dr.

Chandra Irwanadi, SpPD - KGH

 CURRICULUM VITAE
• Nama : dr. Chandra Irwanadi Mohani,SpPD-KGH
0811315672
• Kantor : SMF Ilmu Penyakit Dalam FK UNAIR Surabaya
SMF Ilmu Penyakit Dalam RSUD Dr. Soetomo Surabaya
Instalasi Hemodialisis - RSUD Dr.Soetomo Surabaya

Pendidikan Dokter
FK UNAIR 1979

Pendidikan Spesialis Penyakit Dalam

FK UNAIR 1992

Pendidikan Konsultan Ginjal Hipertensi

FK UNAIR - RSUD dr.Soetomo 2006

Juntendo University Tokyo 2001

Pekerjaan :
• 1980 Puskesmas Alalak Kalimantan Selatan
• 1997 Instalasi Hemodialisis RSU Dr.Soetomo Surabaya
• 2015 Ka. Div. Nefrologi dan Hipertensi Imu Penyakit
Dalam FK Unair – RSUD Dr. Soetomo Surabaya

Organisasi profesi :
• Ikatan Dokter Indonesia (IDI)
• Perhimpunan dokter Ahli Penyakit Dalam Indonesia (PAPDI)
• Perhimpunan Nefrologi Indonesia (PERNEFRI)
• International Society of Nephrology (ISN)
Penulis Utama :
• GGA di RSUD Dr. Soetomo
• Nutrisi pada CKD
• PAD pada CKD
• Hypertension Target Organ Damage: How to Prevent?
• Nutritional Management in CKD and KetoAcid Therapy

Karya Ilmiah Internasional:

• Level of MCPI in Diabetic Hypertensive Patients
• Acute Renal Failure in Sutomo Hospital
HYPERTENSIVE CRISIS
Detection, prevention and
management
Chandra Irwanadi Mohani, M Thaha, Nunuk M, Widodo
Symposium and workshop on emergency in internal medicine
(SWEIM 2017)
OUTLINES
Introduction

Etiology

Pathophyisiology

Definition

Management
Introduction
• Hypertension is silent killer
• Poorly controlled hypertension is major risk for
 Cardio and cerebrovascular morality
 Acute severe elevation in the blood pressure can
cause acute end organ damage
• 1-2% of all the hypertensive patients present in
emergency room with hypertensive emergency at least
once in their lifetime
• Prompt recognition, evaluation and treatment are very
important in preventing permanent end organ damage
• But most of the recent guidelines do not give explicit
the management of Hypertensive crisis

Mallidi et al (2013); J Hypertens 2:2

Rodriguez MA et al (2010); Cardiology in Review 18:2
Aggarwal M, Khan IA (2006); CardioClin 24
Marik PE, Varon J (2007; Chest 131
Hypertension is An Important
Public Health Challenge Worldwide

Population (in millions) with

In 2000, hypertension globally
> quarter of global
population with
2000
hypertension
Predicted increase 60%
1500
26.40%
1000

500

0
introduction Yr 2000 Yr 2025

Kearney PM, et al. Lancet. 2005; 365: 217-223

Rate of Controlled Patients

28% ---------------------------------
Unaware of their
hypertension

39% ---------------------------------
Not Receiving therapy

65% ---------------------------------
Do not have their BP
controlled to levels below
140/90 mmHg

Chobanian A.. NEJM 2009. 361:878-87

 Uncontrolled hypertension carries the same
CV risk as untreated hypertension

Third National Health and Nutrition Examination Survey (NHANES III)

48%
Not treated (n = 2,458) Both are at equally
increased risk compared
with controlled BP
(p>0.05)
35%
BP uncontrolled
(n = 1,756)

17%
BP controlled (n = 872)

Gu Q, et al. Am J Hypertens 2010;23(1):38-45

Percentage of Adult Population
with Hypertension in Indonesia
Adult Population with

Only 24%
Hypertension

Aware of
Hypertensive
Status

Krishnan A. Regional Health Forum. Vol. 17, Number 1. 2013; 7-11

Epidemiology
• 1 billion (2000) become 1.56 billion (2025) Hypertension
• Hypertensive emergencies are common
• Occur in 1-2% of the hypertensive population
• Parallels the distribution of primary hypertension
• Incidence in men 2 times higher than in women

