1. Intracranial Hemorrhage & Emergency Management of Increased ICP
Emergency Neurology Lecture Series
Amy Yu
August 5th 2009

2. ICH by numbers Result of a rupture of blood vessel in the brain
Accounts for 10-15% of all cerebrovascular accidents
2 million strokes every year worldwide
Rise of admissions in the past 10 years by 18%
Prognosis is poor: estimated mortality
30% at 7 days
60% at 1 year
82% at 10 years
>90% at 16 years

3. Outline Intracranial hemorrhage Intracranial hypertension
Mechanism and pathophysiology
Clinical features
Management principles
Intracranial hypertension
Monitoring

4. Mechanisms of ICH Hypertension Vascular malformations
Intracranial tumors
Bleeding diathesis, anticoagulation, fibrinolysis
Cerebral amyloid angiopathy
Granulomatous angiitis & vasculitides
Sympathomimetic agents (amphetamine, cocaine)
Hemorrhagic infarction
Trauma

5. Clinical features Features of intracranial hypertension
Headache, vomiting, decreased LOC
Correlated with hematoma size and prognosis
Progressive over time
Seizures in lobar ICH
Focal neurological deficits depending on the location of ICH

6. POP QUIZ When are patients most likely to suffer from primary ICH?
Midnight (excessive partying…)
8 AM (don’t want to go to work)
Noon (excessive hunger)
5 PM (too much excitement from ending work)

7. POP QUIZ When are patients most likely to suffer from primary ICH?
Midnight (excessive partying…)
8 AM (don’t want to go to work)
Noon (excessive hunger)
5 PM (too much excitement from ending work)

8. Hypertension and ICH Most important risk factor (>70% of 1ry ICH)
Bifurcation of small penetrating arteries (50–700 μm diameter)
Atherosclerosis
Lipid deposition, layering of platelet and fibrin aggregates, breakage of elastic lamina, atrophy and fragmentation of smooth muscle, dissections, and granular or vesicular cellular degeneration
Charcot and Bouchard aneurysm
Fibrinoid necrosis of the subendothelium  focal dilatations  rupture of microaneurysm

9. N Engl J Med 2001;344(19):1450–1460

10. Penetrating cortical branches of ACA, MCA, & PCA
Lobar hemorrhage 25%
Penetrating cortical branches of ACA, MCA, & PCA
Peripheral location  lower frequency of coma
Lower mortality
Better functional outcome
N Engl J Med 2001;344(19):1450–1460

11. Ascending lenticulostriate branches of MCA
Basal ganglia 35-40%
Ascending lenticulostriate branches of MCA
Wide spectrum of severity extending to coma and decerebrate rigidity
Ventricular extension carries very poor prognosis
N Engl J Med 2001;344(19):1450–1460

12. Ascending thalamogeniculate branches of PCA
Thalamus 10-15%
Ascending thalamogeniculate branches of PCA
Abrupt hydrocephalus from aqueductal obstruction from intraventricular clot
Responds to ventriculostomy
N Engl J Med 2001;344(19):1450–1460

13. Paramedian branches of the basilar artery
Pons 5%
Paramedian branches of the basilar artery
Bilateral carries very poor prognosis (coma, quadriplegia, decerebrate posturing, horizontal ophthalmoplegia, pinpoint reactive pupils)
N Engl J Med 2001;344(19):1450–1460

14. Penetrating branches of the PICA, AICA, SCA
Cerebellum 5-10%
Penetrating branches of the PICA, AICA, SCA
Abrupt onset vertigo, h/a, n/v, inability to walk in absence of weakness
Ipsilateral ataxia, horizontal gaze palsy, peripheral facial palsy
Unpredictable deterioration to coma
Posterior compartment
N Engl J Med 2001;344(19):1450–1460

15. Vascular malformations
Aneurysms, AVM, cavernous angiomas
Younger, female patients, familial history
Imaging may show concurrent SAH
Dx by MRI and cerebral angiography
Usually supratentorial, lobar ICH
Cavernous angioma: on MRI (T2) central nidus of irregular bright signal mixed with mottled hypointensity, surrounded by peripheral hypointense ring

16. Vascular malformations

17. Intracranial tumour Accounts for 10% of cases
GBM or metastases (melanoma, bronchogenic carcinoma, renal cell carcinoma)
Suggestive features:
Papilledema
Atypical location (e.g. corpus callosum)
Disproportionate amount of surrounding edema
Multiple sites simultaneously
Non-contrast CT: ring of high-density hemorrhage with low-density center
Contrast CT/MRI: presence of enhancing nodules

