08/12/1431

1

G id li f BP t i ti t ith

AMOHOTOBAMOHOTOBKASR ALAINY KASR ALAINY 18271827

MEDICAL SCHOOLMEDICAL SCHOOL 3000 B.C.

Guidelines of BP management in patients with

acute stroke (neurologist perspectives)

PROF. SHERIF HAMDYKASR ALAINY

CAIRO UNIVERSITYCAIRO UNIVERSITY 1908

Incidence & Prevalence of Strokes in Upper Egypt

• Incidence found to be about ABOUT 1.8 PER 1000 PER YEAR , URBAN 1.5, SUBURBAN 1.8, RURAL 2.1 per 1000 per year

• Prevalence of Strokes: 5.08 per 1000 per 4

5

6

I id

5.085.85.4

4.1p p

year, URBAN 4.1, SUBURBAN 5.8, RURAL 5.4 per 1000 per year

0

1

2

3

URBAN Rural Suburban Total

IncidencePrevalence

Incidence Kandil et al. 2006

Dennis et al. 1989

Fogelholm et al. 1992

5

10

15

20

25

30

35

WINTERSPRINGSUMMERAUTUMN

31.7%27.7%

24.7%

13.8%

1.81.82.1

1.5

M.R. Kandil, H.N El-Tallawy, H.M Farawez, G. Khalifa, M. A. Ahmed, A. Hamed & A.M. Ali, EJNPN, 2006, META-ANALYSIS OF STROKE STUDIES IN EGYPT, EL-TAMAWY et al. ,EJNPN, 2007

Thromboembolic stroke

1.24/1000 1.3/1000 -

Cerebral hemorrhage

0.43/1000 0.43/1000

0.31/1000

Subarachnoid hemorrhage

0.19/1000 0.1/1000 -

TIAs 0.25/1000 0.35/1000

-

0

5

Winter Spring Summer Autumn

The Percentage of Strokes by season In Egypt

08/12/1431

2

Distribution of different stroke subtypes in Egypt

Hemorrhage MCAHemorrhageIschemiaThromboticEmbolic

Ischemia 78%Thrombotic 67.86%Embolic 10.14%

Cerebral Hemorrhage 22%Capsular 12%Lobar 4.5%Intraventricular 3%Subarachnoid 2.8%

MCAACAVBLacunar

MCA 73.7%ACA 10.5%Vertebro-basilar & Lacunar 15.8%

39

30

35

40

SexDistributionMaleFemale

MALES59.5%

FEMALES40.5%

2.1 3.8

13

26.5

16.1

0

5

10

15

20

25

% o

f pat

ient

s

<30 30-40 40-50 50-60 60-70 >70years

Sex Distribution in Egyptian Stroke patientsAge at Onset of Stroke

META-ANALYSIS OF STROKE STUDIES IN EGYPT, EL-TAMAWY & ,ABDGHANY. ,EJNPN, 2007

HIGH BLOOD PRESSURE in Egypt,

• The Epidemiology of intermediate phenotype 60

– Hypertension– Hyperlipidemia– Diabetes mellitus– Carotid stenosis

01020304050

HYPE25y

75yFEMA

MALE

Hypertension

Prevalence of Hypertension in Egypt 26.3% PERTENSION

y y MALES

LES26.3%– Prevalence in 25-34 years old is 7.8%– Prevalence in > 75 years old is 56.6%– Prevalence in females is 26.9%– Prevalence in males is 25.7%

Ibrahim M., Rizk H., Appel L. J., Results of the Egyptian National Hypertension Project NHP,1995

08/12/1431

3

The difference between stroke patients and controls as regard risk factors in Egypt

46%, 31.3%, 24,7%, 39.3%, 42%, 64%

17% 31 7%

Family History OR 11.925, 95%CI 6.84-20.79HYPERTENSION

10

20

30

40

50

60

70

patientscontrols

3

4

5

6

7 HTNHDSmokersDMTIAsHypercholesteremiaOb it U b

6.4% 18% 18.3%17% 31.7% HYPERTENSION

OR 3.836, 95%CI 2.539-5.796

0 FH PAS TIA DM HD HTN

Epidemiological profile in EgyptShalaby E., Helmy S., Douaa Elderwi, Naglaa Elsherbiny. 2004, Cairo university

