WORKUP	Section 5 of 11
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Lab Studies:

• Complete blood count (CBC) with platelets - Monitor for infection and assess hematocrit and platelet count to identify hemorrhagic risk and complications

• Prothrombin time (PT)/activated partial thromboplastin time (aPTT) - Identify a coagulopathy

• Serum chemistries including electrolytes and osmolarity - Assess for metabolic derangements, such as hyponatremia, and monitor osmolarity for guidance of osmotic diuresis

• Toxicology screen and serum alcohol level if illicit drug use or excessive alcohol intake is suspected - Identify exogenous toxins that can cause ICH

• Screening for hematologic, infectious, and vasculitic etiologies in select patients - Selective testing for more uncommon causes of ICH

Imaging Studies:

• Parenchymal imaging

• CT scan
  • CT scan readily demonstrates acute hemorrhage as hyperdense signal intensity (see Image 1). Multifocal hemorrhages at the frontal, temporal, or occipital poles suggest a traumatic etiology.

  • Hematoma volume in cubic centimeters can be approximated by a modified ellipsoid equation: (A x B x C)/2, where A, B, and C represent the longest linear dimensions in centimeters of the hematoma in each orthogonal plane.

  • Perihematomal edema and displacement of tissue with herniation also can be appreciated.

  • Iodinated contrast may be injected to increase screening yield for underlying tumor or vascular malformation.

• MRI
  • The MRI appearance of hemorrhage on conventional T1 and T2 sequences evolves over time because of chemical and physical changes within and around the hematoma (Table 1).

  • Conventional T1 and T2 sequences are not highly sensitive to hemorrhage in the first few hours, but newer gradient refocused echo sequences appear to be able to detect ICH reliably within the first 1-2 hours of onset (see Images 2-3).

  • AVMs and cavernous angiomas may be identified by the presence of multiple flow voids adjacent to the hematoma.

  • Paramagnetic contrast may be injected to increase screening yield for underlying tumor or vascular malformation.

  • Gradient echo sequences may reveal multiple foci of hypointensity attributable to hemosiderin deposition from prior silent cerebral microbleeds. A multilobar distribution of hypointense foci on gradient echo imaging may provide supportive evidence of cerebral amyloid angiopathy, while multiple deep foci may suggest an underlying hypertensive arteriopathy.

  Table 1. MRI Appearance of ICH

  Phase	Time	Hemoglobin	T1	T2
  Hyperacute	<24 hours	Oxyhemoglobin (intracellular)	Iso or hypo	Hyper
  Acute	1-3 days	Deoxyhemoglobin (intracellular)	Iso or hypo	Hypo
  Early subacute	>3 days	Methemoglobin (intracellular)	Hyper	Hypo
  Late subacute	>7 days	Methemoglobin (extracellular)	Hyper	Hyper
  Chronic	>14 days	Hemosiderin (extracellular)	Iso or hypo	Hypo

• Vessel imaging
  • CT angiography permits screening of large and medium-sized vessels for AVMs, vasculitis, and other arteriopathies.

  • MR angiography permits screening of large and medium-sized vessels for AVMs, vasculitis, and other arteriopathies.

  • Conventional catheter angiography definitively assesses large, medium-sized, and sizable small vessels for AVMs, vasculitis, and other arteriopathies.

  • Consider catheter angiography for young patients, patients with lobar hemorrhage, patients without a history of hypertension, and patients without a clear cause of hemorrhage who are surgical candidates. Angiography may be deferred for older patients with suspected hypertensive ICH and patients who do not have any structural abnormalities on CT scan or MRI.

• Timing of angiography depends on clinical status and neurosurgical considerations.

Other Tests:

• ECG frequently identifies cerebrum-induced dysrhythmia or cardiac injury.

Procedures:

• Lumbar puncture in the setting of IVH may reveal xanthochromia and a biochemical profile similar to that observed in subarachnoid hemorrhage.

• Ventriculostomy allows for external ventricular drainage in patients with intraventricular extension of blood products. Intraventricular administration of thrombolytics may assist clot removal.

• Endoscopic hematoma evacuation may be a promising ultra-early stage treatment for intracerebral hemorrhage that improves long-term prognosis.

