Management of

hypertensive crisis
Atma Gunawan
Consultant of nephrology &
hypertension

Definition
HYPERTENSIVE CRISIS
- DBP >120 mmHg with the potential of inflicting irreparable damage to target
organ and endangering patients lives.
- JNC VII 2003 : 180/110
- Recognition of hypertensive crisis depends on the clinical state of the patients,
not on the absolute level of blood pressure
Form : HYPERTENSIVE EMERGENCY and HYPERTENSIVE URGENCY
Malignant hypertension : a syndrome characterized by elevated BP accompanied by
retinal hemorrhages, exudates, or papilledema or acute nephropathy.
Accelerated hypertension : malignant HT with hemorrhages and exudates alone
Hypertensive encephalopathy refers to the presence of signs of cerebral edema

JNC V (1993), JNC VII 2003. CHEST 2007; 131:19491962)Paul E. Marik, MD

Classification of
hypertensive crisis
Hypertensive Urgency
Diastolic BP>120 mmHg, systolic BP>220
Mild or no acute end-organ damage
No clinical symptoms
Hypertensive Emergency
Usually diastolic BP>120 mmHg, systolic
BP>220 mmHg
Acute end organ damage
Clinical symptoms is evident
Pregnant : 170/110 mmHg
Post-operative : >190/100 mmHg
(1997) Report of the Canadian Hypertension Society Consensus Conference: 3.
Pharmacologic treatment of hypertensive disorders in pregnancy. Can Med
Assoc J 157,1245-1254

Mechanisms of vascular
injury
Autoregulation failure
Vascular endothelial
injury
Tissue edema
Fibrinoid necrosis
Activation of
endothelial vasoactive
systems: endothelin,
oxidative stress, RAS

Causes of resistance to
therapy in hypertension
Inappropriate antihypertensive
regimen
Exogenous drugs/agent that raise BP
Non-adherence
Secondary causes

Drugs that can increase BP

Withdrawl of antihypertensive
medications:
clonidine rebound
(methyldopa,reserpine), nifedipine,
propanolol
Phenylpropanolamine (cold preparations)
Sympathomimetics amines
Oral contraceptive, erythtropoieten
Corticosteroids, anabolic steroids
NSAIDS, Cox2 inhibitors
Cocaine, amphetamine, ethanol
NaCl

Prevalence of Hypertensive Crisis

Hypertensive crisis
( % of all pts )
Mainly due to more effective treatment ?

4
3
2
1
1950s

1990s
Zampaglione, et al. AHA ; 27 (1) : 144

Retinal findings in hypertensive

encephalopathy

Evaluation
Initial evaluation for patients with HTN emergency
Hystory
Prior diagnosis & treatment of HTN
Intake of pressor agents; street drugs, sympathomimetics
Symptoms of cerebral, cardiac,pulmonal, and visual dysfunction
Physical examination
Blood pressure
Funduscopy
Neurologic status
Cardiopulmonary status
Blood fluid volume assessment
Peripheral pulses
Laboratory evaluation
Hematocrit and blood smear
Urine analysis
Automated chemistry : creatinin, glucose, electrolytes
ECG
Plasma renin activity & aldosterone (if primary aldosteronism is suspected)
Plasma renin activity before & 1 h after 25 mg captopril (if renovascular HTN is
suspected)
Spot urine or plasma for metanephrine (if pheochromocytoma is suspected)
Chest radiograph (if heart failure or aortic dissection is suspected)

SIMPLE APPROACH TO HYPERTENSIVE

CRISIS
BP > 220/120 mmHg
Neurological sign
(encephalopathy or stroke)
Retinopathy grade 3-4
Severe chest pain
(Ischemia or dissecting
aneurism)
Pulmonary edema
Eclampsia
Cathecolamine excess
Acute renal failure
EMERGENCY
Intravenous therapy

Headache
No neurological signs
No target organ damage
URGENCY
Identify the cause
In panic attacks or anxiety
use analgesic, anxiolytics
Otherwise use oral
antihypertensive agents
recheck in 6-24 hours

Therapy Approach
in Hypertensive Crises
As there have been no large clinical trials
investigating the optimum therapy, treatment is
dictated by consensus on the basis of casecontrolled studies and expert opinion

Principles of Therapy for

Hypertensive Emergencies
Patients must be hospitalized for monitoring
Dire consequences of lowering BP too quickly
Treated with parenteral
Lower MAP {1/3(SBP-DBP)+DBP} by no more
than 25% within minute to 2 hours or diastolic
110 mmHg, then 160/100 mmHg within 2-6
hours (JNC VII). Exception for ischemic stroke
IV infusion is prefer than bolus
Avoid the urge to turn to sublingual nifedipine

