WENDY L. WRIGHT, MD, FCCM, FNCSCHIEF OF NEUROLOGY AND DIRECTOR OF THE

NEUROSCIENCE CRITICAL CARE UNITEMORY UNIVERSITY HOSPITAL MIDTOWNASSOCIATE PROFESSOR OF NEUROLOGY

AND NEUROSURGERYEMORY UNIVERSITY SCHOOL OF MEDICINE

ATLANTA, GA

Neurocritical Care for Stroke

Greetings from the Stroke Belt

Mohr

Stroke Belt & Buckle

Stroke Belt & Buckle

Nahab

Objectives

Determine the role of the NeuroICU in the stroke “chain of survival” Systems of delivery

Identify unique opportunities for the multidisciplinary, multiprofessional neurocritical care team to impact stroke care SAH, ICH, CVST Early detection of neuro changes Monitoring and managing increased intracranial

pressure Examine the basic treatment principles that guide

neurointensive stroke care Interventions Medical management

No financial disclosures

Stroke remains a leading cause of death and disability in the U.S., with more than 750,000 cases per year.

Strokes cause 200,000 deaths and cost more than $57 billion per year in the U.S. alone.

MeyersGonzales

Gonzales

Stroke Care

Prevention Reperfusion Neuroprotection

Penumbral perfusionSupportive care

Rehabilitation

Jovin

Systems of Care: Chain of Survival

Prehospital managementRapid transport to designated stroke centerEmergency evaluationEarly diagnosisRapid implementation of treatmentGeneral “supportive” careManagement of complicationsRehabilitationSecondary prevention

Systems of Care: Chain of Survival

Prehospital managementRapid transport to designated stroke centerEmergency evaluationEarly diagnosisRapid implementation of treatmentGeneral “supportive” careManagement of complicationsRehabilitationSecondary prevention

Expanding role of neurocritical care

Indications for Intensive Care

Patients with stroke who meet medical criteria for intensive care Respiratory, cardiac, etc.

Patients who need for intensive neurologic monitoring/management All subarachnoid hemorrhage

Risk of re-rupture, high-risk treatment modalities, risk of hydrocephalus, risk of vasospasm

Acute intracerebral hemorrhage Risk of rebleed and cerebral edema

Large hemispheric ischemic stroke Risk of cerebral edema

Stroke or hemorrhage in the posterior fossa Imminent risk of neurologic deterioration due to hydrocephalus

and cerebral edema Intracranial pressure monitoring

Traditional Role of NeuroICU in Stroke Care

DiagnosisAcute reperfusion strategies“Supportive” measures

Penumbral perfusionPrevent secondary brain injuryIncluding neuroprotectionPrevent/treat stroke complications

Diagnosis: Stroke Mimics

Metabolic disturbance Hypo- or hyperglycemia, drug toxicity, hypo- or

hypernatremia, renal or hepatic failure, post-anoxic encephalopathy

Meningitis/encephalitisHypertensive encephalopathyHypotensionSeizures with persistent neurologic deficitMigraine with persistent neurologic deficitIntracranial mass

Tumor, hematoma, abscessCraniocerebral/cervical trauma

Acute Reperfusion Strategies

Measures to restore or improve perfusion IV thrombolytics Endovascular therapies Anticoagulants or antiplatelets

Role is secondary prevention, not reperfusion Volume expansion, vasodilators and induced

hypertension Not recommended outside a of research setting

Surgical interventions Not recommended as a reperfusion strategy outside of a

research setting

Adams

“Brain-Oriented” Intensive Care

Balance cerebral metabolic (oxygen and glucose) supply Cerebral perfusion pressure, cerebral oxygenation Controlling intracranial pressure

With cerebral metabolic demand Fever, seizures, agitation, pain, shivering

And minimize compounds that will worsen neurologic damage Excess cerebral glucose, lactic acid, excitotoxic

neurotransmitters, inflammatory mediators, etc.

