Hypertensive Urgency and Emergency: Management and Treatment
Hypertensive Urgency and Emergency: Management and Treatment
Authors: Donald Schreiber, MD, Associate Professor, Division of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA; and Garig Vanderveldt, MD, Clinical Instructor, Division of Emergency Medicine, Stanford University School of Medicine, Palo Alto, CA.
Peer Reviewer: Steven M. Winograd, MD, FACEP, Attending Physician, Emergency Medicine, Horton Hospital, Middletown, New York, and Arden Hill Hospital, Goshen, New York.
Introduction
Hypertension affects more than 50 million people in the United States and has long been recognized as an independent risk factor for cardiovascular, cerebrovascular, and renal disease.
There are many different definitions of hypertension so it is important to clearly understand current nomenclature and definitions. (See Table 1.)
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Hypertensive urgency and emergency are specific areas of concern for emergency physicians. Hypertensive emergency is defined as hypertension with resulting end-organ damage. This would include states of hypertensive encephalopathy, ischemic stroke and intracranial hemorrhage, myocardial ischemia or infarction, aortic dissection, renal failure, and severe preeclampsia and eclampsia.
Once an emergency department patient has been found to be hypertensive, the physician must then decide whether to institute treatment. Thus, it is important for the emergency physician to clearly understand which hypertensive patients require emergent intervention and which patients may be simply asked to follow-up as outpatients for treatment. Unfortunately, many recommendations from a multitude of sources often are conflicting in nature and are of limited applicability to the emergency department setting. In addition, there are numerous antihypertensive agents available that have different efficacies and side-effect profiles. Inappropriate or overzealous use of these drugs may precipitate excessive decreases in blood pressure that may cause significant morbidity.
The purpose of this review is to clarify some of the controversial issues surrounding the management of hypertension in the emergency department, focusing on hypertensive urgencies and emergencies. The first article explores the American College of Emergency Physicians' clinical policy governing these issues, while the remaining articles focus on the management and treatment of specific hypertensive emergencies.
Screening for End-Organ Damage and Emergently Managing Asymptomatic Patients with Hypertension
Source: Decker WW, Godwin SA, Hess EP, et al. Clinical policy: critical issues in the evaluation and management of adult patients with asymptomatic hypertension in the emergency department. Ann Emerg Med 2006;47:237-249.
Managing the asymptomatic patient with either hypertension or a hypertensive urgency is particularly challenging. Considering that, the American College of Emergency Physicians (ACEP) Clinical Policy Subcommittee sought to clarify the evidence and current recommendations for patient management in this scenario. The authors summarize many relevant studies, and make specific recommendations where appropriate.
One question addressed by the article is whether to screen asymptomatic emergency department patients with hypertension for evidence of end-organ damage. Initial screening tests include serum chemistry, urinalysis, electrocardiography, and chest radiography. Unfortunately, the committee found few studies that specifically addressed this issue, and the authors concluded that "a search for evidence to validate each of these screening tests revealed little data." Decker and colleagues, therefore, did not make any specific recommendations about the use of screening tests, but instead summarized the few studies that exist. One study that was cited concluded that routine electrocardiography and chest radiography did not influence treatment decisions in asymptomatic patients.1 The committee also noted that there was a paucity of current scientific evidence to either support or refute the routine use of other screening tests for the asymptomatic hypertensive patient.
The article also discussed the merit of rapidly lowering blood pressure in asymptomatic hypertensive patients. The authors reviewed the sixth (JNC 6) and seventh (JNC 7) reports published by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure.2,3 JNC 6 states that "elevated blood pressure alone, in the absence of symptoms of new or progressive target organ damage, rarely requires emergency therapy."2 However, JNC 7 states that hypertensive urgencies "usually do not require hospitalization, but should receive immediate combination oral antihypertensive therapy."3 JNC 7 recommends that an oral thiazide-type diuretic may be an appropriate initial antihypertensive agent for most hypertensive patients with a SBP (systolic blood pressure) less than 160 or a DBP (diastolic blood pressure) less than 100. For blood pressure values greater than these, a two-drug combination such as a thiazide diuretic and an angiotensin-converting enzyme inhibitor or a beta blocker is recommended. Other comorbidities such as diabetes further complicate management and drug selection.
Decker and colleagues noted that the recommendations made by JNC 7 were specifically aimed at primary care physicians and not necessarily intended for emergency physicians.3 Indeed, the committee states, "we could find no evidence demonstrating improved patient outcomes or decreased mortality or morbidity with acute management of elevated blood pressure (in the absence of end-organ damage) in the emergency department." Thus, the ACEP subcommittee concluded that there is no evidence to directly support the immediate use of antihypertensive medications for treating asymptomatic hypertension in the emergency department (ED), and instead made the following recommendations (all Level B).
