Clinical Management of Hypertensive Urgency in an Urgent Care Setting Urgent message: Effective management of patients presenting to urgent care with acute high starts w ith differentiat- ing between hypertensive emergency and hypertensive urgency and ends with appropriate treatment and counseling.

Sanjeev Sharma, MD, Christy Anderson, PharmD, Poonam Sharma, MD, and Donald Frey, MD

Introduction Pressure (JNC 7) classifies hy- rgent care physicians rou- pertension as shown in Table tinely encounter patients 1. Four categories of blood with high blood pres- pressures are described, the Usure, but management— most significant being Stage particularly for those pa- 2, defined as pressures tients with precarious eleva- >160/100 mmHg. While the tions—remains controversial. JNC 7 does not define a blood Alternative options involve pressure limit for hyperten- the use of various drug-ther- sive urgency or emergency, apy modalities in the urgent the report classifies “severe el- care setting with close obser- evation” in blood pressure as vation, or initiation of oral >180/120 mm HG. medication and releasing the The World Health Organ- patient to home with specif- ization (WHO), Interna- ic instructions. tional Society of Hyperten- The consequences of inap- sion (IHS), and European propriate treatment can be Society of

disastrous, and include my- Inc Researchers, Photo / Evans Brian © (ESH) all classify hyperten- ocardial infarction, , sion as shown in Table 2. In and death. this system, there are six blood pressure categories, with the highest being Stage 3 at >180/110 mmHg. Classification of Hypertension Historically, systolic blood pressure (SBP) >179 and di- Hypertension can be classified in various ways. The Sev- astolic blood pressure (DBP) >109 has broadly been enth Report of the Joint National Committee on Preven- considered to be a “.”1 These pressures tion, Detection, Evaluation, and Treatment of High Blood are further sub-classified as either hypertensive emer-

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gency or hypertensive urgency. Table 1: JNC-7 Classification of Hypertension Hypertensive emergency exists if there are signs of acute end-organ damage Category SBP/DBP (mm Hg) such as encephalopathy, myocardial Optimal <120/80 infarction, unstable angina, pulmonary Prehypertensive 121–139 /80–89 , , stroke, head trauma, life-threatening arterial bleeding, and Stage 1 hypertension 140–159/ 90–99 aortic . As there is no ab- Stage 2 hypertension >160/>100 solute pressure measurement to define hypertensive emergency, it is identi- fied by the physical signs of acute end- Table 2: WHO, ISH, & ESH Classification of Hypertension organ damage. Consequently, patients with a low baseline pressure can pres- Category SBP/DBP (mm Hg) ent with “normal” or mildly elevated Optimal <120/80 pressure and be considered to have a Normal 120-129/80-84 true hypertensive emergency. Patients with markedly elevated High normal 130-139/85-89 blood pressure but who lack these signs Stage 1 hypertension 140–159/90–99 are determined to be in hypertensive ur- Stage 2 hypertension 160-179/100-109 gency.1 Some clinicians classify hyper- Stage 3 hypertension >180/110 tensive urgency as “elevated blood pressure (diastolic pressure usually >120 mm Hg) that is not associated with new or progres- nosed hypertensive individuals. They actually ex- sive end-organ damage”.2 hibit normal pressures in their regular environment. In hypertensive urgency, there is a risk of imminent The goal in hypertensive emergency is to rapidly and end-organ damage, but such damage has not yet oc- carefully control the blood pressure to prevent fatal curred. Particularly susceptible patients often have pre- and irreversible end-organ damage. Action is usually existing conditions, e.g., renal insufficiency, congestive taken in minutes up to a few hours as per the clinical sit- , coronary , CNS disorders, or uation, and intravenous medicines are usually em- retinal changes. ployed. The aim may not be to reduce the blood pres- One to two percent of all hypertensive patients may sure into the normal range in certain clinical scenarios present with hypertensive emergency or crisis at some such as stroke. point of their lives.1 In hypertensive urgency, blood pressure can be con- Other terminologies used in these instances include: trolled safely over period of hours or days in the outpa- Ⅲ Acute hypertensive episode, which is defined as: tient setting. – Stage 3 hypertension –systolic pressure 180 mmHg Etiology – and diastolic pressure 110 mmHg The etiology of hypertensive urgency is not well under- with no signs or symptoms of evolving or impending stood. Most such patients have pre-existent hyperten- target-organ damage. sion,3 and non-adherence with antihypertensive med- Ⅲ Transient hypertension, which is the presence of ications near the time of the episode is seen in about high blood pressure in association with other con- 50% of them.4 Illicit drug usage is also reported to be a ditions such as , alcohol-withdrawal, sudden risk factor for the development of hypertensive emer- medication cessation, and toxic levels of some sub- gency.5 Other causes of both urgency and emergency are stances. In this case, treatment is aimed at the un- shown in Table 3. derlying cause. Ⅲ White-coat hypertension, or anxiety-related high blood Pathophysiology pressure readings seen only in a physician’s office, During the hypertensive episode, there is an abrupt in- with otherwise normal blood pressure. This is a sur- crease in the systemic due to humoral prisingly common finding, especially in newly diag- . This may be the triggering event.6

