevated ICP should be pretreated with a bolus of a muscle relaxant before pretreated with a bolus of a muscle relaxant before airway suctioning. Alternatively, lidocaine may be airway suctioning. Alternatively, lidocaine may be used for this purpose.used for this purpose.


Barbiturate ComaBarbiturate Coma– Short acting thiopental 2-5 mg/kg slow stat then Short acting thiopental 2-5 mg/kg slow stat then

1-5mg/kg/hour1-5mg/kg/hour– Decreased cerebral metabolism, decreased CBF Decreased cerebral metabolism, decreased CBF

and CBVand CBV– Beware of hypotensionBeware of hypotension

– Max reduction in cerebral metabolism is Max reduction in cerebral metabolism is

accompanied by electrocerebral silenceaccompanied by electrocerebral silence


Fluid ManagementFluid Management The goal of fluid management is euvolemia The goal of fluid management is euvolemia CVP should be maintained between 5 and 12 CVP should be maintained between 5 and 12

mm Hg or pulmonary wedge pressure at 10 mm Hg or pulmonary wedge pressure at 10 to 14 mm Hg to 14 mm Hg

Fluid balance is calculated by measuring Fluid balance is calculated by measuring daily urine production and adding for daily urine production and adding for insensible water loss (urine output plus 500 insensible water loss (urine output plus 500 mL for insensible loss plus 300 mL per mL for insensible loss plus 300 mL per degree in febrile patients) degree in febrile patients)

Electrolytes (sodium, potassium, calcium, Electrolytes (sodium, potassium, calcium, and magnesium) should be checked and and magnesium) should be checked and substituted according to normal values substituted according to normal values


Prevention of SeizuresPrevention of Seizures Seizure activity can result in neuronal injury Seizure activity can result in neuronal injury

and destabilization of an already critically ill and destabilization of an already critically ill patient and must be treated aggressively patient and must be treated aggressively

In patients with ICH, prophylactic In patients with ICH, prophylactic antiepileptic therapy (preferably phenytoin antiepileptic therapy (preferably phenytoin with doses titrated according to drug levels with doses titrated according to drug levels [14 to 23 µg/mL]) may be considered for 1 [14 to 23 µg/mL]) may be considered for 1 month and then tapered and discontinued if month and then tapered and discontinued if no seizure activity occurs during treatment, no seizure activity occurs during treatment, although data supporting this therapy are although data supporting this therapy are lacking (level of evidence V, grade C lacking (level of evidence V, grade C recommendation)recommendation)


Body TemperatureBody Temperature Body temperature should be maintained at Body temperature should be maintained at

normal levels normal levels Acetaminophen 650 mgAcetaminophen 650 mg or cooling blankets or cooling blankets

should be used to treat hyperthermia >38.5° should be used to treat hyperthermia >38.5° C C

Febrile patients or those at risk for infection, Febrile patients or those at risk for infection, appropriate cultures and smears (tracheal, appropriate cultures and smears (tracheal, blood, and urine) should be obtained and blood, and urine) should be obtained and antibiotics givenantibiotics given

NutritionNutrition Enteral feeding should be started within 48h Enteral feeding should be started within 48h

to reduce risk of malnutritionto reduce risk of malnutrition


DVT preventionDVT prevention – Dynamic compression stockings Dynamic compression stockings

should be placed on admissionshould be placed on admission– Medications at day 2Medications at day 2

SC heparin 5000u bdSC heparin 5000u bd LMW heparin enoxaparin 40 mg dailyLMW heparin enoxaparin 40 mg daily No increased in intracranial bleedingNo increased in intracranial bleeding

Boeer A, Voth E, Henze T, Prange HW. Early heparin therapy in patients with spontaneous intracerebral haemorrhage.

J Neurol Neurosurg Psychiatry 1991; 54: 466–67.

Reversal of Reversal of coagulationcoagulation

– Warfarin – increase risk of ICH 5-10XWarfarin – increase risk of ICH 5-10X Reverse with FFP & Vit KReverse with FFP & Vit K

– Aim INR <1.4Aim INR <1.4– Low molecule heparinLow molecule heparin

Reverse with protamine sulfate 1mg to Reverse with protamine sulfate 1mg to 1 mg enoxaparin1 mg enoxaparin


Other IssuesOther Issues Many patients who are delirious or stuporous Many patients who are delirious or stuporous

are agitated are agitated Prudent use of minor and major tranquilizers Prudent use of minor and major tranquilizers

is recommended is recommended Short-acting benzodiazepines or propofol are Short-acting benzodiazepines or propofol are

preferred preferred Pulmonary embolism is a common threat Pulmonary embolism is a common threat

during the recovery period, particularly for during the recovery period, particularly for bedridden patients with hemiplegia. bedridden patients with hemiplegia. Pneumatic devices decrease the risk of Pneumatic devices decrease the risk of pulmonary embolism during hospitalizationpulmonary embolism during hospitalization

Depending on the patient's clinical state, Depending on the patient's clinical state, physical therapy, speech therapy, and physical therapy, speech therapy, and occupational therapy should be initiated as occupational therapy should be initiated as soon as possible soon as possible


Surgical TreatmentSurgical TreatmentManagement of cerebral haemorrhage - Management of cerebral haemorrhage -

Karolinska Stroke Update Consensus Karolinska Stroke Update Consensus Statement 2004Statement 2004