0 20 40 60 80

1

2 Obesity UrbanObesity Rural

450 subjects150 stroke patients300 normal subjects

OR=11.925 2.07 2.89 3.53 3.84

METANALYSIS , ELTAMAWY et al., EJNPN 2007

Immediate outcome (at discharge) of cerebrovascular stroke patients admitted to neurology Department of Assiut University during one year (2003).

Total ImprovementOR

StationaryOR

DeteriorationOR

Death0R

100

200

300

400

500

600

700

800

900CVS

Ischemic

hemorrhagic

Outcome

No. % No % No % No % No %

Cerebrovascular stroke

825 100 474 57.4 50 6.1 80 9.7 221 26.8

Ischemic stroke 581 70.4 348 59.9OR

33 5.6 52 9.0 148 25.4

0

100

Total Improve Stationary Deteriorate Death

OR 1.398

Hemorrhagic Stroke

244 29.6 126 51.6 17 6.9 28 11.5 73 30.0OR

1.248

08/12/1431

4

RISK FACTORS

Sherif Hamdy 2010

AGE GENDER OBESITY CORNEAL ARCUSSEX EAR LOBE

CREASE

CERVICALBRUIT &

STENOSISPVDFAMILY H

STROKES

VON

SOCIALDEPRIVATION

PSYCHO-FACTORS

PHYSICAL HCT SEX ALCOHOL

INFECTION

LIPIDS

SNORING

DM

HOMO-CYSTEINE

HTN

VENTILATFUNCTION

FIBRINOGEN

SERUM ALBUMIN

DIET -WILLIBRANDFACTOR

TIAVASECTOMY

PHYSICALACTIVITY

AF

HCTVALUE

LVH

SEX HORMONES

HF

ALCOHOL INTAKE

MI

WBC

CONTROVERSIAL VIEWS• Hypertension occurs commonly after stroke even in patients without

history of HTN• BP is often elevated acutely and typically returns to baseline

spontaneously over the first week.• Both elevated and low BP are associated with high rates of early and

late death, A U shaped relationship between admission BP and death– Castillo et al. Stroke 2004; 35,2:520-526.

• Theoretical reasons in favor of lowering BP acutely are to reduce cerebral edema and to lessen the risk of hemorrhagic transformation

• Allowing BP to remains high, risks of develop the following in population already prone to

M di l i f ti– Myocardial infarction– Pulmonary edema– Renal failure

• However the acute management of BP is controversial.

08/12/1431

5

Hypertension within the first week of stroke

• Concerns of the impaired auto-regulation in the peri-infarct area will result in further reduction ofperi infarct area will result in further reduction of CBF with lowering BP

• PET within the first week after stroke, showed focal impairment of auto-regulationand reduction in MABP in the peri-infarct area

• CBF did fall in some patients with lowering BP• There was an upward shift of the auto-regulatory

curve as a consequence of chronic HTN– Powers et al. Stroke 2007; 38,2:506

AUTOREGULATORY CURVEBelow the lower level of autoregulation the brain loses its ability to maintain constant CBF and flow become pressure passive

CBF

HTN

p p

CPP

Diringer M.N. Continuum June 2009. vol15;3:121-137

08/12/1431

6

BP reduction• Larger BP reduction have been associated with

– early neurological worsening, ea y eu o og ca o se g,– larger infarct volumes, – Higher rates of poor outcome– Death

• American Heart Association guidelines for early management of ischemic stroke,

– Recommend treating – SBP > 220mm Hg or

DBP> 120mm HgAdams et al. Stroke 2007;38,5:1655-1711

Chronic BP

• Risk of exceeding an upward shifted lower li it f t l ti i th tti flimits of auto regulation in the setting of poorly controlled chronic hypertension , pre stroke BP status control data should to be used in decision making