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Increased blood pressure causes en- Table 3: Etiologic Causes of Hypertensive Urgency/Emergency dothelial damage by increasing the en- dothelial permeability and local activa- tion of the clotting cascade ( and fibrin deposition), resulting in fib- Renal •Renal artery rinoid necrosis and intimal prolifera- • tion. The is then unable Vascular • to compensate or auto-regulate for –hemolytic-uremic syndrome –thrombotic thrombocytopenia purpura changes in blood pressure. A vicious cy- cle ensues with further increases in re- Pregnancy- •Preeclampsia sistance and endothelial damage. related •Eclampsia High blood pressure also increases Pharmacologic •Sympathomimetics the stretch on the vessel wall which ac- • withdrawal tivates the renin-angiotensin system. •Beta-blocker withdrawal This plays an important part in severely • elevated blood pressures. •Amphetamines The combined process of endothelial Endocrine •Cushing’s syndrome damage, loss of auto-regulation, acti- •Conn’s syndrome vated renin-angiotensin system, de- • crease in vasodilators (nitric oxide, •Renin-secreting adenomas prostacycline), and sustained blood •Thyrotoxicosis pressure elevation can lead to tissue is- Neurologic •Central nervous system trauma chemia and end-organ damage. Major •Intracranial mass organ systems involved include the central nervous, cardiovascular, renal, Autoimmune •Scleroderma renal crisis and gravid uterus.7, 8 Single-organ involvement is found in approximately 83% of patients presenting with hy- The physical exam should begin with measuring the pertensive emergencies. Dual-organ involvement is blood pressure in both arms, using an appropriately found in 14% of cases, and multi-organ involvement (>3 sized cuff. Smaller cuffs can falsely elevate blood pressure organ systems) is found in approximately 3% of patients readings in obese patients, and vice versa. The physical presenting with a hypertensive emergency.9 exam should also include a supine and standing blood pressure, as well as a measurement in the neck to assess Clinical Presentation for signs of elevated jugular venous pressure. A proper history and physical examination help a physi- Next, pulses should be assessed in all extremities, cian to differentiate between hypertensive urgency and and auscultation performed on the lungs (for signs of emergency. A focused history should be taken to rule out ), the renal (for bruits), and end-organ damage, the signs and symptoms of which the heart (for murmurs or gallops). are shown in Table 4. A focused neurologic and fundoscopic assessment The history should include any previous history of should be done to rule out a cerebrovascular accident. high blood pressure, antihypertensive medications used Lateralizing signs are uncommon in hypertensive en- and adherence to medication regimens, over-the- cephalopathy and are more suggestive of a stroke. Other counter and illicit drug use (cocaine, amphetamines, de- studies which may be employed to help rule out a hy- congestants, stimulants, oral contraceptives, and pertensive emergency include electrocardiogram, chest NSAIDs), and the presence of previous end-organ dam- x-ray, urinalysis, complete blood count, evaluation of age (e.g. renal, cardiac, or cerebrovascular). electrolytes, and serum tests for renal function. Common symptoms related to hypertensive emer- In a patient with severely elevated blood pressure, gencies are (27%), dyspnea (22%), and neu- symptoms suggestive of acute end-organ damage con- rologic deficits (21%).10 Non-specific symptoms like a firm the diagnosis of hypertensive emergency, and the may be present in hypertensive urgency. treatment plan should include immediate transfer to the

