HYPERTENSIVE CRISIS

DEPARTEMEN ILMU PENYAKIT DALAM

FK--UI / RSCM
FK
 Case Scenarios

A 56 yo CM with no significant PMH presents to the ER

with
ith headache,found
h d h f d to
t have
h BP 210/110mmHg
210/110 H and d
papilledema.
An 82 yo male with h/o HTN
HTN,chronic
chronic renal insufficiency
presents for a routine physical,found to have BP of
230/130mmHg.
A 76 yo female is brought to the ER by the family due to
altered mental status.BP is 240/110 mmHg with no focal
neuro findings
findings.
 Hypertension Prevalence (%) in Indonesia
1995 s/d 2007
35 31.6 32 31.3 31.9
30
25
20 17.4
Estimated 1 % of hypertension Males
14.7patient developed hypertensive emergency
15 Females
(Papadopoulos, Blood pressure 2010)
10 9.1
74
7.4
5
0
1995 2001 2004 2007

Source: SKRT, Surkesnas , Riskesdas

Note: 1995 and 2001: mercury blood pressure
2004 and 2007: digital blood pressure
 EPIDEMIOLOGY

In the US: More than 60 million Americans, about 25-

25-30% of the
population, have hypertension. Of these individuals, 70% have mild
disease, 20% moderate, and 10% severe hypertension (diastolic BP [DBP]
>110 mm Hg). Approximately 1- 1-2% develop a hypertensive emergency with
end--organ damage.
end
Mortality/Morbidity: Morbidity and mortality depend on the extent of end-
end-
organ damage on presentation and the degree to which BP is controlled
subsequently. BP control may prevent progression to end-end-organ
impairment. I yr mortality in untreated pts. >90%.5 yr survival of all
presentations is 74%
74%.
Race: African Americans have a higher incidence of hypertensive
emergencies than Caucasians.
Sex: Males are at greater risk of hypertensive emergencies than females.
females
Age:Most commonly in middle
middle--aged people.Peak age:40-
age:40-50yrs.
 Epidemiology

Hypertensive crises represented more than one fourth of all

medical urgencies/emergencies.
g g
76% urgencies
24% emergencies
Hypertensive urgencies frequently present with:
Headache (22%)
Epistaxis (17%)
Faintness and psychomotor
y agitation
g ((10%))
Types of end-
end-organ damage associated with hypertensive
emergencies include:
Cerebral infarction (24%)
Acute pulmonary edema (23%)
Hypertensive encephalopathy (16%)
Cerebral hemorrhage (4.5%)

Blood Pressure, 2010; 19:328-336

 DEFINITION (JNC VII)

Hypertensive Emergency:
With evidence impending
or progressive target
Hypertensive Crisis: organ dysfunction
Severe of BP
>180/120 mmHg
Hypertensive Urgency:
With t iinvolvement
Without l t
target organ dysfunction
 DEFINITIONS

Systolic blood pressure >180 and diastolic >120mmHg.

Patients with hypertension can be classified into categories based upon their
symptoms and the organ systems that are affected at the time of presentation:
-HYPERTENSIVE EMERGENCY:
EMERGENCY: is severe hypertension with acute impairment of an
organ system (e.g., central nervous system [CNS], cardiovascular, renal). In these
conditions,
diti the
th blood
bl d pressure (BP) should
h ld be
b lowered
l d aggressively
i l over minutes
i t
to hours.
hours.
Presence of papilledema indicates MALIGNANT HYPERTENSION.
-HYPERTENSIVE URGENCY:
URGENCY: the BP is a potential risk but has not yet caused acute
end--organ damage. These patients require BP control over hours to days.
end
-ACCELERATED HYPERTENSION: recent significant increase over baseline blood
pressure. Examination usually
p y showed vascular damage
g on fundoscopicp
examination, such as flame-
flame-shaped hemorrhages or soft exudates, but without
papilledema..
papilledema
HYPERTENSIVE ENCEPHALOPATHY: sudden, marked elevation of BP with severe
headache and altered mental status,
status reversible by reduction of BP.
BP
 Hypertensive Crises