1) Initiating treatment for asymptomatic hypertension in the ED is not necessary when patients have follow-up.
2) Rapidly lowering blood pressure in asymptomatic hypertensive patients in the ED is unnecessary and may be harmful in some patients.
3) When ED treatment for asymptomatic hypertension is initiated, blood pressure management should gradually lower blood pressure but not normalize it during the index ED visit.
Commentary
Unfortunately, the ACEP Clinical Policy Subcommittee was unable to answer many areas of physician concern because of lack of existing data. The question of screening tests for asymptomatic hypertensive patients in the emergency department remains largely unresolved. In the absence of conclusive evidence, emergency physicians should decide whether to initiate standard screening tests for end-organ damage. Similarly, there seems to be little evidence to support the initiation of outpatient antihypertensive therapy in the emergency department, especially when close follow-up can be arranged. Nevertheless, there is a clear consensus to avoid the use of intravenous medications in the treatment of asymptomatic hypertensive patients in the emergency department.
Is Aggressive Blood Pressure Reduction Necessary for Acute Ischemic or Hemorrhagic Stroke?
Source: Varon J. Diagnosis and management of labile blood pressure during acute cerebrovascular accidents and other hypertensive crises. Am J Emerg Med 2007;25:949-959.
Varon reviewed all relevant articles published between 2000 and 2007 on the management of hypertension in acute stroke and other hypertensive crises. Cerebrovascular autoregulation maintains a relatively constant cerebral blood flow across a wide range of mean arterial blood pressures. Above and below the limits of autoregulation, cerebral blood flow linearly follows mean arterial blood pressure. After an acute ischemic stroke (AIS), cerebral autoregulation is markedly impaired. In the setting of AIS, cerebral blood flow passively follows arterial blood pressure changes in the territory around the affected areas of cerebral injury. Cerebral perfusion of this ischemic penumbra becomes pressure dependent. Abrupt reductions in mean arterial blood pressure will have deleterious effects on the ischemic territory and worsen the neurologic deficit.
Varon cited the paper by Oliveira-Filho and colleagues who conducted a prospective study of 115 patients with acute cerebrovascular accidents over a two-year period.4 They demonstrated that blood pressure reduction in the first 24 hours was an independent predictor of poor outcome, and that greater reductions correlated with increased mortality.4 An international study paradoxically showed that persistent elevations in blood pressure after a stroke were associated with increased mortality, increased neurologic deficit, and an increased risk of recurrent stroke within 14 days. Currently, permissive hypertension in these patients is the primary therapeutic recommendation, and blood pressure reduction is reserved only for severe hypertension.
The article also discusses the pharmacologic management of hypertension in AIS. The paper cited the management guidelines from the 2003 Stroke Council of the American Stroke Association, that are highlighted below:5
1) If the systolic blood pressure (SBP) is < 220 and the diastolic blood pressure (DBP) is < 120, observe the patient unless there are signs of other end-organ damage.
2) Consider the use of labetalol or nicardipine if either the SBP is > 220 or the DBP is 121-140. The goal of management should be to reduce DBP by 15-20% over a 24-hour period.
3) Nitroprusside at a rate of 0.5 mcg/kg/min IV is recommended for patients with severe elevations in DBP > 140 to achieve a blood pressure reduction of 10-15%.
Varon also reviewed hypertensive management when patients are considered for thrombolytic therapy. Blood pressure elevation greater than 185/110 is a contraindication to thrombolytic therapy. In the absence of other exclusion criteria, the author recommends nitropaste or labetalol 20-40 mg IV for blood pressure reduction. Failure to respond precludes the administration of thrombolytic agents.
Commentary
Varon provides an excellent review of the management of hypertension in the setting of an acute stroke. Blood pressure management is controversial in AIS, and the author recommends the guidelines established by the Stroke Council of the American Stroke Association. Varon does not provide specific guidance for blood pressure management in acute intracerebral hemorrhage. Considering that overzealous blood pressure reduction may increase the extent of neurologic damage, caution is advised, and consultation with the attending neurologist or neurosurgeon is warranted before initiating treatment.
Is Nitroprusside Still the Drug of Choice for the Management of Hypertensive Encephalopathy?
Source: Gardner CJ, Lee K. Hyperperfusion syndromes: Insight into the pathophysiology and treatment of hypertensive encephalopathy. CNS Spectr 2007;12:35-42.