	TREATMENT	Section 6 of 11
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Medical Care: Medical therapy of ICH is principally focused on adjunctive measures to minimize injury and to stabilize individuals in the perioperative phase. Promising clinical trial data suggest that treatment with recombinant factor VIIa (rFVIIa) within 4 hours after the onset of intracerebral hemorrhage limits the growth of the hematoma, reduces mortality, and improves functional outcomes at 90 days. This intervention, however, may result in a small increase in the frequency of thromboembolic adverse events.

• Perform endotracheal intubation for patients with decreased level of consciousness and poor airway protection.

• Cautiously lower blood pressure to a mean arterial pressure (MAP) less than 130 mm Hg, but avoid excessive hypotension.

• Rapidly stabilize vital signs, and simultaneously acquire emergent CT scan.

• Intubate and hyperventilate if ICP is increased; initiate administration of mannitol for further control.

• Maintain euvolemia, using normotonic rather than hypotonic fluids, to maintain brain perfusion without exacerbating brain edema.

• Avoid hyperthermia.

• Correct any identifiable coagulopathy with fresh frozen plasma, vitamin K, protamine, or platelet transfusions.

• Initiate fosphenytoin or other anticonvulsant definitely for seizure activity or lobar hemorrhage, and optionally in other patients.

• Facilitate transfer to the operating room or ICU.

	MEDICATION	Section 7 of 11
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Antihypertensive agents reduce blood pressure to prevent exacerbation of ICH. Osmotic diuretics, such as mannitol, may be used to decrease ICP. As hyperthermia may exacerbate neurological injury, acetaminophen may be given to reduce fever and to relieve headache. Anticonvulsants are used routinely to avoid seizures that may be induced by cortical damage. Vitamin K and protamine may be used to restore normal coagulation parameters. Antacids are used to prevent gastric ulcers associated with ICH.

Drug Category: Antihypertensive agents -- These agents reduce blood pressure to prevent exacerbation of ICH.

Drug Name	Labetalol (Normodyne, Trandate) -- Antagonizes adrenergic receptors, thereby reducing blood pressure.
Adult Dose	20 mg IV, followed by 40 or 80 mg IV q10min; titrate until targeted blood pressure achieved or maximum of 300 mg administered
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; prolonged hypotension; bronchial asthma; cardiac failure; second- or third-degree heart block; severe bradycardia
Interactions	Concomitant use of TCAs may cause tremor; inhibits effects of some bronchodilators; cimetidine increases bioavailability; concomitant halothane anesthesia or nitroglycerin may cause hypotension
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Individuals with hepatic dysfunction may have impaired clearance of labetalol

Drug Name	Nicardipine (Cardene, Cardene SR) -- Calcium channel blocker. Potent rapid onset of action, ease of titration, and lack of toxic metabolites. Effective but limited reported experience in hypertensive encephalopathy.
Adult Dose	Loading dose: 5-15 mg/h IV Maintenance dose: 3-5 mg/h IV
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Fentanyl and alcohol may increase hypotensive effects; calcium channel blocker may increase cyclosporine levels; H2 blockers (cimetidine), erythromycin, nafcillin, and azole antifungals may increase toxicity (avoid combination or monitor closely); carbamazepine may reduce bioavailability (avoid this combination); rifampin may decrease levels (monitor and adjust dose of calcium channel blocker)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adjust dose in renal/hepatic impairment; may cause lower extremity edema; allergic hepatitis have occurred but is rare

Drug Category: Osmotic diuretics -- Osmotic diuretics reverse pressure gradient across the blood-brain barrier, reducing ICP.

Drug Name	Mannitol (Osmitrol, Resectisol) -- Reduces cerebral edema with help of osmotic forces and decreases blood viscosity, resulting in reflex vasoconstriction and lowering of ICP.
Adult Dose	0.75-1 g/kg IV, followed by 0.25-0.5 g/kg IV q3-5h to maintain serum hyperosmolarity (approximately 320 mOsm/L)
Pediatric Dose	Not established; dose is dependent on weight, clinical condition, and laboratory results
Contraindications	Documented hypersensitivity; anuria; severe pulmonary congestion; progressive renal damage; severe dehydration; active intracranial bleeding; progressive heart failure
Interactions	May decrease serum lithium levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Carefully evaluate cardiovascular status before rapid administration of mannitol, since sudden increase in extracellular fluid may lead to fulminating CHF; avoid pseudoagglutination, when blood given simultaneously, add at least 20 mEq of sodium chloride to each liter of mannitol solution; do not give electrolyte-free mannitol solutions with blood

Drug Category: Antipyretics, analgesics -- These agents reduce fever and relieve pain.

