Hospital Practice
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Hypertensive Urgencies and Emergencies in the Hospital Setting Cynthia M. Cooper MD & Andrew Z. Fenves MD, FACP, FASN To cite this article: Cynthia M. Cooper MD & Andrew Z. Fenves MD, FACP, FASN (2016): Hypertensive Urgencies and Emergencies in the Hospital Setting, Hospital Practice, DOI: 10.1080/21548331.2016.1141657 To link to this article: http://dx.doi.org/10.1080/21548331.2016.1141657
Accepted author version posted online: 18 Jan 2016.
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Date: 25 January 2016, At: 16:31
Publisher: Taylor & Francis Journal: Hospital Practice DOI: 10.1080/21548331.2016.1141657 Article Type: Review
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Hypertensive Urgencies and Emergencies in the Hospital Setting
Running Title: Hypertensive Emergencies for Hospitalists Authors: Cynthia M. Cooper MD, Andrew Z. Fenves MD, FACP, FASN Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: Cynthia M. Cooper MD Massachusetts General Hospital 50 Staniford St., Suite 503B Boston, MA 02114 USA Phone 617-643-0595 Fax 617-724-9428 [email protected]
Abstract The prevalence of hypertension in the general population has steadily climbed over the past several decades and hypertension is a primary or secondary diagnosis in nearly a fourth of hospitalized adults. Hospitalization is often a time of pertubation in a patient’s usual blood pressure control, with pain, anxiety and missed medications all risk factors for severe hypertension. Hospitalists are often faced with severe hypertension in a patient not previously known to them and this presents a challenge of how best to assess the clinical importance of blood pressure elevation. An additional challenge is the lack of
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
literature to guide the optimal management of hypertension in inpatients. This review aims to describe the scope of the problem, to describe the near and long-term risks of overzealous blood pressure management, and to identify areas for future study. Keywords: hypertension; hospitalist; inpatient; emergency; urgency
Introduction The incidence of hypertension is rising and more hospitalized patients are admitted for and with hypertension. Little data exists, however, on the optimal inpatient management of hypertension and crises of hypertension, e.g., hypertensive urgency and emergency, in the hospital. We present an overview of inpatient hypertension assessment and management focused on the hospitalist clinician. Definitions
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Hypertensive emergency is typically defined as severe hypertension which results in acute end organ injury. 1 Hypertensive urgency is less clearly defined with definitions in the literature ranging from those based on specific blood pressures, typically SBP>180 mmHg and DBP >120 mmHg, to severe hypertension in a patient with established organ injury and, ostensibly, at high risk for additional injury.
2-6
Hypertensive crisis is a term which encompasses both hypertensive emergency and
hypertensive urgency and is also often used in the literature. In this paper, we will use the term ‘hypertensive emergency’ for a clinical scenario with clear evidence for tissue injury and ‘hypertensive urgency’ for severe hypertension without objective damage. The bulk of the medical literature on hypertensive urgencies and emergencies focus on the Emergency Room (ER) setting.7 Severe hypertension in hospitalized patients is much less well-studied, with small studies suggesting most practitioners extrapolate recommendations from outpatient guidelines, e.g., JNC8, to the inpatient setting.8, 9 Whether this is a valid extrapolation for the management of patients hospitalized for reasons other than hypertension, however, is unclear. In a University of Michigan study of residents and hospitalists looking at beliefs around blood pressure (BP) values that required treatment, intensive care unit (ICU) transfers or delay in discharge showed decisions based on limited factual data.
9
The literature on ER management of hypertension is evolving, and the indications for hospital admission are an area of debate.
10
We intend to review the management of hypertensive crisis for hospitalists,
and delineate the differential diagnosis of severe hypertension which may develop in a hospital setting. Incidence and Risk Factors Over the period from 2006 to 2012, nearly a quarter of all adult ER visits in the US were coded with an ICD-0 code for hypertension. Almost 4% had hypertension as the primary diagnosis, and the populationbased incidence rose 5.2% each year. 11 One of the earliest papers to report incidence of hypertensive
crisis in the ER setting found 3% of patients visiting a single adult Emergency Department had a diastolic blood pressure (DBP) >120mmHg. A quarter of these patients were deemed to have hypertensive emergency. 7 A more recent multicenter study noted 0.4% of adult ER visits had a systolic BP >220 mmHg and/or a diastolic BP of >120 mmHg. Again, one quarter of these were diagnosed as hypertensive emergency.12 The median age of patients with hypertensive emergency in both of these studies was 65 years, and the majority had a prior diagnosis of hypertension. In a case control study of patients presenting to two inner city ERs who were found to have severe
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uncontrolled hypertension but not hypertensive emergency, significant risk factors included male sex, black race, and alcohol or illicit drug use. In this population, a lack of primary care and non-adherence with medications significantly increased the odds of severe uncontrolled hypertension. 13 The NHANES III study found male sex as well as age >65 years to be significant risk factors for uncontrolled hypertension, but found non-Hispanic black race and lack of access as being minor risk factors.14 Nearly all the patients with uncontrolled hypertension in NHANES III had insurance and regular access to medical care, suggesting that other patient and physician factors contributed to the lack of control. 15 Though prior history of hypertension is a risk factor for hypertensive crisis, patients presenting with hypertensive crisis may be unaware of their hypertension. From NHANES III, the prevalence of hypertension among adults in the United States was estimated to be 27%. Nearly a third of the hypertensive individuals were unaware of their hypertension.
