10th Block

Circulation system

HYPERTENSIVE
EMERGENCIES & URGENCIES

P.Pujowaskito

© 2014 General Ahmad Yani University

Why Hypertension ?
 Neurohormonal control of blood pressure
Blood pressure = Cardiac output (CO) x Peripheral resistance (PR)
Hypertension = Increased CO and/or Increased PR

Vasoconstriction
 Preload  Contractility
 Fluid volume

 Fluid volume
Sympathetic Renin-
nervous angiotensin-
Renal sodium system aldosterone
retention system

Excess Genetic
sodium factors
intake
(Adapted from Kaplan, 1994)
Trends in the Awareness, Treatment and Control of
High Blood Pressure in Adults, US, 1976–1994

NHANES II NHANES III NHANES III

(Phase 1) (Phase 2)
(1976–1980) (1988–1991) (1991–1994)

Awareness 51 73 68

Treatment 31 55 53

Control 10 29 27

JNC VI. Arch Intern Med 1997;157:2413-2446.

Percentages of Patients whose
Hypertension is Controlled

< 140/90 mmHg < 160/95 mmHg

USA Canada Finland Spain Australia
16 20.5 20 19
27

England France Germany Scotland India

6 9
24 22.5 17.5

> 65 years

USA: JNC VI. Arch Intern Med 1997 Marques-Vidal P et al. J Hum Hypertens 1997
Canada: Joffres et al. Am J Hypertens 1997
England: Colhoun et al. J Hypertens 1998
France: Chamontin et al. Am J Hypertens 1998 Adapted from G. Mancia / L. Ruilope
 Classification of Blood Pressure for
Adults Aged 18 Years or Older
JNC VII
BP Systolic BP Diastolic BP
Classification "mmHg" "mmHg"

Normal <120 and <80

Prehypertension 120-139 or 80-89

Stage 1 hypertension 140-159 or 90-99

Stage 2 hypertension >160 or >100

2003
 WHO-ISH* 1999: definition and classification
of BP levels
Category Systolic BP (mm Hg) DBP (mm Hg)

Optimal BP <120 < 80

Normal BP <130 < 85
High-normal BP 130-139 85-89

Grade 1 hypertension (mild) 140-159 90-99

Subgroup: borderline 140-149 90-94

Grade 2 hypertension (moderate) 160-179 100-109

Grade 3 hypertension (severe) ≥180 ≥110

Isolated systolic hypertension (ISH) ≥140 <90

Subgroup: borderline 140-149 <90

*World Health Organization–International Society of Hypertension.

When systolic BP and DBP fall into different categories, the higher should apply.

Adapted from the World Health Organization–International Society of Hypertension, J Hypertens, 1999.
 WHO-ISH Guidelines for Management of Hypertension:
Stratification of Cardiovascular Risk

Blood Pressure (mm Hg)

Grade 1 Grade 2 Grade 3
Mild Moderate Severe
hypertension hypertension hypertension
Other risk factors and SBP 140–159 SBP 160–179 SBP  180
disease history or DBP 90–99 or DBP 100–109 or DBP  110
I No other risk factors Low risk Med risk High risk
II 1–2 risk factors Med risk Med risk Very high risk
III 3 or more risk factors High risk High risk Very high risk
or TOD or diabetes
IV ACC Very high risk Very high risk Very high risk

TOD = Target-organ damage Guidelines subcommittee. WHO-ISH

ACC = Associated clinical conditions Guidelines. J Hypertens 1999;17:151-183.
 CVD Risk Factors
 Hypertension*
 Cigarette smoking
 Obesity* (BMI >30 kg/m2)
 Physical inactivity
 Dyslipidemia*
 Diabetes mellitus*
 Microalbuminuria or estimated GFR <60 ml/min
 Age (older than 55 for men, 65 for women)
 Family history of premature CVD
(men under age 55 or women under age 65)

*Components of the metabolic syndrome.

Definition
JNC :
Hypertensive Crisis as
Emergencies or Urgencies.

