THE ROLE OF NICARDIPINE IN THE MANAGEMENT OF HYPERTENSIVE CRISIS Haerani Rasyid 2016
What is Hypertension? JNC-7 (American) Classification of Blood Pressure Category
Systolic
Diastolic
Optimal
<120
and / or
<80
Normal
<130
and / or
<85
High-Normal
130-139
and / or
85-89
Stage 1 (mild hypertension )
140-159
and / or
90-99
Stage 2 (moderate to severe hypertension)
160
and / or
100-109
Isolated Systolic Hypertension (ISH)
140
and
<90
The category pertains to the highest risk blood pressure *ISH=Isolated Systolic Hypertension.
JAMA 2003;289:2560-72
Hypertensive patients
Asymptomatic Severe Hypertension
Hypertensive Urgencies
Hypertensive Emergencies
(70-75%)
(25-30%)
Hypertensive Crisis
Asymptomatic Severe Hypertension - Blood pressure 180/110 mmHg
Hypertensive Urgencies
Hypertensive Emergencies
≥ - No absolute blood pressure - Usually very high blood level. Usually blood pressure ≥180/110 mmHg
pressure (often > 220/140 mmHg)
- Incidental findings in - Rapidity of BP elevation of - Rapidity of BP elevation of asymptomatic patient. greater import than magnitude of the elevation
greater import than magnitude of the elevation
- Abscence of symptoms beyond mild or - Presence of symptoms beyond - Accompanied by evidence moderate headache mild or moderate headache of life-threatening organ dysfunction
- Without evidence of - Without evidence of target organ damage acute target organ damage
acute
Prim Care Clin Office Pract 2008; 35: 475–487
Epidemiology of Hypertensive crisis •
Recently, came down to < 1 % of hypertensive patients, due to better management.
•
Common in the black & elderly patients.
•
Majority of patients have previous history of HTN and
treatment •
Formed 1/4 of the medical urgencies and emergencies
•
Hypertensive urgencies constituted 76 % of the hypertensive crises while emergencies were 24%. Zampaglione et al, Hypertension 1996; 27(1)144-147
Causes of Hypertensive Crisis Essential
hypertension
Medication noncompliance
Secondary
hypertension
Aortic coarctation Cushing’s syndrome Elevated ICP Renal dysfunction Pregnancy Hyperparathyroidism Hyperthyroidism Pheochromocytoma Primary aldosteronism JNC 7, JAMA 2003; 289:2560-2572.
Some Examples of Hypertensive Emergencies and Urgencies Hypertennsive Emergencies
Accelerated/malignant hypertension Hypertensive encephalopathy Acute left ventricular failure Acute aortic dissection Intracranial hemorrhage Pheochromacytoma crisis Monoamine oxidase inhibitor and tyramine interaction Eclampsia Substances/drug-induced acute hypertension
Hypertensive Urgencies
Accelerated/malignant hypertension* Severe hypertension associated with coronary artery disease Severe HT in the organ transplant patient Preoperative hypertension Hypertension associated with burns Severe, uncontrolled HT *Also can be considered an emergency on the basis of acute target organ dysfunction
Fenves et al. Semin. Nephrol. 2005;25:272-280
Pathophysiology Not
well understood
Failure
of normal autoregulation and an abrupt rise in systemic vascular resistance
PATHOPHYSIOLOGY
Endothelial damage
Severe Hypertension
Critical level or rapid rate of rise and increased vascular resistance
↑ Endothelial permeability
Spontaneous natriuresis
Intravascular volume depletion
Platelet and fibrin deposition Activates coagulation & inflammation
Fibrinoid necrosis and intimal proliferation Severe BP elevation
Increase in vasoconstrictors (renin-angiotensin, catecholamines)
Further increase in BP
Tissue ischemia End-organ dysfunction
Vaidya et al. Hospi.Physician.2007:43-50
Principle of Treatment The initial goal of antihypertensive therapy is not to rapidly normalize BP but rather to prevent damage to target organ by gradually decreasing mean arterial pressure (MAP), while minimizing the risk of hypoperfusion
Asymptomatic severe hypertension Admission
may be necessary in those on newly diagnozed or severe non-compliance is suspected. Patients already on treatment need to be reviewed and appropriate measures taken which include optimising treatment by using effective combination therapy
Hypertensive crisis Hypertensive urgencies
These patients need to be admitted Blood pressure measurement should be repeated after 30 minutes of bed rest. Initial treatment should aim for about 25% reduction in blood pressure over 24 hours.
Hypertensive emergencies
All these patients most be admitted The blood pressure need to be reduced relatively quickly It is suggested that the blood pressure be reduced by 25% over 3 to 12 hours This is best achieved with parenteral drugs.
Management of Hypertensive Emergency (general)
1. 2. 3.