14
In the US, nearly 1 in 3 adults has hypertension, yet only about 70% are treated and only half of those are controlled.16 Over a similar timeframe, hospitalizations for hypertension and hypertension related illness have steadily increased.17 18 Pathophysiology Individual organ systems are able to mitigate swings in BP through vasoconstriction and vasodilatation of resistance vessels. With chronic hypertension, the resistance vessels will auto-regulate around a higher mean arterial pressure range. Hypertensive emergency occurs when there is an abrupt rise in systemic vascular resistance with a loss of auto-regulation causing damage to the endothelium and downstream tissue ischemia. 19 This commonly manifests as neurologic dysfunction, as in hypertensive encephalopathy, cardiac injury or renal injury.
The assessment of acute organ damage is paramount to the diagnosis of hypertensive emergency. Signs and symptoms of end-organ damage may be overt, as in an aortic dissection, or may be more subtle as in hypertensive encephalopathy. One challenge is how to distinguish acute injury from the ‘acute discovery’ of chronic damage. This can be especially difficult to determine in a patient with limited prior medical records where a baseline EKG or baseline renal function is not available. The benefit of evaluation of an inpatient with severe hypertension is that the hospitalization provides a natural window to monitor change in symptoms and signs over time. In deciding when and how to
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treat, however, the clinician must take into account the upward shift in the zone of auto-regulation that comes with chronic hypertension, and avoid inducing additional hypo-perfusion injury with overzealous lowering of the BP. History Exacerbated essential hypertension is the most common etiology for uncontrolled hypertension within the first hours of admission. The differential diagnosis for exacerbating factors include pain, anxiety, missed medications and urinary retention. A thorough medication history is necessary to uncover selftreatment with medications that may increase systemic vascular resistance such as non-steroidal antiinflammatory drugs (NSAIDs) and nasal decongestants. The history must inquire about the use of sympathomimetic drugs which vasoconstrict, including cocaine, amphetamines and ma-huang. Special attention should be paid to recently started medications whose side effects may include fluid retention and/or vasoconstriction, such as erythropoetin, corticosteroids and oral contraceptives. Drug withdrawal may precipitate hypertensive crisis, with the most prominent examples being alcohol withdrawal and clonidine.
20, 21
History and symptoms of connective tissue disease, including systemic lupus and scleroderma, should be noted as renal involvement with these diseases can produce unique syndromes of hypertensive crisis. Secondary hypertension should be suspected if a prior history of resistant hypertension exists, as 10% of patients with resistant hypertension will have a secondary cause.22 The percentage of hypertension due to secondary causes rises to 17% in patients older than 60 years, with the most common secondary causes being obstructive sleep apnea, renal parenchymal disease, renal vascular hypertension and aldosteronism. Less common causes of secondary hypertension include hypo- and hyperthyroidism, pheochromocytoma, Cushing’s syndrome and aortic coarctation. 23, 24
Hypertensive disorders of pregnancy, including pregnancy, including preeclampsia, have been increasing in prevalence with a general increase in average maternal age and the rise of obesity.25 Pregnancy influences the differential diagnosis of hypertension in a woman of childbearing age. Antepartum and immediate postpartum hypertension, however, is unexpected to be solely managed by a hospitalist physician. Extensive discussion of the hypertensive disorders of pregnancy is beyond the scope of this review. Physical Examination
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The careful exam should include ophthalmologic evaluation for retinal hemorrhages and papilledema. Blood pressure should be measured in both arms to identify a chronic arterial stenotic lesion, which may yield false BP values, or an acute vascular disruption which may occur with an aortic dissection. Auscultation of the carotid arteries may reveal stenoses that points to chronic atherosclerotic disease as well as raise the risk of cerebral hypotension with overzealous lowering of the BP. The cardiac exam must include palpation for the point of maximum impulse (PMI) to assess for chronicity of hypertension with a prominent sustained impulse consistent with hypertensive cardiomyopathy. The exam should include physical maneuvers to listen for a diastolic murmur, which is an ominous sign of proximal aorta involvement in aortic dissection, and the systolic murmur of aortic stenosis. In aortic stenosis, flow in the epicardial coronary arteries relies on the presssure differential between the diastolic BP and the left intraventricular pressure. Rapid lowering of the systolic BP in severe aortic stenosis may result in cardiac ischemia. Pulmonary edema is a common presentation of hypertensive emergency and its presence can influence subsequent treatment strategy, e.g., administration of diuretics or non-invasive positive airway pressure. 12 The exam must include auscultation of the lungs for congestion and examination of jugular venous volume. The renal arteries are the last aortic arterial branch prior to the iliac bifurcation, and stenoses may result in bruits which can be heard just superior and lateral to the umbilicus. If the patient’s habitus makes auscultation of this area difficult, finding a femoral bruit increases the likelihood that the renal arteries have a similar burden of atherosclerosis. 26 A cautious neurologic exam, including mental status exam to assess for signs of encephalopathy, should be performed and documented as it will serve as a benchmark by which to measure serial exams as