DeGeorgia 2005

Loss of autoregulation

Cerebral ischemia

Free radicals

Reperfusion injury

Loss of membrane integrity

Release of excitotoxins

Mitochondrial dysfunction

Loss of ion homeostasis, including prolonged Ca++

influx

Tisdall, Polderman, Mulvey, DeGeorgia

Inflammatory reactions, proinflammatory cytokines

Loss of autoregulation

Cerebral ischemia

Free radicals

Reperfusion injury

Loss of membrane integrity

Release of excitotoxins

Mitochondrial dysfunction

Apoptosis

Cellular swelling=>↑ICP

Loss of ion homeostasis, including prolonged Ca++

influx

Tisdall, Polderman, Mulvey, DeGeorgia

Inflammatory reactions, proinflammatory cytokines

DeGeorgia 2005

Cerebral Blood Flow Monitor

Brain Tissue Oxygenation Monitor

Cerebral Microdialysis

Continuous EEG

Membrane degradation products, excitotoxic neurotransmiters, inflammatory markers, etc.

Wright 2007

Stroke Critical Care

Emergency measures Airway/breathing/circulation

Penumbral perfusion BP delivery

Secondary injury/neuroprotection Seizures Glucose Infection Temperature management ICP management

Complications DVT/PE Infection Alimentation Hemorrhagic transformation Recurrent stroke

Rehab initiation Early mobilization

Airway Intubate if compromised

Breathing Maintain sats >94% (avoid hypoxia)

Supplemental O2 not recommendedCirculation

Cardiac monitoring Cardiac rhythm Treat/avoid hypovolemia

With fluids that do not contain glucose and are not hypotonic Treat high or low BP Improve blood flow to penumbra?

Volume expanders, vasodilators, induced hypertension and hemodilution

Supportive Measures After Stroke

Jaunch

BP treatment after stroke

If patient received tPA Treat to keep SBP > 180, DBP> 105 for the first 24 hrs Nicardipine, labetolol are the first line recommendations

If patient did not receive tPA Treat if SBP>220, DBP>120 Target 15% reduction on the first day

Oral antihypertensives can probably be added (or restarted) slowly following 24-48 hours of symptoms onset Some use 24-48 hours after symptom stabilization

Wartenberg 2007

*BP Goal:Allow for enough cerebral perfusion pressure and penumbral perfusion, but not so much to cause hemorrhagic transformation

*One goal unlikely to fit all patients

MeyersGonzales

Blood Pressure after Acute Ischemic Stroke

Enhancing Perfusion of the Ischemic Penumbra

Hemodilution Intentional hemodilution does not reduce mortality or

improve outcome in survivors and is therefore not recommended (Class III, Level A)

Only possible exception is in patients with severe polycythemia vera

Volume expansion Trials ongoing with albumin (ALIAS), but not currently

recommendedVasodilators

Not recommended based on current data (Class III, Level A)Induced hypertension

Induced Hypertension- AHA Guidelines

Optimal management of blood pressure remains controversial

Inducing hypertension is attractive in experimental studies Wityk, Hillis, Koenig

Guidelines Adams

In exceptional cases, may prescribe vasopressors to improve cerebral blood flow; if used, close neurologic and cardiac monitoring is recommended (Class I, Level C)

Drug-induced hypertension, outside of the setting clinical trials, is not recommended for most patients with acute ischemic stroke (Class III, Level B)

Induced Hypertension in Clinical Practice

In general, if neurologic symptoms are fluctuating over the first 48-72 hours, there are many neurocritical care units that will try a modest increase in blood pressure Starting with bolus fluid administration to increase

MAP by 10-20%, then using vasopressors if needed to see if neurologic deficits stabilize or improve If so, MAP goals are then reset to this level until

symptoms stabilize, then slowly weaned over ensuing days

Similar steps are taken if symptoms fluctuate or worsen to sudden changes in BP with change in body position, medication administration, etc.