Hypertencive Emergencies are those

situation that require immediate BP reduction
not necessary to normal range to prevent or
to limit target organ damage

Hypertencives Urgencies are those

situation in which it is desirable to reduce BP
within few hours.
 Categories of hypertensive
end-organ damage

Origin Category
Brain Stroke (atherothrombotic or haemorrhagic)
Transient ischaemic attack
Periodic ischaemic spells
Multi-infarct dementia
Ocular fundus Keith-Wagener-Barker grade III–IV
Heart Sudden death
Myocardial infarction
Angina (including variant forms

Arrhythmias

Left ventricular hypertrophy

Heart failure

Birkenhäger and de Leeuw (1992)

 Categories of hypertensive
end-organ damage

Origin Category

Large arteries Loss of compliance

(Dissecting) aneurysm
Peripheral occlusive arterial disease

Kidney Nephrosclerosis

Birkenhäger and de Leeuw (1992)

 HYPERTENSIVE CRISIS
DBP >130 mmHg
URGENCY
 BP within hours < 24 hours
(PARENTERAL / ORAL)
KAPLAN NM . Lancet 344:1335,1994
EMERGENCY
 BP within minutes < 1 hours
(PARENTERAL)
- Accelerated malignant hypertension
- Hypertensive encephalopathy
- Intracerebral/Subarachnoid hemorrhage
- Acute aortic dissection
- Acute left ventricular failure
- Acute myocardial infarction
- Acute glomerulonephritis
- Eclampsia
- Severe epistaxis
- Perioperative hypertension
 Hypertensive Emergencies

Uncommon situation
Require Immediate BP reduction
(not neccesary to normal value )
to limit or to prevent target organ
damage
 Hypertensive Emergencies
1. Hypertensive encephalopathy
2. Malignant hypertension (some cases)
3. Severe hypertension in association with acute complications
A. Cerebrovascular
Intracerebral hemorrhage
Subarachnoid hemorrhage
Acute atherothrombotic brain infarction (with severe
hypertension)
B. Renal
Rapidly progressive renal failure
C. Cardiac
Acute aortic dissection
Acute left ventricular failure with pulmonary edema
Acute myocardial infarction
Unstable angina
 Hypertensive Emergencies

4. Eclampsia or severe hypertension during pregnancy

5. Catecholamine excess states
A. Pheochromocytoma crisis
B. Food or Drug interactions (tyramine) with monoamine oxidase
inhibitors
C. Some cases of rebound hypertension following sudden with
drawl or antihypertensive agents (ie, clonidine, guanabenz,
methyldopa)
6. Drug-induced hypertension (some cases)
A. Overdose with sympathomimetics or drugs with similar action
(eg, phencyclidine, lysergic acid diethylamide [LSD], cocaine,
phenylpropanolamine)
7. Head trauma
8. Post-coronary artery bypass hypertension
9. Postoperative bleeding at vascular suture lines.
 Hypertensive Urgencies

• Are assosiated with severely elevated

Blood Pressure include upper level of
stage 3 Hypertension without severe
symptoms or progressive target organ
dysfuntion.
• Needs adequate treatment within
several hours ,usually with oral agent.
 Hypertensive Urgencies

1. Accelerated and malignant hypertension

2. Extensive body burns*
3. Acute glomerulonephritis with severe hypertension*
4. Scleroderma crisis
5. Acute systemic vasculitis with severe hypertension*
6. Surgically related hypertension
A. Severe hypertension in patients requiring immediate
surgery*
B. Postoperative hypertension*
C. Severe hypertension after kidney transplantation
7. Severe epistaxis
 Hypertensive Urgencies

8. Rebound hypertension after sudden withdrawal of

antihypertensive agents
9. Drug-induced hypertension*
A. Overdose with sympathomimetic agents
B. Metoclopramide-induced hypertensive crisis
C. Interaction between and -adrenergic agonist
and a nonselective -adrenergic antagonist
10. Episodic and severe hypertension associated with
chronic spinal cord injury autonomic hyperreflexia
syndrome
 Epidemiology :
Hypertensive Crisis according to JNC
on Detection,Evaluation,and Treatment of High Blood
Pressure

25% of all patient from E R with

Ht Emergency accounting one
third.
 Critical Degree of Hypertension

Local effects Systemic effects

(Prostaglandine, free (Renin-angiotensin,
radicals, etc) catechol, vasopressin)

