HYPERTENSION EMERGENCIES and

HYPERTENSION URGENCIESCase based approach and management

Introduction

• Hypertension is the most common modifiable risk factor for

cardiovascular diseases.

• Most common indication for adults to visit a physician.

• Its prevalence will continue to increase,both among the young

because of increasing obesity and in older adults because of

longer life expectancy.

• Despite being common, it is inadequately treated.

Epidemiology

• Approximately 1% hypertension pts may develop hypertensive

crises during their lifetime.

• Annual incidence of hypertensive emergencies being

1-2 cases/1,00,000 pts.

• Higher rates have been reported in African Americans,

low socioeconomic people, in developing countries.

• Incidence in men 2 times higher than in women

Curr Opin Cardiol 2006;

Curr Hypertens Rep 2003;

Joseph varon et al.Critical care 2008

Hypertensive Crises

• More generalised term .

• Not defined by a specific blood pressure reading, rather it is a

clinical syndrome that is associated with acute elevation of blood

pressure.

• It includes

– Hypertensive Emergency

– Hypertensive Urgency

• Characterised by severe increase in systolic and/or diastolic blood pressure

assosciated with signs or symptoms of acute end-organ damage.

No blood pressure threshold for diagnosis.

• Usually,

– SBP > 180-220 mm Hg

– DBP > 120-130mm Hg

– MAP > 180 mm Hg

• Requires an immediate BP reduction in few minutes –hours.

• Requires an ICU care.

• IV drugs

Hypertensive Emergency

Hypertensive Emergencies

Hypertensive encephalopathy

Hypertension assosciated with acute cerebrovascular disease

Hypertension assosciated with pulmonary edema

Hypertension assosciated with acute coronary syndromes

Hypertension assosciated with dissecting aortic aneurysm

Pheochromocytoma

Hypertension associated with acute renal failure

Eclampsia

Microangiopathic anemia

What is the primary reason for hypertensive

emergencies ?

1. Renovascular Disease

2. Pheochromocytoma

3. Non-adherence to anti-hypertensive

medication

4. Hyperaldosteronism

5. Erythropoeitin

Hypertensive Urgency

• Severe elevation in BP >180/120 mm Hg without

symptoms or signs of acute target organ involvement.

• Adequate treatment of these conditions, a BP lowering

within 24 hrs by administration of oral drugs.

• ICU admission is usually not required.

Hypertensive Urgency

Severe uncomplicated essential hypertension

Severe uncomplicated secondary hypertension

Postoperative hypertension

Hypertension assosciated with severe epistaxis

Drug induced hypertension

Rebound hypertension (i.e sudden withdrawal of clonidine)

Cessation of prior antihypertensive therapy

Anxiety ,panic attacks or pain

Why rapid reduction of BP not recommended in absence of end organ damage??

An aggressive approach.

A precipitous and unpredictable BP fall

Harmful (esp . In pts with multiple risk factors)

Cardiol clinics 2006;24:135-46.

Accelerated - Malignant Hypertension

• Severe hypertension and presence of retinopathy .

• Exudates,hemorrhages – Accelerated hypertension.

• Papilledema – Malignant hypertension.

Acute target organ damage in hypertension

Target organ Complications

Brain Hypertensive encephalopathy

Cerebral infarction

Cerebral hemorrhage

Advanced retinopathy

Heart Acute coronary syndrome

Acute heart failure

Aorta Aortic dissection

Kidney Acute renal failure

Placenta Eclampsia

• Single organ inv. in approximately 83%.

• Two organ inv. found in 14%,multiorgan inv. in 3 % pts.

Most common clinical presentations

- cerebral infarction (24%)

- pulmonary oedema (22%)

- HTN encephalopathy (16%)

- Cong. HF (12%)

•Less common presentations – IC hemorrhage, Aortic dissection

and Eclampsia ESC/ESH 2013

Joseph varon et al.Critical care 2008

Etiology• Essential hypertension : Inadequate blood pressure control and

noncompliance are common precipitants (MOST COMMON)• Renovascular• Eclampsia/pre-eclampsia• Acute glomerulonephritis• Pheochromocytoma• Anti-hypertensive withdrawal syndromes• Head injuries and CNS trauma• Renin-secreting tumors• Drug-induced hypertension• Burns• Vasculitis• Post-op hypertension• Coarctation of aorta (very rare)

2nd common

• Unclear, but some candidates

– ACE DD genotype

– Absence of the β and γ subunit of ENaC

– Elevated adrenomedullin levels

– Elevated natriuretic peptide level

– Abnormalities in oxidative stress markers and endothelial

dysfunctionVaughan and Delanty Lancet 2000; 356:411

Why only some are affected?

