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; 131:1949–1962)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,
 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 ?

1950’s 1990’s

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 Headache

(encephalopathy or stroke) No neurological signs
Retinopathy grade 3-4 No target organ damage
Severe chest pain
(Ischemia or dissecting
URGENCY
aneurism)
Pulmonary edema
Eclampsia Identify the cause
Cathecolamine excess In panic attacks or anxiety
Acute renal failure use analgesic, anxiolytics
Otherwise use oral
antihypertensive agents
EMERGENCY recheck in 6-24 hours

Intravenous therapy
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 case-
controlled 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, Bradycardia
coronary & renal hypotension
perfusion
Nitroglycerine 2-5 min 3-5 min Coronary Tolerance, variable
perfusion efficacy

Fenoldopan < 5 min 5-10 min Renal perfusion Increase IOP

Hydralazine 10-20 min 3-9 hrs Eclampsia Tachycardia,

headache,ICP î
Nicardipine 5-15 min 1-4 hrs CNS protection Avoid in CHF or
cardiac ischemia or
ICPî
Enalaprilat 15-30 min 6 hrs CHF, acute LV Avoid in MI
failure
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

Labetalol ICP), nitropruside
Nicardipine

Hypertensive Encephalopathy Diltiazem Diazoxide,hydralazine (increase

Nicardipine ICP)
Labetalol
Nitroprusside
Congestive Heart Failure Nitroglycerine Labetalol and Esmolol
Loop Diuretics (decreased HR),
nicardipine,diltiazem
Nitroprusside
Enalaprilate

Myocardial infarct, Angina Diltiazem Diazoxide,hydralazine (increase

Nitroprusside HR,O2 demand
Nitroglyceri
Nicardipinene
Aortic Dissection Nitroprusside Diazoxide,hydralazine,
Labetalol 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
2. HIPERTENSI EMERGENSI
Dosis : 0.5 – 6 Mcg/Kg BB/menit (syeringe pump / infus drip)
4. 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
Nicardipine HIPERTENSI EMERGENSI
injeksi
BERAT DOSIS NICARDIPINE INJEKSI (mcg/kg BB/menit)
1 ampul 10 mg
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
Spuit 50 cc
(mL/jam) 40 kg 6 12 18 24 36 48 60 72 84 96 108 120

Atau 50 kg 8 15 23 30 45 60 75 90 105 120 135 150

60 kg 9 18 27 36 54 72 90 108 126 144 162 180

Pediatric Drip
(=1 cc = 60 70 kg 11 21 32 42 63 84 105 126 147 168 189 210
tetes) 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

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

KECEPATAN
KONSENTRASI KECEPATAN INFUS KONSENTRASI
INFUS
5 x amp 10 ml mll/jam ml/jam
100 μg/ml: 5 x amp 10 ml
nitroglycerine dalam 500 μdrop/menit μdrop/menit
ml nitroglycerine ® dalam 50 ml

10 6 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
 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 non-
adherent 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 : Cerebral Perfusion Pressure

ICP : Intracranial Pressure
MAP : 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)
• 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).
2. if systolic BP is < 180 mmHg and diastolic BP < 105
mmHg, defer antihypertensive therapy.
3. 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).
4. 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
87–97 men
98–127
128-137
138-147
148-157
158-177
178-197
> 198
Diastolic blood pressure
woman
48-68 men
69-83
83-88
88-93
93-98
98-108
108-118
> 118
0 100 200 300 400 500 600 700
800 Mortality ratio in %
 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 %

HERBESSER INJ 50 mg
-------------------- = ---------
Pelarut 50 ml

Contoh : Dosis HERBESSER = 5 mcg/kg/menit ( A )

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: 411–17

 Dosis diltiazem-injeksi pada Hipertensi Krisis

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

Laju infus (ml/jam)
Dosis *
Berat (ug/mnt) 5 10 15
Badan (kg)

40 12 24 36
50 15 30 45
60 18 36 54
70 21 42 63
 Effect of a Drip Infusion Diltiazem on Severe
Systemic Hypertension
250
250

29
200
200 27
205 24 14 14
mmHg * 12 9 9
150
* * * * * * SBP 24.6%
Blood 150
154
Pressure * *
mmHg
mmHg * * * * * mean
100
100 115.8
mmHg
* * DBP 26.9%
* * * * * 83.3
50100
50
mmHg

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

50 50
15

10 10
* P≤0.05 vs
Dose infused
µg/kg/min pretreatment level
5 5

0
0 0.5 1 2 3 4 5 6

0 0.5 1 2 3 4 5 6

Subjects: 29 severe systemic hypertension

Dosage : diltiazem initial dose less 10 µg/kg/min, average infusion rate was 11 µg/kg/min
Curr Ther Res 43, 1988
 Herbesser i.v. causes less increase
of intracranial pressure.
Comparison of intracranial pressure Comparison of Cerebral perfusion pressure
change by different antihypertensives. index (CPP index) by different antihypertensives.
p<0.05
（ mmHg ） p<0.05
20 2.0 1.80±0.11
17.0 1.63±0.13
Change of intracranial pressure

14.2
1.5 1.33±0.07

CPP index
10
6.7
1.0

0 0.0
Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v. Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.
①CPP index=△CPP/△SBP
②CPP index coming close to 1 indicates less
increase of intracranial pressure.
Target 35 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhage
Medication Herbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10
Methods 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