antihypertensive treatment is initiated. Acute hemorrhagic stroke is both a result of severe hypertension and a driver of hypertension through sympathetic nervous system stimulation. Any cause of intracerebral hypertension, including trauma, tumor, hemorrhage and infarction may produce an acute increase in systemic BP.27 Less common neurologic causes of severe hypertension include autonomic dysfunction from spinal cord injury or Guillain Barre syndrome. 28 These neurologic causes of severe hypertension should be evident from the neurologic exam. Initial Laboratory Testing and Imaging
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Initial laboratory testing should include a metabolic panel to assess for renal function, and for hypokalemia, which can suggest possible aldosterone excess. Microscopic hematuria on urinalysis, much like retinal hemorrhages on funduscopic exam, may be due to microvascular injury as a result of severe hypertension, or may be a sign of endothelial inflammation due to a microangiopathic hemolysis (MAHA) or a small-vessel vasculitis.29 If the hematuria is due to glomerulonephritis, proteinuria will often be present in the urinalysis. Toxicology screen may reveal ingestions that had not been suggested by the medical history, and is necessary when the patient is unable to provide a history. The CBC may uncover a new anemia or thrombocytopenia raising concern for microangiopathic hemorrhagic anemia or vasculitis. If either is present, a blood smear, LDH and haptoglobin can further clarify the mechanism of the cytopenias. The cardiac biomarkers troponin T or troponin I, and NT-BNP assess for hypertension-related cardiac ischemia and ventricular overload, respectively. An EKG should be obtained to assess for both chronic changes of hypertension with ventricular enlargement or strain as well as to assess for acute ischemia. Judicious use of a CXR in symptomatic patients can document pulmonary edema related to hypertension-induced cardiac dysfunction. A widened mediastinum may suggest aortic dissection. However, plain radiography alone is not sensitive enough, and bedside transesophageal echocardiography or contrast chest CT angiography are indicated to assess for presence and extent of dissection in concerning clinical scenarios.30 Any physical exam findings suggestive of acute neurologic injury should prompt urgent non-contrast head CT to assess for intracranial bleeding. If negative, an MRI may reveal evidence of hypertensive encephalopathy or a brain neoplasm not readily detected on CT. Pace of Treatment
The necessity for treatment of hypertension with evidence of acute end-organ damage is a widely held opinion. However, a 2008 Cochrane review found insufficient trial evidence to either support or discard this practice. 31 The consensus remains that patients with hypertensive emergency, i.e., acute hypertensive end-organ injury should be treated. The BP should be reduced in a timeframe of minutes to a few hours, and the patient may require an admission to the ICU for closer monitoring.
32
The goal
of treatment is to lower the blood pressure back into the ‘auto-regulated’ range and, in general, means a 25% initial reduction of the BP.
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Exceptions to this 25% rule are the clinical situations of intra-cerebral hemorrhage, ischemic stroke and acute aortic dissection for which rapid lowering to a normal range must be guided by specialist involvement33. 34-36 A recent study of rapid lowering of blood pressure in patients with acute intracerebral hemorrhage found no difference in death or severe disability with rapid reduction in blood pressure, but a significant secondary outcome of improved functional ability. 36 The pace of blood pressure reduction in hypertensive urgency or severe asymptomatic hypertension is unclear with proposed time frames that range from hours to days.
5, 37
The risk of immediate
cardiovascular morbidity in asymptomatic patients is very low. In one of the earliest studies looking at antihypertensive treatment versus placebo in patients with asymptomatic severe hypertension, no patient in the untreated placebo group had an adverse morbid outcome in the first three months of the trial, and only 6% of the placebo group had an adverse event at four months. 38 Overly zealous or rapid correction risks lowering blood pressure beyond the range of auto-regulation and precipitating end-organ ischemia.
39, 40
Elderly patients and patients with a wide pulse pressure,
signifying underlying vascular stiffness, are at high risk for injury from overly rapid reduction. 41 A consideration in patients with asymptomatic severe hypertension is to deescalate the environment and recheck BP at frequent intervals. In an ER study, almost a third of the patients with hypertensive urgency responded with reduction of blood pressures to non-urgent ranges with just a thirty minute period spent resting in a quiet room. 42 Drug Therapy Table 1 shows the drugs studied for treatment of hypertensive emergency by category. A 2008 Cochrane review of drugs for the treatment of hypertensive emergencies found no clear benefit of any pharmacologic therapy for hypertensive emergency. 31 The most commonly used medications in
emergency settings are nicardipine and labetalol. Nicardipine may be more effective at reducing blood pressure to therapeutic goals in hypertensive emergency in the ER. 43-46 There are clear drugs of choice in a few clinical scenarios of hypertensive emergency. Scleroderma renal crisis is a syndrome of acute kidney injury, often with severe hypertension, that is an uncommon but morbid complication of systemic sclerosis. ACE inhibitors are the drugs of choice for treatment and management of this complication. In this setting collaboration with consultants such as nephrology and rheumatology may be desirable.