Pathophysiology

Increase in BP

Mechanical stress

Endothelial injury

Increased permeability

ischemia

RAASActivation of coagulation

cascade,platelets

Deposition of fibrin

IL-6

PRESSURE NATRIURESIS

End organ hypoperfusion,

ischemia,dysfunction

Increase in SVR

Humoral factors

Vaughan and Delanty Lancet 2000; 356:411

Fibrinoid necrosis

Vaughan and Delanty Lancet 2000; 356:411

CASE 1

• A 65 yr old male, hypertensive, chronic smoker, driver by

occupation admitted in ED with c/o headache since 3 days,increased

in severity over the past one day, associated with vomitings and

altered sensorium.

• He has been noncompliant to drugs since 15 days.

• At presentation his pulse rate was 70/min,regular, BP recording was

240/140 mm Hg, CVS- being normal on auscultation, lungs b/l basal

crepts.

• What is the diagnosis ?What would you do ?

• Admit ? What would be BP goal in this patient?

CASE 2

• A 38 yr old male,daily labourer, hypertensive since past

6yrs,came for follow up at OPD.

• His BP was 180/100 mm Hg .

• ECG showed LV strain.

• No symptoms of SOB on exertion,angina.

• Admit ?/ OPD Rx ?

• IV drugs / oral?

CASE 3

• A 28 yr old female, primi (6 months amenorrhea) was referred to physician with

c/o headache,vomitings,decreased urine output.

her BP was recorded to be 170/100 mm Hg

• CBP –leucocytosis,low platelets.• CUE –pus cells,RBC• LFT – mildly raised aminases,bilirubin being 2.8mg/dl• ECG –sinus tachycardia ,LVH with strain.• 2Decho – concentric LVH.

• What to do ?

• Admit ?• Normalize BP ?

CASE 4

• A 54 yr old male was admitted in ED with c/o weakness of right upper limb and lower limb since morning,

• Known hypertensive,diabetic.• Alcoholic• Was unconscious, BP was 190/100 mm Hg• CT brain – large MCA territory ischemic infarct

• What to do ?• Normalize BP?

CASE 5

• A 45 yr old male ,K/C/O CAD, hypertensive,diabetic, smoker

came with sudden onset of ripping pain, sharp sensation in the

back, along with SOB class IV.

• At presentation BP was 240/140 mm Hg

• Pulses discreprenancy on palpation.

• What to do ?

• Normalize BP ?

CASE 6

• A 23 yr old male,degree student, was brought to casualty with

sudden onset of SOB since 2 hours,saturations at room air were

normal.

• BP – 180/100 mm Hg

• CVS/RS –NAD

• What to do ?

• IV/oral/reassurance

Clinical assessment

• Complete history collection

• Detailed physical examination

• Duration and degree of pre existing hypertension

• Evidence of target organ damage

• Details of antihypertensive therapy

• Compliance with medications

• Use of the over counter drugs

• Illicit drugs usage

Symptom End organ damage

Chest pain Acute myocardial infarction

Myocardial ischemia

Thoracic aortic dissection

Back pain (ripping ) Thoracic aortic dissection

Dyspnea Acute pulmonary edema

Delirium,nausea,vomiting,seizures,altered consciousness

Hypertensive encephalopathyIschemic or hemorraghic stroke

Examination of pt

• BP sitting and standing position (if possible) with an appropriate size cuff in both arms(difference - aortic dissection).

• If peripheral pulses are markedly reduced (lower limb BP required).

• RR,HR• O2 saturation• Fundoscopic examination.