Endothelial damage Pressure natriuresis

Platelet deposition Hypovolemia

Mitogenic and migration Further increase in

factors vasopressors

Myointimal proliferation

Further rise in blood pressure

and Vascular damage

Tissue ischemia
Scheme for initiation and progression of
accelerated-malignant hypertension
 Initial Evaluation of Patients with
Hypertensive crises
History
Prior diagnosis & treatment of hypertension
Intake of pressor agents : street drugs, sympathomimectics
Symptoms of cerebral, cardiac, & visual dysfunction
Physical examination
Blood pressure
Funduscopic examination
Neurologic examination
Cardiopulmonary status
Body fluid volume assessment
 Initial Evaluation of Patients with
Hypertensive crises
Laboratory evaluation
Hematocrit and blood smear
Urine analysis
Automated chemistry : creatinine, glucose, electrolytes
Plasma renin & aldosterone (some cases)
(Repeat plasma renin 1 hour after 25 mg captopril if
renovascular hypertension is being considered)
Spot urine for metanephrine if pheochromocytoma is
being considered
Chest radiograph Electrocardiogram
 Management of Hypertensive
Emergencies and Urgencies
KEY POINTS
 Patients with hypertensive emergencies usually require
hospitalization for vasodilator therapy, usually in an intensive
care unit where blood pressure (BP) monitoring can be
maintained.
 The goal of initial treatment in the hypertensive emergency is
to obtain a partial reduction in BP to a safer, noncritical level,
although not necessarily to achieve normotension.
 Most hypertensive urgencies can be managed in the
outpatient setting if appropriate follow-up can be provided.
 Elevated BP alone in the absence of symptoms of
progressive target-organ damage rarely requires emergency
therapy.
Treating hypertension reduces cardiovascular morbidity and
mortality

Major
Relative risk (%) CV coronary
CHF Stroke mortality event All deaths
0

*
–20

*** **
–40
***
*** ‘Older’ patients (mean >65 years)
*** ‘Younger’ patients (<65 years)
–60
* p<0.05; ** p<0.01; *** p<0.001

–80

Gueyffier et al (1996)
 Step-by-step diagnostic approach
NO YES
Increased Mental Status: NEW?
BP NORMAL
NO
YES
YES
Neurologic Exam: NO
NEW?
NON-FOCAL
NO
YES
Diagnostic
YES YES
Algorythm Funduscopy:
PAPILEDEMA/HAEM NEW?
of
HTN NO
NO

EMG
YES
ECG: YES
NEW?
Bakris,2004 ISCHAEMIC
NO
NO
YES
Urin Exam : YES
NEW?
RBC/CAST
NO
NO

YES
Not a Serum Creatinin: YES
HTN EMG INCREASED NEW?

HTN EMG
Begin Th/
Therapy of Hypertensive Crises

HYPERTENSIVE EMERGENCY
PATIENTS should be hospitalized
BP should be reduced :
- immediately
- Gradually
- Specifically
DRUGS should be used i.v :
- take care of the fluid homeostatis
 Recommended Rate of Decrease
in Blood Pressure

EXTRACEREBRAL END-ORGAN DYSFUNCTION

- rapid lowering of BP by no more than 20-25 % of mean BP in 2 hrs
- the decrease of DBP to 100-110 mmHg in 2 hrs

CEREBRAL END-ORGAN DYSFUNCTION

- in patient with stroke antihypertensive therapy is not recommended
routinely !
- gradually decrease BP only if it is extremely high ( > 220 / 130 mmHg )
- in patient with hypertensive encephalopathy we should lower BP by 20% or
to DBP 100 mmHg within 2 hrs
 Current Recommendation of
the AHA :
• Hypertension in the setting of acute ischemic
stroke should only be treated rarely and
cautiously .
• Treat : DBP > 120-130 mmHg , objective
reduction 20 % in the first 24 hours.
• Abandon oral nifedipine.
• Short acting IV. (labetalol, nicardipine,
fenoldopam )
• Sodium Nitropruside increase Intra Cranial
Pressure, cyanide poisoning
Management of Hypertensive Emergencies
JNC-VI RECOMMENDATION