• Common associations
– Previous history of hypertension
– Lack of a primary care physician
– Non adherence to antihypertensive regimen
– Elicit drug use
Thaha
Kirk J.Pak et al The Oschner J 2014
Epidemiology
Emergency cases in ER Hipertensive Crisis
Other case HT Crisis Urgency HT Emergency HT

27% 24%
73% 76%

•Incidence 1-3 case / 100.000/ year in general population

•8%-28% unaware of having HT (men > women)
•>50% with underlying renal disease
•Death due to renal failure (39.7%), stroke (23.8%), MI (11.1%)
•5 year survival >75% Thaha
(Rodriguez, 2010;Zampaglione, 2011)
13
 Etiology hypertension
Renal conditions
Renal parenchymal disease
Renovascular hypertension
Acute glomerulonephritis
Renal crises from collagen-vascular
diseases
Severe hypertension after kidney
transplantation
Hyperaldosteronism
Thyroid disease
Pheochromocytoma
Oral Contraceptives
Obstructive sleep apnea
Coarctation of the aorta
Cushing’s syndrome
Primary hyperparathyroidism
Primary 95% Secondary 5-10%
Agarwal, R., 2005. Hypertension in Chronic Kidney Disease and Dialysis :
Pathophysiology and Management.. Cardiol Clin 23, pp. 237-48.
 Etiology
• Medication noncompliance
• Antihypertensive drug withdrawal (ie, clonidine)
• Renal parenchymal disease
• Drugs (ie, cocaine, PCP)
• Collagen vascular diseases (SLE)
• Cushing disease
• Pheochromocytoma
• Preeclampsia and eclampsia
• Postoperative state
• PCP indicates phencyclidine; SLE, systemic lupus
Erythematous

Hypertensive Crisis. Rodriguez MA, Kumar SK, De Caro M . Cardiology

in Review. Vol 18, No 2, 2010
 Pathophysiology
• Pressure Natriuresis
• Strain Vessels Hypothesis
• Renin Angiotensin System
• Reactive Oxygen Species & Nitric Oxide
Pressure Natriuresis

Intake and output of salt and water

• Renal Insufficiency cause loss
of renal sodium handling

(times nl)
High intake
• Stimulates vasoconstrictor
substance from the kidney
Normal intake
• Initiate & Perpetuate
0 50 100 150 200

Mean Arterial Pressure (mmHg)

OCW: Renal Pathophysiology (S. Gilbert) 2007

The control of peripheral arteriolar resistance. Reproduced with permission from Beevers DG, MacGregor GA. Hypertension in practice. 3rd ed. London:
Martin Dunitz, 1999
Putative vascular pathophysiology of hypertensive
emergencies

THE LANCET • Vol 356 • July 29, 2000

Effects of increased renal sympathetic nerve activity on the three renal neuroeffectors : the
juxtaglomerular granular cells (JGC) with increased renin secretion rate (RSR) via stimulation of the
β, adrenoceptors (AR), the renal tubular epithelial cells (T) with increased renal tubular sodium
reabsorption and decreased urinary sodium excretion (UNaV) via stimulation of α1B AR, and the
renal vasculatore (V) with decreased renal blood flow (RBF) via stimulation of α1A AR

Kaplan’s Clinical Hypertension 10ed, Kaplan N M, Philadelphia, 2010

 Vicious cycle
The release of humoral vasoconstrictor substances from
the stressed vessel wall is thought to be responsible for the
initiation and perpetuation of the hypertensive crisis

PVR increased

HNPE DIC

OCW: Renal Pathophysiology (S. Gilbert) 2007

 Definition
Emergency
Target Organ Damage acute/ progressive
Rapid BP reduction
Parenteral Preparation

(180/120 mm Hg) Accelerated & malignant?

