How to Handle Hypertension Crisis

Transcription

1 How to Handle Hypertension Crisis Learning Objectives 1. Define hypertensive crises: Hypertension urgency and hypertension emergency 2. Outline the pathophysiology of hypertensive urgencies and emergencies 3. Identify treatment goals and treatment options for hypertensive crises Faculty Karol E. Watson, MD, PhD, FACC Professor of Medicine/Cardiology, Co-director UCLA Program in Preventive Cardiology Director, UCLA Barbra Streisand Women s Heart Health Program Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles, California Slides are current as of the time of printing and may differ from the live presentation due to copyright issues. Please reference for the most up-to-date version of slide sets. West Annual Conference Anaheim, California April 27-30, 2016

2 Current State of Hypertensive Crisis Management Hypertension Emergencies in context Hypertensive crises are among the most misunderstood and mismanaged acute medical problems seen in clinical practice Delays in initiating therapy can cause severe complications in target end organs Overzealous therapy or too-rapid reduction in blood pressure may be equally damaging Consideration of the pathophysiologic principles involved in hypertensive crises is of utmost importance Varon J, Marik PE. Chest. 2000;118: Epstein M. Clin Cornerstone. 1999;2: Chronic Hypertension Hypertension Emergencies Hypertension Urgencies Hypertensive Urgencies / Emergencies: Classification / Definition Etiology / Pathophysiology Evaluation Management Follow up Terminology and Definitions (JNC 7) Urgency Emergency Severe The Hypertension diagnosis plus of hypertensive End-organ Damage BP > 180/110 mm Hg CHF emergencies depends on the ACS/AMI clinical manifestations rather Renal failure than only on the absolute Stroke and level ICH of the blood pressure. Encephalopathy Aortic dissection Pre-eclampsia Other? Hypertensive crisis You will almost certainly see a hypertensive urgency in your career You will also likely see a hypertensive emergency - Only occur in 1-2% of the hypertensive population - But, there are 50 million hypertensive Americans - 500,000 hypertensive emergencies/year Higher in the elderly and African Americans Incidence is twice as high in men as compared to women Hypertensive Urgencies / Emergencies: Classification / Definition Etiology / Pathophysiology Evaluation Management Follow up

3 Most Hypertensive Crises are caused by: Sodium excess Extracellular volume expansion Sympathetic overactivation Too Much Sodium (Salt) Too Much Water Too Much Sympathetic Activity Pathophysiology of Hypertensive Emergencies: a Vicious Cycle Hypertensive Emergency Circulating vasoconstrictors End organ ischemia Abrupt Loss of Abrupt Autoregulatory function Endothelial damage SVR BP Vasoconstriction, often with intravascular hypovolemia causes: - Increased circulating catecholamines - Activation of reninangiotensin-aldosterone system - Altered autoregulatory function Ault NJ, et al. Am J Emerg Med. 1985;3(6 suppl): Wallach R, et al. Am J Cardiol. 1980;46: Varon J, et al. Chest. 2000;118: Kincaid-Smith P. J Hypertens. 1991;9: How do patients with hypertensive crises present? Signs and Symptoms Headache Epistaxis Chest Pain Dyspnea Faintness Agitation Signs and Symptoms Neurologic Deficit Vomiting Arrhythmia HTN Urgency (%) HTN Emergency (%) Zampaglione B, et al. Hypertension 1996;27: Signs and Symptoms Headache Epistaxis Chest Pain Dyspnea Faintness Agitation Signs and Symptoms Neurologic Deficit Vomiting Arrhythmia HTN Urgency (%) HTN Emergency (%) Zampaglione B, et al. Hypertension 1996;27: Hypertensive Urgencies / Emergencies: Classification / Definition Etiology / Pathophysiology Evaluation Goals of evaluation Management are to determine Outcomes etiology, and rapidly assess for end organ damage

4 End-Organ Damage Characterizes Hypertensive Emergencies Brain Hypertensive encephalopathy Stroke Cardiovascular System Unstable angina Acute heart failure Acute myocardial infarction Acute aortic dissection Dissecting aortic aneurysm Retina Hemorrhages Exudates Papilledema Kidney Hematuria Proteinuria Decreasing renal function Symptoms Initial Evaluation Medical History - Episodic palpitations and perspiration? Medications - MAO inhibitors - Clonidine Social History - Recreational Drugs Amphetamines Cocaine Phencyclidine Adapted from Varon J, Marik PE. Chest. 2000;118: Physical Exam Blood pressures must be taken in both arms - If the cuff is too small, the BP will be falsely elevated - If the cuff is too low (below the level of the heart), the BP will be falsely elevated Pulses should be checked in upper and lower extremities Neuro exam Cardiac exam Pulmonary exam Ocular exam: only happens in 13% of pts Hypertensive Retinopathy Grade 1 mild narrowing or sclerosis of retinal arteries (arteriolar narrowing) Grade 2 moderate to marked arteriolar narrowing with A-V crossing changes (AV nicking) Grade 3 All the above + hemorrhages or cotton-wool spots Grade 4 All the above + additional swelling of the optic disk (papilledema) Labs / Imaging to consider Comprehensive Metabolic Panel CBC with peripheral smear (which may suggest microangiopathic hemolytic anemia). Urinalysis EKG Chest X-ray Head CT Echocardiogram Hypertensive Urgencies / Emergencies: Classification / Definition Etiology / Pathophysiology Evaluation Management Outcomes