• Continuing the anti-hypertensiveContinuing the anti hypertensive medications used for treatment of chronic HTN before stroke may be recommended

08/12/1431

7

Diffusion/Perfusion Mismatch

Red: Ischemic Red: Ischemic coreOrange: Diffusion wt imageBlue: Ischemic penumbraLight Blue: Perfusion wt image

Lee, et al., 2005

Early CT may be essential ELTOUKHY, et al., 2006 ,KASR ALAINY CAIRO UNIVERSITY

• Non-contrast CT scan is regarded as the most important early diagnostic tool in assessment of suspected acute stroke, to exclude hemorrhage and to demonstrateexclude hemorrhage and to demonstrate early infacrts

• CT perfusion scan CBF in grey matter 50-60mL/100g/min

• CBF 35mL/100g/min 50-60% of normal values: protein synthesis within neurons ceases

• CBF 20mL/100g/min 30-40% of normal values: synaptic transmission is disturbed, loss of function of neurons, Tissue At Risk

• CBF 10mL/100g/min <20% of normal values, leads to irreversible cell death

• REPERFUSION of Tissue At Risk , can ,lead to complete regeneration of neuronal function

• MRI is more sensitive and superior, FLAIR study , Diffusion-Perfusion wt images should be included in a rapid protocol in assessment of patients with suspected acute stroke

CBF CBV

08/12/1431

8

--Avoid dropping of BPAvoid dropping of BP

--Loss of autoregulation of Loss of autoregulation of cerebral blood pressurecerebral blood pressure

--Drop of BP will result in Drop of BP will result in decrease cerebral blood decrease cerebral blood flow.flow.

--Drop of BP will lead to Drop of BP will lead to

National Stroke Research Institute

increase infarction size more increase infarction size more marked in marked in PENUMBRAPENUMBRA areaarea

BP MANAGEMENT• Low BP (< 120/80 mmHg):

• withhold antihypertensive treatment

• Extreme hypertension (>200/120 mmHg):

• optimize environment, bed rest, • IV fluids

• Normal BP – mild elevation (120-160 / 80-95 mmHg):

• optimize environment, bed rest, pain control if appropriate

• no pharmacological intervention needed

• Moderate to severe elevations (160-200 / 95-120 mmHg):

optimi e en ironment bed rest

ppain control if appropriate

• cautious lowering of BP, consider:

» IV labetalol, atenolol» IV enalapril» IV verapamil» IV hydralazine» transdermal GTN» continuos infusion (GTN,

sodium nitroprusside, fenoldopam)

» review for other drugs with possible effects on

• optimize environment, bed rest, pain control if appropriate

• consider additional oral antihypertensives

BP

Geoffrey A. 2003

08/12/1431

9

Handling blood pressureHandling blood pressure

--The general advice is to avoid to lower blood The general advice is to avoid to lower blood pressure at the initial period of an ischemic stroke.pressure at the initial period of an ischemic stroke.

--The sole exceptions are:The sole exceptions are:

--Cardiac insufficiency or ischemiaCardiac insufficiency or ischemia

--Aortic dissectionAortic dissection

Acute Renal shutAcute Renal shut down & failuredown & failure--Acute Renal shutAcute Renal shut--down & failuredown & failure

--Hypertensive encephalopathyHypertensive encephalopathy

--Maintain the antihypertensive drugs which Maintain the antihypertensive drugs which

were used before.were used before.

Antihypertensive treatment in Antihypertensive treatment in acute ischemic strokeacute ischemic stroke

•• STRATEGYSTRATEGY11--SBP > SBP > 220 220 mm Hg and ormm Hg and orgg

DBP > DBP > 120 120 mm Hgmm Hgaa-- Capopril Capopril 66..2525--1212..5 5 mg orally parenterallymg orally parenterallybb-- Labetol Labetol 55--20 20 mg I.V.mg I.V.cc-- Urapidil Urapidil 1010--20 20 mg I.V. followed bymg I.V. followed by

44--8 8 mg I.V. mg I.V. 22-- DBP > DBP > 140 140 mm Hgmm HgNitroglycerin Nitroglycerin 5 5 mg I.V. followed by mg I.V. followed by 11--4 4 mg/h I.V.mg/h I.V.

