New Trends In Management Of

Hypertensive emergencies & Hypertensive

Urgencies

Dr. Sahar Gamal El-DinNational Heart Institute

• Epidemiology

• Definitions.• What causes hypertensive

emergencies & urgencies?• How should hypertensive emergencies

& urgencies be managed?• Monitoring and follow-up.• Case.

Epidemiology• Approximately 1% of hypertensive 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;

•Definitions• 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 Emergencies

– Hypertensive Urgencies

• 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 mm Hg - DBP > 120 mm Hg

• Requires an immediate BP reduction in few minutes -

hours.

• Requires an ICU care & IV drugs

Hypertensive Emergencies

• Single organ damage in approximately 83%.

• Two organ damage found in 14%,multiorgan damage

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

Hypertensive Encephalopathy

• A hypertensive emergency characterized by irritability, headach & mental status changes caused by significant and often rapid elevation in blood pressure

Malignant & Accelerated Hypertension

• A hypertensive emergency characterized by fundoscopic findings of papilledema (KW gr4) &/or acute retinal haemorrhages & exudates (KW gr3)

• Exudates,hemorrhages (KW gr3)– Accelerated

hypertension.

• Papilledema (KW gr4) – Malignant hypertension.

Grade 3 KWB Retinopathy

Hypertensive Urgencies• Elevated BP ( usually systolic > 180 mmHg

&/or diastolic > 120 mmHg ) but without evidence of end-organ damage.

• Usually asymptomatic; or severe headache, shortness of breath, epistaxis, severe anxiety.

• Adequate treatment of these conditions, a BP lowering within 24 hrs by administration of oral drugs.

• ICU admission is usually not required.

European Heart Journal (2013) 34, 2159–2219

Causes of hypertensive emergencies ?• Renovascular Disease• Pheochromocytoma

1. Non-adherence to anti-HTN medications (most common)

2. Hyperaldosteronism

3. Anti-hypertensive withdrawal syndromes

4. Head injuries and CNS trauma

5. Post-op hypertension

6. Drug-induced hypertension

Causes Hypertensive Urgencies• As with hypertensive

emergencies ,severe BP elevations may result from inadequate control on or poor adherence to current antihypertensive drug regimens.

• Another cause for patients reaching hypertensive urgency is previous inaccurate BP measurements that underestimate or do not detect increased BP at all (e.g. poor patient technique for self‐monitoring).

Ann Emerg Med. 2008 Mar;51(3 Suppl):S7‐9.

Causes Hypertensive Urgencies• Drugs:

• Non-Narcotic Analgesics : - Non-steroidal anti-inflammatory

agents including aspirin - Selective COX-2 inhibitors

• Sympathomimetic agents:- Decongestants- Diet pills- Cocaine

• Stimulants:

-Methylphenidate, amphetamine.

Causes Hypertensive Urgencies

• Lifestyle :- High salt diet, excessive alcohol use.

• Comorbid Conditions :- Thyroid storm, trauma, renovascular

disease, acute ischemic stroke or adrenal dysfunction

Chest 2007 Nov;132(5):1721.

Approach to patients with hypertensive emergencies &

urgencies• H History

• E Examination

• A Assessment

• T Treatment

www.uptodate.com.2012

History

• Duration and degree of pre existing hypertension

• Details of antihypertensive therapy

• Compliance with medications

• Use of the over counter drugs

• History of recent operations.

Examination

• Physical exam ‐ focus on any signs of target organ damage (e.g. shortness of breath, chest pain, numbness/weakness)

Assessment

• Lab tests & investigations may be required (e.g.

CBC, ECG, urinalysis, renal function; Echo. ,

Fundoscopy, consider head imaging if neurological

symptoms ).

Treatment of Hypertensive Emergencies

Hypertensive Emergency

Stop progression of Target Organ DamageAvoid organ hypoperfusion during treatment

General Goals:

Points of emphasis:

Parenteral therapy should be initiated immediately

Further diagnostic testing should not delay Rx

ICU admission & intra-arterial BP monitoring is preferred

• 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 like ON-OFF or light

switch properties

No single agent has these characteristics

Sodium nitroprusside• Potent short acting arterial & veno-dilator

(reduces pre- and after- load)• Rapid onset of action.(seconds)• Continuous intra-arterial BP monitoring required. 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). • 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 ,hypokalemia

Clin 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.• 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

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.

•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

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.

Treatment of Hypertensive Urgencies

• Overall Goal of Management: reduce SBP by ~ 25% over 24‐48 hours.

• More conservative BP lowering reduces the risk of potential adverse effects (i.e. perfusion complications worsening incidence of MI, stroke, and death) associated with more aggressive BP lowering if the blood pressure falls below the range at which tissue perfusion can be maintained by autoregulation .

• All treatment strategies should consider the patient’s comorbidities and risk of adverse events. www.uptodate.com.2012

• General strategies :• All patients should be provided with a

quiet room to rest. This will be adequate for some & can lead to a fall in BP of ≥10‐20 mmHg.

• Tilt the head of the bed 15 degrees up. This may also help to decrease BP.

