MANAGEMENT OF HYPERTENSIVE Emergency

COMPLICATIONS OF HYPERTENSION

Acute Complication Chronic complication

- Abruptly - Gradually
- Related with accelerated - Related with duration
elevation of BP of hypertension
- BP must be decreased - BP managed smartly
aggressively
 COMPLICATIONS OF HYPERTENSION

Acute Complication Chronic complication

- Abruptly - Gradually
- Related with accelerated - Related with duration
elevation of BP of hypertension
- BP must be decreased - BP managed smartly
aggressively

Hypertensive Crisis
 Hypertensive Crisis

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 be reduced within hours BP should be reduced immediate
Oral agents Parenteral agents

Kaplan NM ,Hypertensive Crises in : Clinical hypertension 9th Ed,

Lippincott Williams & Wilkins 2006:609-630
Definition :
Hypertensive crisis :
Severe elevation of blood pressure, which must be
reduced immediately

Classification :
• Hypertensive emergency :
• accompanied by acute target organ damage
• BP must be reduced within minutes

• Hypertensive urgency :
• no acute organ damage
• BP must be reduced within hours
Clinical Hypertension, Kaplan 2003
Definition :
• Not determined by BP level, but rather the imminent
compromise vital organ function
• Formerly when :
• systolic  180 mm Hg
• diastolic ≥ 110 mm Hg

The Kidney and Hypertension, Bakris, 2004

 High blood pressure in
asymptomatic chronic hypertension
IS NOT A HYPERTENSIVE CRISES
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
8. Renin secreting tumors
9. Ingestion of cathecolamine precursor in patients
taking MAO inhibitors
HYPERTENSIVE EMERGENCY
Accelerated-malignant hypertension with papilledema
Cerebrovascular conditions
Hypertensive brain infarction with severe hypertension
Intracerebral hemorrhage
Subarachnoid hemorrhage
Head trauma
Cardiac conditions
Acute aortic dissection
Acute left ventricular failure
Acute or impending myocardial infarction
After coronary bypass surgery
Renal conditions
Acute glomerulonephritis
Renovascular hypertension
Renal crises from collagen-vascular diseases
Severe hypertension after kidney transplantation
Hypertensive emergency (cont’d)
Excess circulating catecholamines
Pheochromocytoma crisis
Food or drug interactions with monoamine oxidase inhibitors
Sympathomimetic drug use (cocaine)
Rebound hypertension after sudden cessation of antihypertensive drugs
automatic hyperreflexia after spinal cord injury
Eclampsia
Surgical conditions
Severe hypertension in patients requiring immediate surgey
Postoperative hypertension
Postoperative bleeding from vascular suture lines
Severe body burns
Severe epistaxis
Thrombotic thrombocytopenic purpura
 Sign and symptom in various types of
hypertensive emergency

Type of Typical symptoms Typical signs Comment

hypertensive emergency
Acute stroke in evolution Weakness, altered Focal neruological Hypertension not
(thrombotic or embolic) motor skill(s) deficit(s) usually treated
Suibarachnoid hemorrhage Headache, delerium Altered mental Lumbar puncture
status, meningeal typically shows
signs xanthochromia or red
blood cells
Acute head injury/trauma Headache, altered Lacerations, Computed
sensorium or motor ecchymoses, altered tomographic (CT) scan
skills mental status is helpful to determine
extent of intracranial
injury
Hypertensive Headache, altered papilledema Usually a diagnosis of
encephalopathy mental status exclusion
Cardiac ischemia/infraction Chest discomfort, Abnormal EKG (esp.
nausea, vomiting T-wave elevations)
 Sign and symptom in various types of
hypertensive emergency (cont’d)
Type of Typical symptoms Typical signs Comment
hypertensive emergency
Acute left ventricular Shortness of Rales auscultated
failure/pulmonary edema breath in chest

Aortic dissection Chest discomfort Widened aortic Echocardiogram,

knob on chest x- chest CT, or
ray angiogram usually
needed to confirm
Recent vascular surgery Bleeding, Bleeding at suture Often require surgical
tenderness at lines revision of vascular
suture lines anastamosis

Pheochromocytoma Headache, Pallor, flushing, Phentolamine is very

sweating, rare skin signs useful
palpitations (phakomatoses)
Drug related catecholamine Headache, tachycardia History regarding
excess state palpilations drug exposure is key