18. POP QUIZ Which of the following is TRUE?
Elevated BP in acute ICH is an indication of chronic hypertension
Hematoma is surrounded by an ischemic penumbra & BP should be  with caution
Hyperglycemia is associated with hematoma expansion
Nitroprusside is the agent of choice for BP control in acute ICH

19. POP QUIZ Which of the following is TRUE?
Elevated BP in acute ICH is an indication of chronic hypertension
Hematoma is surrounded by an ischemic penumbra & BP should be  with caution
Hyperglycemia is associated with hematoma expansion
Nitroprusside is the agent of choice for BP control in acute ICH

20. Management principles
A-B-C: Airway support
Decreased level of consciousness
Bulbar muscle dysfunction
Blood pressure control
Acute hemostatic treatment
Anticoagulation reversal
Intracranial pressure control
Monitoring
Neurological and cardiovascular deterioration greatest in the 24hours following symptom onset

21. Blood pressure & ICH
BP is elevated on admission even in patients who have no history of hypertension
MAP > 120mmHg in over 2/3 of patients
Precipitant of the hemorrhage?
Reflection of chronic hypertension?
Attempt to maintain CPP?
Sympathetic activation 2ry to pain & anxiety?
Tends to return to baseline 7-10 days post ICH

22. Acute management of BP
Cerebral autoregulatory curve
CPP = MAP – ICP

23. Acute management of BP PROs CONs  BP associated with poor outcome
 risk of hematoma enlargement
 edema formation
Systemic damage (e.g. ongoing cardiac ischemia)
CONs
Chronic HTN shifts cerebral autoregulatory curve to the right
 ICP may require  BP to maintain CPP
Previously thought to induce ischemic damage to the at risk penumbra

24. Edema & ischemic penumbra?
Up to 75% increase in volume in the first 24 hours
Peaks around 5 to 6 days and lasts up to 14 days
Early large edema relative to hematoma is a predictor of poor outcome
Hibernation phase
Mitochondrial dysfunction causing hypometabolism
Regional hypoperfusion 2ry hypometabolism
Usually not severe enough to cause ischemia
Global cerebral ischemia
Very elevated ICP and low cerebral perfusion pressure

25. Acute management of BP Baseline blood pressure Age
Presumed cause of hemorrhage (ruptured aneurysm or AVM?)
Elevated intracranial pressure
How fast should BP be lowered?
Rapidly lowering MAP by  15% does not lower CBF
Reductions of 20% can affect CBF
Current guidelines suggest a reduction of ≤ 20% in the first 24 hrs
Which agents should be used?
Short and rapidly acting IV antihypertensive
Labetalol, hydralazine, esmolol, nicardipine, enalapril
Sodium nitroprusside and nitroglycerin should be used with caution d/t vasodilation and potential effect on ICP

26. Acute management of BP ASA Guidelines 2007 (Class IIb, Level C)
sBP>200 mmHg or MAP>150 mmHg
Aggressive BP control with IV infusion and BP monitoring q5minutes
sBP>180 mmHg or MAP>130 mmHg WITH elevated ICP
Consider monitoring ICP
Intermittent bolus or continuous infusion to aim for CPP > mmHg
sBP>180 mmHg or MAP>130 mm Hg WITHOUT elevated ICP
Consider modest BP reduction of blood pressure with intermittent bolus or continuous infusion
Aim for MAP of 110 mmHg or BP of 160/90 mmHg

27. Hematoma expansion Hematoma enlargement
>70% have hematoma enlargement w/in 3 hrs of symptom onset; 1/3 clinically significant
Most occur within 3 hrs, can be up to 12 hrs
Independent predictor of worse outcome &  mortality

28. Hematoma expansion
Journal of the Neurological Sciences 261 (2007) 99–107

29. Recombinant Factor VIIa
Factor VIIa has locally action at sites of tissue injury and vascular-wall disruption by binding tissue factor & generating thrombin and activating platelets
Recombinant FVIIa directly activates fX on the surface of activated plts resulting in acceleration of coagulation
Factor Seven for Acute Hemorrhagic Stroke (FAST) trial, N Engl J Med 2008;358:
841 patients, within 4 hours of onset of stroke
Placebo vs. 20 μg/kg vs. 80 μg/kg of rFVIIa
1ry end point: 90-day functional outcome or death

30. Recombinant Factor VIIa
Significant reduction in growth of hematoma volume in the 80 μg/kg group
No significant difference in functional outcome and mortality
Venous thromboembolic events were similar in all three groups
Arterial thromboembolic events were significantly more frequent in the 80 μg/kg group

