UCLA Stroke Center

Implications for Clinical Practice

Jeffrey L. Saver, MDProfessor of Neurology

Director, UCLA Stroke Center

--All slides in presentation are freely available under a Creative Commons “Share Freely with Attribution” License – Saver

Talk Outline

• Implications for clinical practice guidelines» Statistical significance

• Implications for clinicians at bedside» Clinical significance» Systems of care

• Implications for future

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Guidelines

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European EUSI Recommendations 2006

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US AHA/ASA Guidelines 2010

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INTERACT 2: A Near Win Trial

Trial Intervention OR P primary

P ordinal

INTERACT 2 BP↓ for ICH 0.87 (0.75-1.01) 0.06 0.04

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Stroke and Near Win Trials

Trial Intervention OR P primary

P ordinal

INTERACT 2 BP↓ for ICH 0.87 (0.75-1.01) 0.06 0.04

IST 3 TPA to 6 hours 1.13 (0.95-1.35) 0.18 0.001

SPS3 BP Arm BP↓ prevent recurrent stroke

0.81 (0.64-1.03) 0.08

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Meta-Analysis of INTERACT 1, 2 and ATACH Trials

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Clinical Significance

“A difference, to be a difference, must make a difference”

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INTERACT 2

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INTERACT 2

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INTERACT 2

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Benefit on Dichotomized Outcome

• 52.0% vs 55.6%• ARR 3.6%• Benefit per Thousand: 36• NNT: 27.8

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INTERACT 2

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INTERACT 2

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Automated Algorithmic Joint Outcome Table Analysis

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--Saver et al, Stroke 2009;40:2433-7

Benefit Over All Health State Transitions

• Benefit per Thousand: 81• NNT: 12.3

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Benefit in INTERACT 2 vs Other Acute Stroke Interventions

Intervention Net Benefit per ThousandTPA under 3h 290IA Pro-UK 208Coiling in SAH 169TPA 3-4.5h 136BP lowering for ICH 81Clinician worthwhile 50Socioeconomic model worthwhile 20

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--Samsa et al, Am Heart J 1998;136:703-13--Saver, Stroke 2007;38:3055-3062--Saver et al, Stroke 2009;40:2433-7

Door to BP Control in Community Practice in ICH

• 100 patients, 32 Emergency Departments

• At ED arrival» NIHSS 18» Time from LKW 63 mins» Mean BP 176/94

• 54% received BP therapy in ED• Among the 48 patients with SBP ≥

180» Control (<180) never achieved in 19%» Median door to control 118 mins» Door to control ≤ 90m in 31%

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--Sanossian et al, Ann Emerg Med 2012;60: S56

Other Treatment Recommendations for ICH

• ICU monitoring• Antipyretics in febrile patients• Early mobilization• ICP management

» Head of bed, analgesia, sedation» Osmotic diuretics, CSF drainage,

hyperventilation• Maintain serum glucose < 185• Seizures

» Prophylactic antiepileptics for lobar ICH» Antiepileptics for clinical seizures» Antiepileoptics for electrographic

seizures

• DVT prophylaxis» Intermittent compression on arrival» SQ LMWH or UH after 3-4d

• For DVT, consider vena cava filter• Reversal of coagulopathies

» Protamine for heparin» Vitamin K, PCC, rF7 for warfarin

• Surgery» Definite for select cerebellar» Consider for lobar» Consider minimally invasive for deep

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--Morgenstern et al, Stroke 2010

ICH Critical PathwayIdentify Signs of Possible Stroke

Critical EMS Assessments & Actions

Immediate General Assessment/Stabilization

Immediate Neurologic Assessment (stroke team or designee)

Does CT scan show hemorrhage?

