BLOOD PRESSURE MANAGEMENT IN ACUTE STROKE Pat Melanson, MD McGill University

“Brain Attack” Paradigm shift - End of nihilism Early effective interventions Time-sensitive disease Chain of recovery Stroke units and stroke centers - there is a new era concerning the treatment of acute stroke PARADIGM SHIFT over the past 5 years - the next 5 to 10 years should be quite exciting - recent advances have given new hope to the idea that we will be able to actively intervene and positively affect the outcome of a patient with an acute stroke - with the publication of the NINDS tPA study, stroke can now be considered a time-sensitive disease much like AMI or trauma, hence the term BRAIN ATTACK -At the MUHC we are working to create a chain of recovery for the management of acute stroke to ensure that the patient is passed seamlessly and efficiently from the pre-hospital arena, through the ED, with co-ordination between the EP, lab, radiology, neurology, neurosurgery and others - our goal is to create a regional center of excellence for acute stroke - the number of patients who can benefit from tPA or more advanced expertise and technology is small - it is clear that huge improvements in stroke outcome can be achieved with simple, straightforward therapies that can be given anywhere - avoidance of infections such as aspiration pneumonia, UTI -blood glucose and temperature control - BP control

Stroke Protocols Aspiration pneumonia, UTI’s DVT prophylaxis Glucose control Fever control BP management avoidance of overtreatment

Cases Ischemic CVA, BP 225/105 (145) Hemorrhagic CVA, BP 215 /110 (145) Would you actively lower the BP? What target or threshold level? What drug ? Which drugs should be avoided? 1) 60 year-old male with atrial fibrillation who is not on coumadin 2) 70 year-old male with chronic hypertension and a large left basal ganglia intracerebral hemorrhage on CT 3) 40 year-old male with proven or suspected SAH - How would you mange these patients blood pressure? - What would be your threshold levels for treatment? -If you would lower the BP with an anti-hypertensive, which one would you choose? - Which antihypertensives should be avoided?

Lowering BP in Acute Stroke: Pros Chronic hypertension Rebleed/ increase hematoma size Cerebral edema, Raised ICP Hemorrhagic transformation Decrease bleeding with t-PA

Lowering BP in Acute Stroke: Cons Acute hypertension is self-limited RISK OF ISCHEMIA Reflex response to maintain CBF Ischemic penumbra Shift in autoregulation curve More sensitive to BP decreases

Cerebral Blood Flow CBF = CPP / CVR CPP = MAP - ICP MAP = DBP + 1/3 PP Cerebral autoregulation normal between 50 - 150 70/40 to 200/130

Cerebral Autoregulation CBF 50 ml/100g/min 20 50 150 MAP

Cerebral Autoregulation MAP below lower limit hypoperfusion with ischemia MAP above upper limit “breakthrough” vasodilation Segmental pseudospasm (“sausage-string”) fluid extravasation

Cerebral Autoregulation Shift to right Chronic hypertensives ICH, SAH, Ischemic infarct Trauma Cerebral edema Age, atherosclerosis Some hypertensives suffer decrease CBF at MAP higher than 120 (160/100)

How far can BP be safely lowered? Lower limit usually 25% below MAP 50% of chronic hypertensives reached lower autoregulation limit with 11 to 20% reduction in MAP 50% had lower limit above usual mean Kanaeko et al; J Cereb Blood Flow Metab 3:S51,1983 Most ischemic complications develop with reductions greater than 20 - 30 %

Initial Lowering of BP : Therapeutic Guidelines Do not lower BP more than 15 % over the first 1 to 2 hours unless necessary to protect other organs Decreasing to DBP of 110 or patients “normal” levels may not be safe Further reductions should be very gradual ( days) Follow neuro status closely

Pharmacologic Therapy

Drugs Best Avoided Direct-acting cerebral vasodilators Nitroglycerine adversely affect CBF potential to increase ICP shift autoregulation curve to the right Nitroglycerine Nitroprusside Hydralazine Calcium Channel Blockers

Nifedipine Peripheral, cerebral and coronary arteriolar vasodilation Rapid onset of antihypertensive effect 5-20 minute onset peak effect in 30-60 min duration 4-5 hr Potential severe hypotension Several case reports of cerebral or myocardial ischemia after rapid decrease

Sublingual Nifedipine “Should a Moratorium be Placed on Sublingual Nifedipine capsules given for hypertensive emergencies and pseudoemergencies?” Grossman, Messerli, Grodzicki, Kowey JAMA, 276 : 1328 - 1331,1996

Recommended Antihypertensives Beta-blockers Alpha-blockers ACE inhibitors Clonidine

Labetalol Combined a, b adrenergic blockade Usual contraindications to b-blockade Rapidly effective when given IV; Onset < 5 min, peak 5-10 min, duration 2-6 hr (sometimes longer) 5 - 10 mg iv q10 minutes

ACE inhibitors IV enalaprilat, oral captopril potentially useful for acute BP reduction Difficult to titrate (sometimes ineffective,sometimes excessive BP ¯) Positive effects on cerebral autoreg. Captopril 12.5 mg S/L

Recommendations MAP of 140 - 145 (220/120) Max decrease of 15 % MAP Avoid direct acting vasodilators Avoid sublingual nifedipine Labetalol, Captopril Cautious reduction with frequent neurologic exams - McGill stroke protocol - always err on the side of higher rather than lower BP -don’t just do something, stand there - avoid NTP, NTG, CCB, hydralazine

Pharmacological Elevation of BP in Acute Stroke Pharmacological elevation of blood pressure in acute stroke: Clinical effects and safety. Rordorf, Stroke 1997; 28:2133 Retrospective review of 63 patients Ischemic stroke with normal BP 30 received phenylephrine (alpha-agonist) 10 demonstrated a BP threshold Improved outcome

Recommendations MAP of 140 - 145 ( 220/120) Avoid direct acting vasodilators Avoid sublingual nifedipine Alpha or beta blockers, ACEI Cautious reduction with frequent neurologic exams - McGill stroke protocol - always err on the side of higher rather than lower BP -don’t just do something, stand there - avoid NTP, NTG, CCB, hydralazine