• Reduce Mean Arterial BP no more than 25 % over

2 hours then reduce to 160 / 100 mm Hg within 2-
6 hours.
• Avoid excessive falls in blood pressure
• Titrate with intravenous antihypertensives agent.
• Guideline of treatment based on concensus
expert.
 The ideal properties of IV agents
for Hypertensive emergencies

• Ability to regulate and control blood

pressure reduction
• Minimal risk of hypotension
• Rapid and predictable reduction of BP
• Minimal side effects/few adverse
effects
 Parenteral Drugs for Treatment of Hypertensive
Emergency (In Order of Rapidity of Action)1a

Drug Dosage Onset of Action

Vasodilators
Nitroprusside 0.25-10 g/kg/min as IV Instantaneous
(Nipride, Nitropress) infusion
Nitroglycerin 5-100 g/min as IV infusion 2-5 min
Diazoxide (Hyperstat) 50-100 m/IV bolus 2-4 min
repeated, or 15-30 mg/
min by IV infusion
Hydralazine (Apresoline) 10-20 mg IV 10-20 min
10-50 mg IM 20-30 min
Enalaprilat (Vasotec IV) 1.25-5 mg q 6 hr 15 min
Nicardipine* 2-8 mg/hr IV 5-10 min
 Parenteral Drugs for Treatment of Hypertensive
Emergency (In Order of Rapidity of Action)1b
Drug Duration Adverse Effects
of Action

Vasodilators
Nitroprusside 1-2 min Nausea, vomiting, muscle twitching, sweating,
(Nipride, Nitropress) thiocyanate & cyanide intoxication
Nitroglycerin 3-5 min Headache, vomiting, methemoglobinemia,
tolerance with prolonged use
Diazoxide 6-12 hr Nausea, hypotension, flushing, tachycardia,
(Hyperstat) chest pain
Hydralazine 3-8 hr Tachycardia, flushing, headache, vomiting,
(Apresoline) aggravation of angina
Enalaprilat 6 hr Precipitous fall in BP in high renin states;
(Vasotec IV) response variable
Nicardipine* 30-60 min Tachycardia, headache, flushing, local
phlebitis
 Parenteral Drugs for Treatment of Hypertensive
Emergency (In Order of Rapidity of Action)2a

Drug Dosage Onset of Action

Adrenergic Inhibitors
Phentolamine (Regitine) 5-15 mg IV 1-2 min
Trimethaphan (Arfonad) 0.5-5 mg/min as IV infusion 1-5 min
Esmolol (Brevibloc) 200-500 g/kg/min for 4 min, 1-2 min
then 50-300 g/kg/min IV
Labetalol (Normodyne, 20-80 mg IV bolus every 5-10 min
Trandate) 10 min
2 mg/min IV infusion
 Parenteral Drugs for Treatment of Hypertensive
Emergency (In Order of Rapidity of Action)2b

Drug Duration Adverse Effects

of Action

Adrenergic Inhibitors
Phentolamine (Regitine) 3-10 min Tachycardia, flushing
Trimethaphan (Arfonad) 10 min Paresis of bowel & bladder, orthostatic
hypotension, blurred vision, dry mouth
Esmolol (Brevibloc) 10-20 min Hypotension, nausea
Labetalol (Normodyne, 3-6 hr Vomiting, scalp tingling, buming in
Trandate) throat, postural hypotension,
dizziness, nusea

IV : intravenous; IM : intramuscular
*Not approved by Food & Drug Administration
 Preferred Parenteral Drugs for Specific
Hypertensive Emergencies (In Order of Preference)a
Emergency Preferred* Avoid (Reason)
Hypertensive Labetalol Methyldopa (sedation)
encephalopathy Nicardipine Diazoxide (fall in cerebral blood flow)
Nitroprusside Reserpine (sedation)
Trimethaphan
Accelerated-malignant Labetalol
hypertension Enalaprilat
Nicardipine
Nitroprusside
Stroke or head injury Labetalol Methyldopa (sedation)
Trimethaphan Reserpine (sedation)
Nitroprusside Hydralazine (increase cerebral blood flow)
Esmolol Diazoxide (decrease cerebral blood flow)
Left ventricular failure Enalaprilat Labetalol, esmolol, and other beta blockers
(decrease cardiac output) hh
 Preferred Parenteral Drugs for Specific
Hypertensive Emergencies (In Order of Preference)b
Emergency Preferred* Avoid (Reason)