31. ABC of hematoma size Broderick, JP et al. Stroke 1993;24:987-993
1.26 million subjects from Greater Cincinnati

32. ABC of hematoma size Bedside ABC/2 method for hemorrhage volume in cm3
1. Identify the CT slice with the largest area of hemorrhage
2. Measure the largest diameter of the hemorrhage on this slice (A)
3. Measure the largest diameter 90° to (A) on the same slice (B)
4. Approximate number of 10-mm slices on which the ICH was seen was calculated (C)
If area > 75% compared to where the hemorrhage was largest, the slice was considered 1 hemorrhage slice
If area 25% to 75%, the slice was considered 1/2 a slice
If area < 25%, the slice was not considered a slice
A, B, and C were then multiplied and the product divided by 2

33. CT-A “Spot Sign”
Focal area of enhancement within the hematoma on CTA have been shown to be:
Independent predictor of hematoma expansion
Associated with longer median hospital stay
Independent of time to presentation
Sensitivity 91%, specificity 89%, NPV 96%

34. CT-A “Spot Sign”
Recent proposal of a “Spot Sign” definition (Can J Neurol Sci 2009;36: )
Serpiginous and/or spot-like appearance
Within the margin of the parenchymal hematoma without connection to an outside vessel
>1.5mm diameter in maximal axial dimention
>Double the HU density compared to background hematoma (>150 HU)
Multiple or single in number
Comparison to unenhanced CT for mimickers
Calcifications (tumour, choroid, infectious, etc)

35. Anticoagulation associated ICH
Warfarin is a Vit K antagonist
Inhibits biosynthesis of factors II, VII, IX, X
Maximum effect is 48 hrs after administration
Incidence of ICH is % per year in patients on chronic warfarin anticoagulation
Risk factors
Age, chronic hypertension, CAA, leukoaraiosis
Elevation of INR (doubled risk for 0.5  above 4.5!)
INR correlated with hematoma expansion and prognosis

36. Anticoagulation associated ICH
Goal of treatment: fully reverse INR to normal range
High dose Vitamin K mg IV slow infusion
Effect takes 12-24hrs
Helps achieving sustained reversal of INR
Fresh frozen plasma 15cc/kg  4U
Volume overload, insufficient factor IX
ABO compatibility, thawing, infusion time (30hrs)
Prothrombin Complex Concentrates (PCC, Octaplex)
Combination of II, VII, IX, X, variable protein C and S
Dosage dependant on initial INR
Smaller volume, correct INR as fast as 30 min

37. Anticoagulation associated ICH
ICH associated with IV heparin
Rapidly normalize activated partial thromboplastin time
Protamine sulfate 1 mg per 100 U heparin, adjusted for time since last heparin dose
30-60 min: 0.5 to 0.75 mg per 100U heparin
min: to 0.5 mg per 100 U heparin
>120min: 0.25 to mg per 100 U heparin
Slow IV injection (<5 mg/min, max dose 50 mg)
Beware of systemic hypotension
FFP has all the coagulation factors
Cryoppt has factor VIII, fibrinogen, fibronectin, factor XIII, and von Willebrand factor (vWF)

38. AAICH – restarting anticoagulation
1% recurrent ICH in initial 3 mths post ICH
Risk estimated to double with anticoagulation
Nonvalvular AF no CVA 5% per year risk of cerebral embolism
12% if previous stroke
4% in prosthetic valvee
Stroke. 2007;38:

39. Miscellaneous Venous thromboembolism prophylaxis Hyperglycemia
Intermittent pneumatic compression
Heparin SQ prophylaxis (3-4 d if no bleeding)
IVC filter (proximal venous thrombosis)
Hyperglycemia
Associated with poor outcome and  mortality
Marker of outcome or contributor?
Hyperpyrexia
Associated with poor outcome and neuro deterioration
Septic workup, treat with antipyretics or cooling devices
Often central in origin
Acutely used in hemiparetic/plegic patients
How tight of a control is still controversial

40. Part II: Management of Increased Intracranial Pressure

41. Basic concepts of ICP Monro-Kellie doctrine CPP = MAP – ICP
Blood + CSF + Brain = constant
CPP = MAP – ICP
CBF = CPP / CVR
Intracranial elastance =
 ICP /  volume
AAN Continuum Feb 2006

42. POP QUIZ 37♂ MVA, conscious at the scene, became obtunded in the ER.
He was intubated and
underwent CT of the
head.
Right epidural hematoma with right lateral ventricle compression and midline shift