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A unique clinical scenario is a pregnant woman who presents with preeclampsia or eclampsia. In these patients, volume excess is often present and lowering of the blood pressure and/or the rapid delivery of the fetus is often indicated.25 In these special patients, it is important to note that only a limited number of BP lowering medications are deemed safe. These agents include methyldopa, hydralazine, labetalol and, if necessary to manage volume overload, loop diuretics, however optimal management remains unclear and is best guided by obstetrical expertise. 47 The drug of choice and route of administration for hospitalized patients with nonspecific severe hypertension also is unclear. As discussed before, the rapidity of BP reduction must always be weighed against the risk of a potential adverse event. A University of Michigan study looked at PRN orders for intravenous hydralazine and labetalol among patients hospitalized for a reason other than hypertension – only 2.9% of the patients had ICD9 codes at discharge that reflected an established indication for acute treatment – with the majority of that group having a subarachanoid hemorrhage. That study showed wide variation in the dosing of these medications and found an association between receipt of these medication and longer length of stay. 48 Initial studies with propanolol showed worsening of cocaine-induced hypertension and myocardial ischemia due to an unopposed alpha effect. 49 Subsequent guidelines have discouraged the use of similar medications in patients with cocaine use. 50 The risk, though, of worsening myocardial ischemia and hypertension is likely low with ER studies showing no significant increased risk when cocaine use was discovered after initial beta-blocker treatment. 51 Special Situations; Perioperative Setting and Discharge.
Patients with chronic hypertension are at increased risk of complications and death after surgery. 52 The management of preoperative hypertension, however, is controversial as some therapies may increase the risk of intra-operative hypotension. 53-55 Acute postoperative hypertension (APH) is defined as an acute rise in blood pressure in the immediate postoperative period and may result in acute cardiac or neurologic symptoms as well as increased bleeding. APH may occur after any major surgery but is commonly associated with cardiovascular, neurosurgical and head and neck procedures. 56 The pathophysiology underlying APH is not well
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defined. Several factors have been implicated, including held medications, peri-operative volume resuscitation, intra-operative medications and sympathetic stimulation. The acuity and risk for both surgical and medical morbidity from APH requires rapid lowering of blood pressure, and must be tailored to the clinical circumstances such as volume overload or neurologic symptoms. Severe hypertension is often a barrier to discharge though the risk of near-term complication in asymptomatic patients is quite low. 10 Delay of discharge due to asymptomatic hypertension may be a decision driven more by discomfort, on the part of nurses, physicians-in-training and hospitalists, rather than on clear evidence of harm. In a multicenter study looking at trainees in Internal Medicine, Family Medicine and Surgery, however, the numerical threshold for asymptomatic hypertension that should delay discharge varied between attendings and resident trainees.9 All trainees had a strong preference for discharging on the new regimen derived during the hospitalization. Only a small minority, < 10%, indicated that they would seek input from a primary care provider when altering blood pressure medicines in even a complex heart failure patient with difficult-to-control hypertension. 8 Discharge of hypertensive patients on a new regimen runs the risk of post-discharge hypotension and unintended poly-pharmacy. There is also a theoretical loss of care continuity and provider time with a patient’s primary care provider if a previously effective outpatient regimen is altered to control inpatient asymptomatic hypertension. 9 The addition of new antihypertensive medications to a patient’s outpatient regimen can incur both a financial cost to the patient and a time cost to follow-up with the primary care provider. Consideration for direct communication with the primary care provider at the time of discharge may help to limit these costs. It is also highly desirable for patients to have timely outpatient follow-up with their primary care physician in order to monitor the effectiveness of the revised medication regimen.
Conclusions Hypertensive emergency and urgency have primarily been described and studied in the Emergency Room setting and there is little literature to-date to define their optimal management in inpatients. Hypertensive emergency, with clear evidence of tissue damage from hypertension, is an indication for rapid lowering of blood pressure, triage to a site of closer monitoring and may require the consultation of subspecialists to aid in evaluation and management. Hypertensive urgency and severe asymptomatic hypertension in the hospital require careful history and exam to assess for etiology and consequence.
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The decision to treat severe hypertension must come with consideration of the risk of no treatment balanced with the risk of overtreatment. If and how the inpatient treatment of hypertension affects near and long-term clinical outcomes is unknown and is an area for further study.
Financial and competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Table legend
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Table 1: The drugs studied for treatment of hypertensive emergency by category. Mechanism of Action
IV Antihypertensive Drug
Initial Dosage
Onset of Action
Duration of Action
Arterial vasodilators
Hydralazine Fenoldapam ( infusion) Nicardipine (infusion)
10-20 mg 0.03-0.1mcg/kg/min 5 mg/hr
5-10 min 10 min
ISSN: 2154-8331 (Print) 2377-1003 (Online) Journal homepage: http://www.tandfonline.com/loi/ihop20
Hypertensive Urgencies and Emergencies in the Hospital Setting Cynthia M. Cooper MD & Andrew Z. Fenves MD, FACP, FASN To cite this article: Cynthia M. Cooper MD & Andrew Z. Fenves MD, FACP, FASN (2016): Hypertensive Urgencies and Emergencies in the Hospital Setting, Hospital Practice, DOI: 10.1080/21548331.2016.1141657 To link to this article: http://dx.doi.org/10.1080/21548331.2016.1141657
Accepted author version posted online: 18 Jan 2016.