Coronary insufficiency
Nitroglycerin Hydralazine (increase cardiac work)
Nitroprusside Diazoxide (increase cardiac work)
Labetalol
Nicardipine
Dissecting aortic Trimethaphan Hydralazine (increase cardiac output)
aneurysm Nitroprusside Diazoxide (increase cardiac output)
Esmolol
Catecholamine excess Phentolamine All others (less specific)
Labetalol
Postoperative Labetalol Trimethaphan (bowel & bladder atony)
Nitroglycerin
Nicardipine
Hydralazine hhhhh
 Management of Hypertensive Emergencies
ONSET/DURATION OF
AGENT DOSE ACTION (AFTER PRECAUTIONS
DISCONTINUATION)

Parenteral vasodilators 0.25-10 g.kg-1.min-1 as Immediate/2-3 min Nausea, vomiting, muscle twitching:
Sodium nitroprusside IV infusion; maximal after infusion with prolonged use may cause
dose for 10 min only thiocyanate intoxication, methe-
moglobinemia acidosis, cyanide
poisoning; bags, bottles, and
delivery sets must be light
resistant.
Glyceryl trinitrate 5-100 g as IV infusion 2-5 min/5-10 min Headache, tachycardia, vomiting,
flushing, methemoglobinemia;
requires special delivery system
due to drug binding to PVC tubing
Nicardipine 5-15 mg/h IV infusion 1-5 min/15-30 min, but Tachycardia, nausea, vomiting,
may exceed 12 h headache, increased intracranial
after prolonged pressure. Hypotension may be
infusion protracted after prolonged infusions.
 Management of Hypertensive Emergencies
ONSET/DURATION OF
AGENT DOSE ACTION (AFTER PRECAUTIONS
DISCONTINUATION)

Verapamil 5-10 mg IV; can follow 1-5 min/30-60 min Heart block (10, 20, 30), especially with
with infusion of concomitant digitalis or -blockers,
3-25 mg/h bradycardia
Diazoxide 50-150 mg as IV bolus, 2-5 min/3-12h Hypotension, tachycardia, aggravation
repeated or 15-30 or angina pectoris, nausea and
mg/min by IV infusion vomiting, hyperglycemia with
repeated injection
Fenoldopam mesylate 0.1-0.3 mg.kg-1.min-1 IV <5 min/30 min Headache, tachycardia, flushing, local
infusion phlebitis
Hydralazine 10-20 mg as IV bolus or 10 min IV/1 hr (IV) Tachycardia, headache, vomiting,
10-40 mg IM, repeat 20-30 min IM/4-6 h aggravation of angina pectoris
every 4-6 h (IM)
Enalaprilat 0.625-1.25 mg every 6 h 15-60 min/12-24 h Renal failure in patients with bilateral
IV renal artery stenosis, hypotension
 Management of Hypertensive Emergencies
ONSET/DURATION OF
AGENT DOSE ACTION (AFTER PRECAUTIONS
DISCONTINUATION)

Parenteral adrenergic inhibitors

Labetalol 20-80 mg as IV bolus 5-10 min/2-6 h Bronchoconstricion, heart block,
10 min; up to 2 mg/min orthostatic hypotension
as IV infusion
Esmolol 500 g/kg bolus injection 1-5 min/15-30 min First-degree heart block, congestive
IV or 25-100 g.kg-1. Heart failure, asthma
min-1 by infusion. May
repeat bolus after 5 min
or increase infusion rate
to 300 g.kg-1.min-1
Methyldopa 250-500 mg as IV 30-60 min/4-6 h Drowsiness
infusion every 6 h
Phentolamine 5-15 mg as IV bolus 1-2 min/10-30 min Tachycardia, orthostatic hypotension
 Management of Hypertensive Urgencies :
Oral Agents
ONSET/DURATION OF
AGENT DOSE ACTION (AFTER PRECAUTIONS
DISCONTINUATION)