As yet, an advantage of neurosurgical As yet, an advantage of neurosurgical intervention over medical treatment has not intervention over medical treatment has not been establishedbeen established

Surgical TreatmentSurgical Treatment

ICH Treatment TargetsICH Treatment Targets

• • Expanding hematomaExpanding hematoma– – Local shear forcesLocal shear forces– – Mass effectMass effect– ↑ – ↑ Intracranial pressure (ICP)Intracranial pressure (ICP)

• • Local toxic effectsLocal toxic effects– – Direct toxicity of blood Direct toxicity of blood

productsproducts– – EdemaEdema– – ExcitotoxicityExcitotoxicity


Recently, three RCTs evaluating new Recently, three RCTs evaluating new strategies for the treatment of the ICH strategies for the treatment of the ICH have been completed.have been completed.– a. Early surgery versus initial a. Early surgery versus initial

conservative treatment in patients with conservative treatment in patients with spontaneous supratentorial ICH (The spontaneous supratentorial ICH (The International STICH trial);International STICH trial);

– b. Stereotactic aspiration combined with b. Stereotactic aspiration combined with instillation of fibrynolitic agent (The instillation of fibrynolitic agent (The SICHPA trial);SICHPA trial);

– c. Ultra-early haemostatic therapy by c. Ultra-early haemostatic therapy by using the recombinant activated factor using the recombinant activated factor VIIa (The Novo-7 trial)VIIa (The Novo-7 trial)

Comparison between early surgery combined Comparison between early surgery combined hematoma evacuation (within 24 hours of hematoma evacuation (within 24 hours of randomization) with medical treatment.randomization) with medical treatment.

FINDINGS: FINDINGS: A total of 1,033 patients from 83 centers in A total of 1,033 patients from 83 centers in 27 countries were randomized to early surgery (503) or 27 countries were randomized to early surgery (503) or initial conservative treatment (530). At 6 months, 51 initial conservative treatment (530). At 6 months, 51 patients were lost to follow-up, and 17 were alive with patients were lost to follow-up, and 17 were alive with unknown status. unknown status. Of 468 patients randomized to Of 468 patients randomized to early surgery, 122 (26%) had a favorable outcome early surgery, 122 (26%) had a favorable outcome compared with 118 (24%) of 496 randomized to initial compared with 118 (24%) of 496 randomized to initial conservative treatment (odds ratio 0.89, 95% conservative treatment (odds ratio 0.89, 95% confidence interval 0.66 –1.19, confidence interval 0.66 –1.19, PP .414); absolute benefit .414); absolute benefit 2.3% (–3.2 to 7.7), relative benefit 10% (–13 to 33).2.3% (–3.2 to 7.7), relative benefit 10% (–13 to 33).

INTERPRETATION: INTERPRETATION: Patients with spontaneous Patients with spontaneous supratentorial intracerebral hemorrhage in supratentorial intracerebral hemorrhage in neurosurgical units show no overall benefit from early neurosurgical units show no overall benefit from early surgery when compared with initial conservative surgery when compared with initial conservative treatment.treatment.

Early surgery versus initial conservative treatment in Early surgery versus initial conservative treatment in patients with spontaneous supratentorial patients with spontaneous supratentorial intracerebral haematomas in the International intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): Surgical Trial in Intracerebral Haemorrhage (STICH): a randomized triala randomized trial

Mendelow AD, Gregson BA, Fernandes HM, Murray GD,Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH; STICHinvestigators. Lancet 2005;365:387–97.


The results of SICHPA trialThe results of SICHPA trial ( ( Stereotatactic Treatment of Stereotatactic Treatment of Intracerebral Haematoma by means of Intracerebral Haematoma by means of a Plasminogen Activatora Plasminogen Activator

The trial was prematurely stopped because The trial was prematurely stopped because of low recruitment. A cautious conclusion of low recruitment. A cautious conclusion could be made that stereotactic aspiration of could be made that stereotactic aspiration of supratentorial hematoma after instillation of supratentorial hematoma after instillation of a plasminogen activator can be performed a plasminogen activator can be performed safely. It may reduce the hematoma volume safely. It may reduce the hematoma volume significantly significantly


Main results of Novo-7 trial Main results of Novo-7 trial Treatment with rFVIIa within 4 hours Treatment with rFVIIa within 4 hours

reduced hematoma expansion, reduced hematoma expansion, decreased mortality, and improved decreased mortality, and improved clinical outcome significantly, despite clinical outcome significantly, despite slight increase in the risk of slight increase in the risk of thromboembolic events. thromboembolic events.

A phase III trial is needed to confirm the A phase III trial is needed to confirm the beneficial effect of rFVIIa in acute ICHbeneficial effect of rFVIIa in acute ICH

– FAST trial – phase 3FAST trial – phase 3– Doses 20, 80 ug/kgDoses 20, 80 ug/kg– Within 4 hour of ictusWithin 4 hour of ictus

Criteria for surgeryCriteria for surgery

AgeAge Hematoma VolumeHematoma Volume Location (Supra / Infratentorial)Location (Supra / Infratentorial) ProgressionProgression Timing of surgeryTiming of surgery

AgeAge

Predictive role in outcome and mortality rate in patients with Predictive role in outcome and mortality rate in patients with ICHICH1010