• If BP remains above 180/100 mmHg for ≥3 hours, consider antihypertensives.

• General drug treatment options differ depending on whether the patient was previously diagnosed with & treated for HTN.

• Previously Treated Hypertension: trying one the following may be appropriate interventions (in no particular order):

• Increase the dose of current antihypertensive medications.

• Add another antihypertensive agent from another class.

• Restart/resume medications in non‐adherent patients.

• Addition of a diuretic, & reinforcement of dietary sodium restriction, in patients who have worsening hypertension due to high sodium intake.

J Clin Hypertens (Greenwich) 2006; 8:61.

•Untreated hypertension — In the previously untreated patient, several options are available.

• The approach should take into consideration the individual patient's risk with persistence of severe hypertension, the likely duration of severe hypertension, and of cerebrovascular or myocardial ischemia with rapid reduction in blood pressure.J Clin Hypertens (Greenwich) 2006; 8:61.

• Relatively rapid initial blood pressure reduction (over several hours):

• We use one of the following agents: oral furosemide (if the patient is not volume depleted) at a dose of 20 mg ; a small dose of oral clonidine (0.2 mg); or a small dose of oral captopril (6.25 or 12.5 mg).

• Following administration of one of these agents, the patient is observed for a few hours, to ascertain a reduction in blood pressure of 20 to 30 mmHg. Thereafter, a longer acting agent is prescribed and the patient is sent home to follow up within a few days.

• The drop in blood pressure may take relatively longer with  captopril, and may be too large among patients with hemodynamically significant unilateral renal artery stenosis.

• We prefer this approach in patients with known aortic or intracranial aneurysms. This may be the optimal approach in most patients, however this is not proven, and it is often not feasible to provide medications and observe for several hours.

Fast Acting Non IV Antihypertensives For Hypertensive Urgency :

• Blood pressure reduction over one to two days:

• There are no data supporting the use of a particular agent in this setting although we generally do not begin therapy with extended release preparations or with a diuretic alone.

• Depending on the patient, a calcium channel blocker (but not sublingual nifedipine), beta blocker or angiotensin converting enzyme (ACE) inhibitor or receptor blocker can be started.

• Examples in these categories are oral nifedipine 30 mg once daily (of the long-acting preparation), oral metoprolol XL 50 mg daily, or ramipril  10 mg once daily.

2010 Feb 15;81(4):470‐6.

• The choice of agent should take into consideration the type of antihypertensive agent that is most appropriate in the long term (eg, calcium channel blockers and thiazide-like diuretics are preferred over ACE inhibitors and beta blockers as monotherapy in blacks), and underlying conditions that may be favorably or adversely affected by the antihypertensive agent

JAMA 2003; 289:2560.

Considerations for individualizing antihypertensive therapy

Comorbid Comorbid ConditionsConditions

Initial Therapy Initial Therapy OptionsOptions

Heart failureHeart failure ACEI or ARB, beta ACEI or ARB, beta blocker, diuretic, blocker, diuretic, aldosterone antagonistaldosterone antagonist

Post‐MIPost‐MI ACEI or ARB, beta ACEI or ARB, beta blockerblocker

Isolated Systolic HTNIsolated Systolic HTN Thiazide, CCB; ACEI or Thiazide, CCB; ACEI or ARBARB

DiabetesDiabetesACEI (or ARB), Beta ACEI (or ARB), Beta Blocker cardioselective Blocker cardioselective (if age ≤60), Thiazide, (if age ≤60), Thiazide, CCBCCB

Chronic Kidney Chronic Kidney DiseaseDisease ACEI (or ARB)ACEI (or ARB)

• Some experts initiate therapy with two agents or a combination agent, one of which is a thiazide diuretic.

• The rationale is that most patients with blood pressure ≥20/10 mmHg above goal will require two or more antihypertensive agents in order to achieve the goal blood pressure .

Am J Hypertens 2004; 17:793.

• It is unlikely that a diuretic in combination with a modest dose of another agent will cause a dangerous reduction in the blood pressure; however, initiation of two agents simultaneously must be done with close blood pressure follow-up, since the full effects of both agents may not occur for a few days, and adverse consequences may ensue if the blood pressure is lowered too quickly.

• This is particularly true among patients with cerebrovascular disease in whom more cautious blood pressure reduction is warranted.

•Monitoring and follow-up  • The patient should be observed for a few

hours to confirm that they are stable/improving & asymptomatic.

• Once stable, the patient can be sent home with close follow‐up (every 1‐2 days) involving:

- Evaluation for signs of HTN or hypotension.- Attainment of BP goals with the help of

antihypertensives and lifestyle interventions (e.g. low salt diet, increased physical activity)

• BP goals may vary depending on the patient and any existing comorbid conditions. For example, elderly patients (especially those >80 years old) may do better on less aggressive therapy.

• Assessment of medication adherence (consider simplified dosing schedules, & adherence aides, if appropriate)

• If there are concerns about patient compliance to follow up, especially if there is high risk of cerebrovascular or cardiovascular disease,hospital admission may be warranted for initial management

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..