33-- NO TREATMENTNO TREATMENT Systolic BP Systolic BP 220220--240 240 mmHgmmHgDiastolic BP Diastolic BP 120120--130 130 mmHgmmHg

08/12/1431

10

Management of BP after treatment with rt-PA

• Monitor BP– Every 15 min for 2 hrs after treatmente y 5 o s a te t eat e t– Then every 30 min for 16 hrs

• Treat HTN if– SBP > 180 mm Hg OR– DBP >105 mm Hg

• Choice of agents – Labetalol 10 mg IV over 1-2 min up to 2.5-5 mg everyLabetalol 10 mg IV over 1 2 min up to 2.5 5 mg every

5 min to max 15mg/hr– Nicardipine infusion– Hydralazine– Enalapril

Hypertensive encephalopathy, Eclampsia & reversible posterior Leukoencephalopathy

in hypertensive crisis BP should be lowered but,hypertension should not be lowered unless– End organ failure e.g.

microscopic hematuria, oliguria, congestive heart failure, cardiac ischemia

– Administration of tissue plasminogen activatorplasminogen activator

– MABP should be lowered no more than 20-25% in 1-2 hrs over the ensuing hrs to days

08/12/1431

11

INTRACEREBRAL HEMORRHAGE

• Chronic HTN is a major risk factor for spontaneous ICH in most patients even inspontaneous ICH in most patients, even in absence of a history of HTN

• Systemic HTN is commonly seen in the first 24hrs and associated with poor outcome

• While HTN is easily measured and treated, it is unclear whether its treatment will lead tois unclear whether its treatment will lead to improve the outcome or not

BLOOD PRESSURE & INTRACEREBRAL HAEMORRHAGE

• Elevated BP is also observed with intra b l h t i b t it icerebral hematoma expansion, but it is

not known whether it a cause or effect• While a lower BP may decrease the rate

of bleeding, it may also reduce the rate of CBF to ischemic or hypo-perfusedof CBF to ischemic or hypo perfused neurons

08/12/1431

12

Intra-cerebral hemorrhageCerebellum

ThalamusPONS

BG LOBAR

CPP, ABP, ICP , CVR and vessel caliber

• Cerebral perfusion pressure CPP

• CPP = MABP ICP

CRITICAL CARE NEUROLOGYVolume 12 Number 1 February 2006

• CPP = MABP – ICP• Normotensive autoregulate

between CPP between 50-150mm Hg

• CVR cerebrovascular resistance is primarily at arteriole level

• CBF = CPP / CVR cerebro-vascular resistance

• CCP should be maintained 70-100mm Hg

• The goal of therapy is to lower to a mean BP to 100-130 mm Hg

• Lower blood pressure may be poorly tolerated

Becker K, Continuum, 2006;12,1: 30-45

08/12/1431

13

Mean ABP

• Although, it may be a cause of the hemorrhage , it is simply may be a reflection of chronic ofit is simply may be a reflection of chronic of – Chronic HTN– The brain attempt to maintain cerebral perfusion

pressure CPP in response to sudden ICT– Pain, anxiety and sympathetic activation

• Even without treatment BP tends to decline toEven without treatment, BP tends to decline to baseline levels during the first 7-10 days after hemorrhage

MABP is > 120mm Hg in over than 2/3 of patients with ICH, > 140mm Hg in over than 1/3 of patients with ICH

Carlberg et al. 1993

Controversy

• Reasons to treat HTN– Risk of hematoma expansion– Systemic risks, Heart , kidney , blood vessels

• Reasons not to treat HTN– Ongoing peri- hematoma ischemia

Risk of inducing ischemia– Risk of inducing ischemia– Impaired autoregulation

Diringer M.N. Continuum June 2009. vol15;3:121-137

08/12/1431

14

AUTOREGULATORY CURVEBelow the lower level of autoregulation the brain loses its ability to maintain constant CBF and flow become pressure passive