Admit to stroke unit, standard stroke ordersAlimentation

Early dysphagia screen NG/PEG if needed for feeding and meds

Infection Avoid foley

Glucose Avoid/treat hypoglycemia and hyperglycemia

Venous thromboembolism prophylaxis Anticoagulation for DVT prophylaxis SCDs if they cannot tolerate anticoagulation

Early mobilizationEarly meds to prevent stroke recurrent stroke

ASA is appropriate in most patients Statin as indicated (do not discontinue if already taking)

General Supportive Measures After Stroke

Jaunch

Hyperthermia Evaluate and treat causes of fever

Neuroprotective strategies No medications to date have been efficacious in clinical

trial Calcium channel blockers NMDA-receptor antagonists Early administration of magnesium in the field (FAST-

MAG) Nitric oxide synthetase inhibitors Interferon-В Erythropoietin And many more…

Hyperbaric O2 data inconclusive Hypothermia

Supportive Measures After Stroke

Jaunch

Hypothermia

Has been shown to be neuroprotective in experimental and focal brain injury models

Rational is strong, especially since it is multifactorial May delay depletion of energy reserves Lessen intracellular acidosis Slow influx of calcium into ischemic cells Suppress production of oxygen free radicals Lessen impact of excitatory amino acids

Studies are on going to look at factors such as optimal temperature, and timing of rewarming, etc.

Hypothermia is commonly used in neurocritical care units to treat refractory cerebral edema

Treating Complications After Stroke

Infection Avoid foley catheter placement Treat pneumonia, urinary tract infections per usual Prophylactic antibiotics not recommended

Recurrent seizures should be treated Prophylactic AEDs not recommended

Hemorrhagic transformation Avoid/stop high dose anticoagulants, antiplatelets

Ventricular drain for hydrocephalusBrain edema

Do not give corticosteriods Suboccipital craniotomy for cerebellar strokes Decompressive hemicraniectomy is lifesaving in the setting of

malignant cerebral edema from large artery strokes

Jaunch

Don’t Underestimate These Strokes!

Posterior circulation strokes Can look like intoxication or infection (CNS or inner ear) Image vessels with CT-angiography or MR-angiography

Cerebellar strokes Swelling can cause hydrocephalus and herniation, and can be

rapidly fatal Neurosurgical consult is required for ventriculostomy drain or

suboccipital craniotomyLarge ischemic strokes

“Large” is >1/3 the MCA territory, or with mass effect on the ventricle or midline shift

At risk for life-threatening cerebral edema which could lead to herniation and death

Early decompressive hemicraniectomy can be life savingCerebral venous sinus thrombosis

Often misdiagnosed Reluctance to anticoagulate persists

Brain Edema

Tends to occur with infarction of major intracranial arteries and leads to multilobar infarctions

Usually peaks 3-5 days after strokeCan be a problem in the first 24 hours after

large cerebellar infarction

Adams

Increased Intracranial Pressure

The Ultimate Compartment Syndrome!

Intracranial Pressure & Cerebral Perfusion Pressure

Normal ICP varies with age, but in adults it is usually 5-15 mm Hg

Cerebral perfusion pressure (CPP) is the mean arterial pressure (MAP) minus the ICP If the ICP is high, blood can not reach cerebral tissues

ICP of 20-30 mm Hg is generally considered elevated, but cerebral herniation can occur at lower values, especially with pressure gradients across cerebral compartments

Signs and Symptoms of Increased ICP

Declining mental statusHeadacheNausea, vomitingPapilledema

Reliable, but uncommonPupillary dilationDecerebrate posturingApnea“Cushing's Triad” of HTN, bradycardia,

change in respiratory patternRangel-Castillo

ICP Treatment Based on MKD

Plan to quickly assess for and treat any underlying causes such as a subdural hematoma or cerebral abscess This will usually require neurosurgical intervention

Mass-targetedCSF-targetedBrain-targetedBlood-targeted

ICP Management

General (targets blood compartment) Avoid shivering, agitation, fever; head midline and

elevated to 30º; maintain euvolemia or slightly hypervolemic

Hyperventilation (targets blood compartment) Lower PaCO2 30-35 in emergent situations