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Table 4: Signs and Symptoms of End-organ damage hospital for further management. Patients with hypertensive urgency, on the other hand, can be treated in End-organ damage Signs and symptoms the urgent care setting. Hypertensive •Signs of cerebral edema encephalopathy –insidious onset Treatment – The goal of treatment in hypertensive – urgency is to slowly reduce the blood –altered mental status pressure over a period of 24 hours us- –confusion –drowsiness ing oral antihypertensive agents. This is –seizures usually done on an outpatient basis un- –occasional focal deficits less patient follow-up is unpredictable. –coma As non-adherence is the major cause •Retinal hemorrhage or of hypertensive urgencies, restarting •Signs of acute renal failure the previously established regimen is – usually sufficient. Treatment may be – – restarted with a lower dose and gradu- ally increased as tolerated over a period Intracranial •May occur with routine physical activity, especially of several days. hemorrhage/stroke during intense emotional activity or exertion The mean arterial blood pressure syndrome •Headache and vomiting may lead to decrease level of consciousness should not be reduced by more than 10 •Typically,there is gradual progressive worsening of 25% in the first 24 hours. Rapid or ex- symptoms and increasing neurologic deficits, cessive reductions in blood pressure depending upon site of bleed can have deleterious effects, including Acute left •Cough, dyspnea and fatigue rapidly becoming . This is more commonly ventricular failure severe seen in high-risk patients like the eld- with pulmonary •Chest discomfort or pain may be apparent erly, or patients with severe peripheral edema •Tachypnea, tachycardia, S3 and/or S4 sounds, , or severe atheroscle- crackles at the pulmonary bases can be present rotic, cardiac, or intracranial disease.10 •Signs of concomitant right-sided failure,including We should stress the importance of jugular venous distension and pedal edema, may be present lowering blood pressure gradually to acceptable measurements; there is no Acute coronary •Typical or atypical chest pain (atypical chest pain evidence suggesting that immediately especially in diabetic patients and inpatients with syndrome decreasing blood pressure to levels be- known cardiac or non-cardiac atherosclerotic disease) low “normal” reduces risk in the hyper- tensive patient. Acute myocardial •Typical or atypical chest pain Close follow-up, usually within 24 infarction (AMI) •Electrocardiogram changes consistent with AMI hours, is recommended. If there are se- Dissecting aortic •Abrupt onset of thoracic or abdominal pain vere comorbid conditions or safety is- •Mediastinal or aortic widening on chest x-ray sues at home, the patient can be ob- •Absence of proximal extremity or carotid pulse served in an inpatient setting for a day. •Blood pressure difference of more than 20mmHg A reduction in blood pressure to between the right and left arm 160/110 mmHg is all that is required in Worsening renal •Azotemia the first 24 hours. failure •Proteinuria Essential information for oral antihy- •Oliguria pertensive agents commonly used for •Hematuria the treatment of hypertensive urgency Eclampsia •Pregnant patient with nausea, vomiting, or is provided in Table 5. seizures is a dihydropyridine-de- rived calcium channel blocker that has

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Table 5: Oral Antihypertensive Medications used in Hypertensive Urgency

Onset/Duration Special Medication Classification of action Adverse effects Dosing schedule considerations Clonidine Centrally acting Onset: 30–60 •Dry mouth 0.1 to 0.2 mg; •Safe for elderly ␣-2-adrenergic minutes •Drowsiness additional doses or renal failure agonist •Constipation of 0.1 mg given patients Duration: 6–8 •Bradycardia every hour until •Beta-blockers hours •Orthostatic diastolic is <115 may worsen •Hypotension mmHg or a withdrawal •Rebound maximum dose of symptoms •Hypertension 0.7 mg has been •Contraindicated with abrupt given with sinus discontinuation bradycardia, sick sinus syndrome, 1st-degree heart block or obtundation

Captopril Angiotensin- Onset: 15–30 Skin rash, cough, 25 mg; may be •Captopril is the converting minutes taste alterations, repeated every 30 shortest-acting enzyme (ACE) hyperkalemia, minutes as ACE-inhibitor inhibitor Duration: angioedema, renal needed •Blood pressure 4-6 hours failure (in patients will not decrease with bilateral renal significantly if no artery stenosis) response is ob - served within 30 to 60 minutes

Losartan Angiotensin II- Peak: 1-3 hours Generally well- 50 mg; higher Extensive first- receptor (ARB) tolerated with doses have not pass metabolism antagonist incidence of been found to may cause adverse effects produce more bioavailability to similar to placebo significant blood double in patients pressure with hepatic reductions impairment

Nicardipine 2nd-generation Onset: 0.5-2 hours Hypotension, 30 mg •Extensive first- (regular release) dihydropyridine heart palpitations, pass metabolism calcium channel Duration: 8 hours reflex tachycardia, •Do not use in blocker headache, acute heart failure flushing, dizziness or coronary

Labetolol Nonselective Onset: 20 min– •Nausea 200-400 mg; Do not uses in ␣-1, ␤-adrenergic 2 hours •Vomiting repeat every 3 patients with receptor blocker •Dizziness hours as needed •heart failure Duration: dose •Heart block •asthma/COPD dependent •Headache •bradycardia •Fatigue •1st-degree heart •Broncho- block constriction

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been used extensively in the past for the treatment of hypertensive urgency. However, nifedipine has never been approved by the FDA for short-term use in hypertension. More recently, the risks of serious adverse reactions like severe hy- potension, acute coronary events and ischemic stroke have led the U.S. National Heart, Lung, and Blood Institute to issue a warning that this agent should not be used in the treatment of hypertension, angina, and .

Conclusion Initial recognition of an absence of end-organ damage is crucial in dif- ferentiating hypertensive urgency from hypertensive emergency, and establishing a treatment plan. Judi- cious use of oral antihypertensive agents in the outpatient clinical setting can safely lower blood pres- sure over a period of several days, leading to improved outcomes. ■

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