Age older than 60 years implies poor prognosis regardless of Age older than 60 years implies poor prognosis regardless of treatmenttreatment– Mortality rate (surgically treated): (Auer LM et al, J Mortality rate (surgically treated): (Auer LM et al, J

Neurosurgery, 1989)Neurosurgery, 1989) <60 years old<60 years old 25%25% >60 years old>60 years old 65%65%

The relationship between age and outcome more The relationship between age and outcome more pronounced with thalamic hemarrhagepronounced with thalamic hemarrhage1010

Patients with “rapidly progressive*” hematoma by serial CT Patients with “rapidly progressive*” hematoma by serial CT scan, age older than 65 years was associated with 100% scan, age older than 65 years was associated with 100% mortalitymortality1010

• Patients who were obtunded or stuporous without herniation signs

10Youmans Neurological Surgery Fifth Edition Volume 2 : Chapter 105 pages 1733-1768

Hematoma VolumeHematoma Volume

Volume of hematoma based on CT scan measurement is a Volume of hematoma based on CT scan measurement is a strong predictor of functional outcome and death.strong predictor of functional outcome and death.1010

[Volume = 4/3 x [Volume = 4/3 x ΠΠ x LWH ÷ 8 or LWH ÷ 2] x LWH ÷ 8 or LWH ÷ 2] Broderick et JP, Brott TG, Duldner JE, et al: Volume of ICH: A Broderick et JP, Brott TG, Duldner JE, et al: Volume of ICH: A

powerful and easy-to-use predictor of 30-day mortality. powerful and easy-to-use predictor of 30-day mortality. Stroke 24:987-993, 1993Stroke 24:987-993, 1993

MortalitMortalityy

<30cm<30cm33

30-30-60cm360cm3

>60cm>60cm33

DeepDeep 23%23% 64%64% 93%93%

LobarLobar 7%7% 60%60% 71%71%


Hematoma VolumeHematoma Volume

Volpin et al, Neurosurgery (1984) retrospective reviewed of Volpin et al, Neurosurgery (1984) retrospective reviewed of 132 patients with supratentorial ICH, 132 patients with supratentorial ICH, – those with hematoma volume >85cm3 have 100% those with hematoma volume >85cm3 have 100%

mortality irrespective of treatmentmortality irrespective of treatment– Those with hematoma volume <26cm3, all survived Those with hematoma volume <26cm3, all survived

without surgerywithout surgery Large-volume thalamic hematoma are more devastating Large-volume thalamic hematoma are more devastating

than similar sized subcortical or putaminal hematomasthan similar sized subcortical or putaminal hematomas1010

For infratentorial hematoma, all cerebellar hematoma For infratentorial hematoma, all cerebellar hematoma greater than 3 cm in diameter is recommended for surgerygreater than 3 cm in diameter is recommended for surgery1010


ProgressionProgression

Broderick et al (1993) and Fujitsu K et al (1990) found that Broderick et al (1993) and Fujitsu K et al (1990) found that rehemorrhage typically occurs within the first 6 hours of the rehemorrhage typically occurs within the first 6 hours of the primary ictusprimary ictus

Deterioration occur later than 6 hours after hemorrhage can Deterioration occur later than 6 hours after hemorrhage can be contributed by other factors such as edema, be contributed by other factors such as edema, hydrocephalus, new IVH or metabolic abnormality.hydrocephalus, new IVH or metabolic abnormality.

Patients’ clinical severity at 6 hours most accurately Patients’ clinical severity at 6 hours most accurately represented the severity of the ictus:represented the severity of the ictus:– Fulminant Fulminant - Poor outcome despite treatment- Poor outcome despite treatment– Rapidly progressiveRapidly progressive - outcome improved with - outcome improved with

hematoma evacuationhematoma evacuation– Slowly progressive Slowly progressive - no significant difference in - no significant difference in

outcome based on treatmentoutcome based on treatment

Fulminant = comatose, obtunded, herniation signs

Slowly progressive = lethargy at 6 hours

Timing of SurgeryTiming of Surgery In the case of spontaneous ICH, earlier interventions would In the case of spontaneous ICH, earlier interventions would

intuitively appear superiorintuitively appear superior Early evacuation of hematoma improves CBF, brain edema, Early evacuation of hematoma improves CBF, brain edema,

ischemia, and outcome.ischemia, and outcome. It is supported by the following facts:It is supported by the following facts:

– 50% death of patient with ICH occur within 48 hours of 50% death of patient with ICH occur within 48 hours of hemorrhagehemorrhage

– Radiographic expansion or rebleeding occurs maximally Radiographic expansion or rebleeding occurs maximally within 3-4 hourswithin 3-4 hours

– Exacerbation occurs suddenly and most often within 4 to 6 Exacerbation occurs suddenly and most often within 4 to 6 hours of bleedinghours of bleeding

– Secondary changes such as edema occur 7 to 8 hours after Secondary changes such as edema occur 7 to 8 hours after a hemorrhagea hemorrhage

Timing of SurgeryTiming of Surgery

Brott T et al. Brott T et al. StrokeStroke. 1997; Early hemorrhage expansion is . 1997; Early hemorrhage expansion is common. ~1/3 of patients who present within 3 hours of common. ~1/3 of patients who present within 3 hours of symptom onset will have substantial ICH expansionsymptom onset will have substantial ICH expansion

Timing of SurgeryTiming of Surgery

2Neurosurg Focus 15 (4):Article 2, 2003, Update on management of intracerebral hemorrhage, NADER POURATIAN, M.D., PH.D., NEAL F. KASSELL, M.D., AND AARON S. DUMONT, M.D.