5 Elderly woman with hypertension Management of Hypertensive Urgencies (BP > 180/110 mm Hg with NO end organ damage) 78 year old woman with longstanding hypertension During a routine follow up visit BP = 205 / 75 No complaints except not feeling right ; fundi no visualized due to cataracts but otherwise normal exam Admits to running out of her BP medications Goals of Therapy of Hypertensive Crises Hypertensive urgencies can generally be managed with oral medications as an outpatient. BP should be lowered over hours - Important to prevent too-rapid lowering Hypertensive emergencies must be treated as an inpatient, usually in the ICU with intravenous medications. Goal is to reduce MAP by ~ 20% within first hour - Some conditions, such as aortic dissection or hemorrhagic stroke require even more rapid reduction Elderly woman with hypertension 78 year old woman with chronic hypertension; BP = 205 / 75; exam - normal Admitted to running out of her BP medications Placed in a quiet room and administered usual meds 2 hours later BP 165/70; she felt well; normal exam Sent home on usual meds with home health JNC 7, JAMA 2003; 289: year old man with chest pain and shortness of breath Management of Hypertensive Emergencies (BP > 180/110 mm Hg WITH end organ damage) 39 year old male with chronic substance abuse, renal failure (on hemodialysis), and hypertension Missed last dialysis appointment and admits to current methamphetamine use Presents to ED with severe chest pain and shortness of breath BP 250/140 mm Hg

6 39 year old man with chest pain and shortness of breath CxR CHF with pulmonary vascular congestion ECG TW inversions inferiorly Tn I 0.11 (ULN 0.04) DIAGNOSES: Hypertensive EMERGENCY due to: - Missed HD, methamphetamine use, medication nonadherence Myocardial ischemia (NSTEMI) Congestive heart failure Presenting Symptoms Hypertensive Urgencies - Epistaxis - Headache - Psychomotor agitation Hypertensive Emergencies - Neurologic deficits - Chest pain - Dyspnea Zampaglione et al, Hypertension 1996;27:144 How Low Should You Go? Simple answer % reduction in MAP within 1 st hour Better answer - It really depends on clinical condition Less aggressive with ischemic stroke More aggressive with hemorrhagic stroke, acute HF and aortic dissection Hypertensive Encephalopathy PRES: Posterior reversible encephalopathy syndrome Typically symmetrical white matter edema in the posterior cerebral hemispheres Marik and Varon. Critical Care 2003, 7: Cerebral Autoregulation Is Central to Treatment of Hypertensive Crises Cerebral Blood Flow Normal Regulatory (BP ~ 120/70 to 240/150) Range Autoregulation In the uninjured, normotensive brain, autoregulation is effective over mean arterial pressure (MAP) of ~ (that s a BP ~ 80/40 to 190/130) Increasing risk of hypertensive encephalopathy Increasing risk of ischemia 0 (BP ~ 80/40 to 190/130) Normotensive Chronic hypertensive MAP (mm Hg) Adapted from Varon J, Marik PE. Chest. 2000;118: In chronic hypertension, this range isshifted upwards to MAP (BP ~ 120/70 to 240/150) So, in the patients with out of control hypertension, if BP falls too rapidly to below ~120/70 cerebral perfusion can be compromised All blood pressure sensitive organs have some degree of autoregulation