Submit your article to this journal
Article views: 6
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View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ihop20 Download by: [Orta Dogu Teknik Universitesi]
Date: 25 January 2016, At: 16:31
Publisher: Taylor & Francis Journal: Hospital Practice DOI: 10.1080/21548331.2016.1141657 Article Type: Review
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
Hypertensive Urgencies and Emergencies in the Hospital Setting
Running Title: Hypertensive Emergencies for Hospitalists Authors: Cynthia M. Cooper MD, Andrew Z. Fenves MD, FACP, FASN Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Corresponding Author: Cynthia M. Cooper MD Massachusetts General Hospital 50 Staniford St., Suite 503B Boston, MA 02114 USA Phone 617-643-0595 Fax 617-724-9428 [email protected]
Abstract The prevalence of hypertension in the general population has steadily climbed over the past several decades and hypertension is a primary or secondary diagnosis in nearly a fourth of hospitalized adults. Hospitalization is often a time of pertubation in a patient’s usual blood pressure control, with pain, anxiety and missed medications all risk factors for severe hypertension. Hospitalists are often faced with severe hypertension in a patient not previously known to them and this presents a challenge of how best to assess the clinical importance of blood pressure elevation. An additional challenge is the lack of
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
literature to guide the optimal management of hypertension in inpatients. This review aims to describe the scope of the problem, to describe the near and long-term risks of overzealous blood pressure management, and to identify areas for future study. Keywords: hypertension; hospitalist; inpatient; emergency; urgency
Introduction The incidence of hypertension is rising and more hospitalized patients are admitted for and with hypertension. Little data exists, however, on the optimal inpatient management of hypertension and crises of hypertension, e.g., hypertensive urgency and emergency, in the hospital. We present an overview of inpatient hypertension assessment and management focused on the hospitalist clinician. Definitions
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
Hypertensive emergency is typically defined as severe hypertension which results in acute end organ injury. 1 Hypertensive urgency is less clearly defined with definitions in the literature ranging from those based on specific blood pressures, typically SBP>180 mmHg and DBP >120 mmHg, to severe hypertension in a patient with established organ injury and, ostensibly, at high risk for additional injury.
2-6
Hypertensive crisis is a term which encompasses both hypertensive emergency and
hypertensive urgency and is also often used in the literature. In this paper, we will use the term ‘hypertensive emergency’ for a clinical scenario with clear evidence for tissue injury and ‘hypertensive urgency’ for severe hypertension without objective damage. The bulk of the medical literature on hypertensive urgencies and emergencies focus on the Emergency Room (ER) setting.7 Severe hypertension in hospitalized patients is much less well-studied, with small studies suggesting most practitioners extrapolate recommendations from outpatient guidelines, e.g., JNC8, to the inpatient setting.8, 9 Whether this is a valid extrapolation for the management of patients hospitalized for reasons other than hypertension, however, is unclear. In a University of Michigan study of residents and hospitalists looking at beliefs around blood pressure (BP) values that required treatment, intensive care unit (ICU) transfers or delay in discharge showed decisions based on limited factual data.
9
The literature on ER management of hypertension is evolving, and the indications for hospital admission are an area of debate.
10
We intend to review the management of hypertensive crisis for hospitalists,
and delineate the differential diagnosis of severe hypertension which may develop in a hospital setting. Incidence and Risk Factors Over the period from 2006 to 2012, nearly a quarter of all adult ER visits in the US were coded with an ICD-0 code for hypertension. Almost 4% had hypertension as the primary diagnosis, and the populationbased incidence rose 5.2% each year. 11 One of the earliest papers to report incidence of hypertensive
crisis in the ER setting found 3% of patients visiting a single adult Emergency Department had a diastolic blood pressure (DBP) >120mmHg. A quarter of these patients were deemed to have hypertensive emergency. 7 A more recent multicenter study noted 0.4% of adult ER visits had a systolic BP >220 mmHg and/or a diastolic BP of >120 mmHg. Again, one quarter of these were diagnosed as hypertensive emergency.12 The median age of patients with hypertensive emergency in both of these studies was 65 years, and the majority had a prior diagnosis of hypertension. In a case control study of patients presenting to two inner city ERs who were found to have severe
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uncontrolled hypertension but not hypertensive emergency, significant risk factors included male sex, black race, and alcohol or illicit drug use. In this population, a lack of primary care and non-adherence with medications significantly increased the odds of severe uncontrolled hypertension. 13 The NHANES III study found male sex as well as age >65 years to be significant risk factors for uncontrolled hypertension, but found non-Hispanic black race and lack of access as being minor risk factors.14 Nearly all the patients with uncontrolled hypertension in NHANES III had insurance and regular access to medical care, suggesting that other patient and physician factors contributed to the lack of control. 15 Though prior history of hypertension is a risk factor for hypertensive crisis, patients presenting with hypertensive crisis may be unaware of their hypertension. From NHANES III, the prevalence of hypertension among adults in the United States was estimated to be 27%. Nearly a third of the hypertensive individuals were unaware of their hypertension.