• CVS – murmurs (aortic insufficiency, ischemic MR)• S3,gallop,crackles in lung fields, raised JVP (signs of HF)• Renal bruit (renovascular HTN)• Abdominal mass (PCKD)• Level of consciousness ,focal signs of ischemia

Joseph varon et al.Critical care 2008

ESC/ESH,2013

Keith-Wagener-Barker Classification

• Grade 1– Mild narrowing of the arterioles– “Copper Wire”

• Grade 2– Moderate narrowing – – Copper wire and AV nicking

• Changes associated with long standing essential hypertension

Grade 3Severe Narrowing -

Silver wire changes, hemorrhage, cotton wool spots, hard exudatesGrade 4Grade 3 + Papilledema

Grade 3 and 4 highly correlated with progression to end organ damage and decreased survival

Normal

Grade 1

Grade 2

Grade 3 KWB Retinopathy

Investigations

• Blood electrolytes • Creatinine• Urea nitrogen• Cell count• Smear (microangiopathic hemolysis)• ECG• CXR• CT Brain• CT chest/MRI

Management

Normalisation of BP is usually not recommended*

How fast and how much BP to be lowered to be given importance.

*Conditions apply

Why ??

• Sudden fall in BP may cause acute hypoperfusion of vital organs

and results in myocardial ischemia or infarction, hemiplegia,or

acute renal failure.

• Older patients with long lasting hypertension and preclinical organ

involvement (LVH, atherosclerosis and arteriolar remodelling) are

at risk of these complications as the lower limit of autoregulation

shifted to right.

Appropriate treatment is dictated more by the features of the acute syndrome and by the patient’s characteristics than by a body of scientific evidence.

• Controlled trials not available (extremely heterogenous population)• Tailored on individual patient

– Organ at risk.

Varon J et al ;Crtical care 2003

ESC/ESH manual of Hypertension 2009

HYPERTENSIVE EMERGENCIES

Hypertensive Emergency

• Damage Heart - CHF, MI, angina

Kidneys - acute kidney injury, microscopic hematuria

CNS - encephalopathy, intracranial hemorrhage, Grade 3-4 retinopathy

Vasculature - aortic dissection, eclampsia

• GOAL reduce MAP by no more than 20-25%,

DBP to 100-110mm Hg within few minutes to 2 hours.

• More aggressive and rapid BP reduction (Acute Pulmonary

edema ,Aortic dissection)

• More slowly for acute cerebrovascular damages with

monitoring of neurological status.

• Constant infusion of intravenous agents required (no

intermittent IV boluses/oral/sublingual drugs- drastic BP

fall).

Ideal drug

Fast acting

Easily titratable

Rapidly reversible and safe

No single agent has these characteristics

Sodium nitroprusside

• Potent short acting arterial and venous dilator

(reduces pre- and after- load)

• Rapid onset of action.(seconds)

• Continuous intra-arterial BP monitoring required.

• Infusion chamber and tubing to be covered.

• intracranial pressure (caution in intracerebral hemorrhage)

• Induces coronary steal (non selective coronary vasodilation)

• Increases mortality in pts with acute MI. (NEJM,1982)

• Thiocyanate toxicity (nausea,vomiting,lactic acidosis and altered mental status)

– Usually rare, seen in pts with renal ,hepatic dysfunction.Freiderich et al, Anesth Analo 1995:81:152-162

Fenoldopam

• A peripheral dopamine-1 receptor antagonist (DA1).

{highly specific}

• 10 –fold more potent than dopamine as a renal vasodilator.

• Antihypertensive effect by combined natriuretic and vasodilatory effect

(esp. intrarenal arteries)

• Not to be used as prophylactic agent for preventing CIN

(CAFCIN Trial)

• Agent of choice in hypertensive emergencies assosciated with renal

dysfunction.

• Adv effects – hypotension ,hypokalemiaClin Invest 1993;72:60-64

Nicardipine

• Second generation DHP CCB.

• Strong cerebral and coronary vasodilation.

• Onset of action 5-15 min, Duration being 2-6 hrs.

• Increases both stroke volume and coronary blood flow with a favourable

effect on myocardial oxygen balance.

• CAD with Systolic HF. C/I in Aortic stenosis.

• Dosage independent of weight.

• Infusion rate of 5mg/h – 2.5 mg/h increments every 5 min –max being 15 mg/h.

• IV Nicardipine maintained BP in Treatment range > IV Labetalol (CLUE

trial) BMJ,2013

J Emerg Med 1987:5:463-473

Clevidipine

• Third generation, intravenous, dihydropyridine caclium channel antagonist.

• FDA approval (2008)• Ultra short half life of about 1 min.• Potent arterial vasodilation (no effect on venous capacitance,

myocardial contractility)*• No significant adverse effect on heart rate’. • Injectable emulsion.• 99.9% bound to protein.• Safe in pts with renal,hepatic dysfunction.• C/I –allergies to soy products,eggs and egg products,defective lipid

metabolism.