Kaneko and colleagues[1983] also demonstrated superior Kaneko and colleagues[1983] also demonstrated superior outcomes (relative to epidemiological data) when they reported outcomes (relative to epidemiological data) when they reported a 6-month 7% mortality rate in a series of patients with 100 a 6-month 7% mortality rate in a series of patients with 100 putaminal ICHs treated surgically within 7 hours of ictusputaminal ICHs treated surgically within 7 hours of ictus

Zuccarello M, Brott T, Derex, et al [1999] and Morgenstern LB, Zuccarello M, Brott T, Derex, et al [1999] and Morgenstern LB, Frankowski RF, Shedden P, Pasteur W, Grotta JC; Surgical Frankowski RF, Shedden P, Pasteur W, Grotta JC; Surgical treatment for intracerebral hemorrhage (STICH), [1998] are 2 treatment for intracerebral hemorrhage (STICH), [1998] are 2 pilot studies suggested a benefit with early surgery (<12 hours) pilot studies suggested a benefit with early surgery (<12 hours) but were limited by small numbers.but were limited by small numbers.

Morgenstern and colleagues[2001] showed that ultra-early Morgenstern and colleagues[2001] showed that ultra-early surgery (that is, 4 hours after ICH) is associated with increased surgery (that is, 4 hours after ICH) is associated with increased re-hemorrhage and mortality rates re-hemorrhage and mortality rates

A recent surgical evaluation of ultra-early evacuation of ICH (<3 A recent surgical evaluation of ultra-early evacuation of ICH (<3 hours) was stopped after interim analysis because of an hours) was stopped after interim analysis because of an increased rate of rebleeding.2increased rate of rebleeding.2

Patient’s selectionPatient’s selection

Significant consideration for surgical intervention is given in Significant consideration for surgical intervention is given in cases involving younger patients (that is, those cases involving younger patients (that is, those < 60 years< 60 years of age) with of age) with superficial hemorrhagessuperficial hemorrhages (particularly in the (particularly in the non-dominant hemisphere) in whom neurological status non-dominant hemisphere) in whom neurological status deteriorates after an initially good presentationdeteriorates after an initially good presentation22

Patients with relatively normal consciousness (GCS Scores Patients with relatively normal consciousness (GCS Scores 13–1513–15) rarely require surgery, whereas deeply comatose ) rarely require surgery, whereas deeply comatose patients (GCS Scores patients (GCS Scores 3–53–5) rarely benefit from surgery.) rarely benefit from surgery.44

Surgery is therefore usually considered to have the most Surgery is therefore usually considered to have the most potential benefit for the group of patients with GCS scores potential benefit for the group of patients with GCS scores between between 6 and 126 and 12 or in patients with deteriorating status or in patients with deteriorating status44

2Neurosurg Focus 15 (4):Article 2, 2003, Update on management of intracerebral hemorrhage, NADER POURATIAN, M.D., PH.D., NEAL F. KASSELL, M.D., AND AARON S. DUMONT, M.D.

4Neurosurg Focus 15 (4):Article 1, 2003, Spontaneous intracerebral hemorrhage: a review MATTHEW E. FEWEL, M.D., B. GREGORY THOMPSON, JR., M.D., AND JULIAN T. HOFF, M.D

Patient’s selectionPatient’s selection There is a neurosurgical bias toward more aggressive surgery There is a neurosurgical bias toward more aggressive surgery

for nondominant hemispheric hemorrhages, although the for nondominant hemispheric hemorrhages, although the authors of outcome studies have indicated that despite authors of outcome studies have indicated that despite language disability associated with dominant hemispheric language disability associated with dominant hemispheric lesions, functional outcome is not necessarily worse.lesions, functional outcome is not necessarily worse.44

Standard craniotomy for primary Standard craniotomy for primary brainstem or thalamic brainstem or thalamic hemorrhageshemorrhages has been all but abandoned because of poor has been all but abandoned because of poor outcomesoutcomes44

Apparently successful cases of stereotactic aspiration of Apparently successful cases of stereotactic aspiration of pontine hematomas have been reported, but the effect on pontine hematomas have been reported, but the effect on prognosis remains unproven.prognosis remains unproven.44

Kanaya and Kuroda [1992] recommended surgical treatment if Kanaya and Kuroda [1992] recommended surgical treatment if the hematoma volume was larger than 30 ml and the level of the hematoma volume was larger than 30 ml and the level of consciousness was somnolent to semicomatose.consciousness was somnolent to semicomatose.


Summary of Guidelines Summary of Guidelines for Removal of ICHfor Removal of ICH

Nonsurgical candidates1.

Patients with small hemorrhages (<10 cm3) or minimal neurological deficits (levels of evidence II through V, grade B recommendation).

2.

Patients with a GCS score 4 (levels of evidence II through V, grade B recommendation). However, patients with a GCS score 4 who have a cerebellar hemorrhage with brain stem compression may still be candidates for lifesaving surgery in certain clinical situations.

Surgical candidates1.

Patients with cerebellar hemorrhage >3 cm who are neurologically deteriorating or who have brain stem compression and hydrocephalus from ventricular obstruction should have surgical removal of the hemorrhage as soon as possible (levels of evidence III through V, grade C recommendation).