Preeclampsia / eclampsia Headache, uterine Edema, New treatment

irritability hyperreflexia guidelines exist
 Management of
Hypertensive Emergency (general)
 Patients should be admitted to an Intensive Care
Unit for continuous monitoring of BP and parenteral
administration of an appropriate agent
 The initial goal therapy is to reduce mean arterial BP
by no more than 25% (within minutes to 1 hour).
 Then if stable, to 160/100 to 110 mmHg within the
next 2 to 6 hours.
 Excessive falls in pressure that may precipitate
renal, cerebral, or coronary ischemia should be
avoided.
Chobanian AV et al, The JNC 7 report, JAMA 2003;389: 2560-70
 Management of
Hypertensive Emergency (general)
 If this level of BP is well tolerated and the
patients is clinically stable , further gradual
reductions toward a normal BP can be
implemented in the next 24 to 48 hours.
 Exceptions :
1. Patients with ischemic stroke
2. Aortic dissection SBP should < 100 mmHg
3. Patients whom BP is lowered to enable the
use of thrombolytic agents

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 Immediate 1-2 minutes after
nitroprusside infusion stopped
Nitroglycerin 5-500 ug/min 1-3 minutes 5-10 minutes

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

Nicardipine HCl 5-15 mg/h 5-10 minutes 15-90 minutes

Esmolol HCl 250-500 ug/kg/min IV 1-2 minutes 10-30 minutes

bolus, then 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 Emergencies 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
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
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 / Systolic
dysfunction
Acute Pulmonary edema/ Diastolic
dysfunction
Acute Ischemia Coroner
Hypertensive encephalopaty
Acute Aorta Dissection
Preeclampsia, eclampsia
Acute Renal failure /
microangiopathic anemia
Sympathetic crises/ cocaine
oveerdose
Acute postoperative hypertension
Acute ischemic stroke/ intracerebral
bleeding
Nicardipine, fenoldopam, or nitropruside combined with nitrogliceryn and
loop diuretic
Esmolol, metoprolol, labetalol, verapamil, combined with low dose of
nitrogliceryn and loop diuretics
Labetalol or esmolol combined with diuretics
Nicardipine, labetalol, fenoldopam
Labetalol or combined Nicardipine and esmolol or combine nitropruside
with esmolol or IV metoprolol
Labetalol or nicardipine
Nicardipine or fenoldopam
Verapamil, diltiazem, or nicardipine combined with benzodiazepin
Esmolol, Nicardipine, Labetalol
Nicardipine, labetalol, fenoldopam
Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62
 Nitroglycerin
Nitroglycerin is a potent venodilator and only at high doses
affect arterial tone. It reduces BP by reducing cardiac
ouput and preload which are undesirable effects in
patient with compromised cerebral and renal
perfusion

Nifedipine
Nifedipine has been widely used via oral or sublingual
administration in the management of hypertensive
emergencies. This mode of administration has not
been approved by FDA and JNC VI because it may
cause sudden uncontrolled and severe reductions in
blood pressure may precipitate cerebral, renal, and
myocardial ischemia that have been associated with fatal
outcomes
 Clonidine
 Central alfa blocker, sedative effect
 CI : in patient with Cerebrovascular accident
 Rebound effect
 USE OF NICARDIPINE

• Nicardipine :
. Dihydropiridine class of CCB

• Reduce peripheral resistance  blood pressure

• water soluble, light insensitive,  can be

parenteraly used (deference with nifedipine /
sodium nitroprusid)
 Calcium Channel Blocker Mechanism

Ca++ Ca++
Blocking
effect of CCB
 

Ca++ plus Calmodulin Ca++ plus Calmodulin

 
Myosin Kinase Myosin Kinase

   
Actin-Myosin Interaction
 Contraction

 
Ca++ Ca++
 PRIMARY HEMODYNAMIC OF
NICARDIPINE EFFECT

• Peripheral vasodilatation
• Preserve or enhanced cardiac pump activity
 improve tissue perfusion
• Fall in systemic blood pressure, maintain at desired level
• In comparison with sodium nitropruside  equally effective,
but no cyanide toxic effect in long term use
• Not associated adverse effect on cardiovascular and renal
function
 NICARDIPINE
characteristics