Urgency
Increased BP
Without or minimal Target organ Damage
mostly DBP >120 mmHg Reduced BP within hours
Not determined by BP level, but rather the imminent 22
compromise vital organ function Uptodate, 2015
Complications of Hypertension:
End-Organ Damage

Hypertension

Infarct,hemorrhage ACS,ALO
,encephalopathy

Aortic Dissection
Renal Failure,
KW-Papiledema Proteinuria
Slide Source
CHD = coronary heart disease
Thaha
Hypertension Online
CHF = congestive heart failure www.hypertensiononline.org
LVH = left ventricular hypertrophy Chobanian AV, et al. JAMA. 2003;289:2560-2572.
Patient Evaluation

Additional
Physical Evaluation Special
Examination Consideration
Ophthalmoscopy
History Taking BP both arms Radiographic
ECG
Symptoms Cardiac- CT
Electrolytes
Hypertension Pulmonary MRI
Scr
Drugs Pulses TTE/TEE
Urinalysis
Abdominal Cardiac Marker
HCG

Thaha

Uptodate online 2014, Medscape 2013, Kaplan 10th

 Diagnostic Evaluation for Hypertensive
Emergencies and Urgencies
History
Previous diagnosis and treatment of hypertension
Symptoms, previous diagnoses, and treatment of cardiac,
cerebral, renal, and visual damage
Intake of pressor agents: sympathomimetics, illicit
substances
Repeated Blood Pressure Measurements (first measure-
ment in both arms)
Physical Examination
Cardiac
Vascular
Pulmonary
Neurologic
Optic fundi
 Diagnostic Evaluation for Hypertensive
Emergencies and Urgencies
Laboratory Studies
Complete blood count (red cells, platelets, white cells),
urinalysis, creatinine, urea, electrolytes
Plasma renin activity, aldosterone, and catecholamines if
secondary hypertension is suspected
Electrocardiography
Chest Radiograph
Further Investigations(according to clinical presentation)
Renal ultrasound
Brain CT scan or MRI
Echocardiography (transthoracic, transesophageal)
Thoracoabdominal CT scan or MRI
The Signs and Symptoms

28
Hypertension Research 34, 367-371 (March 2011)
 The Patients

Why not using level of BP

Hypertension Research 34, 367-371 (March 2011)
Common clinical scenarios associated with
hypertensive emergency

Mallidi J, Penumetsa S, Lotfi A (2013) Management of Hypertensive Emergencies. J Hypertens 2: 117.

Hypertensive Emergency Management

 Reduce BP immediately with intravenous drugs, and monitor BP

continuously in an intensive care setting (Not Stated)

• Reduce mean arterial BP by no less than 20-25% in the first hour

(within minutes to 1 hour) (Not Stated)

• If stable, to 160/100 - 110 mm Hg within the next 2 to 6 hours

• Further gradual reductions toward a normal BP can be

implemented in the next 24 to 48 hours

www. Gacguidelines.ca
Hypertensive Emergency Management

• For most hypertensive emergencies, mean arterial pressure

should be reduced gradually by about 10 to 20 percent in the first
hour and by a further 5 to 15 percent over the next 23 hours

• After a suitable period (often 8 to 24 hours), oral medications are

usually given and the initial intravenous therapy is tapered and
discontinued.

Major Exception for 1st day :

• Ischemic Stroke → ≥ 185/110 for reperfusion or ≥ 220/120
• Acute Aortic Dissection → Target 100-120 mmHg within 20 minutes
• Goal : break cycle, preserve cardiac output & RBF, limit organ damage