No Hemorrhage Hemorrhage

Possible ischemic stroke

• Consult neurologist or neurosurgeon• If not available, consider transfer

BP Management

ICP Management

Seizure Prevention and Management

Fluid ManagementBody Temperature

Management

Surgical Treatment of ICH Cerebellar hemorrhage >3 cm with

neurologic deterioration or brain stem compression and/or hydrocephalus

Consider in lobar clots <1 cm of surface

AHA Adult Stroke Guidelines. Circulation. 2005;112(suppl 24):IV-111-IV-120; Broderick J, et al. Stroke. 2007;38:2001-2023; Qureshi AI, et al. N Engl J Med. 2001;344:1450-1460.

NINDS Time Goals

Monitor Blood Glucose and Treat (if needed)

Begin ICH Pathway Admit to stroke unit (if available) or ICU Monitor BP and treat (if indicated) Monitor neurologic status

(emergent CT if deterioration) Monitor blood glucose & treat (if needed) Supportive therapy Treat comorbidities

ICH Critical Pathway Sample ChecklistEMS ED (60 min) ICU/NCCU Surgical

Intervention•Medical history (risk factors, similar recent events)

•Determine any medications currently taken

•Cincinnati Prehospital Stroke Scale

•Los Angeles Prehospital Stroke Screen

•ABCs•Time of onset•Medic Alert tag

•ABCs•Vital signs•Medical history •Time of onset•Blood pressure•Neurologic status (GCSS)•Blood glucose

•ABCs•Vital signs•Blood pressure•Intracranial pressure•Neurologic status•Blood glucose•Body temperature

•Routine evacuation of supratentorial ICH with standard craniotomy within 96 hours not recommended

•Surgical candidates (cerebellar hemorrhage >3 cm with neurologic deterioration; consider with lobar clots <1 cm from surface)

•Vital signs•Support ABCs (oxygen if needed)

•Transport (consider triage to stroke center)

•Vital signs•Obtain IV access & blood samples

•Support ABCs•Intubation(?)•Supportive therapy•Treat comorbidities

•Vital signs •Support ABCs•Intubation(?)•Supportive therapy•Treat comorbidities•Fluid management (euvolemia)

•Positional factors (head at midline, raise head of bed 30º)

•Blood glucose (if possible)•12-lead ECG (if possible)

• CT/MRI•Neurologic examination (NIH Stroke Scale, Canadian Neurologic Scale)

•Blood pressure•Electrolytes•Blood glucose•12-lead ECG on admission•CBC, PT, aPTT, INR, electrolytes•Toxicology•Platelet function •CXR

•Blood pressure – MAP, SAP, CPP

•ICP (ventriculostomy, fiberoptic ICP monitor, etc)

•Blood glucose•12-lead ECG•CT/MRI

Ass

essm

ent

Nur

sing

Test

ing

ICH Critical Pathway Sample Checklist

ICH Critical Pathway Sample Checklist (cont.)EMS ED (60 min) ICU/NCCU Surgical Intervention

•Oxygen •Oxygen (if hypoxemic)•Treat blood glucose abnormalities •Blood pressure (labetalol, esmolol, nitroprusside, hydralazine, enalapril)

•Blood pressure (labetalol, esmolol, hydralazine, enalapril, nicardipine)

•ICP (head elevation, osmotic diuretics, CSF drainage; neuromuscular blockade, hyperventilation)

•Seizures (lorazepam, diazepam, phenytoin, fos-phenytoin)

•Warfarin coagulopathy (PCC, FFP, Vitamin K, Factor VIIa)

•Treat blood glucose abnormalities

•Alert hospital •Activate stroke team•Consult neurologist or neurosurgeon

•Consider transfer to stroke center

•Consult neurologist or neurosurgeon

•Begin stroke pathway•Admit to stroke unit (if available) or ICU

•Follow stroke pathway

Adapted from AHA Adult Stroke Guidelines. Circulation. 2005;112(suppl 24):IV-111-IV-120; Broderick JP, et al. Stroke. 1999;30:905-915; Broderick J, et al. Stroke. 2007;38:2001-2023; Marik PE, et al. Chest. 2002;122:699-711; Passero S, et al. Epilepsia. 2002;43:1175-1180; Qureshi AI, et al. Stroke. 2001;33:1916-1919.