2.

ICH associated with a structural lesion such as an aneurysm, arteriovenous malformation, or cavernous angioma may be removed if the patient has a chance for a good outcome and the structural vascular lesion is surgically accessible (levels of evidence III through V, grade C recommendation).

3.

Young patients with a moderate or large lobar hemorrhage who are clinically deteriorating (levels of evidence II through V, grade B recommendation).

Best therapy unclear

American Heart Association : Guidelines for the Management of Spontaneous

Intracerebral Hemorrhage, 1998

Surgical TechniquesSurgical Techniques

In 1903, Cushing first removed an intracerebral hematoma In 1903, Cushing first removed an intracerebral hematoma by craniotomyby craniotomy

However operative mortality are high, ranging from 20-90%However operative mortality are high, ranging from 20-90% Because of this, various less invasive methods of removal Because of this, various less invasive methods of removal

are practised like simple aspiration, stereotactic aspiration, are practised like simple aspiration, stereotactic aspiration, fibrinolytic treatment, mechanically assisted aspiration, and fibrinolytic treatment, mechanically assisted aspiration, and endoscopy.endoscopy.

In particular circumstances, some of these techniques may In particular circumstances, some of these techniques may be more efficacious for deep putaminal or thalamic be more efficacious for deep putaminal or thalamic hemorrhages. hemorrhages.

Others are beneficial for subcortical hematomas.Others are beneficial for subcortical hematomas.


Surgical TechniquesSurgical Techniques

The optimal surgical technique for hematoma evacuation is The optimal surgical technique for hematoma evacuation is not agreed uponnot agreed upon, although craniotomy remains the most , although craniotomy remains the most common.common.44

Traditional stereotaxy or frameless navigational systems, as Traditional stereotaxy or frameless navigational systems, as well as intraoperative ultrasonographic guidance, allow well as intraoperative ultrasonographic guidance, allow more precise clot localization and minimization of injury to more precise clot localization and minimization of injury to normal brainnormal brain44

Compared with craniotomy, minimally invasive techniques Compared with craniotomy, minimally invasive techniques such as stereotactic or endoscopic clot evacuation may offer such as stereotactic or endoscopic clot evacuation may offer the potential for a reduced incidence of surgery-related the potential for a reduced incidence of surgery-related complications and improved efficacy, but this has yet to be complications and improved efficacy, but this has yet to be proven.proven.44

4Neurosurg Focus 15 (4):Article 1, 2003, Spontaneous intracerebral hemorrhage: a review MATTHEW E. FEWEL, M.D., B. GREGORY THOMPSON, JR., M.D., AND JULIAN T. HOFF, M.D.

CraniotomyCraniotomy

The The most widely used surgical interventionmost widely used surgical intervention in ICH is in ICH is craniotomy and evacuation of the gross clot. craniotomy and evacuation of the gross clot.

This is a relatively invasive procedure associated with This is a relatively invasive procedure associated with additional risks by subjecting patients to surgery, potential additional risks by subjecting patients to surgery, potential brain manipulation, and anesthesia. brain manipulation, and anesthesia.

For putaminal hematoma, three general approaches have For putaminal hematoma, three general approaches have been used, ie been used, ie transtemporal, transfrontal and transsylviantranstemporal, transfrontal and transsylvian, , with preferred transcisternal-transsylvian-transinsular with preferred transcisternal-transsylvian-transinsular approach.approach.

Operating microscope is used routinely with bipolar Operating microscope is used routinely with bipolar coagulation, and graduated sucker. coagulation, and graduated sucker.

CraniotomyCraniotomy Avoid usage of Avoid usage of self-retaining retractorsself-retaining retractors as steady retraction is as steady retraction is

deleterious to brain parenchymal.deleterious to brain parenchymal. The The center of hematoma is removed firstcenter of hematoma is removed first with the remaining with the remaining

marginal clot then collapses and can likewise be evacuated.marginal clot then collapses and can likewise be evacuated. Particular attention to bleeding points and possible subtle Particular attention to bleeding points and possible subtle

pathologic findings such as small tumours, cryptic AVMs and pathologic findings such as small tumours, cryptic AVMs and carvenous angiomascarvenous angiomas

All tissue is sent for histologic analysisAll tissue is sent for histologic analysis Hemostasis is ensured by elevating systolic pressure Hemostasis is ensured by elevating systolic pressure

temporarily to identify potential rebleeding sites. temporarily to identify potential rebleeding sites.


CraniotomyCraniotomy

For large hematomas, For large hematomas, transcortical approachestranscortical approaches is evocated. is evocated. Transtemporal approachTranstemporal approach is used if hematomas significantly is used if hematomas significantly

extends into the temporal lobeextends into the temporal lobe The general surgical principles for evacuating hematomas at The general surgical principles for evacuating hematomas at

other locations, is corticotomies are placed other locations, is corticotomies are placed near the near the epicanter of the ICHepicanter of the ICH, their length is minimized, eloquent , their length is minimized, eloquent tissue is avoided.tissue is avoided.

For infratentorial hematomas, a For infratentorial hematomas, a suboccipitasuboccipital craniotomy is l craniotomy is standard, with paramedian incision, craniotomy rather standard, with paramedian incision, craniotomy rather craniectomy, and a ventriculostomy if hydrocephalus. craniectomy, and a ventriculostomy if hydrocephalus.