*Rivera et al .,2010,Polly et al 2011.

50mg/100ml

Dosage

• An IV infusion at 1–2 mg/hour is recommended for initiation and

should be titrated by doubling the dose every 90 seconds.

• As the blood pressure approaches goal, the infusion rate should be

increased in smaller increments and titrated less frequently.

• The maximum infusion rate for Cleviprex is 32 mg/hour.

• Most patients in clinical trials were treated with doses of 16 mg/hour

or less.

No more than 1000 mL (or an average of 21 mg/hour) of Cleviprex infusion is recommended per 24 hours..

Am J Cardiovascular Drugs 2009;9;117-134

Clevidipine• ESCAPE1(pre op),ESCAPE 2(post op) plaebo controlled trials –

15% reduction in SBP within 6 min post infusion.Rivera et al.,2010.

Levy et al .,2007. • ECLIPSE – Clevidipine maintained BP within target range with

minimal excursions.Singla et al .,2008

• VELOCITY study for hypertensive crises. Pollack et al .,2009

• ACCELERATE trial –management of severe HTN with ICHGraffagnino et al., 2009

Labetalol

• Combined selective 1 adrenergic and non selective β adrenergic receptor blocker (1:7).

• Hypotensive effect – in 2-5 min after IV admin.• Maintains cardiac output (unlike other BB).• Reduces SVR, but does not decrease PBF.• Cerebral,renal,coronary blood flow maintained.

• Less placental transfer can be used in pregnancy induced HTN emergency.

• Metabolised by liver.• Oral/IV.

Drugs 1984,Suppl 2 :35-50.

Esmolol

• Ultrashort acting cardioselective β adrenergic blocking agent.

• Ideal β blocker in critical cases.

• Useful in severe postoperative HTN.

• Onset of action is within 60 sec

• Duration of action being 10-20min.

• Rapid hydrolysis of ester linkages by RBC esterases(metabolism),

not dependent on renal or hepatic function.

• 0.5 to 1mg/kg loading dose over 1min,followed by an infusion -

50ug/kg/min.(max 300ug/kg/min) Chest 1988;93:398-403

Not to useSublingual Nifedipine

• Drug is poorly soluble, not absorbed through buccal mucosa

• Sudden uncontrolled and severe reductions in BP,may precipitate

cerebral,renal and myocardial ischemic events.

• Lack of clinical documentation attesting to a benefit from its use.

• The Cardiorenal Advisory Committee of the FDA has concluded

“that the practice of administering SL/oral nifedipine should be

abandoned because this agent is not safe nor efficacious”.

Anaesth Clin North Am.1999.

SPECIAL SCENARIOS

Myocardial ischemia/infarction

• may be assosciated with HTN at presentation

(usually in a previously HTN pt).

• High BP exacerbated by pain and agitation.

• IV Nitrates reducing systemic vascular resistances,LVpreload,

improves coronary perfusion.

• B blockers may contribute to a fall in BP (reduces myocardial O2

consumption)

• BP control mandatory before thrombolysis (BP<180/100 mmHg).

Vaughan et al Lancet 2000;356:411-7

Acute Cardiogenic Pulmonary Edema

• Ventilation• Reduction of LV preload and afterload.• IV nitrate, loop diuretics.• Others – urapidil, nicardipine,sodium nitroprusside.

• {Urapidil is a sympatholytic antihypertensive drug. Peripheral α1-adrenoceptor antagonist and a central 5-HT receptor agonist, does not elicit reflex tachycardia(weak β1adrenoceptor antagonist activity, effect on cardiac vagal drive). Not approved by the USFDA, but it is available in Europe}.

• Bolus 12.5-25 mg (50 mg),infusion 5-40mg/h,onset 3-6 min,duration 4-6 hr .

Salgado et al.Annals of intensive care 2013;3:17

Aortic Dissection

• Most dramatic and rapid fatal complication in HTN emergencies.

• Acute BP reduction reduces shear forces on damaged aorta.

• Aim of treatment to reduce SBP as rapidly as possible down to

100-110 mmHg, simultaneously control tachycardia resulting form

the sympathetic activation.

• B blocker + vasodilator to be given

• Esmolol + nitroprusside would be a better combination.

• Hydralazine is C/I Circulation 2006;114:1384-89

Ischemic stroke

• BP elevations can occur in previously hypertensive and in

normotensive pts.

