crisis of hypertension revised 1
DESCRIPTION
from Dr Atma Gunawan, NephrologistTRANSCRIPT
Management of hypertensive crisis
Atma GunawanConsultant of nephrology &
hypertension
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
DefinitionDefinition
JNC V (1993), JNC VII 2003. CHEST 2007; 131:1949–1962)Paul E. Marik, MD
Classification of hypertensive crisisHypertensive Urgency• Diastolic BP>120 mmHg, systolic BP>220• Mild or no acute end-organ damage• No clinical symptomsHypertensive 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 CrisisPrevalence of Hypertensive Crisis
Mainly due to more effective treatment ?
Hypertensive crisis
( % of all pts )
1950’s 1990’s
1
2
4
3
Zampaglione, et al. AHA ; 27 (1) : 144
Retinal findings in hypertensive encephalopathy
EvaluationEvaluation
Initial evaluation for patients with HTN emergencyHystory Prior diagnosis & treatment of HTN Intake of pressor agents; street drugs, sympathomimetics Symptoms of cerebral, cardiac,pulmonal, and visual dysfunctionPhysical examination Blood pressure Funduscopy Neurologic status Cardiopulmonary status Blood fluid volume assessment Peripheral pulsesLaboratory 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 3-4Severe chest pain
(Ischemia or dissecting aneurism)
Pulmonary edemaEclampsia
Cathecolamine excessAcute renal failure
HeadacheNo neurological signs
No target organ damage
EMERGENCY
URGENCY
Intravenous therapy
Identify the causeIn panic attacks or anxiety use analgesic, anxiolytics
Otherwise use oral antihypertensive agents
recheck in 6-24 hours
Therapy Approach Therapy Approach in Hypertensive Crisesin 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,
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 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 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 DiltiazemLabetalolNicardipine
Diazoxide,hydralazine (increase ICP), nitropruside
Hypertensive Encephalopathy
DiltiazemNicardipineLabetalol Nitroprusside
Diazoxide,hydralazine (increase ICP)
Congestive Heart Failure Nitroglycerine Loop DiureticsNitroprussideEnalaprilate
Labetalol and Esmolol (decreased HR), nicardipine,diltiazem
Myocardial infarct, Angina DiltiazemNitroprussideNitroglyceriNicardipinene
Diazoxide,hydralazine (increase HR,O2 demand
Aortic Dissection NitroprussideLabetalolEsmolol
Diazoxide,hydralazine, nicardipine
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
SYRINGE PUMP
Nicardipine injeksi
1 ampul 10 mg
Spuit 50 cc
(mL/jam)
Atau
Pediatric Drip
(=1 cc = 60 tetes)
INDIKASIKRISIS HIPERTENSI AKUT SELAMA OPERASI
HIPERTENSI EMERGENSI
BERAT BADAN
DOSIS NICARDIPINE INJEKSI (mcg/kg BB/menit)
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 6 12 18 24 36 48 60 72 84 96 108 120
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
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
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. )
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
Dosis :10-200 ug/menit DIENCERKAN
KONSENTRASI KECEPATAN INFUS KONSENTRASIKECEPATAN
INFUS
5 x amp 10 ml nitroglycerine dalam 500
ml
mll/jam
μdrop/menit100 μg/ml: 5 x amp 10 ml
nitroglycerine ® dalam 50 ml
ml/jam
μdrop/menit
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
BAGAN DOSIS NITROGLYCERINE
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
•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
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 PressureICP : Intracranial PressureMAP : Mean arterial pressure
In normal nonhypertensive subjects, CBF is relatively constant with CPPs : 60 to 120 mm Hg
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
Blood pressure management in ICH
1. 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 with history of chronic hypertension in spontaneous ICH (for the first few hours) (AANS. 1995.Daniels F kelly)
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
Recommendation in patients without history of chronic hypertension in spontaneous ICH
Mortality risk in relation to sex and B.P.
87–97
98–127
128-137
138-147
148-157158-177
178-197
> 198
Systolic blood pressuremmHg Standard risk
48-68
69-83
83-88
88-93
93-9898-108
108-118
> 118
Diastolic blood pressure
0 100 200 300 400 500 600 700 800 Mortality ratio in %
womanmen
menwoman
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
Dosage and AdministrationEach ampoule of DILTIAZEM-Injection should be dissolve in
at least 5 mL aquadest or NaCl or glucose solution before use.
DILTIAZEM-Injection
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 -------------------- = ---------
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. =A x B
C
50 mg
Lancet 2000; 356: 411–17
Autoregulation of Cerebral Blood Flow
Dosis diltiazem-injeksi pada Hipertensi Krisis
63422170
54361860
45301550
36241240
15105
Konsentrasi diltiazem-injeksi 0.1% (1mg/ml/100 mg/100 cc)
Laju infus (ml/jam)Dosis *
(ug/mnt)Berat
Badan (kg)
50
100
150
200
250
Effect of a Drip Infusion Diltiazem on Severe Systemic Hypertension
50
75
100
0
5
10
15
0 0.5 1 2 3 4 5 6
250
200
150
100
50
75
50
0
10
5
0.5 1 2 3 4 5 6
Dose infused g/kg/min
Pulse Rate beats/min
Blood Pressure mmHg
2927
*24*
14*
14*
12*
9*
9*
* * * * * * *
* * * * * **
*******
* P0.05 vs
pretreatment level
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
SBP
mean
DBP
24.6%24.6%
26.9%26.9%
8.9%8.9%
205 mmHg
115.8 mmHg
154mmHg
83.3mmHg
87.178.1
Herbesser i.v. causes less increaseHerbesser i.v. causes less increaseof intracranial pressure.of intracranial pressure.
Nicardipine i.v.
Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 1994
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.
①CPP index= CPP/ SBP△ △②CPP index coming close to 1 indicates less increase of intracranial pressure.
Comparison of intracranial pressure change by different antihypertensives.
Ch
an
ge
of
intr
acr
an
ial
pre
ssu
re
Comparison of Cerebral perfusion pressure index (CPP index) by different antihypertensives.
CP
P in
de
x
Herbesser i.v. Nitroglycerin i.v. Nicardipine i.v.Herbesser i.v. Nitroglycerin i.v.
20
10
0
2.0
1.5
0.0
1.06.7
14.2
17.0
1.33±0.07
1.80±0.11
1.63±0.13
p<0.05
p<0.05
（ mmHg ）
Target
Medication
Methods