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 : Patients with ischemic stroke Aortic dissection SBP should < 100 mmHg 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 nitroprusside
0.25-10 ugr/kg/min
Immediate
1-2 minutes after infusion stopped
Nitroglycerin
5-500 ug/min
1-3 minutes
5-10 minutes
Labetalol HCl
20-80 mg every 10-15 min or 0.5-2 mg/min
5-10 minutes
3-6 minutes
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 bolus, then 50-100 ug/kg/min by infusion; may repeat bolus after 5 minutes or increase infusion to 300 ug/min
1-2 minutes
10-30 minutes
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 Nicardipine Esmolol Enalapril Hydralazine Nipride NTG
5 – 20 mg every 15’ NA 250 ug/kg IVP loading dose 1,25-5 mg IVP every 6 h 5 – 20 mg IVP every 30’ NA NA
2 mg/min (max 300mg/d) 5-15 mg/h 25-300 ug/kg/m NA 1,5-5 ug/kg/m 0,1-10 ug/kg/m 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
Nicardipine, fenoldopam, or nitropruside combined with nitrogliceryn and loop diuretic
Acute Pulmonary edema/ Diastolic dysfunction
Esmolol, metoprolol, labetalol, verapamil, combined with low dose of nitrogliceryn and loop diuretics
Acute Ischemia Coroner
Labetalol or esmolol combined with diuretics
Hypertensive encephalopaty
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 / microangiopathic anemia
Nicardipine or fenoldopam
Sympathetic crises/ cocaine oveerdose
Verapamil, diltiazem, or nicardipine combined with benzodiazepin
Acute postoperative hypertension
Esmolol, Nicardipine, Labetalol
Acute ischemic stroke/ intracerebral bleeding
Nicardipine, labetalol, fenoldopam Marik Paul E, Varon Joseph, CHEST 2007;131:1949-62
USE OF NICARDIPINE • Nicardipine : . Dihydropiridine class of CCB • Reduce peripheral resistance --- blood pressure • water soluble, light insensitive, -- can be parenteraly used (difference with nifedipine / sodium nitroprusid)
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 CHARACTERISTIC 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 organs : Renal, coronary artery, cerebral
Actions to increase organ blood flow Pharmacodynamic action
Perdipine: 3 g/kg/min 20 min ⊿%) Blood flow change rate
60 40
Mean blood pressure
Vertebral artery blood flow
Renal blood flow
Coronary blood flow
(Hypertensive patients, n = 9)
Baseline value Mean blood pressure
Mean blood pressure change rate
20 0
-10
103 11 mmHg
Vertebral artery blood flow
183 65 mL/min
Renal artery blood flow
563 29mL/min
Coronary artery blood flow
121 42 mL/min
-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 Drug
Coronary Vasodilation
Suppression of Cardiac Contractility
Suppression of SA Node
Suppression of AV Node
Verapamil (phenylalkylamine)
++++
++++
+++++
+++++
Diltiazem (benzothiazepin)
+++
++
+++++
++++
Nicardipine (dihydropyridine )
+++++
0
+
0
Kerins DM. Goodman Gilman’s.10th ed.2001:843-70
DOSIS
PERDIPINE DIV (g/kg/min)
Bolus (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
Nicardipine for the Treatment of Severe Hypertension in Pregnancy: A Review of the Literature Aim of study: To evaluate the efficacy and safety of intravenous nicardipine for the treatment of severe hypertension in pregnancy Sources: Medline and Cochrane Patients: Had chronic or gestational hypertension with or without marked proteinuria Primary outcomes: •Reduction of systolic/diastolic and/or mean arterial pressure •Reduction of time to target blood pressure, and •Reduction of severe maternal (hypotension, tachycardia) or severe fetal side effects (CTG abnormalities needing direct intervention) Results: •All patients had a significant reduction of both diastolic and systolic blood pressure. •Treatment resulted in a 91% success rate in studies that defined success and 20% reduction of mean arterial blood pressure or systolic/diastolic blood pressure in 87%. •Target blood pressure was reached within 23 minutes in 70% of the patients, 91% reached target blood pressure within 130 minutes Conclusion: Nicardipine is a very effective therapy for treatment of severe hypertension in pregnancy and may be a better alternative to other available treatment options Bijvank SWAN, Duvekot JJ. Obgyn Survey 2010; 65(5):342-7
Bijvank SWAN, Duvekot JJ. Obgyn Survey 2010, 65(5):342-7
Nicardipine Treatment of Hypertension During Pregnancy Objective: To assess the effects of nicardipine, a dihydropyridine CCB, on the fetus and mother in hypertensive pregnant women Methods: -40 pregnant patients with mild or moderate hypertension received oral nicardipine 20 mg 3x/day (mean duration of treatment 9 + 2.1 weeks) -20 patients with severe preeclampsia (diastolic blood pressure ≥110 mmHG and 24-h proteinuria ≥500 mg) received nicardipine IV at 2, 4, or 6 mg/Kg/h (mean duration of treatment 5.3+3.6 days)
Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14
Results:
Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14
Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14
Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14
Nicardipine Treatment of Hypertension During Pregnancy Conclusion: Oral or IV nicardipine seems to be safe in hypertensive pregnant patients with the dose used in our study
Carbonne B, Jannet D, Touboul C et al; Obstet Gynecol 1993;81:908-14
Objective: To evaluate the safety of long-term nicardipine treatment in severely pre-eclamptic women and their fetuses newborns. Methods: We divided 50 pregnant women into three groups according to the length of their treatment: short-term treatment of severely pre-eclamptic women (7 days or less n20); medium-term treatment also of severely pre-eclamptic women (8-28 days, n20); and long-term treatment of women with severe superimposed pre-eclampsia (29 days or more, n10.)
Conclusion Suggest that long-term treatment with nicardipine for severe pre-eclampsia is as effective and safe as a short- and medium-term treatment.
Objectives: To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy. Design: Randomized prospective study. Setting: The obstetric ward of the teaching hospital of Monastir Tunisia. Patients: Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension.
Conclusion Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy.
SUMMARY
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
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