Osmotherapy (targets brain compartment) Hypertonic saline (Na 145-155), mannitol (osm 300-320),

furosemide (less desirable but still used) Metabolic suppression (targets blood compartment)

Narcotics, benzodiazepines, barbiturate coma, propofol CSF drainage (targets CSF compartment)

Especially in pts with hydrocephalus or IVH Neurosurgical (targets brain or “mass” compartment)

Hematoma/infarcted tissue removal, hemicraniectomy Hypothermia (targets brain compartment)

Bhardwaj

Bedside Interventions for ICP Crisis

Immediate steps HOB up, head midline (blood targeted) Hyperventilate with ambu bag (blood targeted) Osmotherapy (brain targeted)

30-60cc of 23.4% saline through central line 250-500cc of 3% saline is an alternative

or 1 gm/kg of mannitol through a peripheral line This must go through a filter

Try to reverse the herniation (i.e., return pupil to normal) or ICP spike and get patient to CT scanner to look for reversible and/or neurosurgical causes

Bedside Interventions for ICP Crisis

ADVANCED management options Cool the patient

Can pack in ice if a cooling blanket is not available

Watch for shivering! Propofol 0.05-0.1mg/kg bolus or 125-250 mg of thiopental IV

Will drop the MAP/CPP, and may make it difficult to examine the patient

If an ICP monitor is in, consider vasopressors to support cerebral perfusion pressure

Don’t Underestimate These Strokes!

Posterior circulation strokes Can look like intoxication or infection (CNS or inner ear) Image vessels with CT-angiography or MR-angiography

Cerebellar strokes Swelling can cause hydrocephalus and herniation, and can be

rapidly fatal Neurosurgical consult is required for ventriculostomy drain or

suboccipital craniotomyLarge ischemic strokes

“Large” is >1/3 the MCA territory, or with mass effect on the ventricle or midline shift

At risk for life-threatening cerebral edema which could lead to herniation and death

Early decompressive hemicraniectomy can be life savingCerebral venous sinus thrombosis

Often misdiagnosed Reluctance to anticoagulate persists

Cerebral Venous Thrombosis

CVT accounts for 0.5% to 1% of all strokesMostly affects young people, especially

women of childbearing ageCommonly presents with headache

Though some present with a focal neurological deficit, decreased level of consciousness, seizures or intracranial hypertension without focal signs

Insidious onset can create a diagnostic challenge

2011 guideline

Cerebral Venous Thrombosis

A prothrombotic factor or direct cause is identified in about 2/3 of patients

Diagnosis is usually made by venographic studies with CT (CTV) or MRI (MRV) to demonstrate obstruction of the venous sinuses

Risk Factors

Acquired Surgery Trauma Pregnancy Puerperium Antiphospholipid syndrome Cancer Exogenous hormones

Oral contraceptives Infections

Mainly in parameningeal locations CVT caused by infection is more

common in children Mechanical precipitants

Epidural blood patch Spontaneous intracranial

hypotension Lumbar puncture

Genetic risks Inherited thrombophilia/

hypercoaguability Antithrombin III deficiency Protein C deficiency Protein S deficiency Factor V Leiden positivity Hyperhomocysteinemia Mutation G2020A of factor II

Hematologic disorders Paroxysmal nocturnal

hemoglobinuria Polycythemia, thrombocythemia

Systemic diseases Systemic lupus erythematosus Inflammatory bowel disease

Pregnancy and the Puerperium

Common causes of prothrombotic statesMost pregnancy related CVTs occur in the

third trimester or 6-8 weeks after birthDuring the puerperium, additional risk

factors include infection; increasing maternal age; hypertension; vomiting; and instrumental delivery or Cesarean section

Treatment

Initiate anticoagulation, unless there is a contraindication In the presence of CVT, intracranial hemorrhage is

NOT an contraindication to anticoagulationTreat any underlying cause, if able

Including antibiotics for infection, or surgical drainage of purulent collections of infectious sources associated with CVT when appropriate

Treat a seizure if one occurs, but routine use of prophylatic antibiotics is not recommended

Put the treatment algo.