Hypertension,Brian C. Poole and Anitha Vijayan in Nephrology and

Subspeciality Consult,Lippincott Williams and Wilkins,2004

Intravenous Agents for Hypertensive

Emergencies
Agent

Onset

Duration

Advantage

Disadvatage

Diltiazem

5-10 min

2-4 hrs

CNSprotection,
coronary & renal
perfusion

Bradycardia
hypotension

Nitroglycerine

2-5 min

3-5 min

Coronary
perfusion

Tolerance, variable
efficacy

Fenoldopan

< 5 min

5-10 min

Renal perfusion

Increase IOP

Hydralazine

10-20 min

3-9 hrs

Eclampsia

Tachycardia,
headache,ICP

Nicardipine

5-15 min

1-4 hrs

CNS protection

Avoid in CHF or
cardiac ischemia or
ICP

Enalaprilat

15-30 min

6 hrs

CHF, acute LV
failure

Avoid in MI

Nitroprusside

Immediate

< 3 min

Potent, titratable

Cyanide,
thiocyanate,>ICP

Preferred Drugs for Selected Hypertensive

Emergencies
Emergency

Preferred Drugs

Drugs to Avoid

CVA

Diltiazem

Diazoxide,hydralazine (increase
ICP), nitropruside

Labetalol
Nicardipine
Hypertensive Encephalopathy

Diltiazem
Nicardipine

Diazoxide,hydralazine (increase
ICP)

Labetalol
Congestive Heart Failure

Nitroprusside
Nitroglycerine
Loop Diuretics
Nitroprusside

Labetalol and Esmolol

(decreased HR),
nicardipine,diltiazem

Enalaprilate
Myocardial infarct, Angina

Diltiazem
Nitroprusside

Diazoxide,hydralazine (increase
HR,O2 demand

Nitroglyceri
Aortic Dissection

Nicardipinene
Nitroprusside
Labetalol

Diazoxide,hydralazine,
nicardipine

Esmolol
Hypertensive emergencies,Roy Colven,in Emergency Medical Therapy,2000. WB saunders Company

Diltiazem inj
1 amp 50 mg. dosis 5-15 ug/kgbb/min
2 amp=100 mg/100 cc NS
100.000 ug/100 cc NS
1000 ug= 1 cc
Misal BB 60 kg, dosis 5 ug/kgbb/min
5x60/1000 x 1cc = 0,3 cc/min=6 tts/min
makro
=18 tts/min
mikro

PANDUAN DOSIS & PENGGUNAAN

NICARDIPINE INJEKSI

INDIKASI
1. HIPERTENSI EMERGENSI
Dosis

: 0.5 6 Mcg/Kg BB/menit (syeringe pump / infus drip)

2. Krisis hipertensi akut selama tindakan operesi

Dosis

: 2 10 Mcg/Kg BB/menit (syeringe pump / infus drip)

10 30 Mcg/Kg BB/menit ( bolus I.V. )

SYRINGE PUMP
KRISIS HIPERTENSI AKUT SELAMA OPERASI

INDIKASI

HIPERTENSI EMERGENSI

Nicardipine
injeksi
1 ampul 10 mg
Spuit 50 cc
(mL/jam)

BERAT
BADAN

0.5

1.0

1.5

2.0

3.0

4.0

5.0

6.0

7.0

8.0

9.0

10.0

40 kg

12

18

24

36

48

60

72

84

96

108

120

Atau

50 kg

15

23

30

45

60

75

90

105

120

135

150

60 kg

18

27

36

54

72

90

108

126

144

162

180

70 kg

11

21

32

42

63

84

105

126

147

168

189

210

80 kg

12

24

36

48

72

96

120

144

168

192

216

240

90 kg

14

27

41

54

81

108

135

162

189

216

243

270

Pediatric Drip
(=1 cc = 60
tetes)

DOSIS NICARDIPINE INJEKSI (mcg/kg BB/menit)

Pelarut / cairan infus yang dapat digunakan a.l :

Sodium Chlorida / NaCl, Dextrose 5%, Potacol-R, Glucose 5%, Ringer Asetat, KN Solution 1A, KN Solution 1B,
kecuali Sodium bicarbonat & Ringer Laktat