Burr Hole AspirationBurr Hole Aspiration

Unpredictable consistency of hematomas makes aspiration Unpredictable consistency of hematomas makes aspiration difficult.difficult.

Experiementally, within one hour of clot genesis, 80% of the Experiementally, within one hour of clot genesis, 80% of the clot becomes dense fibrous tissue.clot becomes dense fibrous tissue.

There is also a propensity to rebleed, which makes the lack There is also a propensity to rebleed, which makes the lack of visualization risker.of visualization risker.

Niizuma et al (1989) study the result of stereotactic Niizuma et al (1989) study the result of stereotactic aspiration in 175 patients with putaminal hemorrhage, noted aspiration in 175 patients with putaminal hemorrhage, noted 75% had more than 50% of the clot removed and 7.4% had 75% had more than 50% of the clot removed and 7.4% had post-operative bleeding.post-operative bleeding.

The low effectiveness and high rates of recurrence are major The low effectiveness and high rates of recurrence are major limitation.limitation.


Stereotactic AspirationStereotactic Aspiration

First used by Benes and coworkers in 1965 with limited First used by Benes and coworkers in 1965 with limited success and only in success and only in 1978,1978, Backlund and Von Holst Backlund and Von Holst performed first successful stereotactic aspiration of an acute performed first successful stereotactic aspiration of an acute hemorrhage.hemorrhage.

It has favourable outcome than craniotomy in It has favourable outcome than craniotomy in deep-seated deep-seated lesionslesions..

However, lack of direct visualization and the risk of However, lack of direct visualization and the risk of rebleeding may limit this technique’s utility especially during rebleeding may limit this technique’s utility especially during the hyperacute phase of hemorrhage.the hyperacute phase of hemorrhage.

Stereotactic Aspiration Stereotactic Aspiration and Clot Lysisand Clot Lysis

In 1985, Niizuma et al reported a In 1985, Niizuma et al reported a CT-guided technique of CT-guided technique of hematoma aspiration and lysis using urokinasehematoma aspiration and lysis using urokinase..

Fibrinolysis is used to fascilitate clot dissolution by activating Fibrinolysis is used to fascilitate clot dissolution by activating plasminogen, which dissolves fibrin.plasminogen, which dissolves fibrin.

Localization by direct-image projection on CT scanner with a Localization by direct-image projection on CT scanner with a radiopaque marker has approximately radiopaque marker has approximately 5mm error5mm error compared to compared to stereotaxy.stereotaxy.

After localization, 3-4mm silicone tube is passed into the clot After localization, 3-4mm silicone tube is passed into the clot and hematoma is aspirated with a syringe repeatedly until no and hematoma is aspirated with a syringe repeatedly until no more clot is removed.more clot is removed.

Then a Dandy ventricular catheter is placed into the hematoma Then a Dandy ventricular catheter is placed into the hematoma bed, and urokinase (bed, and urokinase (6000 U in 3 ml6000 U in 3 ml) is infused, repeated ) is infused, repeated two to two to four times a dayfour times a day in 1 to 6 days until CT documents clot in 1 to 6 days until CT documents clot ressolution.ressolution.


Compared to t-PA, Compared to t-PA, urokinase is cheaper, longer half-life and has urokinase is cheaper, longer half-life and has both fibrinolytic and fibrinogenolytic activityboth fibrinolytic and fibrinogenolytic activity; dissolves existing ; dissolves existing clot and inhibit the formation of new clotclot and inhibit the formation of new clot

Additional risk isAdditional risk is rebleeding rebleeding. . InfectiousInfectious complications of catheter placement and fibrinolysis complications of catheter placement and fibrinolysis

vary between vary between 0 and 5%.0 and 5%.44

Findlay JM, Grace MG, Weir BK, Findlay JM, Grace MG, Weir BK, Neurosurgery;Neurosurgery; [1993] found [1993] found that thrombolytic agents have also been successfully used for that thrombolytic agents have also been successfully used for hemorrhage in the ventricular systemhemorrhage in the ventricular system



Naff Naff et alet al. [Neurosurgery, 2004, Class I] randomized 48 . [Neurosurgery, 2004, Class I] randomized 48 patients with spontaneous IVH to receive placebo or 3 mg patients with spontaneous IVH to receive placebo or 3 mg TPA injected every 12 hours into the ventricle. TPA injected every 12 hours into the ventricle. Clot Clot resolution was faster in the TPA groupresolution was faster in the TPA group, and there was a , and there was a trend toward trend toward lower mortalitylower mortality, although bleeding , although bleeding complications were greater in patients receiving TPA complications were greater in patients receiving TPA

Lee Lee et alet al. [. [Hong Kong Med JHong Kong Med J 2003 , Class III] reported on 29 2003 , Class III] reported on 29 patients with IVH treated with intraventricular streptokinase patients with IVH treated with intraventricular streptokinase or urokinase, and found that or urokinase, and found that blood could be removed safelyblood could be removed safely (infection rate 3%, no bleeding) and effectively (shunt rate, (infection rate 3%, no bleeding) and effectively (shunt rate, 24%). 24%).