Hypertensive Urgency Hypertensive Emergency

Markedly elevated BP Markedly elevated BP

Without severe symptoms or With acute or progressing
progressive target organ damage target organ damage
BP should
h ld bbe reduced
d d within
ithi hours
h BP should
h ld beb reduced
d d immediate
i di t
Oral agents Parenteral agents

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 10th Ed, 2010

Precipitating factors in hypertensive crisis

1. Accelerated sudden rise in blood pressure in patient

with preexisting essential hypertension
2. Renovascular hypertension
3. Glomerulonephritis-acute
4. Eclampsia
5. Pheochromocytoma
6. Antihypertensive withdrawl syndromes
7. Head injuries
j
8. Renin secreting tumors
9 Ingestion of cathecolamine precursor in patients
9.
taking MAO inhibitors
 Pathophysiology
Critical Degree
g of Hypertension
yp

Local effect Systemic effect

Prostaglandin,
g , RAAS,, Catechol,,
freeradical, etc Vasopressin

Endothelial Damage Pressure Natriuresis

Platelet deposition
Hypovolemia

Mitogenic & migration factors

Further increase in vasopressor
Myointimal proliferation

Further rise in BP & Vascular damage

Tissue Ischemia
Kaplans Clinical Hypertension, 2010
CLINICAL MANIFESTATION
The Symptoms
Chest pain (27%)
Dyspnea (22%)
Neurological deficit (21%)
Organ Involvement
One organ (83%)
( )
Two organ ( 14%)
Three or more ( 3%)
(Zampaglione, 1996)
 Main Forms Of Presentation Of Hypertensive
Emergencies in the Emergency Department
Hypertensive Emergencies Symptoms

Hypertensive encephalopathy
h l h Headache,
d h visuall disturbance,
d b
vommiting, altered level of
consciousness

Severe Hypertension with Neurological deficit, altered

stroke/cerebral
k / b lh hemorrhage
h l
level
l off consciousness
i

Hypertensive left ventricular Cough, dyspnea,

Cough dyspnea orthopnea,
orthopnea
failure rapidly progressive dyspnea

Acceleratedmalignant Visual changes, headache,

hypertension renal failure, oligouria,
(Angelats, 2010)
hematuria
 Main Forms Of Presentation Of Hypertensive
Emergencies
g in the Emergency
g y Department.(2)
p ( )
Hypertensive Emergencies Symptoms

Hypertension and
d aortic Chest
h pain and/or
d intense
dissection abdominal pain, vegetatism,
signs
g of ppoor p
perfusion

Hypertension with acute Chest pain

coronary syndrome
d

Use of drugs : amphetamines,

amphetamines Tachycardia, sweating,
Tachycardia sweating altered
LSD, cocaine, xtc mood and/or level of
consciousness

Severe preeclampsia or Oligouria, microangiopathic

(Angelats, 2010)
eclampsia anemia
 JNC VII
Treatment Recommendations
Admit to ICU for continuous BP monitoring and
parenteral administration of appropriate agent.
Initial goal: arterial BP by no more than 25% within
min to 1 hr (aortic dissection 10 min)
min) or DBP to 110
mmHg over 1 hr.
Then, if stable, to 160/100-
160/100-110 mmHg within
next 2-
2-6 hr.
z Excessive BP reduction precipitating renal, cerebral,
or coronary ischemia should be avoided.
z Gradual further reduction over next 24-
24-48 hr
z Exception: ischemic stroke.
Oral agents may be used for HTN urgency
Cobanian AV et al. Hypertension.2003;42:1206
 Sublingual Drugs for Treatment of
H
Hypertensive
i EEmergenciesi
Captopril
z 25 mg SL reduced BP starting at 15 min -
120 min success rate 83%
Nifedipine
z 10 mg SL reduced BP starting at 10 120
min success rate 90%

Wu SG et al. Nephron. 1993;65:284

Haude M et el. Clin Cardiol.1991;14:463
 Management Principles:
H
Hypertensive
i Urgency
U
No need for hospital admission.
Slow and controlled reduction in BP
Treated with oral agents
Close follow
follow--up as out patients

Marik PE.Varon J. Chest.2007;131:1949

 MANAGEMENT
Reduce Mean Arterial
Pressure 20 - 25% within 1st
hour

patients is stable, to Special situation :

