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

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

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

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

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

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)

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)

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

N Engl J Med 2001;344(19):1450–1460

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

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

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

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

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

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

Vascular malformations

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

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

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

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

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

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

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

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

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

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 > 60-80 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

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

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

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;358:2127-37 841 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

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

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

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

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%

CT-A “Spot Sign” Recent proposal of a “Spot Sign” definition (Can J Neurol Sci 2009;36:456-461) 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)

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 0.3-0.6% 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

Anticoagulation associated ICH Goal of treatment: fully reverse INR to normal range High dose Vitamin K 10-20 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

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 60-120 min: 0.375 to 0.5 mg per 100 U heparin >120min: 0.25 to 0.375 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)

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;38:2001-2023

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

Part II: Management of Increased Intracranial Pressure

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

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

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

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

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

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 60-70 mmHg

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

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

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

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

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

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

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

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

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

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

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

Thank you!

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;38:1257-1262 Diringer MN. Update on intracerebral hemorrhage, AAN Continuum, 2009 Kincaid MS and Lam AM, Monitoring and managing ICP, AAN Continuum, 2006