1. health and fitness
2. disease
3. heart disease

Blood Pressure Management in
Acute Stroke
ASNEN Workshops SSA Conference 20141 and
Smart Strokes 20142
Liz O’Brien1 Stroke Nurse Practitioner
Royal North Shore Hospital, Sydney, NSW
Lizzie Dodd2 Clinical Practice Consultant, Acute Stroke
Unit Coordinator
The Queen Elizabeth Hospital SA Health
Liz Mackey2 Stroke Nurse Practitioner
Western Health Melbourne, VIC
Meaghan Osbourne1 Neurology CNC
Gold Coast University Hospital, QLD
The Facts!!!!
• We know that BP is the most common risk for stroke!
• We know that lowering BP in the acute stages should be
done cautiously!
• We know that BP must be treated immediately if > 185/110
for anyone who is eligible for thrombolysis!
• We know that opinions on BP limits differ between type of
stroke, country, states and physicians!
Or do we?
Blood Pressure
• An acute hypertensive response occurs within 24 hrs of
acute stroke.
• Up to 82% of patients presenting to the ED with acute
stroke have a SBP greater than 140mmHg 3,8
• Acute stroke impairs the autoregulation of the cerebral
circulation so that the blood flow in the ischaemic area
becomes passively dependent on mean arterial pressure. 8
Blood Pressure
• Primary cause of the hypertensive response is
compression of the regions in the brain that regulate the
activity of the autonomic nervous system. 8
• Pre-existing HTN, Diabetes, high serum creatinine and the
Cushing’s reflex (reactive rise in BP in response to raised
intracranial pressure) – can all exacerbate HTN. 8
Blood Pressure
• Headache, urinary retention, infection, stress - can
lead to an imbalance in the autonomic nervous
system, activate the sympathetic adrenomedullary
pathway and raise the concentration of circulating
catecholamines and inflammatory cytokines =
hypertensive response 8
Blood Pressure
• There is a U-shaped relationship between presenting BP
and outcome after ischaemic stroke.
• Both low and high extremes of BP are associated with a
poor outcome.
• For every 10mmHg of SBP below 150mmHg the risk of
early death increased by 3.6%, the risk of late death and
dependency increased by 17.9%
• For every 10mmHg increase in SBP above 150mmHg the
risk of early death increased by 3.8%. 3,5
• the best outcomes were observed in patients with
systolic BP 150–160 mmHg
Proportion of patients
who died within 14
days (solid lines) or
were dead or
dependent at 6
months (dashed
lines) by baseline
systolic blood
pressure. 95%
confidence intervals
are represented by T
bars.
Leonardi-Bee J., Bath, M W., Phillips, S J., Sandercock P A. for the IST Collaborative Group (2002) Blood Pressure and Clinical Outcomes
in the International Stroke Trial. Stroke (33) 1315 – 1320
BP and Outcome
• Poor outcome from increased BP is thought to be
due to worsening cerebral oedema
• Poor outcome due to low BP may be because of
cerebral hypo perfusion and cardiac events.
• Uncontrolled BP contributes to the risk of
symptomatic ICH in ischaemic stroke patients treated
with thrombolysis. 3
Acute Management in the
thrombolysis eligible patient
• For those patients eligible for thrombolysis the BP
must be less than 185/110 prior to commencing
therapy.
• Clinical experience has shown that uncontrolled
blood pressure increases the risk for intracerebral
haemorrhage after thrombolysis.
