HYPERTENSIVE EMERGENCIES

HYPERTENSIVE EMERGENCIES Louis Muller 11 March 2009 Content • • • • • • • • • • • • Introduction Definitions Prevalence/morbidity/mortality Etiology & pathophysiology Diagnosis Causes Differential diagnoses Workup Management Treatment Pharmacology IV Anti-hypertensives References Introduction • • • • • Hypertension(HPT) very common Western soc. 50 mil. US – affected (world - approx. 1 billion people) Despite awareness + treatment still 30% adults unaware 40% known with HTN - not on treatment 60% on treatment BP not controlled to <140/90 mm Hg • New data – shown incr. lifetime risk of HPT - incr. risk of CVS complications with “normal” BP levels Classification • Joint National Committee (JNC – 7) introduced a new classification system for HTN – 2004 • Normal – SBP<120 and DBP<80 • Prehypertension – SBP 120-139 or DBP 80-89 • Stage I hypertension – SBP 140-159 or DBP 90-99 • Stage II hypertension – SBP >160 or DBP >100 • Stage II HPT further divided into: – Hypertensive urgency – Hypertensive emergency Other Terminology • Severely elevated BP (JNC VII) • Defined as BP > 180/120 • “accelerated HPT” – term used to describe individuals with chronic hypertension with associated group 3 KeithWagener-Baker retinopathy • “malignant HPT” – describe those individuals with group 4 KWB retinopathy changes + papilledema Definitions • HPT emergency(crisis): Is characterized by a severe elevation in BP, complicated by evidence of impending or progressive target/end organ dysfunction VS • HPT urgency: is a severe elevation in BP without progressive target organ dysfunction NB – these definitions do not specify absolute BP levels Conditions constituting evidence of EOD • • • • • Hypertensive encephalopathy Intracerebral heamorrhage Stroke Head trauma Ischemic heart disease (most common) – AMI – Acute LVF with P/oedema – Unstable angina • Aortic dissection • Eclampsia • Life threatening arterial bleed Prevalence/ morbidity/ mortality Prevalence: - With progress in anti-hypertensive Rx – decrease in the lifetime incidence of HPT emergencies from 7% to 1% - Hypertensive crisis more common among elderly and black patients - Studies – HPT related problems amount for 25% of all pt visits to medical section of ED. 33% of these - HTN emergencies. Morbidity/mortality - Dependent on the extent of EOD on presentation and the degree to which BP is controlled subsequently. - 1year survival rate has increased from 20% to more than 90% with appropriate treatment. - 10-year survival rate approaches 70% with approp treatment - 1-year and 5-year mortality rate - following untreated HPT emergency are 70 to 90% and 100% respectively Etiology • Most common - rapid unexplained rise in BP in pt with chronic essential HPT - most have history of poor treatment/compliance or an abrupt discont of their meds • Other causes Renal parenchymal disease (80% of sec.causes) Systemic disorders with renal involvement (SLE) Renovascular disease (Atheroscleroses/fibromuscular dysplasia) Endocrine ( phaeochromocytoma/cushing syndrome) Drugs (cocaine/amphetam/clonidine withdrawal/diet pills) CNS (trauma or spinal cord disorders – Guillain-Barre Coarctation of the aorta Preeclampsia/Eclampsia Postop. HPT Pathophysiology • Not well understood • Failure of normal autoregulation + abrupt rise in SVR • Increase in SVR due to release of humoral vasoconstrictors from the stressed vessel wall. • Endothelium plays a central role in BP homeostasis via substances as Nitric oxide and prostacyclin • Increased pressure starts a cycle of - endothelial damage - local activation of clotting cascade - fibrinoid necrosis of small vessels - release of more vasoconstrictors • Process leads to progressive increase in resistance and further endothelial dysfunction Pathophysiology • Single organ inv. in approximately 83% • Two organ inv found in 14% • Multiorgan involvement found in 3% of pts • Most common clinical presentations - cerebral infarction(24%) - pulmonary oedema (22%) - HPT encephalopathy(16%) - Cong. HF (12%) • Less common presentations – IC hemorrhage, aortic