Hypertensive Emergencies Alyssa Morris, R3 March 5, 2009 Thanks to Dr Gant!

Definitions Hypertensive Emergency Acute, life threatening, usually a BP> 180/120 Target organ damage Hypertensive Urgency Asymptomatic, severe HTN, usually >180/120 NO target organ damage These are not absolute numbers - nb to treat the patient and not the number

Hypertensive Emergencies Neurological Hypertensive Encephalopathy CVA SAH ICH Cardiovascular MI/ischemia Acute LV dysfxn Ao dissection Pulmonary Acute edema Other Acute renal failure/insufficiency Retinopathy Eclampsia MAHA

Components of BP BP= CO x SVR CO= HR x SV Think of the components as: CO= heart BP= arteries SVR= arterioles - Other systems impact these factors. The RAAS system and the ANS play a role.

CPP=MAP-ICP -throughout the normal range of BP, cerebral blood flow is maintained by fluctuation in the vascular tone of the cerebral resistance vessels (which are have ability to constrict to prevent too much pressure). So they dilate to increase flow at the bottom of curve and then constrict to prevent to much flow in the upper portion of the curve. - In patients with HTN, cerebral autoregulation is reset at a higher level Lower part of curve, you won’t perfuse brain In upper part of brain you can get brain edema because previously constricted vessels reach a critical level and then suddenly dilate, leading to leakage of fluid thru BBB

Secondary causes of HTN Conn’s is primary hyperaldosteronism: increase aldo leads to increase Na therefore increase volume - RAS- bilateral increases RAAS but can’t filter voume like you can with unilateral , therefore, bilat is volume HTN and unilat is constriction HTN - mineralcorticoids increase Na retention - catecholamines increase vasoconstriction

CASE 1

Hypertensive Encephalopathy Uncommon syndrome Acute and reversible Results from an abrupt, sustained rise of BP that exceeds the limits of cerebral autoregulation of the small resistance arteries in the brain Arises from “breakthrough” hyperperfusion and leakage of fluid thru BBB

Flow diagram of pathophys

Clinical Presentation Severe h/a Drowsiness ALOC Vomitting Seizures Focal neuro deficits Blindness Focal neuro do not follow a specific territory or anatomic pattern

Tx Various recommendations 25% over 3-4hrs 10% in first hour, 15% in next 2-3 hours *will not be able to perfuse brain if you drop it too fast or too much -various recommendations but basically 25% over 3-4 hours EMR suggested 10% in first hour, then 15% in next 2-3 hours - will not be able to perfuse brain b/c will drop off curve and then get ischemia

CPP=MAP-ICP -throughout the normal range of BP, cerebral blood flow is maintained by fluctuation in the vascular tone of the cerebral resistance vessels (which are have ability to constrict to prevent too much pressure). So they dilate to increase flow at the bottom of curve and then constrict to prevent to much flow in the upper portion of the curve. - In patients with HTN, cerebral autoregulation is reset at a higher level Lower part of curve, you won’t perfuse brain In upper part of brain you can get brain edema because previously constricted vessels reach a critical level and then suddenly dilate, leading to leakage of fluid thru BBB

Drug Options VASODILATORS Nitroprusside Nitroglycerin Fenoldopam Hydralazine BETA BLOCKERS Labetalol Esmolol CALCIUM CHANNEL BLOCKERS Enalaprilat/enalipril ALPHA BLOCKERS Phentolamine Clonidine

Nitroprusside Potent smooth muscle relaxing agent Reduces both preload and afterload Rate of onset rapid, duration very short Also a cerebral vasodilator Can increase ICP secondary to increased cerebral blood flow Unstable in UV light, therefore wrapped in tinfoil Infusion at 0.25-0.5ug/kg/min -then increase by 0.5mcg/kg/min Max of 10 mcg/kg/min This is an excellent choice in hypertensive crisis for these reasons - b/c of reduction in preload by venous dilation, the CO often improves if CHF or bad LV fxn is present - can get hypotension and get a reflex tachycardia as a result

Nitroglycerine Activates guanylate cyclase Accumulation of cGMP Sequestration of Ca into SR Relaxation of Vascular smooth muscle Dose dependent Low dose: venodilator (preload) High dose: veno and arteriodilator (afterload) Therefore, usually reduce BP by reducing preload and CO Start with 10-20ug/min infusion Titrate up 5-10ug/minQ3-5min Doses as high as 200- 300 ug/min may be needed for maximal antihypertensive effect - reduction in preload and CO might not be desirable in pts with poor cerebral and renal perfusion - careful when using it in patients with RV dysfxn to avoid hypotension (preload dependent) - best used in pts with cardiac ischemia or pulmonary edema

Hydralazine Direct arteriolar vasodilator Used to be used as first line in pregnancy htv emergencies Starting dose is 5mg IV Repeat doses of 5-10mg IV every 20 mins to maintain desired BP Complications: Marked hypotension Reflex tachycardia (can give angina) Flushing and nausea H/a - Now using labetolol or nicardipine

Labetalol Selective α-1 blocker and nonselective β-blocker α:β blockade ratio between 1:3 and 1:7 Not a significant drop in CO like other βB Does not affect cerebral blood flow or renal fxn BP starts to fall in 5-10m, max effect at 30m How much do you guys give?