This review article focused on the pathophysiology, diagnosis, and current treatment of hypertensive encephalopathy. Autoregulation normally preserves cerebral blood flow, keeping it relatively constant despite fluctuations in blood pressure. However, cerebral blood flow often is compromised following abrupt, severe increases in blood pressure. During these episodes, endothelial dysfunction, along with the failure of cerebral vessel autoregulation, results in marked cerebral edema. Clinically, patients will present with symptoms of a change in mental status, headache, seizures, visual changes, or nausea and vomiting. Based on their review of the literature, Gardner and Lee recommend that in hypertensive encephalopathy, the mean arterial pressure should be decreased by 20% to 25% within one hour of arrival. Thereafter, more gradual reduction of blood pressure should ensue over the subsequent 24 hours. However, unlike other hypertensive emergencies, the authors note that care must be taken when using either nitroprusside, the traditional drug of choice in the United States, or nitroglycerin, as both drugs may result in elevated intracranial pressure. The authors concluded that to avoid elevations in intracranial pressure, intravenous labetalol or nicardipine is preferred in the initial management of hypertensive encephalopathy.
Commentary
As with the management of AIS, careful attention must be paid to avoid excessive reductions in blood pressure as this may precipitate further cerebral ischemic injury. The ideal drug should be both easily adjustable and have a predictable response. Nicardipine and labetalol fulfill these requirements without adversely affecting intracranial pressure. The authors recommend these drugs over nitroprusside as first-line antihypertensive therapy. Labetalol should be administered as an initial 20 mg bolus infused over 2 minutes. If necessary, repeat doses may be given every 10 minutes in increments of 20, 40, and 80 mg to a total of 300 mg. Nicardipine is administered as a 5 mg/hr infusion. The infusion rate may be increased by 2.5 mg/hr every 15 minutes until a maximum of 15 mg/hr has been reached or the desired reduction in blood pressure has been achieved. Future studies directly comparing these drugs in hypertensive encephalopathy are needed.
Aortic Dissection: Which Antihypertensive Drug Should Be Used?
Source: Khoynezhad A, Plestis KA. Managing emergency hypertension in aortic dissection and aortic aneurysm surgery. J Card Surg 2006;21(Suppl 1):S3-S7.
Acute aortic dissection is a hypertensive emergency. The majority of patients with aortic dissection have underlying essential hypertension. Blood pressure reduction in acute aortic dissection is essential to prevent retrograde propagation and aortic branch occlusion. Khoynezhad and Plestis reviewed the advantages and disadvantages of several antihypertensive agents in the management of aortic dissection.
Nitroprusside, the traditional first-line drug, is an arterial and venous vasodilator that has been used for many years. It has a rapid onset of action and a relatively short half-life of 3-4 minutes. However, its use requires meticulous monitoring, including frequent dosage adjustments and special handling because of the drug's photosensitivity. With nitroprusside, hypotensive episodes may be sudden and somewhat unpredictable and necessitate close titration of the drug. Cyanide toxicity may result from metabolism of the drug in the setting of poor tissue perfusion and altered hepatic function. Reflex tachycardia also occurs. Nitroprusside increases intracranial pressure, which is deleterious in the setting of hypertensive encephalopathy and reduced cerebral blood flow. Therefore, the authors no longer recommend nitroprusside as the primary therapeutic agent in acute aortic dissection. Most consultants are now utilizing fenoldopam or nicardipine.
Nicardipine, a calcium channel blocker with potent vasodilatory properties, has equivalent therapeutic efficacy to nitroprusside but has the added advantage of ease of administration. Therapy is initiated with an intravenous infusion at 5 mg/hr that can be rapidly titrated upward by 2.5 mg/hr every 5 minutes to a maximum of 15 mg/hr. The drug has no significant negative inotropic effects and can be combined with beta-blocker therapy. Nicardipine primarily is metabolized in the liver and can be safely used in the setting of renal insufficiency. The drug also dilates cerebral and coronary arteries, potentially resulting in reduced cerebral and myocardial ischemia.
Fenoldopam, a dopamine-1 agonist and renal vasodilator, also has a rapid onset of action and a short half-life of 5 minutes. The drug improves creatinine clearance and sodium excretion and studies suggest that it may be the drug of choice in patients with renal insufficiency. Fenoldopam may produce a reflex tachycardia and electrocardiographic changes such as T wave inversion and ventricular extrasystoles.
Finally, beta blockers are an essential component of therapy for acute aortic dissection and should be initiated first, prior to any other anti-hypertensive agent. One of the specific goals of therapy in aortic dissection is the reduction of aortic wall stress or the velocity of left ventricular contraction to reduce the risk of propagation. Unless contraindicated, combination therapy with fenoldopam or nicardipine should be instituted with a beta blocker such as rapid acting esmolol, or alternatively, metoprolol. Insufficient data on labetalol has been reported and the authors only state that labetalol may be substituted.