dissection and eclampsia Case example - HPT Encephalopathy • 52yr male presents to ED • worsening headache and confusion, numbness and weakness involving right side of body, blurry vision over past 12 hrs • PMx: HPT, bilateral artery stenosis, cocaine abuse, hyperlipidemia. • Exam: – – – – – – BP 213/134 confused, papilledema on fundoscopy Mild motor weakness (4/5) right arm Lab studies rased creatinine ECG – LVH CT Brain – diffuse bilateral white matter changes – HPT encephalopathy Case example – HPT Encephalopathy • Mx – admitted ICU – started on IV Nitroprusside – BP decreased to 190/100 mmHg over first 3hrs • Outcome: – Neurology symptoms resolved within 5hrs – he was switched to his usual oral regimen on 3rd day in hospital – discharged day 5 – controlled BP Hypertensive encephalopathy • Clinical manifestation of cerebral edema and microhemorrhages seen with dysfunction of cerebral autoregulation • Defined as an acute organic brain syndrome or delirium in the setting of severe hypertension HTN Encephalopathy • Symptoms – – – – – Severe headache Nausea and vomiting Visual disturbances Confusion focal or generalized weakness • Signs – Disorientation – Focal neurologic defects – Focal or generalized seizures – nystagmus HPT Encephalopathy • Not adequately treated – cerebral heamorrhage, coma and death. • BUT with proper treatment – completely reversible • Clinical diagnoses (exclusion) Hypertensive Retinopathy • Fundoscopy used to be considered a definitive tool in diagnosing HTN encephalopathy • NOW – still usefull in recognizing acute EOD as in HTN encephalopathy, but the absence of retinal exudates, hemorrhages, or papilledema does not exclude the diagnoses. • Fundoscopy findings HPT Retinopathy Fundoscopy • Keith-Wagener classification – Stage I arteriolar sclerosis with thickening, irregularity and tortuosity – Stage II AV dipping or compression – Stage III Flame shaped haemorrhages and cotton wool spots – Stage IV Papilledema • “presence of stage III and IV lesions – implies failure of the CNS vascular autoregulation and makes the Dx of Malignant HPT definitive” HPT Retinopathy AV crossing changes HPT retinopathy HPT retinopathy PanOptic ophtalmoscope Diagnosis • History 1) focus on presence of Sx of end-organ dysfunction(eod) 2) any identifiable etiology • Hypertension Hx – – – last known normal BP prior diagnoses + Rx dietary and social factors Steroid use Estrogens Sympathomimetics MAO inhibitors smoking, alcohol illicit drugs (cocaine, stimulants) early HPT in family members cardiovascular and cerebrovascular disease Diabetes Pheochromocytoma • Medication – – – – • • Social history – – – – – – Family history • Pregnant? Diagnoses • History (cont) • Symptom spesific Hx – suggesting EOD • CVS Hx – previous MI/angina/arrhythmias – chest pain/SOB/Sx of CF/claudication/flank or back pain • Neurologic Hx – prior strokes, neuro dysfunction – visual changes, blurriness, loss of visual fields, severe headaches, nausea and vomiting, change in mental status • Renal Hx – Underlying renal disease (RF) – Acute onset changes in renal frequency (anuria/oliguria) • Endocrine Hx – diabetes, thyroid dysfunction, Cushing’s syndrome Diagnoses Examination 1) Confirm elevated BP » » Proper position, appropriate cuff size Supine and standing and both arms 2) • Asses – EOD present Fundoscopy • Chronic HPT will have findings • Acute changes new retinal bleeds Superficial/flame shaped Deep/punctuate exudates hard/cotton wool spots papilledema Neck Enlarged thryoid, carotid bruit, jugular venous distention CVS Enlarged heart, S3, asymmetric pulses, arrhythmias Pulmonary Signs of LV dysfunction ( crackles, rhonchi) Renal Renal bruit, abdominal masses Neurologic Level of consciousness, evidence of stroke, any focal signs • • • • • Workup • Lab studies Electrolytes, urea and creatinine FBC and smear Urinalysis – dipstix + microscopy Optional - tox screen - BHCG - Endocrine testing Imaging studies CXR (chest pain or SOB) Head CT/MRI brain (abn neurology) Chest CT/TEE/Aortic angio (Aortic dissection) • - • Other Tests - ECG Management • ED considerations - Many HPT pts – only small number will require emergent treatment Primary goal of EP? The pts – syptoms of EOD and require immediate iv parenteral therapy. VS The pt with acutely elev BP(SBP>200 or DBP>120) without EOD symptoms, who require initiation of medical therapy and close follow up as outpatient /inpatient Management • The EP must be capable of: - Appropriately evaluating pts with an elevated BP - Correctly classify the HPT - Determine the aggressiveness and timing of therapeutic interventions - Making disposition decisions Remember - “treat the patient and not the number” Treatment • Prehospital care - Address the manifestations of a HPT emergency eg.chest pain or HF - Reduction of BP not indicated in prehospital setting - Rapid lowering of BP can critically decrease end-organ perfusion Treatment • 1. 2. ED Care - general principles Consider context of elevated BP (pain, anxiety) Screen for EOD (Hx/workup) - Pts without evidence of EOD – d/c + f/up Misconception - never d/c patient from ED with elevated BP ? - oral nifedipine – NOT indicated and may be dangerous! - Pts with EOD – require ICU admission and rapid but gradual lowering of BP - 3. - using IV meds. BP should not be lowered to normal levels Rapid reduction in BP – below the autoregulatory range results in reduction in organ blood flow – risk of ischemia and infarction General rule – the MAP should be lowered by no more than 20% - 1st hour remains stable - BP lowered to 160/110 in next 2-6hrs NB Exceptions BP goals best achieved by a continuous infusion of a short-acting, titratable, parenteral anti-HPT agent, along with constant intensive patient monitoring Treatment • Medication options 1. Oral antihypertensives • • Chronic hypertensive Hypertensive urgency 2. IV antihypertensives • Hypertensive emergency Pharmacology – IV anti-HPT 1. Vasodilators • • • • • • Sodium nitroprusside Nitroglycerin Nicardipine Fenoldapam Hydralazine Enalapril 2. Adrenergic inhibitors • • • Labetalol Esmolol Phentolamine “IDEAL IV ANTI-HYPERTENSIVE” • Lower the BP without compromising blood flow to critical organs • Vasodilators generally considered 1st , because they preserve organ blood flow in the face of reduced perfusion and also tend to increase CO. Profile of an ideal IV antihypertensive • Preserves GFR and renal blood flow • Few or no drug reactions • Little or no potential for exacerbation of co-morbid conditions • Rapid onset and offset of action • Minimal hypotension “overshoot” • Minimal need for continuous BP monitoring and frequent dose titration • No acute tolerance • Ease of use and convenience • Safe and no toxic metabolites • Multiple formulations for short and long term use • Minimal symphathetic activation Sodium Nitroprusside (Hypoten L) • MoA: – – – – • • • Direct smooth muscle dilator (art + ven) Nitric oxide compound Potent preload and afterload reducer Causes cerebral vasodilation Ultra short acting Immediate onset - DoA : 10min Dose: 0.1-0.5mcg/kg/min IV infusion titrate to desired effect rates>10mcg/kg/min – cyanide toxicity Adverse affects/Precautions: • – Cyanide and thiocyanate toxicity (pts with liver/renal dysfunction) Max dose, max 10min – Can cause precipitous drop in BP (hypotensive effects unpredictable) Ideally Art.line with continuous BP monitoring – Causes significant reflex tachycardia ( incr Oxygen demand) (angina/aortic dissection/cerebral oedema) – Nausea and vomiting – Increased ICP • Drug of choice: – Perioperative HPT – Cocaine toxicity – Aortic dissection(combination) – Neurologic syndromes Nitroglycerin (Nitrocine / Isoket / Tridal) • MoA: – – – Potent vasodilator (nitric oxide compound) Primary affects the venous system, decrease preload (CO + BP) Decreases coronary vasospasm • • • Dose: cont infusion start 5mcg/min, incr by 5mcg/min every 3-5min to 20mcg/min If NO Response increase by 10mcg/min every 3-5min,up 200mcg/min Onset : 2-5min/DoA : 5-10min Adverse effects/precautions: – – – Constant monitoring is essential Tolerance from uninterrupted use (12hr withdrawal) Headache, tachycardia, flushing • Contra ind: – – – Concurrent use with PDE-5 inhibitors - causes significant hypotension Head trauma/cerebral haemorrhage Severe anaemia • Drug of choice: – – Acute HF ACS Nicardipine (Nimodipine – Nimotop) Ca channel blocker – selective arterial vasodilator Onset: 1-5min DoA: 15-30min Dose: start 5mg/hr IV infusion, titrate every 15min to max 15mg/hr. • Advantages: – Cause cerebral and coronary vasodilatation • • • • • Precautions: can worsen/cause HF and liver failure can exacerbate renal insuff. • Ideal for CNS emergencies • Not available SA Fenoldapam (Carlopam) • • New (not available SA) MoA: – – – – Peripheral dopamine agonist (high vs low doses) causes selective neuro vasodilatation mesenteric vasodilatation increases renal blood flow and sodium excretion • • • Onset – <5min, but more gentle, lasts for 30min (titratable, predictable and stable) Standard BP monitoring is sufficient, no toxic metabolites Dosing: • • • Start at 0.1-0.3mcg/kg/min IV infusion May be increased in increments of 0.05-0.1mcg/kg/min every 15min, until target BP reached Max infusion rate – 1.6mcg/kg/min • Precautions: – – – – – Pts with glaucoma or intraocular hypertension Dose related tachycardia can occur – angina Close BP monitoring Close K monitoring Caution with raised ICP Renal insuffiency Strokes ( combination with nicardipine) • Drug of choice – – Hydralazine (Apresoline) • MoA: – Decreases systemic resistance by direct vasodilation of arterioles • • Dose: – – – – 5-20mg IV bolus or 10-40mg IM repeat every 4-6hrs used too much boluses takes 20min to work not titratable “old school” • Adverse effects/Precautions – – – – – tachycardia, flushing, headache sodium and water retention increased ICP adjust dose in severe renal dysfunction response may be delayed and unpredictable • • Still drug of choice in pregnancy(Eclampsia), but B-blocker/Labetalol and Fenoldapam are also safe options Only available PO, Dihydralazine discontinued Enalaprilat • The active component of Enalapril (hydrolyzed in liver and kidney) • • • • MoA: – ACE inhibitor Dose: – 0.625-2.5mg every 6hr IV – Not titratable Onset – within 30 min + long half life Adverse effects/Precautions – Contra-indicated – volume depletion, renal vascular disease – Prolonged ½ life • Expensive, not available SA Labetalol (Trandate) • MoA: – selective alpha blocker – will reduce vascular smooth m. resistance – non-selective Beta blocker – decrease cardiac inotropy and miocard O2 consumption, will prevent reflex tachycardia Dose: – Bolus: effect in 5-10min,max effect at 20min. (DoA: 2-6hrs) 1st dose 20mg then every 10-20min 2nd dose 40mg, 3rd dose 80mg. – Cont. infusion: 0.5 – 2mg/min – titrate to response,max 300mg total dose – Difficult to titrate due to very wide dose range Advantages: – smooth onset – Transition to oral Rx easy (dose equivalent) – Improve cerebral bloodflow – stroke pt – No need for ICU/Arterial line • • • • • Adverse effects/precautions – Relative CI – Heart failure, heart block, Asthma (bronchoconstriction) – Vomiting, scalp tingling – Impaired hepatic function – Elderly patients Contraindicated in HPT secondary to Cocaine use/Phaeochromocytoma (B-blocker effect outway the alpha effect, thus unapposed alpha constriction) Drug of choice: – Aortic dissection – Hypertensive emergencies Esmolol (Brevibloc) • • MoA: – highly selective beta blocker Dose: (titratable) – – – bolus: 250-500mcg/kg IV over 1-3min infusion: 50-100mcg/kg/min may repeat bolus after 5min or increase infusion rate to 300mcg/kg/min • • Onset 1-2min / short acting Adverse effect/Precautions – – – – – Hypotension common nausea Asthma 1st degree AV block heart failure Sinus bradycardia Heart block Cardiogenic shock Bronchial asthma Uncompensated CF pregnancy Aortic dissection ( with nitrate) • Contraindications – – – – – – • • Drug of choice: – Not availalble anymore Phentolamine (Regitine) • • • • MoA: – – – alpha adrenergic receptor blocker load 5-20mg IV every 5min or infusion 0.2-0.5mg/min Dose: Onset 1-2min Adverse effect/precautions – – – – tachycardia flushing/headache MI cerebrovascular