Drug Name	Acetaminophen (Tylenol, Feverall, Aspirin Free Anacin) -- Reduces fever, maintains normothermia, and reduces headache.
Adult Dose	650 mg PO/PR q4-6h; not to exceed 4 g/d
Pediatric Dose	Infants: 10-15 mg/kg PO/PR q4-6h Children: 65 mg/y up to 650 mg PO/PR q4-6h; not to exceed 15 mg/kg q4h
Contraindications	Documented hypersensitivity; known G-6-P deficiency; hepatic dysfunction
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatotoxicity possible in chronic alcoholics following various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; contained in many OTC products, and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose

Drug Category: Anticonvulsants -- These agents reduce the frequency of seizures and provide seizure prophylaxis.

Drug Name	Fosphenytoin (Cerebyx) -- Diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin in turn stabilizes neuronal membranes and decreases seizure activity. To avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express dose as phenytoin sodium equivalents (PE). Although can be administered IV and IM, IV route is route of choice and should be used in emergency situations. Concomitant administration of IV benzodiazepine usually necessary to control status epilepticus. Full antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, not immediate.
Adult Dose	15-20 mg/kg IV loading dose, followed by 300 mg IV q24h
Pediatric Dose	Not established; suggested weight-adjusted dose is as in adults
Contraindications	Documented hypersensitivity; sinus bradycardia; sinoatrial and third-degree AV block; Adams-Stokes syndrome
Interactions	Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), omeprazole, phenacemide, phenylbutazone, succinimides, fluconazole, isoniazid, metronidazole, miconazole, sulfonamides, trimethoprim, and valproic acid may increase toxicity Barbiturates, carbamazepine, theophylline, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, and sucralfate may decrease effects May decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, methadone, metyrapone, mexiletine, oral contraceptives, quinidine, theophylline, valproic acid
Pregnancy	D - Unsafe in pregnancy
Precautions	Avoid rapid administration to reduce risks of hypotension and cardiac arrhythmias; monitor for blood dyscrasias with serial blood tests; discontinue use if skin rash appears and do not resume use if rash is exfoliative, bullous, or purpuric; use caution in patients with acute intermittent porphyria, diabetes, or hepatic dysfunction

Drug Category: Antidotes -- This agent reverses some coagulopathies or bleeding diatheses.

Drug Name	Phytonadione; vitamin K (Konakion, Mephyton, AquaMEPHYTON) -- Promotes hepatic synthesis of clotting factors that inhibit warfarin effects.
Adult Dose	2.5-10 mg SC/IM, repeat q6-8h until PT normalized
Pediatric Dose	Not established; suggested dose is as in adults
Contraindications	Documented hypersensitivity
Interactions	Antagonizes effects of warfarin sodium and dicumarol
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Ineffective in hereditary hypoprothrombinemia

Drug Name	Protamine sulfate -- Forms a salt with heparin and neutralizes its effects.
Adult Dose	Dosage adjusted to time interval since discontinuation of IV heparin Immediately: 1-1.5 mg/100 U heparin 30-60 min: 0.5-0.75 mg/100 U heparin >60 min: 0.25-0.375 mg/100 U heparin If SC heparin used, give 1-1.5 mg/100 U heparin; not to exceed 50 mg IV over 10 min
Pediatric Dose	Not established; suggested dose is as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Heparin rebound associated with anticoagulation and bleeding may occur

Drug Category: Antacids -- These agents provide prophylaxis of gastric ulcers.

Drug Name	Famotidine (Pepcid) -- Minimizes development of gastric ulcers. Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen concentration.
Adult Dose	20 mg IV/PO bid
Pediatric Dose	Not established; suggested dose is as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

	FOLLOW-UP	Section 8 of 11
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Further Inpatient Care:

• Initial management of ICH generally is conducted in the ICU. Subsequent care generally includes the following:

• Serial neurologic examinations

• Treatment of elevated ICP

• Placement of ventricular catheter should hydrocephalus develop

• Avoidance of hypotension or hypertension (MAP = 70-130 mm Hg)

• Use of isotonic solutions, such as normal saline, to minimize cerebral edema

• Treatment with 3 X isotonic saline should hyponatremia due to cerebral salt wasting occur

• Avoidance of hyperthermia

• Treatment or prophylaxis of seizures

• Treatment of urinary tract infections

• Prevention of venous thrombosis with intermittent compression stockings plus or minus low-dose subcutaneous unfractionated or low-molecular-weight heparin

• Prophylaxis for gastric ulcers

• Physical, occupational, and speech therapy

• Psychological support with cautious use of sedatives, if necessary

• Repeat CT scan in case of clinical deterioration

Further Outpatient Care:

• After hospital discharge, continued physical, occupational, and speech therapy may be required.