Esmolol Selective β-1 blocker Very short acting Elimination ½ life of 9 minutes No intrinsic sympathomimetic activity -b/c the half life is 9 mins, you get substantial recovery from B blockade in 10-20 mins

Phentolamine α-blocking agent Used for the Mx of catecholamine-induced HTV crisis MAOI, Pheo, Cocaine Immediate effect Effect lasts up to 15 mins 1-5mg IV boluses MAOI - pheo Cocaine

CASE 2 Head CT demonstrates multiple, bilateral, patchy foci of hypoattenuatin within subcortical white matter in the occipital regions - MR shows hyperintensity within the subcortical white matter of the bilateral occipital and anterior parietal lobes.

PRES Posterior reversible encephalopathy syndrome Pathophysiology Cerebral vasospasm leading to cytotoxic edema Vasodilattion leading to vasogenic edema - again, disorder of cerebral autoregulation with two theories.

CASE 3 - What kind of stroke is this? L MCA - Given this, would you treat the blood pressure? (200/110)

HTN Mx in Ischemic Stroke Consensus guidelines published in the journal of stroke. Stroke. 2007;38:1655-1711.

- Want to monitor BP after giving TPA as well. Same goals.

HTN Mx in Ischemic Stroke HTN common in 1st hours after stroke SBP>160 found in 60% pts with acute ischemic stroke For every 10mmHg raise >180, risk of neurologic deterioration increases by 40% and risk of poor outcome by 23% In these patients, htn is usually the physiologic response to the stroke itself and is not the immediate cause - can try to reduce modifiable factors that could be contributing to the htn

HTN Mx in Ischemic Stroke Theoretical reasons for lowering BP in stroke Decrease formation of brain edema Lessening risk of hemorrhagic transformation of infarction Preventing further vascular damage Forestalling early recurrent stroke BUT remember aggressive tx of BP may lead to neurologic worsening by decreasing perfusion pressure to ischemic areas of brain

CPP=MAP-ICP -Do not want to get them too low or won’t perfuse brain and the penumbra is depending on flow to deliver O2 and reduce the ischemic area

CASE 4 - What kind of stroke is this? L MCA - Given this, would you treat the blood pressure? (200/110)

HTN Mx in Ischemic Stroke A lot of studies showing harm with reduction of BP Most pts have a decrease in BP a few hours post- stroke w/o intervention Oliveira-Filho et al. Neurology. 2003;61:1047-1051 Found >90% pts had a decrease in SBP by 28% in 24hrs post-stroke with no intervention Outside TPA window - DO NOT want to decrease pressure to much b/c penumbra dependant on perfusion pressure

Consensus Statement “ emergency administration of antihypertensive agents should be withheld unless DBP>120 and SBP>220” “reasonable goal to decrease blood pressure by 15-25% within 24 hours” This is a case-by-case decision More research needs to be done -typically recommend labetalol 10mg IV over 1-2 minutes with rpt doses as needed unless there is a contraindication to BB then use nicardipine infusion - Stated that the CHIPPS trial might be able to give more evidence

Case 4

Stroke, 2007;38:2001-2023

HTN Mx in Hemorrhagic Stroke Primary rational for reducing BP is to avoid hemorrhagic expansion from potential sites of bleeding BP is correlated with increased ICP and volume of hemorrhage Difficult to determine whether increased BP is a cause of hemorrhage growth or an effect of increased volumes of ICH and increased ICP

HTN Mx in Hemorrhagic Stroke Summary of studies Isolated SBP<210 is not clearly related to hemorrhagic expansion or neurologic worsening Decrease in MAP by 15% does not result in decreased CBF Baseline BP was not associated with growth of ICH in largest prospective study Hemorrhage enlargement occurs more frequently in pts with increased SBP but it is not clear if this is an effect of increased growth of ICH with associated increase in ICP or a contributing cause to the growth of ICH Evidence supports maintaining CPP >60mmHg WE DON’T KNOW

Not a strong stand on the subject - State that much more research needs to be done and could be answered by the ATACH study and the INTERACT study.

HTN Bleeds Where do you get HTN bleeds in the brain? Cerebellum Pons Basal ganglia Thalamus - Areas in brain affected by chronic htn are the perforating arteries which serve these areas -what about BP in the setting of hemorrhagic stroke??

Case 4 With nipride can get increased SV and a reflex tachycardia so you want to avoid it first - go by R arm b/c flap flapping over is falsely lowering L arm BP - remember to check leg BP if arms normal and you are thinking about dissection - want to reduce shear force and pulse pressure - Use a BB to reduce BP (labetalol or esmolol) for a goal of SBP<110 or 90-100 - if becoming too brady, can switch to nipride because you have sufficiently BB her and will blunt reflex tachycardia and

HTN Mx in Ao Dissection Remember to check BP in legs if you are thinking dissection b/c the flap can give you falsely low BP in arms Want to avoid shear stress and wide pulse pressures Reduce the LV ejection force Goal is to get SBP 90-110 but just do what you can Use labetalol or esmolol Can use nipride after have sufficiently BB b/c will blunt the reflex tachycardia and increased SV

Case 6 - Discuss who would treat an urgency with risk factors and who would not

Drug Summary Nitroprusside Nitro Labetalol 0.25-0.5ug/kg/min Inc by 0.5ug/kg/min quickly Nitro 10-20ug/min Inc by 5-10ug/min Q3-10min Labetalol 10-20mg IV Q5-10min Infusion at 1-2mg/min