spasm renal impairment Concurrent use with PDE-5 inhibitors coronary or cerebral arteriosclerosis Cocaine associated HPT crisis Pheochromocytoma HPT crisis • Contra-indications – – – • • Drug of choice – – Not available in SA anymore Neurological emergencies • Hypertensive encephalopathy – reduce MAP by 25% or diastole to 100mmHg over 8 hrs – If neurology worsens, suspend Rx – Drug of choice: • Sodium nitroprusside • Labetalol Neurological emergencies • Acute Ischemic stroke – – – – – often loss of cerebral autoregulation ischemic region more prone to hypoperfusion thus BP reduction not recommended unless SBP>220 or DBP>120 UNLESS planning fibrinolysis – SBP<185 and DBP< 110 – Drug of choice: • Labetalol • Nicardipine • Sodium Nitroprusside Neurological emergencies • Acutes ICH/SAH – Treatment based on clinical/radiographic evidence of raised ICP – Raised ICP – MAP<130 (1st 24hrs) – No raised ICP – MAP<110 – Drug of choice: • Sodium Nitroprusside • Labetalol • Nicardipine Cardiovascular emergencies • ACS – treat if SBP>160 and/or DBP>100 – Reduce MAP by 20 -30% of baseline – nitrates should be given till symptoms subside or until DBP<100 – Drug of choice: • Nitroglycerine • Labetalol • Nicardipine CVS emergencies • Acute HF (pulmonary edema) – treat with vasodilator (additional to diuretics) – Sodium Nitroprusside in conjunction with morphine, oxygen and loop diuretic – Enalaprilat also an option CVS emergencies • Aortic dissection – anti-hypertensive Rx is aimed at reducing the shear stress on aortic wall (BP and Pulse) – immediate lowering of BP – lifesaving – maintain SBP<110, unless signs of end organ hypoperfusion – preferred Rx is combination of Morphine, B-blocker and vasodilator – Nitroprusside + Labetalol Other disorders • Cocaine toxicity/pheochromocytoma – Hpt and tachycardia rarely require spesific Rx – Alpha adrenergic blockers – preferred – B – blockers can be added, but only after alpha blockade. – Drug of choice • Phentolamine • Labetalol • Diazepam Other disorders • Pre-eclampsia/Eclampsia – Goal SBP<160 and DBP<110 in pre-andintrapartum periods. – Platelets < 100 000, BP should be maintained < 150/100 – IV Magnesium to prevent seizures – Drug of choice: • Methyldopa • Hydralazine Other disorders • Perioperative hypertension – target BP to within 20% of baseline, except if potential for life threatening arterial bleeding – typically related to catecholamine surge postop. – Drug of choice: • B-blocker • Labetalol Local • Tygerberg – F1(medical outpatients) • Nitroglycerine – Cardiology ICU • Nitroglycerine – Renal unit • Labetalol – Obstetrics • Labetalol • Hydralazine Local • Grootte Schuur (C15) – Nitroglycerine (Tridal) • Victoria – Nitroglycerine (Tridal/Nitrocine) – Labetalol – Can get Sodium nitroprusside Summary • HPT crisis - serious condition - associated with EOD, if left untreated • High mortality - untreated • Main causes – non-compliance and poorly controlled chronic hypertension. • Urgency vs emergency • Treatment should be tailored to the individual’s condition • HPT urgency – initial goal max 25% drop in MAP in first 3 hours • Precipitous drop just as bad – good continuous monitoring essential References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure.Seventh Report. Hypertension 42:2003; 1206-1252 Kitiyakara C, Guzman NJ. Malignant hypertension and hypertensive emergencies.J Am Soc Nephrol 1998;9:135 Vaidya CK, Ouellette JR. Hypertensive Urgency and Emergency. Hospital Physician March 2007; 43-50 Vidt D. Hypertensive Crises: emergencies and urgencies. The Cleveland clinic disease management project. 12 Jan 2006. Available at www.clevelandclinicmeded.com/diseasemanagement/nephrology/crises/crises.htm McCowan C. Hypertensive Emergencies. Available at www.emedicine.medscape.com/emergencymedicine/cardiovascular. Updated Jan 26, 2009 Hollander JE. Cocaine intoxication and hypertension. Ann Emerg Med. Mar 2008;51:S18-20 Characteristics and management op patients presenting to the emergency department with hypertensive urgency. 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