160/100-110 mmHg Aortic dissection(or impending)
over
needsd rapid
id off SBP within
ithi
2 6 hours 20 minutes to <120 mmHg

no evidence of target
organ damage
damage, over
24 48 hours
(Rodriguez, 2010)
 The management of BP during an
acute stroke
There still are no large clinical studies on
which to base definitive recommendations
Remains
i controversial.
t i l

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

 The management of BP during an
acute stroke
BP is often elevated in the immediate
poststroke period and is thought by some to be
a compensatory physiological response to
improve cerebral perfusion to ischemic brain
tissue.
tissue
As a result, it has been common practice after
acute cerebral infarction to reduce or withhold
BP treatment until the clinical condition has
stabilized.
stabilized
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70
 Hypertensive Encephalopaty

C
Cerebral
b l bl
blood
d flflow autoregulated
l d within
i hi specific
ifi limits
li i
Normotensive individuals cerebral blood flow between MAP
60 mm Hg and 120 mm Hg.
At MAP 180 mm Hg autoregulation fails and overwhelmed
cerebral vasodilation and cerebral oedema develops HT
Encephalopaty
Chronic hypertension developed adaptive mechanism
maintenance of cerebral blood flow requires higher MAP 100
mm Hg to 200 mm Hg.
 Protective Physiological
St k /C b
Stroke/Cerebrovascular
l E Events
t
Response

BP Reduction Worsen
clinical condition

Cerebral
Neurological signs Dysfunction Severe Elevation of BP

BP Reduction improves
clinical condition

Cerebral
Hypertensive Encephalopaty autoregulation failure
 American Stroke Association guidelines
Inpatients with recent ischemic stroke whose
SBP is > 220 mm Hg or DBP 120 to 140 mm
Hg, cautious reduction of BP by about 10%
to15%
to15% is suggested, while carefully
monitoring the patient for neurological
deterioration related to the lower pressure.

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

 American Stroke Association guidelines
In patients with recent ischemic stroke whose
SBP is > 220 mm Hg or DBP 120 to 140 mm
Hg, cautious reduction of BP by about 10%
to15%
to15 % is suggested, while carefully
monitoring the patient for neurological
deterioration related to the lower pressure.
If the DBP is 140 mm Hg, g carefully
y monitored
infusion of sodium nitroprusside should be
used to reduce the BP by y 10 to
to15%.
15%.

Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70

 Parenteral Drugs for Treatment of
Hypertensive Emergencies based on JNC 7
Drugs Dose Onset Duration of
Action
Sodium 0.25--10 ugr/kg/min
0.25 Immediate 1-2 minutes after
nitroprusside infusion stopped
Nitroglycerin 5-500 ug/min 1-3 minutes 5-10 minutes

Labetolol HCl 20
20--80 mg every 10
10--15 min 5-10 minutes 3-6 minutes
or 0.5-
0.5-2 mg/min
Fenoldopan HCl 0.1-
0.1-0.3 ug/kg/min <5 minutes 30
30--60 minutes

Nicardipine HCl 5-15 mg/h 5-10 minutes 15-

15-90 minutes

Esmolol HCl 250

250--500 ug/kg/min IV 1-2 minutes 10
10--30 minutes
bolus, then 50-
50-100
ug/kg/min by infusion;
may repeat bolus after 5
minutes or increase
infusion to 300 ug/min
Chobanian AV et al, The JNC 7 report, JAMA 2003;389-2560-70
 Parenteral Drugs for Treatment of
Hypertensive
yp Emergencies
g based on
ASA Guideline

Drug I.V. Bolus Dose Continous Infus Rate

Labetalol 5 20 mg every 15 2 mg/min (max 300mg/d)
Nicardipine NA 5-15 mg/h
Esmolol 250 ug/kg IVP loading dose 25 300 ug/kg/m
25-300
Enalapril 1,25-5 mg IVP every 6 h NA
Hydralazine 5 20 mg IVP every 30 1,5-5 ug/kg/m
Nipride NA 0 1 10 ug/kg/m
0,1-10
NTG NA 20-400 ug/m

This parenteral drugs are approved for hypertensive emergency

in acute ischemic stroke and intracerebral hemmorhage

AHA/ASA Guideline, 2007 update. Stroke. 2007;38: 2001-2023.