Neuroendoscpic Neuroendoscpic TechniquesTechniques

Endoscopy has not been used extensively to treat ICHEndoscopy has not been used extensively to treat ICH This minimally invasive techniques designed to decrease This minimally invasive techniques designed to decrease

hematoma size while limiting surgical trauma.hematoma size while limiting surgical trauma. In a study with 6 mm diameter neuroendoscope which was In a study with 6 mm diameter neuroendoscope which was

placed through a burr hole and guided by intraoperative placed through a burr hole and guided by intraoperative ultrasonography. The procedure was associated with ultrasonography. The procedure was associated with good good outcome where evacuation more than 50% in all outcome where evacuation more than 50% in all patientspatients with 45% patients with more than 70% clot with 45% patients with more than 70% clot evacuated. There were no differences in outcome for evacuated. There were no differences in outcome for putaminal or thalamic hemorrhage.putaminal or thalamic hemorrhage.


Neuroendoscpic Neuroendoscpic TechniquesTechniques

Auer and colleagues (1989)found of all p;atients whom Auer and colleagues (1989)found of all p;atients whom underwent burr hole, neuroendoscopic navigation, and underwent burr hole, neuroendoscopic navigation, and aspiration of hematoma, those benefit of surgery with aspiration of hematoma, those benefit of surgery with respect to QOL was limited to patients withrespect to QOL was limited to patients with lobar lobar hematomas and those hematomas and those younger than 60younger than 60 years of age. years of age.

Benefit may in fact be due to the Benefit may in fact be due to the reduced stressreduced stress provided provided by this less invasive surgical procedure, with the persistent by this less invasive surgical procedure, with the persistent benefit of reducing clot volume. benefit of reducing clot volume.

Longatti PL, Longatti PL, et al in et al in review of 13 patients having endoscopic review of 13 patients having endoscopic removal of IVH at one institution during 7 years reported removal of IVH at one institution during 7 years reported safe and successful removal of blood with favorable safe and successful removal of blood with favorable outcome in 62% [outcome in 62% [StrokeStroke 2004, Class III]. 2004, Class III].

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 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:

SurgicalSurgical MedicalMedical

MortalityMortality 42%42% 70%70%

Poor Poor OutcomeOutcome 58%58% 74%74%

Odds Ratio of Death and Dependency:0.46 (0.20-1.04) surgery better

VentriculostomyVentriculostomy

Comatose patients in whom neurological status is severely Comatose patients in whom neurological status is severely impaired at baseline (GCS score < 9), impaired at baseline (GCS score < 9), ICP monitoringICP monitoring, with , with the aid of either a fiberoptic intraparenchymal monitor or the aid of either a fiberoptic intraparenchymal monitor or ventriculostomy, may be considered. ventriculostomy, may be considered.

The advantage of the ventriculostomy is that it can also be The advantage of the ventriculostomy is that it can also be used as a used as a therapeutictherapeutic means of reducing ICP. means of reducing ICP.

Adams RE, Diringer MN, Neurology. [1998] study the Adams RE, Diringer MN, Neurology. [1998] study the response to external ventricular drainage in spontaneous response to external ventricular drainage in spontaneous intracerebral hemorrhage with hydrocephalus in 24 patients intracerebral hemorrhage with hydrocephalus in 24 patients concluded that external ventricular drains did not improve concluded that external ventricular drains did not improve hydrocephalus, and changes in ventricular volume did not hydrocephalus, and changes in ventricular volume did not correlate with changes in level of alertness correlate with changes in level of alertness

Surgical Evacuation of Surgical Evacuation of Cerebellar ICHCerebellar ICH

There seems to be a general consensus regarding the role of There seems to be a general consensus regarding the role of surgery in patients with infratentorial hematomas. surgery in patients with infratentorial hematomas. 44

This agreement exists despite that fact that there are no This agreement exists despite that fact that there are no randomized controlled trials evaluating surgical methods in randomized controlled trials evaluating surgical methods in posterior fossa SICH.posterior fossa SICH.44

Several series have reported good outcomes associated with Several series have reported good outcomes associated with surgical evacuation for patients with cerebellar hemorrhages surgical evacuation for patients with cerebellar hemorrhages greater than 3 cmgreater than 3 cm, or with , or with brainstem compressionbrainstem compression and and hydrocephalushydrocephalus..44


Surgical Evacuation of Surgical Evacuation of Cerebellar ICHCerebellar ICH

No evidence from randomized trials of benefits of surgical No evidence from randomized trials of benefits of surgical evacuation in ICH.evacuation in ICH.

Evidence mostly in the form of case series. Evidence mostly in the form of case series. Kobayaski S, Miyata A, Serizawa T, et al. Treatment of Kobayaski S, Miyata A, Serizawa T, et al. Treatment of

cerebellar hemorrhage—surgical or conservative. Stroke. cerebellar hemorrhage—surgical or conservative. Stroke. 1990; 21(8) Suppl: I-62. 1990; 21(8) Suppl: I-62. Design: Non-randomized Prospective Design: Non-randomized Prospective Patients: 75 patients with Patients: 75 patients with cerebellar hemorrhagecerebellar hemorrhage were were

studied. studied. 45 treated medically 45 treated medically 30 treated with decompressive surgery. 30 treated with decompressive surgery.

Patients with GCS < 13, and hematoma > 40 mmPatients with GCS < 13, and hematoma > 40 mm Good outcome occurred Good outcome occurred 58%58% with surgery while only with surgery while only 18%18%

with conservative medical therapy with conservative medical therapy

Summary of Surgical Summary of Surgical Treatment Treatment

RecommendationsRecommendations44

Patients with small hemorrhages or minimal neurological deficit Patients with small hemorrhages or minimal neurological deficit generally do well by undergoing generally do well by undergoing medical treatment alonemedical treatment alone..

