Management of hypertensive crisisAtma 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 pressureForm : 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 edemaDefinitionJNC V (1993), JNC VII 2003. CHEST 2007; 131:19491962)Paul E. Marik, MD

Classification of hypertensive crisisHypertensive UrgencyDiastolic BP>120 mmHg, systolic BP>220Mild or no acute end-organ damageNo clinical symptomsHypertensive EmergencyUsually diastolic BP>120 mmHg, systolic BP>220 mmHgAcute end organ damageClinical symptoms is evidentPregnant : 170/110 mmHgPost-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 injuryAutoregulation failureVascular endothelial injuryTissue edemaFibrinoid necrosisActivation of endothelial vasoactive systems: endothelin, oxidative stress, RAS

Causes of resistance to therapy in hypertension Inappropriate antihypertensive regimenExogenous drugs/agent that raise BPNon-adherenceSecondary causes

Drugs that can increase BPWithdrawl of antihypertensive medications:clonidine rebound (methyldopa,reserpine), nifedipine, propanololPhenylpropanolamine (cold preparations)Sympathomimetics aminesOral contraceptive, erythtropoietenCorticosteroids, anabolic steroidsNSAIDS, Cox2 inhibitorsCocaine, amphetamine, ethanolNaCl

Prevalence of Hypertensive CrisisMainly due to more effective treatment ? Hypertensive crisis( % of all pts )1950s1990s1243Zampaglione, et al. AHA ; 27 (1) : 144

Retinal findings in hypertensive encephalopathy

EvaluationInitial 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 CRISISBP > 220/120 mmHgNeurological sign(encephalopathy or stroke)Retinopathy grade 3-4Severe chest pain(Ischemia or dissecting aneurism)Pulmonary edemaEclampsiaCathecolamine excessAcute renal failureHeadacheNo neurological signsNo target organ damageEMERGENCYURGENCYIntravenous therapyIdentify the causeIn panic attacks or anxiety use analgesic, anxiolyticsOtherwise use oral antihypertensive agentsrecheck in 6-24 hours

Therapy Approach in Hypertensive CrisesAs 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 EmergenciesPatients must be hospitalized for monitoringDire consequences of lowering BP too quicklyTreated with parenteralLower 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 bolusAvoid the urge to turn to sublingual nifedipineHypertension,Brian C. Poole and Anitha Vijayan in Nephrology and Subspeciality Consult,Lippincott Williams and Wilkins,2004

Intravenous Agents for Hypertensive Emergencies

AgentOnsetDurationAdvantageDisadvatageDiltiazem 5-10 min2-4 hrsCNSprotection,coronary & renal perfusionBradycardiahypotensionNitroglycerine2-5 min3-5 minCoronary perfusionTolerance, variable efficacyFenoldopan< 5 min5-10 minRenal perfusionIncrease IOPHydralazine10-20 min3-9 hrsEclampsiaTachycardia, headache,ICP Nicardipine5-15 min1-4 hrsCNS protectionAvoid in CHF or cardiac ischemia or ICPEnalaprilat15-30 min6 hrsCHF, acute LV failureAvoid in MINitroprussideImmediate< 3 minPotent, titratableCyanide, thiocyanate,>ICP

Preferred Drugs for Selected Hypertensive EmergenciesHypertensive emergencies,Roy Colven,in Emergency Medical Therapy,2000. WB saunders Company

EmergencyPreferred DrugsDrugs to AvoidCVADiltiazemLabetalolNicardipineDiazoxide,hydralazine (increase ICP), nitroprusideHypertensive EncephalopathyDiltiazemNicardipineLabetalol NitroprussideDiazoxide,hydralazine (increase ICP)

Congestive Heart FailureNitroglycerine Loop DiureticsNitroprussideEnalaprilateLabetalol and Esmolol (decreased HR), nicardipine,diltiazemMyocardial infarct, AnginaDiltiazemNitroprussideNitroglyceriNicardipineneDiazoxide,hydralazine (increase HR,O2 demandAortic DissectionNitroprussideLabetalolEsmololDiazoxide,hydralazine, nicardipine

Diltiazem inj1 amp 50 mg. dosis 5-15 ug/kgbb/min2 amp=100 mg/100 cc NS100.000 ug/100 cc NS1000 ug= 1 ccMisal BB 60 kg, dosis 5 ug/kgbb/min5x60/1000 x 1cc = 0,3 cc/min=6 tts/min makro =18 tts/min mikro

PANDUAN DOSIS & PENGGUNAAN NICARDIPINE INJEKSI

INDIKASIHIPERTENSI EMERGENSIDosis : 0.5 6 Mcg/Kg BB/menit (syeringe pump / infus drip) Krisis hipertensi akut selama tindakan operesiDosis : 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

SYRINGE PUMPNicardipine injeksi 1 ampul 10 mgSpuit 50 cc(mL/jam)