Increased Intracranial Pressure

Monitor for visual field lossMay require cerebrospinal fluid diversionGuidelines say that acetazolamide is reasonable

to decrease CSF productionPatients with neurologic deterioration due to

severe mass effect or intracranial hemorrhage causing intractable intracranial hypertension may be eligible for hemicraniectomy

Steroids are not indicated to treat cerebral edema Unless needed for another underlying disease

Systems of Care

Primary stroke center certification Preferential routing of stroke patients whose symptoms

started within time windows amenable to interventionComprehensive stroke centers

Act as a regional resource for stroke care and will be pivotal for further advancement in acute stroke care, stroke prevention and rehabilitation Dion, Rymer, Silverman

Designed to care for patients with Complicated types of stroke, intracerebral hemorrhage or

subarachnoid hemorrhage And those requiring specific interventions (surgery or

endovascular procedures) or an intensive care setting Currently about 75 in the US, estimated need is 300

Mobile Stroke Units

Studies showed a reduction in EMS activation-to-treatment time from 104 minutes to 64 minutes

Future Directions

Continued move toward regionalization of stroke care

Focus on candidate selection for acute stroke therapy For recanalization, hemicraniectomy, hypothermia and

other advanced therapies Advanced radiology techniques to assess core vs.

penumbraThe quest for neuroprotection continuesFine tune care delivery systems

Conclusions

Stroke remains an actively advancing field of medicine

We are all a link in the chain of survivalDue to multidisciplinary, multiprofessional

collaboration, neurocritical care unit teams have a specialized ability to detect and manage Patients in need of acute stroke interventions Secondary brain injury after stroke Complications after stroke

References

Adams, HP, del Zoppo, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: A guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38:1655-1711.

Hillis AE, Ulatowski JA, Barker PB, et al. A pilot randomized trial of induced blood pressure elevation: effects on function and focal perfusion in acute and subacute stroke. Cerebrovasc Dis 2003;16:236-246.

Wityk RJ, Restrepo L. Hypoperfusion and its augmentation in patients with brain ischemia Curr Treat Options Cardiovasc Med 2003;5:193-199. Jovin TG, Yonas H, Gebel JM, et al. The cortical ischemic core and not the consistently present penumbra is a determinant of clinical outcome in acute middle cerebral artery occlusion.

Stroke 2003;34:2426-2435. Levy EI, Ecker RD, Horowitz MB et al. Stent-assisted intracranial recanalization for acute stroke: early results. Neurosurgery 2006:58;458-463. Levy EI, Mehta H, Gupta R, et al. Self-expanding stents for recanalization of acute cerebrovascular occlusions. AJNR 2007;28:816-822. Leary MC, Saver JL, Gobin YP, et al. Beyond tissue plasminogen activator: mechanical intervention in acute stroke. Ann Emerg Med 2003;41:838-846. Meyers PM, Schumacher C, Higashida RT, et al. Indications for the performance of intracranial endovascular neurointerventional procedures: a scientific statement from the American

Heart Association Council on Cardiovascular Radiology and Intervention, Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Interdisciplinary Council on Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research. Circulation 2009;119:2235-2249.

Lin R, Vora N, Zaidi S, et al. Mechanical approaches combined with intra-arterial pharmacological therapy are associated with higher recanalization rates than either intervention alone in revascularization of acute carotid terminus occlusion. Stroke 2009;40:2092-2097.

Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005; 36; 2311-2320. Alexandrov AV, Grotta JC. Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology 2002;59:862-867. Meyers PM, Schumacher C, Alexander MJ, et al. Performance and training standards for endovascular stroke treatment. Stroke Cerebrovas Dis 2009;18(6):411-415. Gerorgiadis AL, Memon MZ, Shah QA, et al. Comparison of partial (.6mg/kg) versus full-dose (.9mg/kg) intravenous recombinant tissue plasminogen activator followed by endovascular

treatment for acute ischemic stroke: a meta-analysis. J Neuroimaging 2009. epub ahead of print. Gonzales RG. Imaging-guided acute ischemic stroke therapy: from “Time is Brain” to Physiology is Brain” AJNR 2006; 27:728-735. Smith WS, Sung GS, Starkman S, et al. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke 2005;36(7):1432-8. Smith WS, Sung GS, Saver, et al. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke 2008;39(4):1205-12. Hayden MG, Lee M, Guzman R, et al. The evolution of cerebral revascularization surgery. Neurosurg Focus 2009;26(5)1-7. Gupta R, Vora NA, Horowitz MB, et al. Multimodal reperfusion therapy for acute ischemic stroke: factors predicting vessel recanalization. Stroke 2006;37:986-990. Walters BB, Ojemann RG, Heros RC. Emergency carotid endarterectomy. J Neurosurg 1987;66:817-823. McCormick PW, Spetzler RF, Bailes JE, et al. Thromboendarterectomy of the symptomatic occluded internal carotid artery. J Neurosurg 1992;76:752-758. Sbarigia E, Toni D, Speziale F, et al. Emergency and early carotid endarterectomy in patients with acute ischemic stroke selected with a predefined protocol: a prospective pilot study.

Int Angiol 2003;22:426-430. Weinstein PR, Rodriguez y Baena R, Chater NL. Results of extracranial-intracranial arterial bypass for intracranial internal carotid artery stenosis: review of 105 cases. Neurosurgery

1984;15(6):787-94. Yoshimoto Y, Kwak S. superficial temporal artery-middle cerebral artery anastomosis for acute cerebral ischemia: the effect of small augmentation of blood flow. Acta Neurochir (Wien)

1995;137:128-137. Kakinuma K, Ezuka I, Takai N, et al. The simple indicator for revascularization of acute middle cerebral artery occlusion using angiogram and ultra-early embolectomy. Surg Neurol

1999;51:332-341. Breckenfeld C, Remonda L, Nedeltchev K, et al. Endovascular neuroradiological treatment of acute ischemic stroke: techniques and results in 350 patients. Neurol Res 2005;27(suppl

1):S29-S35. Alexandrov AV, Molina CA, Grotta JC, et al. CLOTBUST investigators. Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J med 2004;351:2170-2178. Chen M. Stroke as a complication of medical disease. Semin Neurol. 2009; 20(2):154-162. Nadav L, gur AY, Korczyn AD, Bornstein NM. Stroke in hospitalized patients: are there special risk factors? Cerebrovasc Dis 2002;13(2):127-31. Farooq MU, Reeves MJ, et al; Paul Coverdell National Acute Stroke Registry Michigan Prototype Investigators. In-hospital stroke in a statewide stroke registry. Gupta R, Jovin TG. Endovascular management of acute ischemic stroke: advances in patient and treatment selection. Expert Rev. Neurotherapeutics 2007;7(2):143-153. Nogueira RG, Liebeskind DS, Sung G, et al. Predictors of good clinical outcomes, mortality and successful revascularization in patients with acute ischemic stroke undergoing

thrombectomy. Pooled analysis of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and MultiMERCI trials. Stroke 2009; 40:epub ahead of print. Lai BK, Brott TG. The carotid revascularization endarterectomy vs. stenting trial completes randomization: Lessons learned and anticipated results. Journal of Vascular Surgery

2009;50(5):1224-1231. Koenig MA, Geocadin RG, deGouchy M, et al. Safety of induced hypertension therapy in patients with acute ischemic stroke. Neurocrit Care 2006;4:3-7. Nahab F, Le S, et al. Racial and geographic differences in fish consumption. Neurology, 2010. Levy EI Ecker RD, Horowitz MB, et al. Stent-assisted intracranial recanalization for acute stroke: early results. Neurosurgery 2006;58:458-463. Khatri P, Abruzzo KP, Yeatts SD, Nichols C, et al. Good clinical outcome after ischemic stroke with successful revascularization is time-dependent. Neurology 2009;73(13):1006-72.