• Administer medications to control hypertension and to prevent complications such as seizures, urinary tract infections, or venous thromboses.

In/Out Patient Meds:

• Antihypertensives for modification of blood pressure

• Mannitol or other osmotic diuretics for elevated ICP

• Acetaminophen for fever and headache relief

• Fosphenytoin or other anticonvulsants for posttraumatic seizures

• Famotidine or other antacids for gastric ulcer prophylaxis

• Anticholinergics for bladder complications

• Baclofen, diazepam, or tizanidine for spasticity

• Amitriptyline, carbamazepine, or gabapentin for neuropathic pain

Transfer:

• Following prehospital and emergent stabilization, patients with ICH should be transferred to a medical facility with neurosurgical expertise.

Deterrence/Prevention:

• Early detection and aggressive treatment of hypertension

• Cautious management of anticoagulation and other antithrombotic medications

• Careful selection of subjects suitable for thrombolysis

• Consideration of cerebral amyloid angiopathy as a significant risk factor for ICH

• Public education campaigns emphasizing the dangers of heavy alcohol intake and sympathomimetic use

• Public education regarding traumatic brain injury, including appropriate use of safety equipment, precautions, and measures that may reduce the incidence of head injury

• Prevention and management of preterm labor that may reduce IVH due to germinal matrix hemorrhage

Complications:

• Neurological deficits or death

• Seizures

• Hydrocephalus

• Spasticity

• Urinary complications

• Aspiration pneumonia

• Neuropathic pain

• Deep venous thrombosis

• Pulmonary emboli

• Cerebral herniation

Prognosis:

• Early reduction in the level of consciousness carries an ominous prognosis.

• The size and location of ICH provide useful prognostic information.

• Larger hematomas have a worse outcome.

• Lobar hemorrhage has a better outcome than deep hemorrhage.

• Significant volume of intraventricular blood is a poor prognostic indicator.

• The presence of hydrocephalus is associated with a poor outcome.

• Good outcome in medium to large ICH can be predicted on admission by neurologic severity, ICH location, and fibrinogen levels.

Patient Education:

• Educate patients regarding the following:

• Treatment of hypertension

• Warning signs and symptoms of stroke as well as preventive measures

• Traumatic brain injury

• Adverse effects of alcohol and sympathomimetic substances

	MISCELLANEOUS	Section 9 of 11
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Medical/Legal Pitfalls:

• Delayed transfer and triage

• Failure to consider clinical diagnosis of ICH

• Failure to obtain emergent CT scan

• Failure to perform serial neurologic assessments and detect delayed deterioration

Special Concerns:

• Consider the relative risks and benefits of anticoagulation for individuals with ICH at high risk of embolic phenomena, such as mechanical cardiac valves. Anticoagulation usually may be restarted within 2-3 weeks after ICH.

• Diagnosis and management of pregnant women with ICH require careful selection of neuroradiologic studies and medications, with due consideration of teratogenic effects.

	PICTURES	Section 10 of 11
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Caption: Picture 1. Intracranial hemorrhage. CT scan of right frontal intracerebral hemorrhage complicating thrombolysis of an ischemic stroke.
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Picture Type: CT

Caption: Picture 2. Intracranial hemorrhage. Fluid-attenuated inversion-recovery, T2-weighted, and gradient echo MRI illustration of intracerebral hemorrhage associated with a right frontal arteriovenous malformation.
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Picture Type: MRI

Caption: Picture 3. Intracranial hemorrhage. Fluid-attenuated inversion-recovery, T2-weighted, and gradient echo MRI depiction of left temporal intracranial hemorrhage due to sickle cell disease.
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Picture Type: MRI

	BIBLIOGRAPHY	Section 11 of 11
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Intracranial Hemorrhage excerpt