ABCs = airway-breathing-circulation aPTT = activated partial thromboplastin timeCBC = complete blood count CPP = cerebral perfusion pressureCXR = chest x-rayED = emergency departmentFFP = fresh frozen plasma

GCSS = Glascow Coma Scale scoreICP = intracranial pressureINR = international normalized ratio MAP = mean arterial pressure NCCU = neuro-critical care unitPCC = prothrombin complex concentrate PT = prothrombin timeSAP = systolic arterial pressure

Med

icat

ions

Con

sults

Path

way

sICH Critical Pathway Sample Checklist (cont.)

Next Steps

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Time is Brain for Hemorrhagic Stroke

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--Arima et al, Stroke 2012;43:2236-8

Dynamics of Hyperacute Hematoma Growth 0-120 Minutes: Not Well Delineated

--Kazui et al, Stroke 1996;27:1783-1787

Intracerebral Hemorrhage and the Golden Hour

• Narrow therapeutic time window

• Early intervention critical• Prehospital personnel

» 35-70% of stroke patients arrive by ambulance

» Unique position: first medical professional to come in contact with stroke patient

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-15 -5 0 20 30 40 60 100 160 200 3600

5

10

15

20

25

30

35

40

45

Time in minutes from onset of symptoms

Volu

me

of H

emat

oma

in m

L

Rupture of blood vessel

Onset of Symptoms

Activation of EMS

EMS Arrival

EMS Transport

EMS Arrival in ED

Initial ED Evaluation CT scan

obtained

CT scan evaluated

Hospital Treatment initiated

Final Hematoma Volume Established

Sanossian, FAST-BP Trial

-15 -5 0 20 30 40 60 100 160 200 3600

5

10

15

20

25

30

35

40

45

Time in minutes from onset of symptoms

Volu

me

of H

emat

oma

in m

L

Rupture of blood vessel

Onset of Symptoms

Activation of EMS

EMS Arrival

EMS Transport

EMS Arrival in ED

Initial ED Evaluation CT scan

obtained

CT scan evaluated

Hospital Treatment initiated

Final Hematoma Volume Established

Field Treatment Initiated

Goal: Control Hematoma expansion Earlier in

Course

Sanossian, FAST-BP Trial

-15 -5 0 20 30 40 60 100 160 200 3600

5

10

15

20

25

30

35

40

45

--All hypertensive pts--All severely hypertensive pts--Likely ICH pts

Time in minutes from onset of symptoms

Volu

me

of H

emat

oma

in m

L

Rupture of blood vessel

Onset of Symptoms

Activation of EMS

EMS Arrival

EMS Transport

EMS Arrival in ED

Initial ED Evaluation CT scan

obtained

CT scan evaluated

Hospital Treatment initiated

Final Hematoma Volume Established

Field Treatment Initiated

Goal: Control Hematoma expansion Earlier in

Course

Sanossian, FAST-BP Trial

Onset to Treatment Times in Recent Trials Enrolling ICH Patients

Trial Setting Intervention Onset to Treatment

INTERACT 1 Hospital Target SBP ≤ 140 4h 00mATACH 1 Hospital Nicardipine 4h 17mINTERACT 2 Hospital Target SBP ≤ 140 4h 00mRIGHT Prehospital Glyceryl trinitrate 55mPIL-FAST Prehospital Lisinopril 1h 17mFAST-MAG Prehospital Magnesium 47m

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Preserve / Treat / Cure

Condition EMS ED OR/Cath LabAcute ischemic stroke

Neuroprotection TPA Endovascular recanalization

Acute intracerebral hemorrhage

BP lowering Hemostatic agent Minimally invasive hem evacuation

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Preserve / Treat / Cure

Condition EMS ED OR/Cath LabAcute ischemic stroke

Neuroprotection TPA Endovascular recanalization

Acute intracerebral hemorrhage

BP lowering Hemostatic agent Minimally invasive hem evacuation

UCLA Stroke Center