Case

Joel

Stu dies
MD,

in

H y p e r t e n s i o n
E d i t o r

Handl er,

S ec tio n

Hypertensive Urgency
Joel Handler, MD

74-year-old man came for a routine clinic appointment and a physical examination, complaining of a moderate posterior cervical headache for a few days. There was no history of medical problems. He rarely saw a physician and could not recall any prior blood pressure (BP) determinations. His headache had occurred off and on for the past couple of months, but had become more bothersome during the past week. He was not taking any prescription medications, but had been taking two to three tablets of over-the-counter ibuprofen daily for the past week for his headache. The patient denied any chest discomfort or breathing difficulty. He was a nonsmoker and a nondrinker. His mother had hypertension. On examination, he was comfortable but complaining of headache. His BP was 224/120 mm Hg, with a heart rate of 72 bpm. Otherwise, there were minimal physical findings: fundi were normal; there was an S4 gallop but no heart murmurs and no bruits. All pulses were present, and his lungs were clear. There was trace bipedal edema. Cervical range of motion was slightly reduced, without elicitation of any tenderness. Following about 30 minutes, a repeat BP was 218/120 mm Hg. The patient was administered 0.2 mg clonidine p.o., but an hour later he became severely dizzy, with a systolic BP (SBP) of 60 mm Hg. He was brought to the emergency department (ED) and given 1 L of normal saline IV, with a follow-up BP of 92/72 mm Hg, but he still felt dizzy. Laboratory results revealed a blood urea nitrogen level of
From Kaiser Permanente, Anaheim, CA Address for correspondence: Joel Handler, MD, Kaiser Permanente, 411 Lakeview Avenue, Anaheim, CA 92807 E-mail: joel.handler@kp.org

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13 mg/dL (normal, 718 mg/dL), creatinine level of 0.7 mg/dL (normal, 0.41.2 mg/dL), and potassium of 3.8 mEq/L (normal, 3.55.0 mEq/L). Urinalysis showed no protein or cells, and a 12lead ECG was normal. He was kept in the hospital overnight and felt better the next morning, with a BP of 156/88 mm Hg. The patient was discharged on hydrochlorothiazide 25 mg daily and when seen in clinic 1 week later had a BP of 142/84 mm Hg; he still complained of an occipital headache. Case 2: A 72-year-old woman was seen in the Hypertension Clinic, having been referred because of hypertension refractory to three medications. She had a 5-year history of poorly controlled hypertension, but she stated that she was compliant with a regimen of 20/25 mg daily of lisinopril/hydrochlorothiazide, and 180 mg daily of extended-release verapamil. She also had a history of polymyalgia rheumatica, managed with 5 mg daily of prednisone. The patient had a home BP monitor and was told to take clonidine 0.1 mg every time she had a home monitor SBP reading >180 mm Hg. Following these instructions, she began taking her BP six times daily and was averaging two clonidine tablets daily. She denied any symptoms of headache, chest discomfort, or breathing difficulty but did complain of dry mouth, anxiety, fatigue, and dizziness. In the Hypertension Clinic, the patients BP was 162/82 mm Hg, with a heart rate of 62 bpm. She had an S4 gallop and a soft left femoral bruit with a good pulse. Her creatinine level was 1.2 mg/dL and her potassium level was 3.7 mEq/dL. When asked to demonstrate her self-BP monitoring technique, the arm was unsupported and the cuff was too small. The patient was instructed to add felodipine 5 mg daily to her medication, to reduce home BP readings to no more than once daily, and not to use clonidine for elevated readings. Proper BP
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The Journal of Clinical Hypertension (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright 2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.