 Parenteral Drugs for Treatment of
Hypertensive Emergencies based on CHEST 2007
Acute Pulmonary edema / Nicardipine, fenoldopam, or nitropruside combined with
Systolic dysfunction nitrogliceryn and loop diuretic
Acute Pulmonary edema/ Esmolol, metoprolol,
Esmolol metoprolol labetalol,
labetalol verapamil,
verapamil combined with
Diastolic dysfunction low dose of nitrogliceryn and loop diuretics
Acute Ischemia Coroner Labetalol or esmolol combined with diuretics
Hypertensive encephalopaty Nicardipine labetalol,
Nicardipine, labetalol fenoldopam
Acute Aorta Dissection Labetalol or combined Nicardipine and esmolol or combine
nitropruside with esmolol or IV metoprolol
Preeclampsia, eclampsia Labetalol or nicardipine
Acute Renal failure / Nicardipine or fenoldopam
microangiopathic anemia
Sympathetic
y crises/ cocaine Verapamil, diltiazem, or nicardipine combined with
oveerdose benzodiazepin
Acute postoperative Esmolol, Nicardipine, Labetalol
hypertension
Acute
A t ischemic
i h i stroke/
t k / Ni di i
Nicardipine, l b t l l fenoldopam
labetalol, f ld
intracerebral bleeding
Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62
 Recommended treatment of hypertensive emergencies according
to end organ involved

Time line and target Ist line therapy Alternative therapy Recommended
BP unit
Hypertensive crisis with Several hours, MAP - Labetalol Nitroprusside Medium care/ICU /
retinopathy, micro 20 to 25% Nicardipine Urapidil CCU
angiopathy or acute
renal insufficiency

Hypertensive Immediate, MAP 20 Labetalol Nicardipine ICU/ Medium care/

encephalopathy to -25% Nitroprusside Stroke unit

Acute aortic dissection Immediate, systolic Nitroprusside and Labetalol ICU

BP < 110 mmHg esmolol

Acute pulmonary Immediate, MAP 60 to Nitroprusside ( with Nitroglycerine Urapidil CCU / ICU
oedema 100 mmHgg loop
p diuretic ) ( with loop
p diuretic )

Myocardial ischaemia / Immediate, MAP 60 to Nitroglycerine Labetalol CCU

infarction 100 mmHg

Acute ischaemic stroke I hour, MAP 15% Labetalol Nicardipine Stroke unit / ICU
and BP > 220 / 120 Nitroprusside
mmHg*

Cerebral haemorrhage I hour, systolic BP < Labetalol Nicardipine Stroke unit / ICU
and BP > 180 systolic or 180 mmHg and MAP < Nitroprusside
MAP > 130 mmHg 130 mmHg

The Netherland Journal of Medicine; may 2011, vol. 69, no 5

 Recommended treatment of hypertensive emergencies according
to end organ involved
Time line and Ist line therapy Alternative Recommended
target BP therapy unit

Acute ischaemic stroke with I hour, MAP 15% Labetalol Nicardipine Stroke unit / ICU
indication for thrombolytic Nitroprusside
therapy and BP > 185 / 110
mmHg

Cocaine / XTC intoxication Several hours Phentolamine ( next Nitroprusside Medium care / ICU
to benzodiazepines)

Adrenergic crisis associated with Immediate Phentolamine Nitroprusside Medium care / ICU
pheochromocytoma or autonomic Urapidil
hyperreactivity

Peri and postoperative Immediate Nicardipine Urapidil or Recovery or ICU

hypertension during or after Nitroglycerine
coronary bypass graft

During or after craniotomy Immediate Nicardipine Labetalol Recovery or ICU

Severe pre eclampsia / Immediate, BP < Labetalol (next to Ketanserin Medium care / ICU
eclampsia 160 / 105 mmHg magnesium sulphate Nicardipine
and oral
antihypertensive
therapy)