Nicardipine inj
1 amp 10cc=25 mg. Dosis 0,5-6 ug/kgbb/min
25 mg/50 cc NC
25.000 ug/50 cc
500 ug/1 cc
Misal BB 60 kg dgn dosis 0,5 ug/kgbb/min
0,5x60/500 x 1cc=0,06 cc/min=0,06 x 60=3,6
cc/jam

Nitroglycerine inj
10 mg/10cc. Dosis 5-100 ug/min
10 mg/50 cc NS
10.000 ug=50 cc NS
200 ug=1 cc
Bila butuh dosis 10 ug/min :
10/200 x 1cc= 0,05 cc/min
=0,05 x 60= 3 cc/jam

BAGAN DOSIS NITROGLYCERINE

Dosis :10-200 ug/menit

DIENCERKAN

KONSENTRASI

KECEPATAN INFUS

KONSENTRASI

5 x amp 10 ml
nitroglycerine dalam 500
ml

mll/jam
drop/menit

10

10

0,6

20

12

20

1,2

30

18

30

1,8

40

24

40

2,4

50

30

50

3,0

60

36

60

3,6

70

42

70

4,2

80

48

80

4,8

90

54

90

5,4

100

60

100

6,0

110

66

110

6,6

120

72

120

7,2

130

78

130

7,8

140

84

140

8,4

150

90

150

9,0

100 g/ml: 5 x amp 10 ml

nitroglycerine dalam 50 ml

KECEPATAN INFUS
ml/jam
drop/menit

Management of HTN
Urgencies
No proven benefit of rapid BP reduction in
asymptomatic patients
Goal BP 160/110 mmHg or fall less than
25% MAP within 6 -48 hours
Oral medications preferred,shortacting
given in repeated doses
Close monitoring for overshoot hypotension
Thereafter, a longer acting agent is
prescribed
Hypertensive emergencies: Malignant hypertension and hypertensive encephalopathy .UpToDate.
Norman M Kaplan, MD. Last literature review version 16.3: September 2008

Management of HTN
Urgencies
Previously treated hypertension :
Increase the dose of existing
antihypertensive medications, or add
diuretic or another agent.
Reinstitution of medications in nonadherent patients
Reinforcement of dietary sodium
restriction

Management of HTN
Urgencies
Untreated hypertension
Relatively rapid initial blood pressure
reduction (over several hours):
- oral clonidine (0.30 mg)
- oral captopril (6.25 or 12.5 mg).
- furosemide 20 mg(if the patient is not
volume
depleted)

Management of HTN
Urgencies
Blood pressure reduction over one to two
days
oral nifedipine 30 mg once or twice daily
(of the long-acting preparation)
oral metoprolol 50 mg twice daily
or enalapril 5 mg twice daily

Clonidine:8-12 hrs,captopril : 4-6 hrs, labetalol: 4-8 hrs

Blood pressure
management in Acute
Ischemic Stroke

Blood pressure management in Acute Ischemic

Stroke
No specific data defining the levels of hypertension that
should trigger treatment in these settings.
By consensus, recommended that acute treatment be
withheld in patients with SBP is >220 mm Hg or the DBP is
>120 mm Hg
Exceptions to the recommendation to avoid treatment of
acute hypertension noted in the American Stroke Association
scientific statement include patients with hypertensive
encephalopathy, aortic dissection, acute renal failure,
acute pulmonary edema, acute myocardial infarction, or
severe hypertension
Hypertension. January 12, 2004;43:137.)

Blood pressure management

in Acute Ischemic Stroke
Most neurologists prefer that blood
pressure not drop below 160 mmHg/110
mmHg soon after stroke.
Thrombolytic therapy is not given to
patients who have a systolic blood pressure
>185 mm Hg or a diastolic blood pressure
>110 mm Hg at the time of treatment
Raised blood pressure usually falls
spontaneously within a few days. 10 days
after an ischaemic stroke two thirds of
patients are normotensive

Blood pressure
management in ICH

Cerebral Perfussion Pressure

CPP = MAP ICP
CPP
ICP
MAP

: Cerebral Perfusion Pressure

: Intracranial Pressure
: Mean arterial pressure

In normal nonhypertensive subjects, CBF is relatively constant

with CPPs : 60 to 120 mm Hg

Blood pressure management in ICH

In general:
Treatment of BP in patients with spontaneous ICH
more aggressive than ischemic stroke
Rationally theoretical
Lowering BP decrease the risk of ongoing bleeding
Over aggressive treatment of BP CPP
brain injury >> if ICP

Recommendation in patients with

history of chronic hypertension in
spontaneous ICH (for the first few hours) (AANS.
1995.Daniels F kelly)

1.