Atau

Pediatric Drip(=1 cc = 60 tetes)INDIKASIKRISIS HIPERTENSI AKUT SELAMA OPERASIHIPERTENSI EMERGENSIBERAT BADANDOSIS NICARDIPINE INJEKSI (mcg/kg BB/menit)0.51.01.52.03.04.05.06.07.08.09.010.040 kg612182436486072849610812050 kg81523304560759010512013515060 kg918273654729010812614416218070 kg11213242638410512614716818921080 kg12243648729612014416819221624090 kg1427415481108135162189216243270

Nicardipine inj1 amp 10cc=25 mg. Dosis 0,5-6 ug/kgbb/min 25 mg/50 cc NC25.000 ug/50 cc500 ug/1 ccMisal BB 60 kg dgn dosis 0,5 ug/kgbb/min0,5x60/500 x 1cc=0,06 cc/min=0,06 x 60=3,6 cc/jam

Nitroglycerine inj10 mg/10cc. Dosis 5-100 ug/min10 mg/50 cc NS10.000 ug=50 cc NS 200 ug=1 ccBila 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/menitDIENCERKANKONSENTRASIKECEPATAN INFUSKONSENTRASIKECEPATAN INFUS5 x amp 10 ml nitroglycerine dalam 500 mlmll/jamdrop/menit100 g/ml: 5 x amp 10 mlnitroglycerine dalam 50 mlml/jam drop/menit

106100,62012201,23018301,84024402,45030503,06036603,67042704,28048804,89054905,4100601006,0110661106,6120721207,2130781307,8140841408,4150901509,0

Management of HTN UrgenciesNo proven benefit of rapid BP reduction in asymptomatic patientsGoal BP 160/110 mmHg or fall less than 25% MAP within 6 -48 hoursOral medications preferred,shortacting given in repeated dosesClose monitoring for overshoot hypotensionThereafter, a longer acting agent is prescribedHypertensive emergencies: Malignant hypertension and hypertensive encephalopathy .UpToDate. Norman M Kaplan, MD. Last literature review version 16.3: September 2008

Management of HTN UrgenciesPreviously 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 UrgenciesUntreated hypertensionRelatively 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 UrgenciesBlood pressure reduction over one to two daysoral 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 HgExceptions 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 hypertensionHypertension. January 12, 2004;43:137.)Blood pressure management in Acute Ischemic Stroke

Blood pressure management in Acute Ischemic StrokeMost 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 treatmentRaised 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 pressureIn 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 strokeRationally theoreticalLowering BP decrease the risk of ongoing bleedingOver aggressive treatment of BP CPP brain injury >> if ICP Blood pressure management in ICH

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). if systolic BP is < 180 mmHg and diastolic BP < 105 mmHg, defer antihypertensive therapy. 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.879798127128-137138-147148-157158-177178-197> 198Systolic blood pressuremmHg Standard risk48-6869-8383-8888-9393-9898-108108-118> 118Diastolic blood pressure0 100 200 300 400 500 600 700 800Mortality ratio in %womanmenmenwoman

Drugs for hypertensive urgenciesCaptoprilEnalaprilClonidine Labetalol Prazosinenitroglycerineminoxidil

Differentiate secondary from essential HTNPrepubertal children(

Dosage and AdministrationEach ampoule of DILTIAZEM-Injection should be dissolve in at least 5 mL aquadest or NaCl or glucose solution before use. DILTIAZEM-InjectionBOLUS 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 INJEKSIContoh : HERBESSER INJ. Konsentrasi 0,1 % HERBESSER INJ -------------------- = ---------Pelarut 50 mlContoh :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 BC50 mg

Lancet 2000; 356: 41117Autoregulation of Cerebral Blood Flow

Dosis diltiazem-injeksi pada Hipertensi Krisis

Effect of a Drip Infusion Diltiazem on Severe Systemic Hypertension 25020015010050755001050.5123456Dose infused g/kg/minPulse Rate beats/minBlood Pressure mmHg2927*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 SBPmeanDBP24.6%26.9%8.9%205 mmHg115.8 mmHg154mmHg83.3mmHg87.178.1

Herbesser i.v. causes less increaseof intracranial pressure.Nicardipine i.v.Hirayama A, Katayama Y, et al:Neurological Research 16; 97-99, 199435 patients who had surgical evacuation of spontaneous intracerebral haematomas after cerebral hemorrhageHerbesser i.v.: 12, Nitroglycerin i.v.: 13, Nicardipine i.v.:10Compare the intracranial pressure when the same blood pressure reduction level is achieved in each group.CPP index=CPP/SBPCPP index coming close to 1 indicates less increase of intracranial pressure.Comparison of intracranial pressure change by different antihypertensives.Change of intracranial pressureComparison of Cerebral perfusion pressure index (CPP index) by different antihypertensives.CPP indexHerbesser i.v.Nitroglycerin i.v.Nicardipine i.v.Herbesser i.v.Nitroglycerin i.v.201002.01.50.01.06.714.217.01.330.071.800.111.630.13p