1.VASOSELECTIVITY
Nicardipine selectivity 30.000 x in smooth muscle cells blood
vessels compared with myocardium
2. Myocardial depression (-)
3. Negative inotropic (-)
4. Rapid and stable antihypertensive effects, reduce blood
pressure gradually < 25% in 2 hours, minimal effects to
heart rate
5. Increase blood flow in major organ : Renal, coroner, cerebral
 Actions to increase organ blood flow
Pharmacodynamic action

Perdipine: 3 g/kg/min  20 min

⊿%)
Mean blood Vertebral Renal Coronary (Hypertensive patients, n = 9)
pressure artery blood flow blood flow
60
Blood flow change rate

blood flow

Baseline value
40
Mean blood pressure 103  11 mmHg

20 Vertebral artery
183  65 mL/min
blood flow
Renal artery
563  29mL/min
0 blood flow
Mean blood pressure

Coronary artery
121  42 mL/min
change rate

blood flow
-10

-20
(⊿%)
(Shoji Suzuki, et al., The 20th Annual Scientific Meeting of the Japanese Society of Hypertension: 1997)
Tissue selectivity between
Calcium Antagonist

Bristow et al. Br J Pharmacol1984; 309:82

 Comparison between Calcium Antagonist

Coronary Suppression
Suppression Suppression
Drug Vasodilati of Cardiac of SA Node of AV Node
on Contractility
Verapamil
++++ ++++ +++++ +++++
(phenylalkylamine)
Diltiazem
+++ ++ +++++ ++++
(benzothiazepin)

Nicardipine
(dihydropyridine )
+++++ 0 + 0

Kerins DM. Goodman Gilman’s.10th ed.2001:843-70

 Nicardipine vs Nitrovasodilators
Drug Nicardipine Nitroprusside Nitroglycerin
(Perdipine® IV)
Rapid Onset of Peak Effect ++++ ++++ +++

Afterload Reduction ++++ ++++ +

Preload Reduction 0 ++ ++++

Coronary Steal Reported 0 + 0

Coronary Dilation: Large Vessel +++ + ++++

Coronary Dilation: Small Vessel +++ +/- +/-

Tachycardia + ++ ++

Potential for Symptomatic + ++ +++

Hypotension
Ease of Administration ++++ ++ +++

Cyanide Toxicity 0 ++++ 0

Pepine CJ. Intravenous nicardipine: cardiovascular effects and clinical relevance. Clin Ther. 1988;10:316-25.
Perdipine for preeclampsia
 DOSIS PERDIPINE
DIV Bolus
(g/kg/min) (g/kg)
Acute hypertensive crises during surgery 2 - 10 10 – 30

Hypertensive emergencies 0.5 – 6

Acute hypertensive crises during surgery

Hypertensive emergencies

0.5 1 2 6 (g/kg/min) 10
 Dosage and Administration
Start with the lowest dose.
Eg 0.5 mcg/BW/min  15 drops  monitoring, if in 5-15
minutes there’s no significant blood pressure reducing 
Increasing drip until 20 drop , and then can be increased
until desirable blood pressure achieved ( about 3-5 drops
each after monitoring)
Monitoring blood pressure and heart rate frequently
Before choose to switch to oral, 1 hour before Perdipine
is stopped, give oral drugs and Perdipine is tappered of
 PERDIPINE ®
The 1st line treatment of Hypertensive Emergency

Could be used : Couldn’t be used :

Sodium Chloride / NaCl
Sodium bicarbonat
( OTSU-NS : 100/250/500 ml ) Ringer Laktat
Dextrose 5%
( OTSU-D5 : 100 / 250 / 500 ml )
Glucose 5%
Potacol – R
Ringer Asetat
KN 1A / 1B / 4A
 Conclusions

 Hypertensive Crises is an urgent situation that need rapid

management to prevent organ damage
 Antihypertensive agent that preffered in this condition
should be fast action, parenteral, and titratable
 Nicardipine is the only Calcium Antagonist recommended
by JNC 7, AHA, 2007, CHEST 2007 to manage
hypertensive emergency
 Nicardipine has favorable antiischemic profile because of
an increase myocardial , brain, and kidney oxygen supply