Elderly patients in whom the GCS score is Elderly patients in whom the GCS score is less than 5less than 5 and those and those with with brainstem hemorrhagesbrainstem hemorrhages also do also do not typically benefitnot typically benefit from from surgerysurgery

Patients with Patients with cerebellar hemorrhages greater than 3 cmcerebellar hemorrhages greater than 3 cm in whom in whom are symptoms or neurological deterioration have occurred, or in are symptoms or neurological deterioration have occurred, or in whom brainstem compression and hydrocephalus are present, whom brainstem compression and hydrocephalus are present, should undergo evacuationshould undergo evacuation of the clot. of the clot.

Evacuation should be considered in patients with moderate- or Evacuation should be considered in patients with moderate- or large-sized large-sized lobar hemorrhageslobar hemorrhages, those with , those with large-sized basal large-sized basal gangliaganglia hemorrhages, and those exhibiting hemorrhages, and those exhibiting progressive progressive neurological deterioration.neurological deterioration.

Ultra-earlyUltra-early removal of the hematoma by localized minimally removal of the hematoma by localized minimally invasive surgical procedures is promising invasive surgical procedures is promising but unprovenbut unproven..


ICH Evaluation and ICH Evaluation and TreatmentTreatment

FUTURE DIRECTIONSFUTURE DIRECTIONS

With the improved understanding of the pathophysiological With the improved understanding of the pathophysiological changes that result in changes that result in hematoma expansionhematoma expansion, the development of , the development of cerebral edemacerebral edema, and the identity of , and the identity of hemoglobin degradation hemoglobin degradation neurotoxinsneurotoxins will lead to more focused pharmacological will lead to more focused pharmacological treatments.treatments.

Mayer SA [2003] has suggested there may be a role for ultra-Mayer SA [2003] has suggested there may be a role for ultra-early hemostatic therapy with early hemostatic therapy with recombinant factor VIIarecombinant factor VIIa to prevent to prevent further hematoma expansion. further hematoma expansion.

Best medical management has yet to be defined and may Best medical management has yet to be defined and may include future treatments of blood pressure and hypothermia, include future treatments of blood pressure and hypothermia, tight glucose control, and selected use of glucocorticoids.tight glucose control, and selected use of glucocorticoids.

Results from the STICH have provided important information Results from the STICH have provided important information about the utility of surgical evacuation of ICH but do not address about the utility of surgical evacuation of ICH but do not address questions about the timing, approach, and technique of other questions about the timing, approach, and technique of other procedures.procedures.

FUTURE DIRECTIONS -FUTURE DIRECTIONS -Stem cell therapy Stem cell therapy

After the clot is removed, there is possibility of After the clot is removed, there is possibility of improving improving functional outcome by using stem cellsfunctional outcome by using stem cells to restore the to restore the damaged cerebral architecture.damaged cerebral architecture.

Transplanted neural human stem cells have been shown to Transplanted neural human stem cells have been shown to improve functional recovery in an animal model of ICH improve functional recovery in an animal model of ICH (Jeong SW, stroke, 2003)(Jeong SW, stroke, 2003)

Nonaka M, Nonaka M, et al.et al.((Neurol ResNeurol Res 2004), had human neural stem 2004), had human neural stem cells were injected intravenously 1 day after experimental cells were injected intravenously 1 day after experimental ICH in rats. After 2 months, stem cells had migrated to the ICH in rats. After 2 months, stem cells had migrated to the perihematomal regionperihematomal region where they where they differentiated into differentiated into neurons and astrocytesneurons and astrocytes. These animals had better motor . These animals had better motor function compared with control subjectsfunction compared with control subjects

Hemostatic Therapy: Hemostatic Therapy: Future? Future?

The lack of surgery-related benefit may suggest that The lack of surgery-related benefit may suggest that clot clot evacuation after hematoma expansion is not beneficialevacuation after hematoma expansion is not beneficial. .

Hemostatic therapyHemostatic therapy, however, is intended to stimulate , however, is intended to stimulate clotting in individuals in whom the coagulation cascade is clotting in individuals in whom the coagulation cascade is otherwise normal, to otherwise normal, to modify the evolution of the hematoma modify the evolution of the hematoma

Much attention has been given to Much attention has been given to factor VIIafactor VIIa, which , which promotes local hemostasis at sites of vascular injury in promotes local hemostasis at sites of vascular injury in patients with and without coagulopathies.patients with and without coagulopathies.

Level of evidence

Level I Data from randomized trials with low false-positive ( ) and low false-negative (ß) errors

Level II Data from randomized trials with high false-positive ( ) or high false-negative (ß) errors

Level III Data from nonrandomized concurrent cohort studies

Level IV Data from nonrandomized cohort studies using historical controls

Level V Data from anecdotal case series

Strength of recommendation

Grade A Supported by Level I evidence

Grade B Supported by Level II evidence

Grade C Supported by Levels III through V evidence

Thank YouThank You

the pathophysiology and management of hemorrhagic stroke

Health & Medicine

haemorrhagic ich

epidemiology incidence

bloodbrain barrier

brains blood vessels

common inmen ethnic

subarachnoid hemorrhage

brain stem6

cerebral infarction