• BP less than 185/110 must be maintained post
thrombolysis 1
Thrombolysis and BP
Some local Guidelines
Western Health
If Systolic Blood pressure >185 mmHg or Diastolic >110 mmHg
• Intravenous Labetalol
OR
• Transdermal Glyceryl trinitrate patch 25 mg
OR
•Metoprolol 5 mg Intravenous Infusion (IVI) over 3-5 minutes. Dose
may be repeated at 5 minute intervals to a total of 10-15 mg
OR
•Hydralazine 5-10 mg slow IVI. Dose may be repeated after 20-30
minutes
Thrombolysis and BP
Some local Guidelines
RNSH
Ischaemic Stroke AND thrombolysis: if BP >180/110mmhg
•IV Hydralazine (3 doses of 20mg, 10 minutes apart unless therapeutic goal
achieved)
OR
•IV Metoprolol (Doses of 2.5mg or 5mg 10 minutes apart unless therapeutic
goal achieved
OR
•IV Clonidine (Doses of 75microg or 150microg, 10 minutes apart unless
therapeutic goal achieved)
Escalation:
•IV Labetalol (Doses of 10mg, 20 mg, 40 mg, and 80 mg, 10 minutes apart
unless therapeutic goal achieved)
•BP measurements every 5 minutes
Management Hypertension with
Alteplase
SA Health
 BP>180/110mmHg: recheck manually
 Recheck again 5 minutes if >180/110 mmHg
 IV labetalol 10-20mg bolus. Repeat every 10- 20
minutes max dose 300mg in 6 hours. OR
 IV Labetalol 10mg bolus then commence infusion 28mg max dose 300mg in 6 hours OR
 GTN infusion 30mg in 100mls commence 3ml/hr titrate
1ml/hr 5-10 minute intervals
Persistent hypertension
 SA Health: HDU or ITU
 Nitroprusside 0.5micrograms/kg/min titrate for BP
 IV Hydralazine 5mg bolus repeat every 20 minutes
(max 5 boluses in any 6 hour period)
Note if HTN continues >185/110 mmHg longer than 15
minutes despite tx stop alteplase infusion. Restart if BP
controlled and TPA can be finished within 51/2 hrs of
onset
Labetalol
 Alpha & Beta-blocker
 Comes as a 100mg in
20mL glass ampoules
(5mg/mL)
 Available under the
Special Access Scheme –
only for use in the Acute
Stroke Unit.
 Cost = $78 (cost price) for
a box of ampoules
Case study thrombolysis
 Mrs B 70 year old
 Slurred speech, face droop, left arm numbness and
weakness, visual neglect
 NIHSS = 11. CT no established infarct
 Presented within 90 minutes BP 194/105
 5 minute recheck = 192/108
 Prescribed Bolus labetalol 10mg, for infusion at
4mg/min
Labetalol 100mg/20ml






Give 10mg (2ml) bolus 1-2 minutes
First infusion
Remove 28mls from 100mg bag 0.9%sodium chloride
Add remainder of labetalol 18ml / 90mg
1mg/ml (90mg in 90mls)
Infuses at 4mg/min = 240mls hour (90mg in 22.5
minutes)
Labetalol Infusion Rates
Infusion rate in mg/min
Infusion rate in mL/hour
Infusion rate (mg/hour)
& time til infusion
complete
2 mg/min
120 mL/hour
120mg/hour
(90mg in 45min)
4 mg/min
240 mL/hour
240mg/hour
(90mg in 22.5min)
6 mg/min
360 mL/hour
360mg/hour
(90mg in 15min)
8 mg/min
480 mL/hour
480mg/hour
(90mg in ≈11min)
Case study
 After 10 minutes BP reduced to 179/98 thrombolysis
commenced.
 Labetalol Infusion completed within 22 minutes.
 BP check every 5 minutes. 15 minutes later BP 182/108
 Second labetalol infusion commenced 100mg at
4mg/minute prescribed. BP controlled <175 /100. TPA
completed
 Third final infusion commenced 2mg/ hr: 120mg/ hr
(100mg in 50 minutes). Held BP post TPA ,160/90
Labetalol Infusion Rates
Infusion rate in mg/min
Infusion rate in mL/hour
Infusion rate (mg/hour)
& time til infusion
complete
2 mg/min
120 mL/hour
120mg/hour
(100mg in 50 minutes)
4 mg/min
240 mL/hour
240mg/hour
(100mg in 25 minutes)
6 mg/min
360 mL/hour
360mg/hour
(100mg in 16.5minutes)
8 mg/min
480 mL/hour
480mg/hour
(100mg in ≈12.5min)
Enchanted Study 4
• Because the management of BP remains controversial this is
a great study that will hopefully answer some questions!!!
• “international randomised controlled trial to establish the
effect of low dose rtPA and the effects of early intensive
blood pressure lowering in patients with acute ischaemic
stroke”
• Comparing standard dose rtPA to low dose rtPA – is low dose at
least as effective/ does it reduce the risk of sICH
• Compared with current guidelines is early intensive BP lowering
superior in reducing death or disability/ reduce the risk of sICH
Patient eligible for rtPA – BP < 185mmHg,
no contra indication to either dose
Randomisation Arm
(A)
Standard Dose
rtPA 0.9 mg/kg
Low dose rtPA
0.6 mg.kg rtPA
SBP >150mmHg: no definite
contraindications to rapid intensive BP
lowering to 140-150,mmHG
Randomisation Arm
(B)
Standard BP
control to SBP
<180mmHg
Best Practice Care during treatment and
follow up periods
ENCHANTED International Coordinating Centre, The George
Institute for Global Health, University of Sydney. Enhanced
Control of Hypertension and Thrombolysis Stroke Study.