self-monitoring technique was demonstrated and a BP taken by her was within 5 mm Hg (both systolic and diastolic) of an immediately subsequent office BP. She was also told that if a home SBP reading was >180 mm Hg, she should obtain a reading the next day, and if that reading was >180 mm Hg, to call for advice. Two weeks later she reported that she did not have any SBP readings >180 mm Hg, and her clinic BP was 148/78 mm Hg. Felodipine was advanced to 10 mg daily and was well tolerated, with a follow-up clinic BP of 136/72 mm Hg. DISCUSSION Hypertensive urgencies are distinguished from hypertensive emergencies by the lack of acutely progressive target organ damage such as acute myocardial infarction, acute pulmonary edema, intracerebral hemorrhage, aortic dissection, unstable angina, eclampsia, or hypertensive encephalopathy.1 Urgencies may have associated symptoms such as headache, shortness of breath, or anxiety,1 but may also be completely asymptomatic. The frequency of signs and symptoms of hypertensive urgencies and emergencies determined in a 1-year experience in 1634 patients in an ED is described in Table I. Headache was particularly common in the urgency group that lacked target organ damage. In another study, the prevalence of hypertensive urgency/emergency was assessed over 1 year in an ED in Milan, Italy and found to be significant. Three percent of the total patients, and 27% of all of the urgent ED patient evaluations, were found to be hypertension related.2 Of the ED hypertension-related patients, 76% were identified as urgencies and 24% as emergencies. Of all of the urgency/emergency hypertensive patients, 75% were known hypertensives who were either undertreated and poorly controlled on a chronic basis or noncompliant and had stopped medication. A literature review of hypertensive urgency revealed that the most consistent definition of urgency was a diastolic BP (DBP) >120 mm Hg.3 Very few studies described an SBP threshold for urgency; two of those trials used 200 mm Hg.3 The studies were generally of poor quality, marked by small sample size, open-label design, contamination, and follow-up ranging from 15 minutes to 1 week, but usually <24 hours.3 Oral drugs tested included nifedipine, captopril, clonidine, furosemide, prazosin, nicardipine, and lacidipine; IV drugs included labetalol, enalaprilat, urapidil, fenoldopam, and nitroprusside. Only two placebocontrolled studies have been performed, and, as expected, both showed at least some BP reduction

without medication.4,5 In one study, 22% (6/27) of patients with a baseline DBP of 120 mm Hg had a spontaneous drop of 20 mm Hg or a follow-up DBP of 100 mm Hg after 2 hours of rest.4 In the other study, 58% (7/19) of the placebo patients with a DBP of 100114 mm Hg responded to overnight hospitalization with a decrease in DBP to <95 mm Hg.5 Aggressive therapy for hypertensive urgency is predicated on the assumptions that: 1) prompt BP reduction will prevent a hypertensive emergency; 2) there are no adverse consequences to acute therapy; and 3) acute medication loading results in improved short-term BP control. In fact, there is very little ground to support any of these assumptions. None of the hypertensive urgency drug comparison trials that showed significant differences in the effectiveness of different medications in the acute reduction of BP demonstrated any difference in cardiovascular events. The two placebo-controlled trials did not demonstrate any short-term adverse consequence of placebo and observation. In fact, the only significant adverse consequences have occurred in treatment groups. Cases of acute myocardial infarction and coronary ischemia, transient ischemic attack, syncope, conduction disturbances, stroke, and acute retinal ischemia with transient blindness have been directly attributed to rapid BP reduction by short-acting nifedipine.69 One case of fatal stroke following a cumulative dose of 0.4 mg clonidine over 2 hours has been reported when an initial BP of 230/139 mm Hg fell to 150/100 mm Hg.10 Symptomatic hypotension is a not uncommon sequela of aggressive treatment for asymptomatic hypotension, sometimes requiring overnight hospitalization.3,10 Jaker et al.11 noted In our clinical experience some patients who receive 0.2 mg of clonidine as their initial dose become hypotensive or excessively sedated. This experience formed the basis of their decision to use a 0.1-mg starting dose of clonidine in their study of urgent hypertension. It was a 0.2-mg dose of clonidine that caused significant symptomatic hypotension and led to the overnight hospitalization of the first case presented here. One prospective controlled trial compared acute medication loading for hypertensive urgency. Seventy-four asymptomatic patients with DBPs of 116139 mm Hg were divided into three groups.12 All patients received clonidine 0.2 mg and chlorthalidone 25 mg and were started on daily doses of these two drugs. Group I received up to four hourly doses of clonidine 0.1 mg to reduce the DBP by 20 mm Hg or to <105 mm Hg.

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The Journal of Clinical Hypertension (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright 2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.