14
In the US, nearly 1 in 3 adults has hypertension, yet only about 70% are treated and only half of those are controlled.16 Over a similar timeframe, hospitalizations for hypertension and hypertension related illness have steadily increased.17 18 Pathophysiology Individual organ systems are able to mitigate swings in BP through vasoconstriction and vasodilatation of resistance vessels. With chronic hypertension, the resistance vessels will auto-regulate around a higher mean arterial pressure range. Hypertensive emergency occurs when there is an abrupt rise in systemic vascular resistance with a loss of auto-regulation causing damage to the endothelium and downstream tissue ischemia. 19 This commonly manifests as neurologic dysfunction, as in hypertensive encephalopathy, cardiac injury or renal injury.
The assessment of acute organ damage is paramount to the diagnosis of hypertensive emergency. Signs and symptoms of end-organ damage may be overt, as in an aortic dissection, or may be more subtle as in hypertensive encephalopathy. One challenge is how to distinguish acute injury from the ‘acute discovery’ of chronic damage. This can be especially difficult to determine in a patient with limited prior medical records where a baseline EKG or baseline renal function is not available. The benefit of evaluation of an inpatient with severe hypertension is that the hospitalization provides a natural window to monitor change in symptoms and signs over time. In deciding when and how to
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
treat, however, the clinician must take into account the upward shift in the zone of auto-regulation that comes with chronic hypertension, and avoid inducing additional hypo-perfusion injury with overzealous lowering of the BP. History Exacerbated essential hypertension is the most common etiology for uncontrolled hypertension within the first hours of admission. The differential diagnosis for exacerbating factors include pain, anxiety, missed medications and urinary retention. A thorough medication history is necessary to uncover selftreatment with medications that may increase systemic vascular resistance such as non-steroidal antiinflammatory drugs (NSAIDs) and nasal decongestants. The history must inquire about the use of sympathomimetic drugs which vasoconstrict, including cocaine, amphetamines and ma-huang. Special attention should be paid to recently started medications whose side effects may include fluid retention and/or vasoconstriction, such as erythropoetin, corticosteroids and oral contraceptives. Drug withdrawal may precipitate hypertensive crisis, with the most prominent examples being alcohol withdrawal and clonidine.
20, 21
History and symptoms of connective tissue disease, including systemic lupus and scleroderma, should be noted as renal involvement with these diseases can produce unique syndromes of hypertensive crisis. Secondary hypertension should be suspected if a prior history of resistant hypertension exists, as 10% of patients with resistant hypertension will have a secondary cause.22 The percentage of hypertension due to secondary causes rises to 17% in patients older than 60 years, with the most common secondary causes being obstructive sleep apnea, renal parenchymal disease, renal vascular hypertension and aldosteronism. Less common causes of secondary hypertension include hypo- and hyperthyroidism, pheochromocytoma, Cushing’s syndrome and aortic coarctation. 23, 24
Hypertensive disorders of pregnancy, including pregnancy, including preeclampsia, have been increasing in prevalence with a general increase in average maternal age and the rise of obesity.25 Pregnancy influences the differential diagnosis of hypertension in a woman of childbearing age. Antepartum and immediate postpartum hypertension, however, is unexpected to be solely managed by a hospitalist physician. Extensive discussion of the hypertensive disorders of pregnancy is beyond the scope of this review. Physical Examination
Downloaded by [Orta Dogu Teknik Universitesi] at 16:31 25 January 2016
The careful exam should include ophthalmologic evaluation for retinal hemorrhages and papilledema. Blood pressure should be measured in both arms to identify a chronic arterial stenotic lesion, which may yield false BP values, or an acute vascular disruption which may occur with an aortic dissection. Auscultation of the carotid arteries may reveal stenoses that points to chronic atherosclerotic disease as well as raise the risk of cerebral hypotension with overzealous lowering of the BP. The cardiac exam must include palpation for the point of maximum impulse (PMI) to assess for chronicity of hypertension with a prominent sustained impulse consistent with hypertensive cardiomyopathy. The exam should include physical maneuvers to listen for a diastolic murmur, which is an ominous sign of proximal aorta involvement in aortic dissection, and the systolic murmur of aortic stenosis. In aortic stenosis, flow in the epicardial coronary arteries relies on the presssure differential between the diastolic BP and the left intraventricular pressure. Rapid lowering of the systolic BP in severe aortic stenosis may result in cardiac ischemia. Pulmonary edema is a common presentation of hypertensive emergency and its presence can influence subsequent treatment strategy, e.g., administration of diuretics or non-invasive positive airway pressure. 12 The exam must include auscultation of the lungs for congestion and examination of jugular venous volume. The renal arteries are the last aortic arterial branch prior to the iliac bifurcation, and stenoses may result in bruits which can be heard just superior and lateral to the umbilicus. If the patient’s habitus makes auscultation of this area difficult, finding a femoral bruit increases the likelihood that the renal arteries have a similar burden of atherosclerosis. 26 A cautious neurologic exam, including mental status exam to assess for signs of encephalopathy, should be performed and documented as it will serve as a benchmark by which to measure serial exams as