The Netherland Journal of Medicine; may 2011, vol. 69, no 5

 Overview of intravenous drugs for the treatment of
hypertensive emergencies
Drug Onset of Half life Dose Contraindications and
action adverse effects
Esmolol 1 2 min 10 - 30 min 0.5 I mg/kg as bolus; 50 -300 2nd or 3rd degree AV block,
g/kg/min as continuous infusion systolic heart failure, COPD
((relative);
); bradycardia
y
Phentolamine 1 2 min 3 5 min 1 5 mg, repeat after 5 15 min, until Tachyarrhythmia, angina
goal BP is reached; 0.5 1.0 mg/h as pectoris
continuous infusion
Ketanserin 1 2 min 30 60 min 5 mg as bolus injection, repeat after 5 Prolonged QT interval, 2nd or
min
i (max
( 30 mg);) 2 6 mg/h /h as 3rdd d
degree AV bl k
block;
continuous infusion bradycardia, hypokalaemia
Labetalol 5 10 min 3 6 hr 0.25 0.5 mg/kg; 2- 4 mg/min until goal 2nd or 3rd degree AV block;
BP is reached, thereafter 5 20 mg/h systolic heart failure, COPD
(relative); bradycardia
Nicardipine 5 15 min 30 40 min 5 15 mg/h as continuous infusion, Liver failure
starting dose 5 mg/h, increase every 15
30 min with 2.5 mg until goal BP,
thereafter decrease to 3 mg/h
Nitroglycerine 1 5 min 3 5 min 5 200 g/min,
g/min 5 g/min increase every
5 min

Nitroprusside Immediate 1 2 min 0.3 10 g/kg/min, increase by 0.5 Liver/ kidney failure (relative);
g/kg/min every 5 min until goal BP cyanide intoxication
Urapidil 3 5 min 46h 12.5
12 5 25 mg as bolus injection; 5 40
mg/h as continuous infusion

The Netherland Journal of Medicine; may 2011, vol. 69, no 5

Diltiazem in Hypertensive
Emergency
Diltiazem injection Drip infusion:
5 40 g/kg/min
5~40 /k / i
Average BP reduced
224/119 mmHg to 170/95 mmHg
(mean change 27.3 9.0 %, P<0.001)

HR didnt change significantly

Subject: 11 patients with

hypertension emergency
Design: Open study

Current Therapeutic Research 42:1223,19

 Effect of a Drip Infusion Diltiazem on Severe
250 250
Systemic Hypertension
29
200
200 27
205 24 14 14
BP mmHg * 12 9 9
150
* * * * * * SBP 24.6%
(mmHg) 150
154
* * mmHg
* * * * * mean
100
100 115.8
mmHg
* * DBP 26.9%
* * * * * 83 3
83.3
50
50
mmHg

Pulse Rate * *
75
87.1 * * * * * 8.9%
beats/min 78.1

50 15

10 10
* P0.05
P0 05 vs
Dose
infused pretreatment level
5 5

g/kg/min
0
0 0.5 1 2 3 4 5 6

0 05
0.5 1 2 3 4 5 6
Subjects: 29 severe systemic hypertension
Dosage : diltiazem initial dose less 10 g/kg/min, average infusion rate was 11 g/kg/min
Curr Ther Res 43, 1988
PROGNOSIS
5 years survival expectancy of the renal function after hypertensive
emergency 84 %, 10 years 72%

Before the discovery of effective therapy and guidelines maximum

life expectancy < 2 years.

Present times development of effective medication and procedures

including
g dialysis,
y , 1 yyear survival rate >90%,
9 , 5 years
y >80%

C
Cause off deathCardiovascular,
d thC di l Stroke,
St k and
d Renal
R l Failure
F il
 So,.
A 56 yo CM with no significant PMH presents to the
ER with headache,found to have BP 210/110mmHg
and papilledema. - MALIGNANT HYPERTENSION,
HYPERTENSIVE EMERGENCY

An 82 yo male with h/o HTN

HTN,chronic
chronic renal
insufficiency presents for a routine physical,found to
have BP of 230/130mmHg.- ACCELERATED HYPERTENSION,
HYPERTENSIVE
S URGENCY
U G C

76 yo female is brought to the ER by the family due

to altered mental status.BP is 240/110 mmHg with no
f
focall neuro findings.
fi di HYPERTENSIVE ENCEPHALOPATY,
HYPERTENSIVE EMERGENCY