7 Hypertensive Emergency: Goals of Therapy Immediate and controlled BP reduction - Reduce BP 20-25% within minutes to 1 hour - If BP is then stable, target toward 160/ mm Hg over the next 2-6 hours - If this level of BP is well tolerated and the patient is clinically stable, further gradual reductions toward normal BP over the next hours More immediate BP reduction in certain cases in - e.g. Aortic dissection, hemorrhagic stroke Increased caution in acute ischemic stroke patients - In general, BP should not be lowered too aggressively JMC 7. US Dept of HHS; NIH publication No ; 2003:54. Adams HP, et al. Stroke. 2005;36: Other Important Points ***ICU, ICU, ICU*** - Some studies suggest that only 15% of pts are admitted 1 st line to an ICU Once BP is stable, oral medications should be started as parenteral (IV) medications are titrated off Do not use sublingual nifedipine or other therapies that lower BP too quickly Be cautious with nitroprusside (except with aortic dissection) because it can decrease BP too quickly, and may increases intracranial pressure Many patients are volume depleted from pressure naturesis so use caution with diuretics BP may drop too quickly Treatment Typically Parenteral (IV) Adrenergic receptor blockers - Esmolol (β 1 ) - Labetalol (α 1 and β) - Phentolamine (α 1 ) - Urapidil (α 1 ) Ca 2+ channel blockers - Nicardipine - Clevidipine ACE inhibitors - Enalaprilat Nitric Oxide (NO) donors Nitroprusside Nitroglycerin Dopamine agonist Fenoldopam Direct vasodilator Hydralazine Agent IV Antihypertensive Agents Onset/ Duration Elimination Half-Life Clevidipine 2-4 mins 5-15 mins Enalaprilat Esmolol Fenoldopam mesylate Hydralazine Labetalol Nicardipine Nitroglycerin Sodium nitroprusside <15 min/ h 1 2 min/ min 5 15 min/ 30 min 4 h min/ 1 4 h <5 min/ 3 6 h 5 15 min/ 15 min 6 h 2 5 min/ 5 10 min Immediate/ 2 3 min 11 h 2 9 min 5 min 1 h 5.5 h 44.8 min 1 4 min 2 3 min Adverse Events Tachycardia, headache, nausea, dizziness, hypotension and vomiting. Precipitous fall in BP in high-renin states, headache, cough, renal failure, hyperkalemia, angioedema Heart block, hypotension, nausea, bronchospasm, overt heart failure, cardiogenic shock Tachycardia, headache, nausea, dizziness, flushing, hypotension, increased intraocular pressure Marked hypotension, tachycardia, flushing Bradycardia (heart block), overt heart failure, cardiogenic shock, edema, nausea, vomiting Tachycardia, headache, nausea, flushing, thrombophlebitis, hypotension, vomiting Flushing, headache, vomiting, hypotension, methemoglobinemia, decreased arterial resistance, reflex tachycardia Nausea, muscle twitching, sweating, thiocyanate and cyanide intoxication, hypotension Cautions/Concerns Contraindicated in patients with allergies to soybeans, soy products, eggs, or egg products. Cautious use in heart failure Avoid in acute MI, long duration of action Reduces cardiac output, which may impair organ perfusion Caution with glaucoma Avoid in aortic dissection, MI, severe renal disease; prolonged and unpredictable effects; difficult to titrate Avoid in acute heart failure; severe bradycardia; heart block, asthma Avoid in acute heart failure; caution with coronary ischemia; long duration of action Reduction in preload and cardiac output undesirable in patients with compromised renal and cerebral perfusion Increases intracranial pressure; may reduce coronary perfusion pressure (coronary steal ); cyanide toxicity 39 year old man with chest pain and shortness of breath Admitted to ICU, treated with IV Nitroglycerine and IV Nicardipine for BP control Given emergent hemodialysis for volume reduction and BP control Over next 2 hours BP decreased to 160/100 mm Hg Chest pain, SOB resolved; ECG normalized Conditions requiring special management 1. Ischemic stroke 2. Aortic dissection 3. Sympathetic crises

8 BP Management in Acute Stroke Most acute stroke patients present with hypertension There is a U-shaped relationship between BP and neurologic outcomes Thus, SBP should be maintained ~ mm Hg during acute stroke and not normalized Mortality Rate (%) month 12 months 80 * mm Hg 60 0 < >220 SBP (mm Hg) Adapted from Vemmos KN, et al. J Intern Med. 2004;255: BP Management in Aortic Dissection If aortic dissection is suspected, treatment of HTN should begin immediately Goal of therapy is to aortic stress by rapidly lowering BP and controlling pulse rate Target is to reduce MAP by 10-15%, or reduce SBP to ~110 mm Hg, in 5-30 minutes Usual drugs are vasodilator + beta blocker, usually Nitroprusside + Esmolol ***NB all vasodilators cause a reflex tachycardia, so they MUST be used in combination with a beta blocker in dissection Varon J, Chest 2000;118: BP Management in Sympathetic Crisis Examples of sympathetic crises In a sympathetic crisis, Beta-blockers will result in unopposed alpha-adrenergic stimulation Thus, in this situation, Beta blocker use can - Paradoxically INCREASE blood pressure - Worsen coronary artery vasoconstriction - Decrease survival In a sympathetic crisis, Avoid beta blockers (including non selective agents such as labetolol) Recommended Drugs in a sympathetic crisis - Nicardipine, Fenoldopam, Verapamil, Benzodiazepines - If pheochromocytoma is suspected use phentolamine Pheochromocytoma Cocaine/amphetamines/OTC herbals (ephedra) Clonidine withdrawal Monoamine oxidase inhibitor + tyramine - Tyramine is found in many foods, and is a sympathomimetic (like amphetamine - Patients on MAOIs experience an exaggerated response to tyramine, resulting in prolonged and severe hypertension Foods containing tyramine Beer Wine Aged cheeses Chocolate Coffee Pickled herring Citrus fruites Broad beans Chicken livers Medications that interact w/ MAOI Meperidine Ephedrine TCAs Reserpine Dopamine Methyldopa Guanethidine Clonidine withdrawal Occurs in patients on clonidine who abruptly discontinue therapy Symptoms are similar to pheochromocytoma symptoms (but usually lesser severity) Occur hours after last dose Treatment is to re-start clonidine