CBF

HTN

p p

CPP

Diringer M.N. Continuum June 2009. vol15;3:121-137

ISCHEMIC PENUMBRA IN HEMATOMA EXPANSION

• Concepts was believed that ischemic penumbra may be a consequence of hematoma

• Determinant factors– Level of HTN

consequence of hematoma compresses surrounding tissues with reduced CBF

• PET, SPECT & MRI Findings , it was not associated with increased oxygen extraction , findings indicative of metabolic suppression rather than ischemia

– LABILITY of BP– Staff familiarity of

antihypertensive agents – Co-morbidity– Chronicity of HTN & left LVH– Retinopathy– Signs of acute cardiac ischemia– HFischemia

• Goal should be optimizing perfusion, not treating hypertension, and treating increased ICP

Diringer M.N. Continuum June 2009. vol15;3:121-137, Anderson et al., Lancet Neurol. 2008; 7,5:391-399

08/12/1431

15

ATACH, INTERACT, INTERACT 2

– ATACH• HTN after ICH

– Early aggressive reduction BP may

• PILOT , 60 PTS• NICARDIPINE

– INTERACT• Randomized, open label• 400 PTS• Intensive BP reduction

– INTERACT 22800 PTS

reduce risk of hematoma expansion

– MAP 100mm Hg AVOIDE REDUCTION

– MAP over 120mm Hg 10-15% may be reasonable

• 2800 PTS• AGGRESSIVE BP

reduction • Furosemide, urapidil,

phentolamine

– Modest reduction of BP 15%-20% may not increase ischemia

Anderson et al., Lancet Neurol. 2008; 7,5:391-399

Recommendations differs from American Stroke

Association Guidelines– Bolus administrationBolus administration

of Labetalol, Furosemide , urapidil, enalaprilat , metoprolol, hydralazine, phentolamineContinuous drip Ca

–– Agents that are Agents that are Venodilators such as Venodilators such as Na Nitroprusside or Na Nitroprusside or nitrates should not be nitrates should not be used because their used because their tendency to increase ICPtendency to increase ICP– Continuous drip Ca

Channels Blockers nicardipine , clevidipine NEW‼

Anderson et al., Lancet Neurol. 2008; 7,5:391-399

08/12/1431

16

Guidelines in the first few hours of acute stroke with intracerebral

hemorrhage • Hypertension

– SBP > 230mm Hg or DBP >140 mm Hg on two– SBP > 230mm Hg or DBP >140 mm Hg on two readings 5 min apart

• Institute nitroprusside or nicardipine – SBP 180-230mm Hg or DBP 105-140mm Hg or

MABP 130mm Hg or greater on two readings 20 min apart

• Institute labetolol, esmolol, nicardipine or enalapril• avoid oral or sublingual nifedipine

– SBP > 180mm Hg or DBP > 105 mm Hg• Defer anti-hypertensive unless coronary ischemia suspected

– CPP should be maintained > 70mm Hg at all times

American stroke association guidelines

Hypotension in ICH• The etiology of hypotension should be

establishedestablished• Volume replenishment is the first approach• If hypotension persists after correction of volume

deficit, continuous perfusion of vasopressors should be considered, particularly for SBP less than 90 mm Hg– Phenylephrine 2mcg/kg/min to 10mcg– Dopamine 2mcg/kg/min to 20mcg– Noepinephrine 0.05mcg/kg/min to 0.2mcg

American stroke association guidelines

08/12/1431

17

Conclusions •• Avoid dropping of BPAvoid dropping of BP• BP is often elevated acutely and typically returns toBP is often elevated acutely and typically returns to

baseline spontaneously over the first week in strokes.

• Even without treatment, BP tends to decline to baseline levels during the first 7-10 days after cerebral hemorrhage

• Choice of agents e.g. Labetalol, Hydralazine, Enalapril, or Nicardipine infusion

• Venodilators such as nitrates should not be used because their tendency to increase ICP