Group II received hourly placebo for the same indication, and group III was discharged from the ED without any further treatment. Patient followup at 24 hours, 4872 hours, and 1 week showed no significant difference in mean arterial pressure (Figure). Although no adverse consequences of sequential hourly clonidine loading were seen in this trial, the fact that the peak hypotensive effect of clonidine can occur up to 3 hours after dosing13 may have exposed patients randomized to hourly clonidine to symptomatic hypotension and possible adverse cardiovascular sequelae. The first case presentation illustrates the potential harm of acute oral therapy in a patient with repeated SBP >200 mm Hg, DBP >120 mm Hg, and moderate headache, following a dose of 0.2 mg clonidine. Headache persisted with BP normalization and was more likely due to cervical osteoarthritis. Ibuprofen may have played some role in causing this patients hypertension, but the dose was small. The positive family history and need for chronic antihypertensive therapy indicated the presence of underlying essential hypertension. Acute hypotension secondary to sequential loading of clonidine at intervals of less than 4 hours for hypertensive urgency with minimal symptoms is not an uncommon observation. Furthermore, individual patients may have an unpredictable hypotensive response to 0.2 mg clonidine, as was the experience of Jaker and colleagues;11 this also occurred with our patient. Such a response may be less likely to occur in the patient with hypertensive urgency who has a history of inadequately treated hypertension or has been noncompliant with a drug regimen. The second case presentation illustrates three issues: 1) a patient with uncontrolled hypertension who needed an increase in chronic oral therapy; 2) potential difficulty with overuse of a home BP apparatus, particularly when the patient is uninformed with regard to proper BP technique; and 3) exposure to the potential danger of unobserved as needed use of clonidine at home according to a BP parameter. The latter practice is not an uncommon physician instruction as home BP apparatuses come in wider use and patients check their BP multiple times per day. The advice to self-medicate is becoming more common. Patients are fearful of stroking out and want to know what to do if it gets too high. Every new stage 2 hypertensive patient needs a history, physical, and laboratory examination directed toward detection of a possible emergency. Is there any chest discomfort or breathing difficulty? Is there any history of substance abuse, particularly cocaine? Does the patient have a history of

200

Group 1 Group 2

MABP (mm Hg)

150

152 142 141 113 109 108 110

Group 3

100

103 106

109

102 104

50

0
Baseline 24 h 4872 h 1 wk

Figure. Sitting mean arterial blood pressures (MABPs) in patients with hypertensive urgency completing 1-week follow-up. All groups received clonidine 0.2 mg and chlorthalidone 25 mg initially and were discharged on clonidine 0.2 mg and chlorthalidone 25 mg b.i.d. Group 1 patients received hourly clonidine 0.1 mg up to four doses until diastolic BP (DBP) fell by 20 mm Hg or a DBP of 105 mm Hg was achieved. Group 2 received hourly placebo with the same directions. Group 3 was immediately discharged from the emergency department. Adapted with permission from Arch Intern Med. 1989;149:21862189.12

Table I. Frequency of Signs and Symptoms in Hypertensive

Urgencies and Emergencies FREQUENCY (%)

URGENCIES EMERGENCIES (N=341) (N=108) P VALUE* SIGNS/SYMPTOMS 22.0 3.0 <0.001 Headache 17.0 0.0 <0.001 Epistaxis 9.0 27.0 <0.005 Chest pain Dyspnea 9.0 22.0 <0.02 10.0 10.0 NS Faintness 10.0 0 <0.004 Psychomotor agitation Neurologic deficit 3.0 21.0 <0.001 7.0 3.0 NS Vertigo 6.0 8.0 NS Paresthesia Emesis 2.0 3.0 NS Arrhythmia 6.0 0.0 <0.04 NS=nonsignificant; *determined by 2 test for comparison of urgencies vs. emergencies. Adapted with permission from Hypertension. 1996;27:144147.2

hypertension, and, if so, have medications been taken as directed? Target organ damage needs to be evaluated with attention to the cardiovascular and neurologic examination. Immediate laboratory tests should include renal function, electrolytes, and a urinalysis, which may show proteinuria or red blood cells and cellular casts indicative of renal parenchymal disease. An ECG should be checked.

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The Journal of Clinical Hypertension (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright 2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.

Table II. Algorithm for Triage of Hypertensive Urgency/Emergency

HIGH BP BP >180/110 mm Hg Symptoms Headache, anxiety, often asymptomatic Exam No target damage, no cardiovascular disease Therapy URGENCY >180/110 mm Hg Severe headache, shortness of breath, edema Target organ damage, clinical cardiovascular disease present/stable EMERGENCY Usually >220/140 mm Hg Shortness of breath, chest pain, nocturia, dysarthria, weakness, altered consciousness Encephalopathy, pulmonary edema, renal insufficiency, cerebrovascular accident, cardiac ischemia Baseline labs, IV line, monitor BP, may initiate parenteral therapy in emergency department Immediate admission to ICU, treat to initial goal BP, additional diagnostic studies