Specific targets for blood pressure reduction in acute aortic dissection are poorly defined. The authors cite studies that specify any of the following goals:
1) Systolic blood pressure < 120 within 20 minutes of initiation of therapy; or
2) Diastolic blood pressure < 110 within 5 minutes; or
3) A 20% reduction in mean arterial pressure.
With regard to heart rate, the authors also recommend a target of 55 to 65 when using beta-blocker therapy.
Commentary
Khoynezhad and Plestis provide a concise and practical review of pharmacologic therapy for hypertension in acute aortic dissection. As cardiothoracic surgeons, their recommendations are influenced by their surgical experience in managing acute aortic dissection in the pre-operative and post-operative period. It is interesting that the authors did not support the use of nitroprusside when other antihypertensive agents are available despite its history as the drug of choice in acute aortic dissection. In addition, labetalol, a drug increasingly utilized in the management of many hypertensive emergencies in the emergency department, was only briefly mentioned, and no supporting evidence for its efficacy or safety profile was listed.
Is Labetalol an Acceptable Alternative to Hydralazine for Severe Hypertension in Pregnancy?
Source: Vigil-De Gracia P, Lasso M, Ruiz E, et al. Severe hypertension in pregnancy: hydralazine or labetalol? A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2006;128:157-162.
For many years, hydralazine has been considered the drug of choice in the management of severe hypertension in pregnancy. However, due to the emergence of intravenous labetalol as a safe and effective antihypertensive agent for the management of other hypertensive emergencies, much interest has been generated in its use as an antihypertensive agent in pregnant patients. Vigil-De Gracia and colleagues compared the safety and efficacy of intravenous labetalol and hydralazine. The study randomized 200 pregnant women over 24 weeks gestation with severe hypertension as defined by SBP of at least 160 and/or DBP greater than 110. The women were randomized to receive either intravenous hydralazine (5 mg bolus and repeated every 20 min to a maximum of 25 mg) or labetalol (20 mg IV bolus followed by repeat doses if not effective of 40 mg IV at 20 min and then 80 mg IV every 20 minutes to a maximum dose of 300 mg). The primary endpoints were successful blood pressure reduction, defined by either DBP < 110 or SBP < 160 following drug administration, and maternal hypotension. At the conclusion of the study, there were no statistically significant differences between the two drugs with respect to either primary endpoint.
The authors reported an increased incidence of maternal tachycardia and palpitations in the hydralazine group. However, the authors noted that both of these adverse effects were well tolerated, and the degree of maternal tachycardia was minimal. During the trial, the authors also recorded the blood pressures and heart rates of infants whose mothers had received their last dose of antihypertensive medication less than 24 hours before delivery. The authors found increased rates of neonatal hypotension (defined as a SBP < 40) and bradycardia (defined as a heart rate less than 110) in the labetalol group following delivery. Despite these findings, labetalol was not associated with either increased rates of neonatal death or neonatal intensive care unit admissions. The authors concluded that both drugs are safe and effective in the treatment of severe hypertension in pregnancy, in pre-eclampsia, and in eclampsia.
Commentary
Although not blinded, the study's authors did utilize a randomized design. The study protocol used repeated boluses of labetalol at 20-minute intervals instead of the currently recommended intervals of 10 to 15 minutes. Although not primary endpoints in this study, the authors reported an increased incidence of labetalol-induced neonatal bradycardia and hypotension when labetalol was administered within the 24 hours prior to delivery. The authors concluded that there were no increases in the rates of neonatal intensive care unit admission or death due to the use of labetalol. However, the duration of the postpartum observation period was not stated and the long-term consequences of the drug on neonates remained unclear. The clinical significance of labetalol-induced neonatal bradycardia and hypotension is uncertain. Finally, the relatively small sample size also was a limitation of this study. Overall, the data did suggest that labetalol may be safely used as an alternative to hydralazine in the management of pregnancy-related hypertensive crises in patients with pre-eclampsia and eclampsia.
Is Intravenous Nicardipine Safe and Effective Treatment Alternative for Hypertensive Emergencies?
Source: Curran MP, Robinson DM, Keating GM. Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indicators. Drugs 2006;66:1755-1782.