• BP declines to pre stroke values within 3-4 days after an ischemic

stroke.

• Severe HTN Rx controversial issue.

Lesions in cerebral area

Impaired neurogenic

control of CVS HIGH BP

Arch Intern Medicine 2003;163:211-216

Shift to right in case of chronic HTN

AHA recommendation

• Threshold for treatment BP > 220/120 mmHg

• Target BP should be a 10-15% lowering of BP.

• Raised ICP – MAP<130 (1st 24hrs)

• No raised ICP – MAP<110

• IV Labetalol or Nicardipine .

• IV tPA (if to be given) BP <185/110mm Hg.

Stroke 2003;34:1056-83

IC bleed

• To prevent rebleeding and reduce edema formation.

• BP >180/105 mmHg ,may benefit from gradual 20-25%

reduction in BP.

Nimodipine, a dihydropyridine calcium blocker,is effective

(antagonist effects on cerebro vasospasm).

AHAguidelines;Critical care Med 2006;34:1975-1980

Hypertensive Encephalopathy

• Potential lethal complication of severe or abrupt BP elevation.

• Previously HTN/normotensive pts.

• Acute glomerular nephropathy, Eclampsia, TTP, Pheochormocytoma,

Erythropoietin administration, immunosupressive drugs

HIGH BLOOD PRESSU

RE

Excessive

increase in

cerebral blood flow

HYPERFILTRATION

LOCALISED OR WIDESPRE

AD EDEMAHinchey J et al,NEJM 1996;334:494-500

• Cerebral ischemia resulting from arteriolar spasm*.

• Severe headache,vomitings,visual disturbances,confusion, focal or

generalized seizures.

• Fundoscopic examination(key role)

• Mean BP should be reduced by 20% within first hour.

• IV sodium nitroprusside is DOC (rapid onset of action)

ESC/ESH 2003

• IV labetalol,nicardipine,hydralazine . Circulation,2004;110:2241-5

Eclampsia

• Hypertension complicates 12% pregnancies, 18% maternal deaths.• Volume expansion,MgSo4 for seizure prophylaxis. • MgSo4 4-6 g in 100ml 5%D over 15- 20 min - 1-2g/h infusion

(hourly DTR,urine output).• Antihypertensive therapy (to prevent complications in mother).• SBP :155-160 mmHg,DBP>105mm Hg.(initiation of Rx)• ICH is a devastating complication.

• Methyl dopa,Hydralazine DOC,• Others being IV labetalol,nicardipine.• Avoid sublingual or oral nifedipine.• Nitroprusside,ACEI – C/I

Am J Obst 2000:183:S1-S22

HTN emergencies due to catecholamine excess

Abrupt increase in alpha adrenergic tone.

• IV labetalol• Pheochromocytoma crisis (IV alpha blocker phentolamine)

followed by B blocker(for tachycardia or VPCs).

Withdrawal of centrally acting anti HTN drugs (clonidine)

Pheochromocytoma

Cocaine intoxication

Abuse of sympathomimetics

Post operative Hypertension

ORAL DRUGS FOR HTN URGENCIESDrug Initial dose Onset duration Adverse effects

Labetalol 200-400 mg 30-120 min 2-12 h Orthostatic hypotension,bronchoconstriction

Clonidine 0.150-0.300 mg 30-60 min 8-16 h Hypotension,dry mouth.

Prazosin 1-2 mg 60-120 min 8-12 h Syncope(1 dose),tachycardia

Nicardipine 20-40 mg 30-60 min 8-12 h Headache,tachycardia

Amlodipine 5-10 mg 60-120 min 12-18h Headache,flushing

Captopril 25-50 mg 15-45 min 6-8h Renal failure in B.R.A.S

Acute and transient BP elevations

• Anxiety• Panic attacks• Pain

Rx - Administration of anxiolytic or analgesic drugs.

• Refractory nose bleeding– IV drugs to be used sometimes

TAKE HOME MESSAGE

• Most common cause for HTN crises is

UNDIAGNOSED/UNTREATED/

INADEQUATELY TREATED HYPERTENSION

• Differentiation of emergency from urgency is absence of target

organ damage in the later.

• Clevidipine is the new drug approved for hypertensive emergencies.

• IV Nicardipine , IV Labetalol are preferred for most of

emergency situations.

• SL/oral nifedipine not to be used..

THANK YOU