9 IV Antihypertensive Utilization Nitroglycerin 1,400,000 1,200,444 1,200,000 1,133, Labetalol 1,000, , , , ,518 Nitroprusside 400, , , , ,104 8,288 0 Nitroglycerin Labetalol Hydralazine Enalaprilat Esmolol SNP Nicardipine Fenoldopam Caution with Nitroprusside Disadvantages of sodium nitroprusside - Decrease cerebral blood flow and increases intracranial pressure - Can reduce regional blood flow in coronary artery disease - Risk of cyanide toxicity Use when other agents not effective - Monitor thiocyanate levels - Avoid in renal or hepatic dysfunction Thomson Patient Level Data Hypertensive Urgencies / Emergencies: Classification / Definition Etiology / Pathophysiology Evaluation Management Outcomes Follow-up care in hypertensive emergencies Goal: Transition to oral therapy as soon as patient can take po therapy Monitor carefully: Abrupt switch may result in Blood pressure Most patients may be discharged on oral medication within hours Hospitalization for a hypertension crisis is a teachable moment. This is an opportunity to stress improved BP control and medication adherence Vidt DG. In: Hypertension Primer. In press. STAT Registry: Addressing knowledge gaps in contemporary acute hypertension Studying the Treatment of Acute Hypertension Frequency Management with IV agents Patient characteristics Clinical outcomes Study Population Patients 1,588 Age - median 58 (49-70) Female sex 49% Black race 56% White race 34% Qualifying BP Systolic 200 mm Hg ( ) Diastolic 110 mm Hg (93-123) Length of stay 5 days (range 2-9)

10 Medical History Condition % Hypertension 89 Tobacco or alcohol use 38 Diabetes 35 Chronic kidney disease 31 End stage renal disease 11 Previous hospitalization for HTN 27 Neurological event 23 Drug abuse 15 Presenting Characteristics Symptoms % Shortness of breath 29 Chest pain 26 Headache 23 Altered mental status 20 Weak and dizzy 17 Predisposing Factors Contributing to Hypertensive Event Number of IV Antihypertensives During Hospitalization One Two Three or more Factors % Labetolol (n=501) 32% 42% 25% Medication non-adherence 25 Chronic 16 Current 10 Missed or incomplete dialysis 3 Anxiety/psychosocial reaction 2 Drug abuse 11 First IV Antihypertensive Metoprolol (n=277) Nitroglycerin (n=241) Hydralazine (n=235) Nicardapine (n=121) Sodium nitroprusside (n=82) 40% 41% 41% 51% 22% 32% 37% 27% 45% 28% 23% 32% 14% 21% 46% Percent of Patients Outcomes STAT Results 1500 pts, 21 hospitals, 79% Rx in ED Median age 58, Women 49%, AA 58% Initial BP 201/ New End-organ Damage* Granger et al. SCCM February In-hospital Death* 8.4 Admit to 90- day Death* day Readmission day Readmission Due to HTN Median time to SBP of <160 mmhg: 4 hrs 60% increased to >180 after initial control 4% had iatrogenic hypotension 29% had recurrent, severe HTN necessitating reinstitution of parenteral therapy Multiples antihypertensive agents were necessary to achieve control 65% had no documentation of follow-up appointment being scheduled or attended

11 Short-Term (2 to 6 month) Outcomes for various clinical conditions Acute Condition Death Rehospitalization ACS 1,2,3 5-7% 30% CHF 4 8.5% 26% Severe Hypertension 5 7-9% 37% 1. OASIS-5 NEJM GUSTO IIb NEJM GRACE JAMA IMPACT-HF J Cardiac Failure STAT Registry results Summary Acute severe hypertension is - Associated with medical NONadherence - If a hypertensive EMERGENCY, requires ICU admission, IV drugs - Alarmingly low rates of follow-up - High mortality and morbidity, especially with new or worsening end-organ damage Major need to improve prevention and treatment of this important clinical condition