Captopril 25mg PO, repeat as 15-30 min/6-8 h SL Hypotension, renal failure in

needed SL, 25 mg 15-30 min/2-6 h bilateral renal artery stenosis

Clonidine 0.1-0.2 mg PO, repeat 30-60 min/8-16 h Hypotention, drowsiness, dry

hourly as required to mouth
total dose of 0.6 mg

Labetalol 200-400 mg PO, repeat 30 min-2 hrs/2-12 h Bronchocontriction, heart block,

every 2-3 h orthostatic hypotension

Prazosin 1-2 mg PO; repeat 1-2 hr/8-12 h Syncope (1st dose), palpitations,
hourly, as needed tachycardia, orthostatic
hypotension
 Bolus I.v.
0.2 mg/kg
10% MBP reduction
10’
From Baseline
Drip infusion
50 mg/hour
20% MBP reduction
20’ From Baseline
Drip infusion
30 mg/hour
Target MBP
30’ Level
Drip infusion
5-10 mg/hour
Every 30-60 minutes observation

Switch to Oral
DILTIAZEM CD 200
DILTIAZEM INTRAVENOUS
The role in Renoprotection:
•Maintenance Renal Blood Flow
•Maintenance Glomerular Filtration Rate
•Normalized Intraglomerular Pressure
•Inhibit Proteinuria
•Inhibit cyclosporine nephrotoxicity
The role in Cardioprotection:
•Maintenance Cardiac Index
•Increase Coronary Blood Flow
•Inhibit Coronary spasm
•Without Reflex Tachycardia
•Has Antiarrhythmic Effect
The role in Cerebroprotection:
•Maintenance Cerebral Blood Flow
•Normalized Intracranial Pressure
•Inhibit Vasospasm
Epstein M. 1991 Wagner K., et al.; Amer J Nephrol 1987; Fasol R, et al.Drug of Today 1998;
Hirayama T., et al; Neurol Res 1994;Kuroda K.; et al; Neurol Res 1997;
 DILTIAZEM-Injection
Dosage and Administration

Each ampoule of DILTIAZEM-Injection should be dissolve in at

least 5 mL aquadest or NaCl or glucose solution before use.

BOLUS I.V. INJECTION

0.20 – 0.35 mg/kg BW
Adult (50kg) : 1 Ampoule (1 – 3 minutes)

DRIP I.V. INFUSION (Flat)

5 – 15 mcg/kg BW/min
Adult (50kg) : 15mg/hour – 45 mg/hour

DRIP I.V. INFUSION (maintenance)

1 – 5 mcg/kg BW/min
Adult (50kg) : 5mg/hour – 15 mg/hour
CONSENTRATION DILTIAZEM Inj. 50 mg CONSENTRATION DILTIAZEM Inj. 100 mg
0,05 % INFUS Vol. 100 ml 0,1 % INFUS Vol. 100 ml
Dose Dose
g/kg/min 5 10 15 g/kg/min 5 10 15
Weight Weight
30 kg 18.0 36.0 54.0 30 kg 9.0 18.0 27.0
40 kg 24.0 48.0 72.0 40 kg 12.0 24.0 36.0
50 kg 30.0 60.0 90.0 50 kg 15.0 30.0 45.0
60 kg 36.0 72.0 108.0 60 kg 18.0 36.0 54.0
70 kg 42.0 84.0 126.0
70 kg 21.0 42.0 63.0
CONSENTRATION DILTIAZEM Inj. 150 mg
0,15 % INFUS Vol. 100 ml
Dose
g/kg/min 5 10 15
Weight
30 kg 6.0 12.0 18.0
40 kg 8.0 16.0 24.0
50 kg 10.0 20.0 30.0
60 kg 12.0 24.0 36.0
70 kg 14.0 28.0 42.0
 COMMONLY USED DRUG IN
HYPERTENSIVE EMERGENCY
DILTIAZEM I.V. (HERBESSER)
• Useful for hypertensive emergency and urgency.
• Acts as calcium slow-channel blockers.
• Dose-dependent :
• Predictable onset of action
• Rapidly reduced BP.
• No rebound on withdrawn
• Adverse effect : bradycardia, hypotension, headache,
flushing.
• Has antiischemic and antiarrhythmic effect (class-IV)