antihypertensive treatment is initiated. Acute hemorrhagic stroke is both a result of severe hypertension and a driver of hypertension through sympathetic nervous system stimulation. Any cause of intracerebral hypertension, including trauma, tumor, hemorrhage and infarction may produce an acute increase in systemic BP.27 Less common neurologic causes of severe hypertension include autonomic dysfunction from spinal cord injury or Guillain Barre syndrome. 28 These neurologic causes of severe hypertension should be evident from the neurologic exam. Initial Laboratory Testing and Imaging
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Initial laboratory testing should include a metabolic panel to assess for renal function, and for hypokalemia, which can suggest possible aldosterone excess. Microscopic hematuria on urinalysis, much like retinal hemorrhages on funduscopic exam, may be due to microvascular injury as a result of severe hypertension, or may be a sign of endothelial inflammation due to a microangiopathic hemolysis (MAHA) or a small-vessel vasculitis.29 If the hematuria is due to glomerulonephritis, proteinuria will often be present in the urinalysis. Toxicology screen may reveal ingestions that had not been suggested by the medical history, and is necessary when the patient is unable to provide a history. The CBC may uncover a new anemia or thrombocytopenia raising concern for microangiopathic hemorrhagic anemia or vasculitis. If either is present, a blood smear, LDH and haptoglobin can further clarify the mechanism of the cytopenias. The cardiac biomarkers troponin T or troponin I, and NT-BNP assess for hypertension-related cardiac ischemia and ventricular overload, respectively. An EKG should be obtained to assess for both chronic changes of hypertension with ventricular enlargement or strain as well as to assess for acute ischemia. Judicious use of a CXR in symptomatic patients can document pulmonary edema related to hypertension-induced cardiac dysfunction. A widened mediastinum may suggest aortic dissection. However, plain radiography alone is not sensitive enough, and bedside transesophageal echocardiography or contrast chest CT angiography are indicated to assess for presence and extent of dissection in concerning clinical scenarios.30 Any physical exam findings suggestive of acute neurologic injury should prompt urgent non-contrast head CT to assess for intracranial bleeding. If negative, an MRI may reveal evidence of hypertensive encephalopathy or a brain neoplasm not readily detected on CT. Pace of Treatment
The necessity for treatment of hypertension with evidence of acute end-organ damage is a widely held opinion. However, a 2008 Cochrane review found insufficient trial evidence to either support or discard this practice. 31 The consensus remains that patients with hypertensive emergency, i.e., acute hypertensive end-organ injury should be treated. The BP should be reduced in a timeframe of minutes to a few hours, and the patient may require an admission to the ICU for closer monitoring.
32
The goal
of treatment is to lower the blood pressure back into the ‘auto-regulated’ range and, in general, means a 25% initial reduction of the BP.
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Exceptions to this 25% rule are the clinical situations of intra-cerebral hemorrhage, ischemic stroke and acute aortic dissection for which rapid lowering to a normal range must be guided by specialist involvement33. 34-36 A recent study of rapid lowering of blood pressure in patients with acute intracerebral hemorrhage found no difference in death or severe disability with rapid reduction in blood pressure, but a significant secondary outcome of improved functional ability. 36 The pace of blood pressure reduction in hypertensive urgency or severe asymptomatic hypertension is unclear with proposed time frames that range from hours to days.
5, 37
The risk of immediate
cardiovascular morbidity in asymptomatic patients is very low. In one of the earliest studies looking at antihypertensive treatment versus placebo in patients with asymptomatic severe hypertension, no patient in the untreated placebo group had an adverse morbid outcome in the first three months of the trial, and only 6% of the placebo group had an adverse event at four months. 38 Overly zealous or rapid correction risks lowering blood pressure beyond the range of auto-regulation and precipitating end-organ ischemia.
39, 40
Elderly patients and patients with a wide pulse pressure,
signifying underlying vascular stiffness, are at high risk for injury from overly rapid reduction. 41 A consideration in patients with asymptomatic severe hypertension is to deescalate the environment and recheck BP at frequent intervals. In an ER study, almost a third of the patients with hypertensive urgency responded with reduction of blood pressures to non-urgent ranges with just a thirty minute period spent resting in a quiet room. 42 Drug Therapy Table 1 shows the drugs studied for treatment of hypertensive emergency by category. A 2008 Cochrane review of drugs for the treatment of hypertensive emergencies found no clear benefit of any pharmacologic therapy for hypertensive emergency. 31 The most commonly used medications in
emergency settings are nicardipine and labetalol. Nicardipine may be more effective at reducing blood pressure to therapeutic goals in hypertensive emergency in the ER. 43-46 There are clear drugs of choice in a few clinical scenarios of hypertensive emergency. Scleroderma renal crisis is a syndrome of acute kidney injury, often with severe hypertension, that is an uncommon but morbid complication of systemic sclerosis. ACE inhibitors are the drugs of choice for treatment and management of this complication. In this setting collaboration with consultants such as nephrology and rheumatology may be desirable.