Intensive BP
lowering to SBP
140-150mmHg
Acute Management in the ischaemic
stroke patient
• Guidelines and recommendations only…
• Current Australian guidelines (NSF) indicate that if a
BP is 220/120 then antihypertensive therapy can be
commenced or increased.7
• BP should be reduced gradually.
• Should not exceed 10-20%
• Monitoring for neurological deterioration
• Consensus opinion to date is not to actively lower BP
in the first 24-48 hours (Enchanted will help to clarify
and guide).
Acute Management in the ischaemic
stroke patient
• Within one week of stroke BP should be lowered
using ACE-Inhibitor, Angiotensin receptor
antagonists, calcium channel blockers and glyceryl
trinitrates 7 , all these shown to decrease SBP and
DBP
• Can continue to use current antihypertensive regimen
and increase as needed.
• Monitoring on stroke units which can reduce post
stroke mortality and disability by 20% 8
Relevant Study
PROGRESS Trial 6:
• 6105 patients
• Hypertensive and non hypertensive
• 50% assignment to perindopril 4 mg (+/- indapamide) vs
placebo
• 4 years follow up
• BP lower by 9/4 mmHg
• Over 4 years annual stroke risk was reduced from 3.8%
to 2.7%
• This risk was reduced for those who were hypertensive
and non hypertensive
Lancet 2001
PROGRESS Trial 6:
Some local guidelines
RNSH:
Ischaemic Stroke: if BP >200/110mmhg
•IV Hydralazine (3 doses of 20mg, 10 minutes apart unless
therapeutic goal achieved)
OR
•IV Metoprolol (Doses of 25mg or 50mg, 10 minutes apart unless
therapeutic goal achieved
OR
•IV Clonidine (Doses of 75microg or 150microg, 10 minutes apart
unless therapeutic goal achieved)
Escalation:
•IV Labetalol (Doses of 10mg, 20 mg, 40 mg, and 80 mg, 10
minutes apart unless therapeutic goal achieved)
•BP measurements at least every 15 minutes
Some local guidelines
Non-/Post-thrombolysed Stroke patient on the ward (RNSH):
1.Increase pre-existing antihypertensives
•
•
•
•
ACE inhibitor
Beta-blockers
Calcium channel blocker
Diuretic
2.No prior antihypertensives – choice of antihypertensive will depend
on co-morbid disease/s (usually start with ACE inhibitor, augment with
calcium channel blocker and diuretic and consider beta-blocker if
heart disease present)
Begin to aim for known secondary prevention BP guidelines of <
140/90
Acute Management in the
haemorrhagic stroke patient
Haemorrhagic Stroke
Risk factors:
•
•
•
•
•
•
•
Hypertension
Race
Anticoagulant therapy
Thrombolytic therapy
High ETOH
Previous strokes
Illicit drug use
(Magistris, Bazak, & Martin, 2013)
Haemorrhagic Stroke
• ICH
• Consists of three phases:
• Initial haematoma
• Haematoma expansion
• Peri- haematoma oedema
Thinking about ICP…
Monro Kellie hypothesis
• Intracranial pressure: pressure-volume
relationship between volume of brain
tissue (80%), CSF (10%) and blood (10%)
• The sum of volumes of brain, CSF, and
intracranial blood should be constant.
• An increase in one should cause a decrease
in one or both of the remaining two.