2.
3.
4.

if systolic BP is >180 mmHg, diastolic BP >105

mmHg, or MAP 130 mmHg on 2 readings 20
minutes apart, institute intravenous medications
(level of evidence V, grade C recommendation).
if systolic BP is < 180 mmHg and diastolic BP < 105
mmHg, defer antihypertensive therapy.
In patients with ICP who have an ICP monitor, CPP (MAP
ICP) should be kept > 70 mm Hg (level of evidence V, grade C
recommendation).
MAP > 110 mm Hg should be avoided in the
immediate postoperative period

Recommendation in patients without

history of chronic hypertension in
spontaneous ICH
Increased risk of hemorrhagic formation
when diastolic BP > 100 mmHg.
After ICH as a rule, systolic pressure of
approximately 140-160 mmHg and diastolic
pressure of 90-100 mmHg suffice for
adequate systemic, cerebral and coronary
perfusion

Mortality risk in relation to sex and B.P.

Systolic blood pressure
mmHg
Standard risk
woman
men

8797
98127
128-137
138-147
148-157
158-177
178-197
> 198

Diastolic blood pressure

woman
men

48-68
69-83
83-88
88-93
93-98
98-108
108-118
> 118
0
800

100

200

300

Mortality ratio in %

400

500

600

700

Drugs for hypertensive

urgencies

Captopril
Enalapril
Clonidine
Labetalol
Prazosine
nitroglycerine
minoxidil

Differentiate secondary from

essential HTN
Prepubertal children(<15 yo) generally have some form of
secondary HTN while adolescents and postpubertal children
usually have essential HTN
Severe HTN (stage 2 HTN) and resistant HTN, is usually
secondary HTN, while essential HTN is characterized by mild
or stage 1 HTN.
Essential HTN is associated with overweight and/or a positive
family history of HTN.
Symptoms or signs suggestive of an underlying disorder
indicate secondary HTN.
- symptoms of sympathetic overactivity (catecholamine
excess),
such as tachycardia and flushing, raise the possibility of
pheochromocytoma,
- while edema, elevations in serum creatinine, and/or an
abnormal
urinalysis are consistent with underlying renal disease

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

PEDOMAN DOSIS HERBESSER INJEKSI

Contoh : HERBESSER INJ. Konsentrasi 0,1 %
50 mg
--------50 ml

HERBESSER INJ
-------------------=
Pelarut

= 5 mcg/kg/menit ( A )
Contoh : Dosis HERBESSER
Berat badan pasien
= 50 kg ( B )
Konsentrasi HERBESSER = 0,1 % = 50 mg/50 ml ( C )

HERBESSER INJ.

AxB
C

Autoregulation of Cerebral Blood Flow

Lancet 2000; 356: 41117

Dosis diltiazem-injeksi pada Hipertensi Krisis

Konsentrasi diltiazem-injeksi 0.1% (1mg/ml/100 mg/100 cc)

Laju infus (ml/jam)
Dosis *

10

15

40

12

24

36

50

15

30

45

60

18

36

54

70

21

42

63

Berat

(ug/mnt)

Badan (kg)

Effect of a Drip Infusion Diltiazem on Severe

Systemic Hypertension
250
29
200
Blood
Pressure
mmHg

150

205
mmHg

27
*

24
*

*
100

115.8

mmHg

*
*

50
Pulse Rate
beats/min

14
*

12
*

9
*

9
24.6%
* SBP
154
mmHg
* mean
* DBP 26.9%
83.3
mmHg

*
75

14
*

87.1

8.9%

78.1
50
10
Dose infused
g/kg/min

* P0.05 vs
pretreatment level

5
0

0.5

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

Herbesser i.v. causes less increase

of intracranial pressure.
Comparison of intracranial pressure
change by different antihypertensives.

Comparison of Cerebral perfusion pressure

index (CPP index) by different antihypertensives.
p<0.05
p<0.05
2.0

1.800.11

17.0

1.630.13

14.2

10
6.7

Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.

CPP index

Change of intracranial pressure

mmHg
20

1.5

1.330.07

1.0

0.0

Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.

CPP index=CPP/SBP
CPP index coming close to 1 indicates less
increase of intracranial pressure.

Target
Medication
Methods

35 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhage
Herbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10
Compare the intracranial pressure when the same blood pressure reduction level is achieved in each group.
Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 1994