Curran and colleagues conducted a review of articles published after 1980 on the use of intravenous nicardipine that focused on its use in critically ill patients or in those undergoing surgery. Several trials were cited by the authors that specifically evaluated the use of intravenous nicardipine, a calcium channel antagonist, in hypertensive emergencies. Wallin and colleagues enrolled 123 severely hypertensive patients in a double-blind, placebo-controlled trial using a constant infusion of intravenous nicardipine (maximum rate 15 mg/hr).6 The study demonstrated that more than 90% of patients treated with nicardipine achieved therapeutic blood pressure reduction as defined by the study within a mean time of 77 minutes. This was similar to the results achieved with nitroprusside.6
Curran discussed several other studies that directly compared nitroprusside and nicardipine that found similar results. In the trial conducted by Neutel and coworkers, nicardipine was directly compared with nitroprusside in 121 patients with hypertensive urgency, and both drugs resulted in similar degrees of SBP and DBP reduction using standard dosing regimens.7
Curran and researchers concluded in their extensive review of the literature that intravenous nicardipine is as effective as intravenous nitroprusside for the short-term reduction of blood pressure in patients with hypertensive emergencies.
The authors also concluded that intravenous nicardipine is an effective antihypertensive medication for the treatment of severe hypertension that is associated with aortic dissection and pre-eclampsia, despite the fact that only a few preliminary limited studies have been completed.
Commentary
Hypertensive emergencies require carefully controlled but rapid reduction of blood pressure. Oral antihypertensive medications are impractical because they are difficult to titrate and have delayed onsets of action. In the past, nitroprusside has been the first-line drug in the emergency department. However, because of the concern for cyanide toxicity and the need for frequent adjustments of rate and special handling (photosensitivity), other pharmacologic agents have been evaluated. Labetalol has been proven to be safe and effective in the treatment of hypertensive emergencies. It is contraindicated in patients with acute asthma or severe chronic obstructive pulmonary disease, in the setting of high-grade atrioventricular block, and in congestive heart failure. Therefore, there are many patients for whom labetalol is not a treatment option. Because of nicardipine's relative selectivity for vascular smooth muscle, it should be considered as a treatment option when other intravenous agents are either impractical or contraindicated. Many of the studies reviewed in Curran et al's paper enrolled relatively small patient numbers, but the accumulating data suggests that nicardipine is safe and effective. Additional studies are recommended to evaluate nicardipine in the setting of specific hypertensive emergencies.
Conclusions
The treatment of hypertension in the emergency department remains a challenging issue for emergency physicians. One must carefully differentiate those patients with hypertensive urgencies from those with hypertensive emergencies. Treatment is then tailored as necessary. There are a number of newer antihypertensive agents available to the emergency physician. Due to the differences in such factors as ease of administration, half-life, side-effect profile, and clinical efficacy, the emergency physician should be familiar with a number of different antihypertensive medications. Newer agents such as nicardipine and labetalol are replacing more traditional drugs such as nitroprusside and hydralazine as the treatment of choice for many hypertensive emergencies. There are no clear consensus guidelines to assist the clinician, and specific management often is guided by local preference. Consultation with the appropriate specialist as soon as possible is prudent.
Ongoing uncertainty clouds the management of asymptomatic hypertension and hypertensive urgency. The routine use of emergency department resources to screen asymptomatic patients with hypertension for evidence of end-organ damage is not yet supported by the medical literature. The physician must realize that there is no emergency to treat a hypertensive urgency. Adverse outcomes repeatedly have been reported with the overzealous use of intravenous antihypertensive medication to treat hypertensive urgencies. Management must not be dictated by the degree of blood pressure elevation in the absence of end-organ damage. Instituting oral antihypertensive therapy according to the JNC 7 recommendations3 and arranging close follow-up is the most prudent course.
References
1. Bartha GW, Nugent CA. Routine chest roentgenograms and electrocardiograms. Usefulness in the hypertensive workup. Arch Intern Med 1978;138:1211-1213.
2. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413-2446.
3. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-2572.
4. Oliveira-Filho J, Silva SC, Trabuco CC, et al. Detrimental effect of blood pressure reduction in the first 24 hours of acute stroke onset. Neurology 2003;61:1047-1051.
5. Adams HP Jr, Adams RJ, Brott T, et al. Guidelines for the early management of patients with ischemic stroke: a scientific statement from the Stroke Council of the American Stroke Association. Stroke 2003;34:1056-1083.
6. Wallin JD, Fletcher E, Ram CV, et al. Intravenous nicardipine for the treatment of severe hypertension. A double-blind, placebo-controlled multicenter trial. Arch Intern Med 1989;149:2662-2669.
7. Neutel JM, Smith DH, Wallin D, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens 1994;7(7 Pt 1):623-628.
Hypertension affects more than 50 million people in the United States and has long been recognized as an independent risk factor for cardiovascular, cerebrovascular, and renal disease.Subscribe Now for Access
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