• Cerebral perfusion pressure
Recent Research
INTERACT1
• The Intensive Blood Pressure Reduction in Acute
Cerebral Haemorrhage Trial
• Purpose:
• Early intensive blood pressure to control haematoma
growth within the first 24hrs of management and perihaematomal oedema within 72 hrs
• Outcome:
• Decreased haematoma and swelling
• Promoting improved patient outcomes
(Arima et al., 2012)
Recent Research
INTERACT2
• To determine whether rapid lowering of elevated
blood pressure improved outcomes in ICH patients
• Primary Outcome: 90-day death and major disability
(mRS 3-6)
• Secondary Outcomes:
• Shift in mRS at 90 days
• Health related quality of life (EQ-5D)
INTERACT2 Aims:
• To determine if a management policy of:
• early intensive blood pressure (BP) lowering (target of
<140 mmHg systolic) when compared to the
• guideline-recommended ‘standard’ control of BP (target of
<180 mmHg systolic)
• survival free of major disability in acute spontaneous
intracerebral haemorrhage (ICH)
• Standardised treatment protocols – locally available
intravenous (IV) BP lowering agents of physician’s choice
Protocol schema
from INTERACT1 (Lancet Neurol 2008) and (Int J Stroke 2010)
Acute spontaneous ICH confirmed by CT/MRI
Definite time of onset within 6 hours
Systolic BP 150 to 220 mmHg
No indication/contraindication to treatment
R
Intensive BP lowering
SBP <140 mmHg
N=2800 gives 90% power for
7% absolute (14% relative)
decrease (50% standard vs
43% intensive) in outcome
Standard BP management
Guidelines SBP <180 mmHg)
In-hospital vital signs, NIHSS, GCS and BP over 7
days
Independent 90 day outcome
with modified Rankin scale (mRS)
Intensive
(N=1399)
Standard
(N=1430)
Any intravenous treatment
90%
43%*
Combination bolus + infusion
30%
18%*
Multiple agents
26%
8%*
Variable
*P<0.001
80%
%
Key secondary outcome
Ordinal shift in mRS scores (0-6)
Odds ratio 0.87 (95%CI 0.77 to 1.00); P=0.04
0
1
Intensive
8.1%
21.1%
Standard
7.6%
18.0%
2
18.7%
18.8%
Disability but independent
3
15.9%
16.6%
4
18.1%
19.0%
Major disability
5
6
6.0%
\
12.0%
8.0%
12.0%
Death
INTERACT2 Outcomes
• Primary Outcome: 90-day death and major disability
(mRS 3-6): Not significant (P=0.06)
• Secondary Outcomes:
• Shift in mRS at 90 days: Significant improvement
(P=0.04)
• Health related quality of live (EQ-5D): Significant
improvement (p=0.002)
• Rapid blood pressure lowering is safe and may be
beneficial
Considerations
• Optimum level of blood pressure should be based on:
• Chronic hypertension
• ICP
• Age
• Cause of haemorrhage (Amyloid angiopathy ,SAH)
• Interval from onset
• Elevated ICP potential for ischemia
(Broderick et.al, 2007)
Ongoing Research
• Blood pressure management in the acute phase of
haemorrhagic stroke requires further investigation
and research to prove efficacy and improved patient
outcomes
Clinical Guidelines
• Nil national guidelines
• Recommendations:
• Keep systolic blood pressure under 140
• Local areas use antihypertensive:
•
•
•
•
•
Hydralazine
GTN patches
ACE inhibitors- perindopril
Calcium channel blockers
Consider Intensive care support when needed
Nursing Management
• Recommendations:
• 1/24 hrly Blood pressure
• Close nursing care acutely/ close observation bay
• Close neurological observations
• Facilitating decreased ICP
• Limit visitors when hypertensive
• Adequate head positioning to assist drainage- venous
flow and lowering ICP
• Analgesia- caution due to masking potential
deterioration
• Anti emetics
(Alexander, 2013)
ICH Hypertensive Management
Case Study
 68 year old female
 No medical history (had not been to GP since 1998)
 Obese, family noted pt short of breath on exertion





Primary carer for 96 year old mother
High functioning
Lives with mother and brother
Non-smoker, non-drinker
mRS=O
History of presenting complaint
 Over night / early in the morning
 Nausea & vomiting, unsteady gait, drowsiness,
collapse. Complained of visual disturbance
 Presented via ambulance at 0645hr
 GCS = 13 (E 3, V4, M6)
 T 36.8 HR 83 reg, BP 170/100, SpO2 87%
 CPAP in ED for short period
On Examination
NIHSS = 8
1a = 1
Drowsy
5 = L-0, R-1 UL weakness
1b = 1
Month = x
6 = L-0, R-1 LL weakness
1c = 0
2-step command
7=0
Ataxia
2=0
Normal gaze
8=1
Sensory loss
3=1
Partial hemianopia
9=1
Mild dysphasia
4=1
Mild facial droop
10 = 1
Mild dysarthria
11 = 0
No inattention
CT scan
 L) occipital lobe haemorrhage
 4.8 x 3.5 x 4.8 cm (80mL) consistent with
possible amyloid angiopathy.
 Mild midline shift
Our patient
 Persistent hypertension on Acute Stroke Unit
 Commenced:
 prazosin (α1-adrenergic blocker)
 perindopril (ACE-I)
 metoprolol (β-blocker)
 indapamide (diuretic)
 GTN patches PRN (peripheral vasodilator)
General principles of
hypertension management
 IF Hypertension not managed with one drug… ADD
 a second drug from a different class with a different
mechanism of action and different pattern of toxicity
 Response still inadequate (but pt adherence = good)
…ADD
 a third drug should be added.