Observe 13 h, initiate/ Observe 36 h, lower BP with short-acting resume medication, oral agent, adjust current therapy increase dosages Arrange follow-up evaluation within 24 h Plan Arrange follow-up within 72 h; if no prior evaluation, schedule appointment BP=blood pressure; ICU=intensive care unit. Adapted with permission from J Clin Hypertens (Greenwich). 2004;6:520525.15

A reasonable algorithm for triage of BP >180/110 mm Hg is presented in Table II.14,15 The recommendation for no or minimal symptoms is to observe for an hour and discharge with an initiation or increase in antihypertensive drugs. For the new patient, initiation of a combination drug tablet is usually the preferred choice. For the patient who has stopped previous drug therapy, the reinitiation of the prior regimen may be best. A second group of patients with BP >180/110 mm Hg has more severe symptomatic complaints and evidence of target organ damage, or clinical cardiovascular disease felt to be of a chronic and stable nature. One example would be a newly identified individual with a history of stroke or myocardial infarction. Such a patient should be observed for a few hours following the use of a short-acting agent and discharged if the pressure is reduced, with early follow-up. Clonidine loading, particularly sequential clonidine loading for asymptomatic or minimally symptomatic BP elevations in the absence of target organ damage, is overused; as noted, patient instructions for as-needed unobserved usage of clonidine based on home BP determinations poses risks. In his review, Vidt16 best sums up the evidence when he states No data currently exist to show immediate benefit from acutely lowering BP in asymptomatic patients with severe hypertension, but data do suggest that an aggressive approach may be harmful. Probably the most urgent instruction to provide such urgency patients is a confirmed clinic follow-up appointment within a few days following an advance in daily antihypertensive therapy directed at the time of their evaluation.

REFERENCES
1 Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High

Blood Pressure. Hypertension. 2003;42:12061252. 2 Zampaglione B, Pascale C, Marchisio M, et al. Hypertensive urgencies and emergencies. Prevalence and clinical presentation. Hypertension. 1996;27:144147. 3 Cherney D, Straus S. Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature. J Gen Intern Med. 2002;17:937945. 4 Habib GB, Dunbar LM, Rodrigues R, et al. Evaluation of the efficacy and safety of oral nicardipine in the treatment of urgent hypertension: a multicenter, randomized, double-blind, parallel, placebo-controlled trial. Am Heart J. 1995;129:917923. 5 Rutledge J, Ayers C, Davidson R, et al. Effect of intravenous enalaprilat in moderate and severe hypertension. Am J Cardiol. 1988;62:10621067. 6 OMailia JJ, Sander GE, Giles TD. Nifedipine-associated myocardial ischemia or infarction in the treatment of hypertensive urgencies. Ann Intern Med. 1987;107:185186. 7 Hirschl MM, Seidler D, Mullner M, et al. Efficacy of different antihypertensive drugs in the emergency department. J Hum Hypertens. 1996;10:S143S146. 8 Sanchez M, Sobrino J, Ribera L, et al. Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase. J Cardiovasc Pharmacol. 1999;33:479484. 9 Pitlik S, Manor RS, Lipshitz I, et al. Transient retinal ischaemia induced by nifedipine. Br Med J (Clin Res Ed). 1983;287:18451846. 10 Spitalewitz S, Porush JG, Oguagha C. Use of oral clonidine for rapid titration of blood pressure in severe hypertension. Chest. 1983;83:404407. 11 Jaker M, Atkin S, Soto M, et al. Oral nifedipine vs oral clonidine in the treatment of urgent hypertension. Arch Intern Med. 1989;149:260265. 12 Zeller KR, Von Kuhnert L, Matthews C. Rapid reduction of severe asymptomatic hypertension. A prospective, controlled trial. Arch Intern Med. 1989;149:21862189. 13 Hoffman BB. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. In: Hardman JG, Limbird LE, eds. Goodman & Gilmans The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw-Hill; 2001:215268. 14 Vidt DG. Emergency room management of hypertensive urgencies and emergencies. J Clin Hypertens (Greenwich). 2001;2:158164. 15 Vidt DG. Hypertensive crises: emergencies and urgencies. J Clin Hypertens (Greenwich). 2004;6:520525. 16 Vidt DG. Treatment of hypertensive emergencies and urgencies. In: Izzo JL Jr, Black HR, eds. Hypertension Primer. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:452455.

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The Journal of Clinical Hypertension (ISSN 1524-6175) is published monthly by Le Jacq Ltd., Three Parklands Drive, Darien, CT 06820-3652. Copyright 2005 by Le Jacq Ltd., All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at showell@lejacq.com or 203.656.1711 x106.