www.gacguidelines.ca
 Treatment of Hypertensive Emergencies
Drug Mechanism Dose Onset of Duration Adverse Effects*
Vasodilators of Action Action of Action
Nicardipine Calcium 5-15 mg IV 5-15 min 15-30 Tachycardia, Most hypertensive
hydrochloride channel every hour min, headache, emergencies except
blocker may flushing, nausea, acute heart failure
exceed vomiting, local
4 hr phlebitis
Fenoldopam Dopamine- 0.1-0.3 µg/ >5 min 30 min Tachycardia, Most hypertensive
mesylate 1receptor kg/min IV headache, nausea, emergency; caution
agonist infusion flushing with glaucoma
Clevidipine Calcium 1-2 mg/hr 2-4 min 5-15 min Tachycardia, Most hypertensive
butyrate channel IV infusion; headache, emergencies; caution
blocker inc rease flushing, heart with severe aortic
every 5-10 failure stenosis, acute heart
min up to deterioration failure
16 mg/hr
Sodium ↑ Cyclic 0.25-10 Immedia 1-2 min Nausea, vomiting, Caution in situations
nitroprusside GMP, µg/kg/min te muscle twitching, associated with CNS
blocks IV thiocyanate and manifestations,
intracellular infusion† cyanide hepatic or renal
Ca2+ increase intoxication, failure; probably
impaired cerebral should be avoided if
autoregulation, given other agents,
coronary steal especially
syndrome fenoldopam
 Treatment of Hypertensive Emergencies
Drug Mechanism Dose Onset of Duration Adverse Effects*
Vasodilators of Action Action of Action
Nitroglycerin ↑ Nitrate 5-100 µg/min 2-5 min 5-10 min Headache, Coronary ischemia,
receptors IV infusion vomiting, pulmonary edema
methemoglobine-
mia,tachyphylaxis,
tolerance with
prolonged use
Enalaprilat ACE 1.25-5 mg 15-30 6-12 hr Precipitous fall in Acute left
inhibitor every 6 hr IV min BP in high-renin ventricular
states, variable failure; avoid in
response, acute acute myocardial
renal failure infarction
Isradipine Calcium 0.15 µg/kg 1-10 1-2 hr Headache, flushing, Perioperative,
channel /min IV, incre- min peripheral edema, pregnancy
blocker ase by 0.0025 dizziness,
µg/kg /min tachycardia
every 15 min.
Maintenance
infusion 0.15
µg/kg/min
Hydralazine Opens K+ 10-20 mg IV 10-20 1-4 hr Tachycardia, Must be given with
hydrochloride channels min flushing, concomitant IV
headache, β-blockers to avoid
vomiting, precipitation of
aggravation of angina but not a
 Treatment of Hypertensive Emergencies
Drug Mechanis Dose Onset of Duration Adverse Effects*
Vasodilators m Action of Action
of Action
Adrenergic Inhibitors

Labetalol α1-, β- 20-80 mg IV bolus 5-10 3-6 hr Nausea, vomiting, Most

hydrochloride Blocker every min scalp tingling, hypertensive
10 min or 0.5-2 bronchoconstricti emergencies
mg/ min IV on, dizziness, except acute
infusion heart block, heart heart failure
failure
Esmolol Esmolol 0.5-2.0 mg/min IV 1-2 min 10-30 Nausea, asthma, Aortic dissection,
hydrochloride hydrochlo infusion or 250- min first-degree heart Perioperative,
ride 500 µg/kg/min IV block, heart increased heart
bolus, then 50- failure, output or heart
100 µg/kg/min by thrombophlebiti, rate
infusion; may COPD
repeat bolus after
5 min or increase
infusion to 300
µg/min
Urapidil α1-Blocker, 12.5-25 mg IV 3-5 min 4-6 hr Headache, Headache,
serotonin bolus dizziness dizziness
(5-HT1A) followed by 5-40
receptor mg/hr IV infusion
agonist
Hypertensive Urgency

The optimal management of patients with severe asymptomatic

hypertension is unclear
Target BP : ≤ 160/100 but not more 20% MAP
Rapidity : Over period of hours vs a period of days

Discharge :
After exclusion of acute end-organ damage
Ascertain that the blood pressure is stable or improving
Patients at high risk for acute cardiovascular events
should probably be admitted

Joseph Varon. Uptodate online. 2015.

Hypertensive Urgency

Optimize (or restart) their current treatment regimens

Considering oral shor-acting agents (e.g captopril, labetalol,

clonidine)

Do not treat aggressively with intravenous drugs or oral loading

Ensure that the patient has a follow-up appointment

within a few days

www.gacguidelines.ca
Within Few Hours
Oral furosemide (if the patient is volume overloaded) at a
dose of 20 mg (or higher if the renal function is not normal)

Oral clonidine (but not intended as long-term therapy)

at a dose of 0.2 mg

Oral captopril (if the patient is not volume depleted) at a dose

of 6.25 or 12.5 mg

• Observed few hours, reduction 20-30 mmHg, longer acting afterwards, follow up
• Sublingual nifedipine is contraindicated in this setting
and should not be used.