43. POP QUIZ Should this candidate have invasive
intracranial pressure monitoring?
Yes No
It depends

44. POP QUIZ Should this candidate have invasive
intracranial pressure monitoring?
Yes No
It depends

45. Indications for ICP monitoring
ABSOLUTE
Severe head injury (GCS  8) AND abnormal CT
Severe head injury (GCS  8), normal CT, AND at least 2 of the following:
Age 40 years or greater
Motor posturing
Systolic BP  90 mm Hg
RELATIVE
Impossible serial neurological examination due to:
Intubation, deep sedation or paralysis
Immediate non-neurosurgical procedure
Large cerebral infarction with high risk of cerebral edema
SAH with hydrocephalus
CNS tumor
CNS infection

46. Rationale for ICP monitoring
Development of pressure gradient and brain herniation
Help guide blood pressure management
Goals of treatment
ICP should be maintained < 20 mmHg
CPP should be maintained between mmHg

47. POP QUIZ What is the most appropriate next step in
management in the ER pending
neurosurgical evaluation?
Immediate insertion of an external ventricular drain
Hyperventilation
Mannitol followed by hypertonic saline
Head elevation

48. POP QUIZ What is the most appropriate next step in
management in the ER pending
neurosurgical evaluation?
Immediate insertion of an external ventricular drain
Hyperventilation
Mannitol followed by hypertonic saline
Head elevation
Prompt evacuation of epidural hematoma

49. Approach to ICP management
Blood volume
Mannitol or hypertonic saline
Hyperventilation
Hypothermia
Head elevation, neutral neck position
Deep propofol or barbiturate sedation ± paralysis
CSF volume
Mannitol or hypertonic solution
External CSF drainage
Ventricular catheter
Ventriculo -peritoneal or atrial shunt
Lumbar drain
Serial lumbar punctures
Brain volume
Mannitol or hypertonic saline
Decompressive craniectomy
Resection of tumor or other mass lesion
Seizure Control

50. Hyperventilation
Useful in initial resuscitation: effectively and rapidly reduce ICP in acute rises until definitive therapy
Generalized vasoconstriction:  cerebral blood volume,  ICP
Chronic hyperventilation should be avoided because  CBF puts the brain at risk of ischemia
Safety of duration is uncertain

51. Resection of mass lesion
Subdural or epidural hemorrhage
Hematoma evacuation
Tumours
Surgical resection

52. CSF drainage Communicating hydrocephalus (e.g. SAH, IVH)
Temporary external ventricular drain
Long term VP or VA shunt
Obstructive hydrocephalus (e.g. tumours)
Temporary external ventricular drain until definitive tumour resection
Arachnoid granulations decreased absorption

53. Head elevation
Head of bed at 20 to 30 is optimizes cerebral venous return
Ensure neutral neck position
Caution in hypovolemic patients to avoid reduction in MAP and therefore CPP
CPP = MAP – ICP

54. Paralysis, Sedation, Hypothermia
To prevent excess motor activity (posturing, coughing, straining against ventilator)
To  cerebral metabolic rate and  CBF (must maintain MAP to improve CPP  caution in HD unstable patients)
Role of EEG
Rule out ongoing seizure activity
Titration of sedation with goal of achieving burst suppression
Hypothermia, controversial
Attenuates deleterious biochemical cascade
 cerebral metabolic rate
 risk pneumonia, wound infection, abnormal lytes/coags

55. Mannitol and Hypertonic saline (HS)
Mannitol 20% or 25% solution (0.25 – 1gm/kg IV)
Intravascular fluid shift from osmotic effect
Decreased blood viscosity and improved flow (? reflex vasocontriction)
Decreases production of CSF
Follow serum osmolarity (<320 mOsm)
Avoid systemic dehydration & renal injury
Can consider adding Furosemide
Hypertonic saline, if refractory to mannitol
BBB is impermeable to Na+ ions  Osmotic gradient
Less severe electrolyte disturbances, less brisk diuresis
Lack of standard guideline (3-7.5% solution at 20-40cc/h)
Slow taper to avoid rebound hyponatremia

56. Decompressive craniectomy
Surgical removal of cranial bone flap to relieve intracranial pressure
Useful in large ischemic CVA with profound edema
Role in traumatic brain injury still needs to be established

57. Conclusions
ICH has an increasing incidence, but continues to have a very poor prognosis
Hypertension is a major risk factor
Acute BP reduction of 15-20% is safe
Anticoagulation should be reversed ASAP
Absolute indications for ICP monitoring
Major categories of increased ICP management

58. Thank you!

59. References
Goldstein, JN et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage, Neurology 2007;68:889–894
Qureshi AI et al. Intracerebral hemorrhage, Lancet 2009; 373: 1632–44
Wada, R et al. CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage, Stroke 2007;38:
Diringer MN. Update on intracerebral hemorrhage, AAN Continuum, 2009
Kincaid MS and Lam AM, Monitoring and managing ICP, AAN Continuum, 2006