 If three drugs (usually including a diuretic) are
inadequate, dietary sodium restriction and an
additional drug may be necessary.
Katzung BG, Masters SB, Trevor J Basic & Clinical Pharmacology, 12th ed
Hypertensive emergency
Day 3
 BP 240/110mmHg, GCS 13-14 (E3-4, V4, M6)
 Second 25mg GTN patch applied
Decision making re antihypertensive management:
 Bolus medications: difficult to maintain steady BP
 IV continuous infusion: more stable BPs
 Transfer to ICU for IV continuous infusion
(hydralazine)
 Repeat CT brain: no growth in haematoma size
Outcomes
 Patient returned to Acute Stroke Unit next day
 Discharged to rehabilitation, then home
 Seen in outpatient stroke clinic twice:
 BP more stable, remains on multiple
antihypertensives
 losing weight,
 back to caring for mum
Acknowledgments
• George Institute
• Acute Stroke Nurses Education Network
References – Ischaemic
1.
2.
3.
4.
5.
6.
7.
8.
Geeganage CM and Bath PM. (2008) Interventions for deliberately altering blood pressure in
acute stroke. Cochrane Database of Systematic Reviews, Issue 4, Art No. CD000039.
Geeganage CM and Bath, PM. (2009) Relationship between therapeutic changes in blood
pressure and outcomes in acute stroke. A metaregression. Hypertension, 54, 775-781
Grise EM and Adeoye O. (2012) Blood Pressure Control for acute ischaemic and
haemorrhagic stroke. Current Opinion in Critical Care 18 (2) 132-138
ENCHANTED International Coordinating Centre, The George Institute for Global Health,
University of Sydney. Enhanced Control of Hypertension and Thrombolysis Stroke Study.
Leonardi-Bee J., Bath, M W., Phillips, S J., Sandercock P A. for the IST Collaborative Group
(2002) Blood Pressure and Clinical Outcomes in the International Stroke Trial. Stroke (33)
1315 – 1320
MacMahon, S., Neal, B., Tzourio, C., Rodgers, A. et al. (2001) Randomised trial of a
perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous
stroke or transient ischaemic attack. The Lancet. (358) 1033-41
National Stroke Foundation (2010) Clinical Guidelines for Stroke Management
Tikhonoff V., Zhang H., Richart T. and Staessen J. (2009) Blood Pressure as a prognostic
factor after acute stroke. The Lancet Neurology (8) 938 – 948
References - Haemorrhagic
• Alexander, S. (2013). Evidenced- based nursing care for stroke and other neurovascular conditions.
West Sussex: Wiley-Blackwell.
• Arima, H., Huang, Y., Wang, G., Heeley, E., Delcourt, C., Parsons, M., . . . Anderson, C. (2012).
Earlier blood pressure- lowering and greater attenuation of haematoma growth in acute
intracerebral haemorrhage INTERACT pilot phase. Stroke, 43, 2236-2238.
• Broderick, J., Connolly, S., Feldmann, E., Hanley, D., Kase, C., Krieger, D., . . . Zuccarello, M.
(2007). Guidelines for the management of spontaneous intracerebral haemorrhage in
adults:2007 update. Stroke, 38, 2001-2023.
• Butcher, K., Jeerakathil, T., Hill, M., Demchuk, A., Dowlatshahi, D., Coutts, S., . . . Shuaib, A.
(2013). The intracerebral haemorrhage acutely decreasing arterial pressure trial. Stroke, 44,
620-626.
• Clinical guidelines for stroke management. (2010). (ISSBN09780980593334). Melbourne.
• Magistris, F., Bazak, S., & Martin, J. (2013). Intracerebral haemorrhage: pathophysiology,
diagnosis and managment. MUMJ, 10(1), 15-22.
• Manning, l., Hirakawa, Y., Arima, H., Wang, X., Chalmers, J., Wang, J., . . . Anderson, C. (2014).
Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc
analysis of INTERACT2, a randomised controlled trial. Lancet Neurology, 13, 364-374.
• Sandset, E., Murray, G., Bath, P., Kjeldsen, S., & Berge, E. (2012). Relation between change in
blood pressure in acute stroke and risk of early adverse events and poor outcome. Stroke, 43,
2108-2114.
• Katzung BG, Masters SB, Trevor J Basic & Clinical Pharmacology, 12th ed