Joseph Varon. Uptodate online. 2015 38

 Ideal drug

 Fast acting
 Easily titratable
 Rapidly reversible and safe
 No single agent has these characteristics
Drugs alternatives
Primary Condition
Acute aortic dissection
Hypertensive encephalopathy
Acute myocardial ischemia
Congestive heart failure
Eclampsia
Pheochromocytoma
Acute pulmonary edema
Acute ischemic stroke/intracerebral bleed
Acute renal failure/MAHA
Therapy
Labetalol or nicardipine + esmolol,
nitroprusside + esmolol
Labetalol, nicardipine, fenoldopam,
clevidipine
Nitroglycerin + esmolol, fenoldopam,
labetolol
Loop diuretic, Nitrogliserin, enalaprilat
Hydralazine, nicardipine, labetalol
Phentolamine, labetalol
Sodium nitroprusside, nicardipine,
fenoldopam, loop diuretic, nitroglycerin
Nicardipine, fenoldopam, labetalol,
clevidipine
Nicardipine, fenoldopam
40
Adapted from Varon et al. 2012
 Nicardipine
• Second generation DHP CCB.
• Strong cerebral and coronary vasodilation. J Emerg Med 1987:5:463-473

• 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.

• Dosage independent of weight.
• 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
 Conclusion
• Hypertensive crisis can be further classified as hypertensive
urgency and emergency depending end organ involvement
including cardiac, neurologic and renal injury
• Hypertensive crisis defined as a SBP > 180 mmHg or a DBP >
120 mmHg
• Acute and severe elevation in BP
• The precise patophysiology is not well understood
• Severely hypertensive patients with acute end-organ damage
warrant admission to an intensive care unit for immediate
reduction of blood pressure
 Conclusion
• Rapid and short-acting titratable intravenous antihypertension
drugs commonly used are nicardipine, labetalol, sodium
nitroprusside
• While continuously monitoring BP, neurologic status, and urine
output
• No high-quality prospective study about lowering BP
• Treatment objective is to decrease BP gradually, not abruptly
• Complete evaluations in patients who present with
hypertensive crisis to effectively reverse the crisis, intervene
and correct the underlying trigger, to improve longterm
outcomes after the episode
Prof. M. Thaha
Dr. Nunuk M
Dr. Widodod
WHO Age-standardized Estimates of The Prevalence
of Hypertension in South East Asia Region

Estimates of age-standardized prevalence (%) of raised blood pressure in adults aged

25+ years in countries of the SEA Region, 2008
Country Men Women Both
44.3 39.8 42.0
Myanmar
(37.7-50.5) (33.1-46.5) (37.2-46.8)
42.7 39.2 41.0
Indonesia
(35.3-49.9) (32.5-46.0) (35.9-45.8)
36 34.2 35.2
India
(29.7-41.8) (28.6-39.9) (30.9-35.2)
37.0 31.6 34.2
Thailand
(31.3-42.5) (26.0-37.1) (30.0-38.1)
37.6 35.4 36.6
Asia Tenggara
(32.6-42.4) (30.9-39.8) (33.1-39.8)
40.8 36.0 38.4
Global
(37.7-43.7) (33.3-38.6) (36.3-40.5)
Krishnan A. Regional Health Forum. Vol. 17, Number 1. 2013; 7-11
Onion Skin Appearance

I, arterial intima showing gross proliferative change and ‘onion skin’ appearance; L, severely
narrowed arterial lumen; M, arterial media; T, tubular atrophy and interstitial fi brosis.
Oxford Handbook of Nephrology and Hypertension. Simon Steddon,
Neil Ashman, Alistair Chesser John Cunningham. 2nd Edition, 2014.
Rostral ventrolateral medulla (RVLM) (+)

Renal sympathetic nerve

Kidney

1 receptors  Renin Ang II Aldosterone

(JGA) release

1 receptors Na reab-  Cardiac HYPERTENSION

(proximal sorption output
tubules)

1 receptors
Vasoconstriction
 Renal blood flow
Wall thickening of artery / arteriole

FUNCTIONAL ROLES OF RENAL SYMPATHETIC NERVE

IN THE INITIATION OF HYPERTENSION
Kumagai H et al. Involvement of Renal Sympathetic Nerve in Pathogenesis of Hypertension. In: Kidney and Blood Pressure Regulation. Eds Suzuki H, Saruta T. Karger,2004
Severe Asymptomatic Hypertension
• How quick should the BP be reduced
– Hours/day, slower in adult w/ high risk
• What’s the target & period of time

– <should
• How 160/100,
thislong-term <140/90 mmHg
goal be achieved

• Rapidity
– Moreof/ blood pressure
less quickly, lowering
quite room

– Controversial, gradual if no symptoms, risk

Varon, Uptodate, 2015