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A unique clinical scenario is a pregnant woman who presents with preeclampsia or eclampsia. In these patients, volume excess is often present and lowering of the blood pressure and/or the rapid delivery of the fetus is often indicated.25 In these special patients, it is important to note that only a limited number of BP lowering medications are deemed safe. These agents include methyldopa, hydralazine, labetalol and, if necessary to manage volume overload, loop diuretics, however optimal management remains unclear and is best guided by obstetrical expertise. 47 The drug of choice and route of administration for hospitalized patients with nonspecific severe hypertension also is unclear. As discussed before, the rapidity of BP reduction must always be weighed against the risk of a potential adverse event. A University of Michigan study looked at PRN orders for intravenous hydralazine and labetalol among patients hospitalized for a reason other than hypertension – only 2.9% of the patients had ICD9 codes at discharge that reflected an established indication for acute treatment – with the majority of that group having a subarachanoid hemorrhage. That study showed wide variation in the dosing of these medications and found an association between receipt of these medication and longer length of stay. 48 Initial studies with propanolol showed worsening of cocaine-induced hypertension and myocardial ischemia due to an unopposed alpha effect. 49 Subsequent guidelines have discouraged the use of similar medications in patients with cocaine use. 50 The risk, though, of worsening myocardial ischemia and hypertension is likely low with ER studies showing no significant increased risk when cocaine use was discovered after initial beta-blocker treatment. 51 Special Situations; Perioperative Setting and Discharge.
Patients with chronic hypertension are at increased risk of complications and death after surgery. 52 The management of preoperative hypertension, however, is controversial as some therapies may increase the risk of intra-operative hypotension. 53-55 Acute postoperative hypertension (APH) is defined as an acute rise in blood pressure in the immediate postoperative period and may result in acute cardiac or neurologic symptoms as well as increased bleeding. APH may occur after any major surgery but is commonly associated with cardiovascular, neurosurgical and head and neck procedures. 56 The pathophysiology underlying APH is not well
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defined. Several factors have been implicated, including held medications, peri-operative volume resuscitation, intra-operative medications and sympathetic stimulation. The acuity and risk for both surgical and medical morbidity from APH requires rapid lowering of blood pressure, and must be tailored to the clinical circumstances such as volume overload or neurologic symptoms. Severe hypertension is often a barrier to discharge though the risk of near-term complication in asymptomatic patients is quite low. 10 Delay of discharge due to asymptomatic hypertension may be a decision driven more by discomfort, on the part of nurses, physicians-in-training and hospitalists, rather than on clear evidence of harm. In a multicenter study looking at trainees in Internal Medicine, Family Medicine and Surgery, however, the numerical threshold for asymptomatic hypertension that should delay discharge varied between attendings and resident trainees.9 All trainees had a strong preference for discharging on the new regimen derived during the hospitalization. Only a small minority, < 10%, indicated that they would seek input from a primary care provider when altering blood pressure medicines in even a complex heart failure patient with difficult-to-control hypertension. 8 Discharge of hypertensive patients on a new regimen runs the risk of post-discharge hypotension and unintended poly-pharmacy. There is also a theoretical loss of care continuity and provider time with a patient’s primary care provider if a previously effective outpatient regimen is altered to control inpatient asymptomatic hypertension. 9 The addition of new antihypertensive medications to a patient’s outpatient regimen can incur both a financial cost to the patient and a time cost to follow-up with the primary care provider. Consideration for direct communication with the primary care provider at the time of discharge may help to limit these costs. It is also highly desirable for patients to have timely outpatient follow-up with their primary care physician in order to monitor the effectiveness of the revised medication regimen.
Conclusions Hypertensive emergency and urgency have primarily been described and studied in the Emergency Room setting and there is little literature to-date to define their optimal management in inpatients. Hypertensive emergency, with clear evidence of tissue damage from hypertension, is an indication for rapid lowering of blood pressure, triage to a site of closer monitoring and may require the consultation of subspecialists to aid in evaluation and management. Hypertensive urgency and severe asymptomatic hypertension in the hospital require careful history and exam to assess for etiology and consequence.
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The decision to treat severe hypertension must come with consideration of the risk of no treatment balanced with the risk of overtreatment. If and how the inpatient treatment of hypertension affects near and long-term clinical outcomes is unknown and is an area for further study.
Financial and competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Table legend
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Table 1: The drugs studied for treatment of hypertensive emergency by category. Mechanism of Action
IV Antihypertensive Drug
Initial Dosage
Onset of Action
Duration of Action
Arterial vasodilators
Hydralazine Fenoldapam ( infusion) Nicardipine (infusion)
10-20 mg 0.03-0.1mcg/kg/min 5 mg/hr
5-10 min 10 min
